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1. The effect of perioperative packed red blood cells transfusion on patient outcomes after liver transplant for hepatocellular carcinoma

Author

Peter Yoon, Trevor Reichman, Marco P. A. W. Claasen, Adam Badenoch, Phillipe Abreu, David P. Al-Adra, Hala Muaddi, Andre Gorgen, Stuart A. McCluskey, Gonzalo Sapisochin, Anand Ghanekar, and Tommy Ivanics

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Erythrocytes, Hepatology, PRBC Transfusion, business.industry, medicine.medical_treatment, Liver Neoplasms, Gastroenterology, Perioperative, Liver transplantation, medicine.disease, Liver Transplantation, Red blood cell, medicine.anatomical_structure, Internal medicine, Hepatocellular carcinoma, Propensity score matching, medicine, Humans, Cumulative incidence, Packed red blood cells, business, Retrospective Studies
Abstract

Background The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC. Methods Patients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders. Results Of the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p = 0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p = 0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71–1.78, p = 0.61) or OS (HR 1.04, 95%CI 0.71–1.54, p = 0.83). Conclusion Perioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.

Published
2022

2. Adherence, resistance, and viral suppression on dolutegravir in sub-Saharan Africa: implications for the TLD era

Author

Suzanne M. McCluskey, Ravindra K. Gupta, Andrew Hill, Mark J. Siedner, Toby Pepperrell, and Willem D F Venter

Subjects
medicine.medical_specialty, Efavirenz, Sub saharan, Anti-HIV Agents, Pyridones, Immunology, HIV Infections, Article, Piperazines, chemistry.chemical_compound, Oxazines, medicine, Humans, Immunology and Allergy, Viral suppression, Intensive care medicine, business.industry, Antiretroviral therapy, VIROLOGIC FAILURE, Clinical trial, Infectious Diseases, chemistry, Dolutegravir, business, Heterocyclic Compounds, 3-Ring, HIV drug resistance
Abstract

Dolutegravir (DTG) is now a component of preferred first-line antiretroviral therapy (ART) worldwide. ADVANCE and NAMSAL were two landmark clinical trials conducted exclusively in sub-Saharan Africa, which studied the effectiveness of DTG-based first-line regimens for ART-naive individuals. In this review, we examine the data from these studies to consider the contributions of adherence and HIV drug resistance to treatment failure on DTG-based ART, as compared with efavirenz (EFV)-based ART, which has a lower genetic barrier to resistance. We also discuss the implications of virologic failure on DTG and consolidate currently available data to conclude with recommendations for virologic monitoring on DTG-based ART.

Published
2021

3. Epidemiology and survival trends of motor neurone disease in Northern Ireland from 2015 to 2019

Author

Karen E. Morrison, Colette Donaghy, Stephanie Duguez, Gavin McCluskey, Stephen Haffey, and William Duddy

Subjects
Male, Pediatrics, medicine.medical_specialty, education.field_of_study, business.industry, Proportional hazards model, Incidence, Incidence (epidemiology), Amyotrophic Lateral Sclerosis, Population, Prevalence, Northern Ireland, Confidence interval, Neurology, Epidemiology, medicine, Humans, Neurology (clinical), Motor Neuron Disease, Family history, Age of onset, education, business, Aged
Abstract

BACKGROUND AND PURPOSE This study evaluates the incidence, prevalence and survival trends of motor neurone disease (MND) in Northern Ireland from 2015 to 2019. METHODS A capture-recapture analysis was performed using five independent data sources. Incidence and prevalence rates were standardized to the European Standard Population. Survival outcomes were analysed using Kaplan-Meier curves and Cox regression analysis. RESULTS Amongst 254 total cases of MND, capture-recapture analysis estimated three missing cases (case ascertainment 98.8%). Age standardized incidence of captured cases was 3.12 per 100,000 (2.73, 3.50) and standardized prevalence ranged from 9.45 to 6.49 per 100,000 from 2015 to 2019. Standardized incidence and prevalence rates in 2006 were 1.4 and 3.3 per 100,000 respectively. Of identified cases, 133 (52.4%) were male; 94.5% had amyotrophic lateral sclerosis; median age of onset was 67 years; median time to diagnosis was 12 months (95% confidence interval 11.2, 12.8); survival from diagnosis was 12 months (95% confidence interval 10.6, 15.4); 25 (9.8%) reported a family history of MND or frontotemporal dementia; and a known MND-associated genetic mutation was identified in 7.9% of total cases, of which the most common was C9orf72 (5.7% of all patients). Factors associated with improved survival were younger age at onset, longer time to diagnosis, attendance at regional MND clinic, and initial neurology presentation as outpatient (all p

Published
2021

4. Fluid management for kidney transplantation: is it really about more or less?

Author

S. Joseph Kim, Paula Perez Jimenez, and Stuart A. McCluskey

Subjects
medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, Anesthesiology, Anesthesia, Pain medicine, medicine, General Medicine, Fluid management, business, medicine.disease, Intensive care medicine, Kidney transplantation
Published
2021

5. Infective Necrotizing Scleritis After XEN Gel Stent With Mitomycin-C

Author

Sophia Zagora, Ezekiel J Kingston, Jed Lusthaus, Richard Symes, Pushpa Raman, and Peter McCluskey

Subjects
medicine.medical_specialty, Intraocular pressure, Visual acuity, Mitomycin, medicine.medical_treatment, Glaucoma, Staphylococcus lugdunensis, medicine, Glaucoma surgery, Humans, Glaucoma Drainage Implants, Intraocular Pressure, Aged, Past medical history, biology, business.industry, Stent, Cataract surgery, biology.organism_classification, medicine.disease, Surgery, Ophthalmology, Treatment Outcome, Female, Stents, medicine.symptom, business, Glaucoma, Open-Angle, Scleritis
Abstract

Purpose The purpose of this study was to report a case of infective necrotizing scleritis following XEN Gel Stent with mitomycin-C. Methods Case report. This is a case report of a 68-year-old woman. Results XEN Gel Stent glaucoma surgery enhanced with mitomycin-C 0.04% and combined with cataract surgery was performed at a regional center to manage the patient's primary open-angle glaucoma. Past medical history was significant for rheumatoid arthritis requiring treatment with methotrexate and adalimumab. Periocular pain and swelling developed 14 months after the initial operation, followed by a rapid deterioration of visual acuity to 20/60, intraocular pressure of 4 mm Hg, and worsening pain 5 months later. On initial presentation to Sydney Eye Hospital, 180 degrees of scleral necrosis was evident with a moderate anterior segment inflammatory reaction and a large temporal choroidal effusion due to hypotony. Empirical hourly topical ofloxacin and cephalothin 5% drops, with oral moxifloxacin, were initiated. Conjunctival swab grew Staphylococcus aureus and Staphylococcus lugdunensis. Significant clinical improvement occurred, but the XEN Gel Stent became exposed after 9 days of treatment with worsening hypotony. Urgent surgical revision was performed to remove the XEN Gel Stent and apply a tutoplast plug with overlying amniotic membrane graft. Intraocular pressure gradually improved over 6 weeks to 15 mm Hg with reversal of hypotonous changes, and visual acuity stabilized at 20/40. Conclusions To our knowledge, this is the first reported case of necrotizing scleritis following XEN Gel Stent insertion. It is a reminder that infection should always be the primary differential diagnosis in patients with surgical-induced necrotizing scleritis.

Published
2021

6. UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES

Author

Michael Giblin, Eline Whist, Ming-Lee Lin, Li-Anne Lim, Peter McCluskey, Lyndell L Lim, John H Chang, Tanya Karaconji, Andrew Symons, Richard Symes, John R. Grigg, and Vivek Chowdhury

Subjects
medicine.medical_specialty, medicine.medical_treatment, Case Report, 01 natural sciences, Case review, Uveitis, 03 medical and health sciences, Drug treatment, checkpoint, 0302 clinical medicine, melanoma, medicine, Humans, 0101 mathematics, Macular edema, Retrospective Studies, business.industry, Melanoma, 010102 general mathematics, Panuveitis, General Medicine, Immunotherapy, medicine.disease, Dermatology, Ophthalmology, 030221 ophthalmology & optometry, business, Retinopathy
Abstract

Supplemental Digital Content is Available in the Text. The largest case series to date describing uveitis occurring secondary to systemic treatments for malignant melanoma. Twenty-two cases are described. Uveitis occurred after treatment with checkpoint, BRAF, and mitogen-activated protein kinase inhibitors., Background/Purpose: To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma. Methods: A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified. Results: Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment. Conclusion: We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.

Published
2021

7. Barriers and facilitators to diabetic retinopathy screening within Australian primary care

Author

Mohamed Estai, John R. Grigg, Peter McCluskey, Yogesan Kanagasingam, Matthew J. G. Watson, and Judith Daire

Subjects
Adult, Male, medicine.medical_specialty, Medicine (General), National Health Programs, Eye, R5-920, Phone, Diabetic retinopathy, Diabetes Mellitus, medicine, Photography, Humans, Mass Screening, Aged, Primary Health Care, business.industry, Research, Diabetes, Australia, Champion, Middle Aged, Primary care, Schedule (workplace), Snowball sampling, Incentive, Family medicine, Facilitator, Screening, Thematic analysis, Family Practice, business, Qualitative research
Abstract

Background Despite recent incentives through Medicare (Australia’s universal health insurance scheme) to increase retinal screening rates in primary care, comprehensive diabetic retinopathy (DR) screening has not been reached in Australia. The current study aimed to identify key factors affecting the delivery of diabetic retinopathy (DR) screening in Australian general practices. Methods A descriptive qualitative study involving in-depth interviews was carried out from November 2019 to March 2020. Using purposive snowballing sampling, 15 general practitioners (GPs) were recruited from urban and rural general practices in New South Wales and Western Australia. A semi-structured interview guide was used to collect data from participants. All interviews were conducted over the phone by one facilitator, and each interview lasted up to 45 min. The Socio-Ecological Model was used to inform the content of the interview topic guides and subsequent data analysis. Recorded data were transcribed verbatim, and thematic analysis was conducted to identify and classify recurrent themes. Results Of 15 GPs interviewed, 13 were male doctors, and the mean age was 54.7 ± 15.5 years. Seven participants were practising in urban areas, while eight were practising in regional or remote areas. All participants had access to a direct ophthalmoscope, but none owned retinal cameras. None of the participants reported performing DR screening. Only three participants were aware of the Medicare Benefits Schedule (MBS) items 12,325 and 12,326 that allow GPs to bill for retinal screening. Seven themes, a combination of facilitators and barriers, emerged from interviews with the GPs. Despite the strong belief in their role in managing chronic diseases, barriers such as costs of retinal cameras, time constraints, lack of skills to make DR diagnosis, and unawareness of Medicare incentives for non-mydriatic retinal photography made it difficult to conduct DR screening in general practice. However, several enabling strategies to deliver DR screening within primary care include increasing GPs’ access to continuing professional development, subsidising the cost of retinal cameras, and the need for a champion ace to take the responsibility of retinal photography. Conclusion This study identified essential areas at the system level that require addressing to promote the broader implementation of DR screening, in particular, a nationwide awareness campaign to maximise the use of MBS items, improve GPs’ competency, and subsidise costs of the retinal cameras for small and rural general practices.

Published
2021

8. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial

Author

Michael Pulley, Mikko Kuoppamäki, Carolyn A Young, Jesus S. Mora Pardina, Kumaraswamy Sivakumar, Toni Sarapohja, Michael A. Elliott, Chafic Karam, Sandeep Rana, Orla Hardiman, Nathan P. Staff, Letizia Mazzini, Gabriele Mora, Thomas F. Meyer, Colleen O'Connell, Stéphanie Delstanche, Elham Bayat, Michael D. Weiss, Waqar Waheed, Nenad Mitrovic, Philippe Corcia, Marie-Hélène Soriani, Edward J. Kasarskis, Claudia Caponnetto, Dale J. Lange, Tuan Vu, Leo McCluskey, Berthold Schrank, Angela Genge, Matthew C. Kiernan, Valtteri V Aho, Manu Jokela, Philip Van Damme, Juan F. Vázquez Costa, Maurizio Inghilleri, Wolfgang Löscher, David Schultz, Tero Tapiola, Susanne Petri, Adriano Chiò, Gary L. Pattee, Julian Großkreutz, Ammar Al-Chalabi, Aziz Shaibani, Susan Mathers, Kevin J. Felice, Kimberly Goslin, James Caress, Matthias Boentert, Albert C. Ludolph, Aleksandar Radunovic, Robert D. Henderson, James Wymer, Todd Levine, Jakob Rath, Merrilee Needham, William Camu, Gaurav Guliani, Rune Johansson, Leonard H. van den Berg, Namita Goyal, Mark B. Bromberg, Bjorn Oskarsson, Annie Dionne, Eduardo Locatelli, Brent T. Harris, Suma Babu, Richard Bedlack, John Ravits, Jinsy A. Andrews, Philippe Couratier, Gabriele Siciliano, Hannu Laaksovirta, Kourosh Rezania, Lawrence Korngut, Eduardo Aguera Morales, Peter M Andersen, Eva Farrero Munoz, David Lacomis, Stephen N. Scelsa, Chris Garratt, Matthew Burford, Merit Cudkowicz, Nicholas J. Maragakis, Wendy Johnston, Martin M. Brown, Johannes Prudlo, Justin Y. Kwan, Dominic B. Fee, Senda Ajroud-Driss, Stephen A. Goutman, John Turnbull, Michael H. Rivner, Timothy M. Miller, Jan De Bleecker, Caroline Ingre, Luis Varona, Genevieve Matte, Daragh Heitzman, Robert Untucht, Lorne Zinman, Adam Quick, and Jonathan S. Katz

Subjects
education.field_of_study, medicine.medical_specialty, Supine position, business.industry, Amyotrophic Lateral Sclerosis, Population, Administration, Oral, Levosimendan, Placebo, Treatment Outcome, amyotrophic lateral sclerosis, levosimendan, randomised, double-blind, placebo-controlled trial, Double-Blind Method, Respiratory failure, Internal medicine, Clinical endpoint, Humans, Medicine, Respiratory function, Neurology (clinical), business, Adverse effect, education, Simendan, medicine.drug
Abstract

Summary Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function. Methods The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60–90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178 ) has also been completed, but will be reported separately. Findings Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50·1 (IQR 37·5–51·1) weeks. The median duration of treatment was 47·9 (IQR 26·4–48·1) weeks. Change from baseline in supine SVC at 12 weeks was –6·73% with levosimendan and –6·99% with placebo, with no significant difference between the treatments (estimated treatment difference 0·26%, 95% CI –2·03 to 2·55, p=0·83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10·69, 95% CI –15·74 to 37·12; nominal p value=0·43). The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%]). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis. Interpretation Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation. Funding Orion Corporation.

Published
2021

9. The true cost of hidden waiting times for cataract surgery in Australia

Author

Anna Palagyi, Peter McCluskey, Blake Angell, Lisa Keay, Andrew White, Hugh R. Taylor, and Jessie Huang-Lung

Subjects
Waiting time, medicine.medical_specialty, Waiting Lists, business.industry, Health Policy, General surgery, medicine.medical_treatment, Public Health, Environmental and Occupational Health, Australia, COVID-19, Cataract Extraction, Cataract surgery, Cataract, medicine, Humans, business
Abstract

Cataract surgery is a safe, effective and common elective procedure in Australia but access is inequitable. True waiting times for cataract care are undisclosed or inconsistently reported by governments. Estimates of true waiting times range from 4 to 30 months and have been extended during the coronavirus disease 2019 (COVID-19) pandemic. Comparative analysis revealed that reducing waiting periods from 12 to 3 months would result in estimated public health system cost savings of $6.6 million by preventing 50 679 falls. Investment in public cataract services to address current unmet needs would prevent avoidable vision impairment and associated negative consequences.

Published
2022

10. Suicide and Self-Harm in Children and Adolescents Admitted to PICUs in the United States

Author

Sarah Steward, Alexandre T. Rotta, Margaret J. Klein, and Casey K. McCluskey

Subjects
Male, medicine.medical_specialty, Adolescent, Databases, Factual, Patient demographics, education.educational_degree, Psychological intervention, Psychiatric rehabilitation, Intensive Care Units, Pediatric, Critical Care and Intensive Care Medicine, Drug ingestion, Epidemiology, Humans, Medicine, Child, education, Retrospective Studies, Asphyxia, Suicide attempt, business.industry, United States, Hospitalization, Harm, Pediatrics, Perinatology and Child Health, Emergency medicine, Female, medicine.symptom, business, Self-Injurious Behavior
Abstract

OBJECTIVES To characterize the epidemiology of children and adolescents admitted for deliberate self-harm to PICUs in the United States by examining patient demographics, diagnoses, modes of self-harm, and outcomes. DESIGN Descriptive analysis of a large, multicenter, quality-controlled database. SETTING The 137 PICUs participating in the Virtual Pediatric Systems database during the study period. PATIENTS Children between 6 and 18 years old admitted to a participating PICU from January 1, 2009, to December 31, 2017, with a diagnosis involving deliberate self-harm or a suicide attempt. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of 9,197 admissions for self-harm, females accounted for 6,740 (73.3%), whereas males incurred 174 of the 284 deaths (61.3%). Admissions for self-harm doubled over the study period (0.56% in 2009 vs 1.13% in 2017), with an increase observed across every age group. After PICU care, most patients were transferred to a general care floor (51.1%) or to a psychiatric rehabilitation facility (31.8%). Intentional drug ingestion (84%) was the most common mode of self-harm but was associated with less than 1% of the fatalities. Asphyxia/hanging or firearms were a factor in 411 (4.5%) and 106 (1.2%) of the admissions but were associated with 117 (28.5%) and 55 (51.9%) of the deaths, respectively. CONCLUSIONS PICU admissions due to self-harm increased for all age groups during the study period. Females accounted for most of these admissions, whereas males accrued most of the in-hospital deaths. Intentional drug ingestion was the most common mode of self-harm and was rarely fatal, whereas asphyxia and firearms were the mechanisms associated with the highest mortality.

Published
2021

11. Can you trust clinical practice guidelines for laparoscopic surgery? A systematic review of clinical practice guidelines for laparoscopic surgery

Author

Kurinchi Selvan Gurusamy, Aled McCluskey, Bo Zhen Hao, Brian R. Davidson, Kenneth Au Yeung, Jeffrey Leung, Jonathan Leong, and Yusuf Kayani

Subjects
Laparoscopic surgery, medicine.medical_specialty, business.industry, medicine.medical_treatment, Odds ratio, Guideline, Confidence interval, Rigour, Surgery, Clinical Practice, Quartile, Physical therapy, Medicine, Clinical care, business
Abstract

Background Clinical practice guidelines aim to support clinicians in providing clinical care and should be supported by evidence. There is currently no information on whether clinical practice guidelines in laparoscopic surgery are supported by evidence. Methods We performed a systematic review and identified clinical practice guidelines of laparoscopic surgery published in PubMed and Embase between March 2016 and February 2019. We performed an independent assessment of the strength of recommendation based on the evidence provided by the guideline authors. We used the ‘Appraisal of Guidelines for Research & Evaluation II’ (AGREE-II) Tool’s ‘rigour of development’, ‘clarity of presentation’, and ‘editorial independence’ domains to assess the quality of the guidelines. We performed a mixed-effects generalised linear regression modelling. Results We retrieved 63 guidelines containing 1905 guideline statements. The median proportion of ‘difference in rating’ of strength of recommendation between the guideline authors and independent assessment was 33.3% (quartiles: 18.3%, 55.8%). The ‘rigour of development’ domain score (odds ratio 0.06; 95% confidence intervals 0.01–0.48 per unit increase in rigour score; P value = 0.0071) and whether the strength of recommendation was ‘strong’ by independent evaluation (odds ratio 0.09 (95% confidence intervals 0.06–0.13; P value Conclusion A considerable proportion of guideline statements in clinical practice guidelines in laparoscopic surgery are not supported by evidence. Guideline authors systematically overrated the strength of the recommendation (i.e., even when the evidence points to weak recommendation, guideline authors made strong recommendations).

Published
2021

12. Normal Saline for Kidney Transplantation Surgery: Less Is More

Author

Duminda N. Wijeysundera and Stuart A. McCluskey

Subjects
medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, medicine.medical_treatment, medicine, MEDLINE, medicine.disease, business, Saline, Kidney transplantation, Surgery
Published
2021

13. Classification Criteria for Fuchs Uveitis Syndrome

Author

Douglas A. Jabs, Jennifer E. Thorne, Peter McCluskey, Soon-Phaik Chee, Debra A. Goldstein, Philip I. Murray, Nisha R. Acharya, Neal Oden, Brett Trusko, James T. Rosenbaum, and Alan G. Palestine

Subjects
Adult, Male, medicine.medical_specialty, Training set, Adolescent, Fundus Oculi, business.industry, Iris, Middle Aged, Fuchs uveitis syndrome, Article, Confidence interval, Uveitis, Young Adult, Ophthalmology, Humans, Medicine, Female, Anterior uveitis, Fluorescein Angiography, business
Abstract

Purpose To determine classification criteria for Fuchs uveitis syndrome. Design Machine learning of cases with Fuchs uveitis syndrome and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 146 cases of Fuchs uveitis syndrome, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for Fuchs uveitis syndrome included unilateral anterior uveitis with or without vitritis and either: 1) heterochromia or 2) unilateral diffuse iris atrophy and stellate keratic precipitates. The overall accuracy for anterior uveitides was 97.5% in the training set (95% confidence interval [CI] 96.3, 98.4) and 96.7% in the validation set (95% CI 92.4, 98.6). The misclassification rates for FUS were 4.7% in the training set and 5.5% in the validation set, respectively. Conclusions The criteria for Fuchs uveitis syndrome had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Published
2021

14. Classification Criteria for Vogt-Koyanagi-Harada Disease

Author

Annabelle A. Okada, Alastair K Denniston, Andrew D. Dick, Peter McCluskey, Russell W. Read, Alan G. Palestine, Brett Trusko, Jennifer E. Thorne, Douglas A. Jabs, Michal Kramer, Neal Oden, and James P. Dunn

Subjects
Adult, Male, Vogt–Koyanagi–Harada disease, Pediatrics, medicine.medical_specialty, Training set, Fundus Oculi, business.industry, Middle Aged, Fundus (eye), medicine.disease, Article, eye diseases, Confidence interval, Ophthalmology, medicine, Humans, Fluorescein angiogram, Female, Fluorescein Angiography, Uveomeningoencephalitic Syndrome, business, Tomography, Optical Coherence
Abstract

Purpose To determine classification criteria for Vogt-Koyanagi-Harada (VKH) disease Design Machine learning of cases with VKH disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve cases of panuveitides, including 156 cases of early-stage VKH and 103 cases of late-stage VKH, were evaluated. Overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for early-stage VKH included: 1) exudative retinal detachment with characteristic appearance on fluorescein angiogram or optical coherence tomography or 2) panuveitis with ≥2 of 5 neurologic symptoms/signs. Key criteria for late-stage VKH included history of early-stage VKH and either: 1) sunset glow fundus or 2) uveitis and ≥1 of 3 cutaneous signs. The misclassification rates in the learning and validation sets for early-stage VKH were 8.0% and 7.7%, respectively, and for late-stage VKH 1.0% and 12%, respectively. Conclusions The criteria for VKH had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Published
2021

15. Classification Criteria for Juvenile Idiopathic Arthritis–Associated Chronic Anterior Uveitis

Author

Philip I. Murray, Peter McCluskey, Nisha R. Acharya, Debra A. Goldstein, Jennifer E. Thorne, Soon-Phaik Chee, Alan G. Palestine, Douglas A. Jabs, James T. Rosenbaum, Brett Trusko, and Neal Oden

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Consensus, Arthritis, Newly diagnosed, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, 030304 developmental biology, 0303 health sciences, Training set, business.industry, Middle Aged, Enthesitis-Related Arthritis, medicine.disease, Uveitis, Anterior, Insidious onset, Arthritis, Juvenile, Confidence interval, Ophthalmology, Chronic Disease, 030221 ophthalmology & optometry, Chronic anterior uveitis, Female, Polyarthritis, business
Abstract

Purpose To determine classification criteria for juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis (CAU). Design Machine learning of cases with JIA CAU and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 202 cases of JIA CAU, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for JIA CAU included 1) chronic anterior uveitis (or if newly diagnosed insidious onset) and 2) JIA, except for the systemic, rheumatoid factor-positive polyarthritis, and enthesitis related arthritis variants. The misclassification rates for JIA CAU were 2.4% in the training set and 0% in the validation set, respectively. Conclusions The criteria for JIA CAU had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Published
2021

16. Tectonic Deep Anterior Lamellar Keratoplasty to Treat Corneal Perforation and Descemetocele from Microbial Keratitis

Author

Hong The Nguyen, Ngoc Dong Pham, Tung Quoc Mai, Hang Thi Thuy Do, Thi Nga Duong Nguyen, Peter McCluskey, and Trong Van Pham

Subjects
medicine.medical_specialty, genetic structures, medicine.medical_treatment, Perforation (oil well), corneal perforation, Lamellar keratoplasty, Glaucoma, Ocular hypertension, Keratitis, deep anterior lamellar keratoplasty, Ophthalmology, medicine, Corneal transplantation, Original Research, descemetocele, business.industry, Clinical Ophthalmology, Corneal perforation, medicine.disease, eye diseases, corneal transplantation, Dissection, DALK, sense organs, business
Abstract

Hong The Nguyen,1,2 Ngoc Dong Pham,3 Tung Quoc Mai,2 Hang Thi Thuy Do,3 Duong Thi Nga Nguyen,3 Peter McCluskey,4 Trong Van Pham2 1Department of Ophthalmology, 108 Military Central Hospital, Hanoi, Vietnam; 2Department of Ophthalmology, Hanoi Medical University, Hanoi, Vietnam; 3Department of Cornea, Vietnam National Eye Hospital, Hanoi, Vietnam; 4Department of Ophthalmology, University of Sydney, Sydney, NSW, AustraliaCorrespondence: Tung Quoc MaiDepartment of Ophthalmology, Hanoi Medical University, 1 Ton That Tung Street, Hanoi, 100000, VietnamTel +84 915644181Email maiquoctung@hmu.edu.vnPurpose: To evaluate the result of tectonic deep anterior lamellar keratoplasty (DALK) for keratitis with perforation and descemetocele.Patients and Methods: A prospective clinical study of 36 patients (36 eyes) treated with tectonic DALK for corneal perforation or descemetocele from microbial keratitis managed at the Vietnam National Eye Hospital over a two-year period. The surgical technique was manual lamellar dissection. The grafts were harvested from the anterior corneal cap of pre-cut donor tissues used for DSAEK or donor corneas with a low endothelial cell count.Results: A mean age was 55.36 ± 13.98 years (ranged from 25 to 75 years). Female gender represented 52%. causative agents were herpes simplex virus (58.3%), bacteria (22.2%), fungi (13.9%) and microsporidia (5.6%). There were 24 eyes with descemetocele (66.7%) and 12 with perforation (33.3%). There were 33 successful cases (91.7%) and 3 failed cases (8.3%). Best corrected visual acuity (BCVA) improved in 28 eyes (84.8%). The range of post-operative BCVA was from hand motions to 20/70. Eleven eyes (33.3%) attained vision 20/200 and higher. Clear graft was obtained in 15 eyes (45.5%), while mild or severe graft opacity was observed in 14 eyes (42.4%), and 4 eyes (12.1%), respectively. Surgical complications included descemet rupture (20.8%), pseudo anterior chamber (41.6%), persistent corneal epithelial defects (8.3%), reinfection (11.1%), glaucoma or ocular hypertension (5.6%) and cataract (8.3%).Conclusion: The study demonstrates that DALK is an effective procedure to treat corneal descemetocele, especially when an urgent penetrating keratoplasty (PKP) cannot be performed.Keywords: deep anterior lamellar keratoplasty, DALK, descemetocele, corneal perforation, corneal transplantation

Published
2021

17. Classification Criteria for Varicella Zoster Virus Anterior Uveitis

Author

Alan G. Palestine, Debra A. Goldstein, Nisha R. Acharya, Douglas A. Jabs, Philip I. Murray, Soon-Phaik Chee, Jennifer E. Thorne, James T. Rosenbaum, Neal Oden, Peter McCluskey, Laure Caspers, and Brett Trusko

Subjects
Adult, Male, Herpesvirus 3, Human, medicine.medical_specialty, Adolescent, viruses, Eye Infections, Viral, Aqueous humor, medicine.disease_cause, Article, Aqueous Humor, Machine Learning, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, medicine, Humans, 030304 developmental biology, 0303 health sciences, Training set, business.industry, Varicella zoster virus, virus diseases, Middle Aged, Uveitis, Anterior, Confidence interval, DNA, Viral, Herpes Zoster Ophthalmicus, 030221 ophthalmology & optometry, Female, Anterior uveitis, business
Abstract

Purpose To determine classification criteria for varicella zoster virus (VZV) anterior uveitis DESIGN: Machine learning of cases with VZV anterior uveitis and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 123 cases of VZV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for VZV anterior uveitis included unilateral anterior uveitis with either 1) positive aqueous humor polymerase chain reaction assay for VZV; 2) sectoral iris atrophy in a patient ≥60 years of age; or 3) concurrent or recent dermatomal herpes zoster. The misclassification rates for VZV anterior uveitis were 0.9% in the training set and 0% in the validation set, respectively. Conclusions The criteria for VZV anterior uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Published
2021

18. Classification Criteria for Multifocal Choroiditis With Panuveitis

Author

Susan E Wittenberg, Douglas A. Jabs, Peter McCluskey, Albert T. Vitale, Antoine P. Brézin, Alan G. Palestine, Jennifer E. Thorne, Brett Trusko, Russell W. Read, Neal Oden, and Ralph D. Levinson

Subjects
Adult, Male, medicine.medical_specialty, Anterior Chamber, Posterior pole, Visual Acuity, Article, Multifocal choroiditis, Machine Learning, Set (abstract data type), 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030304 developmental biology, 0303 health sciences, Training set, business.industry, Multifocal Choroiditis, Panuveitis, Middle Aged, Confidence interval, Ophthalmology, 030221 ophthalmology & optometry, Chorioretinal scars, Female, Radiology, business
Abstract

Purpose To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU) DESIGN: : Machine learning of cases with MFCPU and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the posterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 138 cases of MFCPU, were evaluated by machine learning. Key criteria for MFCPU included: 1) multifocal choroiditis with the predominant lesions size >125 µm in diameter; 2) lesions outside the posterior pole (with or without posterior involvement); and either 3) punched-out atrophic chorioretinal scars or 4) more than minimal mild anterior chamber and/or vitreous inflammation. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for MFCPU were 15% in the training set and 0% in the validation set. Conclusions The criteria for MFCPU had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Published
2021

19. Classification Criteria for Behçet Disease Uveitis

Author

Russell W. Read, Douglas A. Jabs, Annabelle A. Okada, Steven Yeh, Jennifer E. Thorne, Michal Kramer, Andrew D. Dick, Alan G. Palestine, Neal Oden, Peter McCluskey, James P. Dunn, and Brett Trusko

Subjects
Adult, Male, medicine.medical_specialty, Consensus, Article, Machine Learning, Uveitis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Retrospective Studies, 030304 developmental biology, 0303 health sciences, Training set, business.industry, Behcet disease, Retinal vasculitis, Behcet Syndrome, Panuveitis, medicine.disease, Dermatology, Confidence interval, stomatognathic diseases, Ophthalmology, Posterior uveitis, 030221 ophthalmology & optometry, Female, Anterior uveitis, business
Abstract

Purpose To determine classification criteria for Behcet disease uveitis. Design Machine learning of cases with Behcet disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve of cases panuveitides, including 194 cases of Behcet disease with uveitis, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for Behcet disease uveitis were a diagnosis of Behcet disease using the International Study Group for Behcet Disease criteria and a compatible uveitis, including: 1) anterior uveitis; 2) anterior chamber and vitreous inflammation; 3) posterior uveitis with retinal vasculitis and/or focal infiltrates; or 4) panuveitis with retinal vasculitis and/or focal infiltrates. The misclassification rates for Behcet disease uveitis were 0.6 % in the training set and 0% in the validation set, respectively. Conclusions The criteria for Behcet disease uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Published
2021

20. Classification Criteria for Sarcoidosis-Associated Uveitis

Author

Alastair K Denniston, Douglas A. Jabs, Brett Trusko, Annabelle A. Okada, Alan G. Palestine, Neal Oden, Peter McCluskey, Nisha R. Acharya, Susan Lightman, Jennifer E. Thorne, and Albert T. Vitale

Subjects
Adult, Male, Bilateral hilar adenopathy, medicine.medical_specialty, Sarcoidosis, Biopsy, Article, Uveitis, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Uvea, 030304 developmental biology, 0303 health sciences, Training set, business.industry, Panuveitis, Middle Aged, medicine.disease, Confidence interval, Ophthalmology, 030221 ophthalmology & optometry, Intermediate uveitis, Female, Anterior uveitis, Radiology, business
Abstract

Purpose To determine classification criteria for sarcoidosis-associated uveitis DESIGN: Machine learning of cases with sarcoid uveitis and 15 other uveitides. Methods Cases of anterior, intermediate, and panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were analyzed by anatomic class, and each class was split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training sets to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation sets. Results One thousand eighty-three anterior uveitides, 589 intermediate uveitides, and 1012 panuveitides, including 278 cases of sarcoidosis-associated uveitis, were evaluated by machine learning. Key criteria for sarcoidosis-associated uveitis included a compatible uveitic syndrome of any anatomic class and evidence of sarcoidosis, either 1) a tissue biopsy demonstrating non-caseating granulomata or 2) bilateral hilar adenopathy on chest imaging. The overall accuracy of the diagnosis of sarcoidosis-associated uveitis in the validation set was 99.7% (95% confidence interval 98.8, 99.9).The misclassification rates for sarcoidosis-associated uveitis in the training sets were: anterior uveitis 3.2%, intermediate uveitis 2.6%, and panuveitis 1.2%; in the validation sets the misclassification rates were: anterior uveitis 0%, intermediate uveitis 0%, and panuveitis 0%, respectively. Conclusions The criteria for sarcoidosis-associated uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Published
2021

21. Classification Criteria for Birdshot Chorioretinitis

Author

Russell W. Read, Jennifer E. Thorne, Antoine P. Brézin, Neal Oden, Douglas A. Jabs, Albert T. Vitale, Alan G. Palestine, Brett Trusko, Peter McCluskey, Ralph D. Levinson, and Susan E Wittenberg

Subjects
Male, medicine.medical_specialty, Consensus, Training set, Choroid, Fundus Oculi, business.industry, Indocyanine green angiography, Birdshot Chorioretinopathy, Birdshot chorioretinitis, Middle Aged, Retina, Article, Confidence interval, Multifocal choroiditis, Machine Learning, Ophthalmology, medicine, Humans, Female, Fluorescein Angiography, business
Abstract

Purpose To determine classification criteria for birdshot chorioretinitis. Design Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with: 1) the characteristic appearance a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); 2) absent to mild anterior chamber inflammation; and 3) absent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either: 1) classic "birdshot spots" or 2) characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set. Conclusions The criteria for birdshot chorioretinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Published
2021

22. Albumin use in bleeding cardiac surgical patients and associated patient outcomes

Author

Ciara Hanley, Justyna Bartoszko, Keyvan Karkouti, Stuart A. McCluskey, and Jeannie Callum

Subjects
medicine.medical_specialty, Resuscitation, business.industry, Acute kidney injury, General Medicine, Odds ratio, Perioperative, medicine.disease, Intensive care unit, law.invention, Cardiac surgery, Anesthesiology and Pain Medicine, law, Anesthesia, Heart failure, Anesthesiology, medicine, business
Abstract

Albumin solution is a colloid used for resuscitation in cardiac surgical patients, but it is unclear if it offers advantages over crystalloids. We examined current clinical practice across 11 cardiac surgical centres and the association of albumin with outcomes in a cohort of bleeding cardiac surgical patients. This was a post hoc analysis of data from the Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery (FIBRES) trial. Multivariable regression models adjusted for demographic and surgical characteristics were used to examine predictors of early albumin administration (within the initial 24 perioperative hours), late albumin administration (from 24 hr to seven days after cardiopulmonary bypass), and the association of albumin use with 28-day acute kidney injury, mortality, and length of hospital and intensive care unit (ICU) stay. Of the 735 patients included, 525 (71%) received albumin, ranging from 4.8% to 97.4% of patients across institutions, with 475 (64.6%) receiving albumin early (5% or 25% solution). In the adjusted models, female sex and preoperative hospital admission were associated with early use, while heart failure, female sex, bleeding severity, older age, and prior albumin use were predictors of later administration. Early albumin use was not associated with differences in acute kidney injury (adjusted odds ratio [aOR] 1.77; 95% confidence interval [CI], 0.96 to 3.27; P = 0.07), mortality (aOR 1.66; 95% CI, 0.99 to 2.78; P = 0.05), or length of ICU stay (P = 0.11) or hospital stay (P = 0.67). Albumin use is common but highly variable within and across sites. Albumin use was not associated with improved outcomes. High quality randomized controlled trials should clarify its role in cardiac surgical patients.

Published
2021

23. MERTK retinopathy: biomarkers assessing vision loss

Author

Lisa Ewans, Dhimas Hari Sakti, Benjamin M. Nash, Afsah Zaheer, Peter McCluskey, Clara W. T. Chung, Sulekha Rajagopalan, Robyn V. Jamieson, John R. Grigg, Stephanie Retsas, Nina Mustafic, and Elisa E Cornish

Subjects
medicine.medical_specialty, Retinal pigment epithelium, genetic structures, medicine.diagnostic_test, business.industry, Disease progression, MERTK, medicine.disease, eye diseases, Ophthalmology, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Retinitis pigmentosa, Medicine, Biomarker (medicine), sense organs, business, Erg, Genetics (clinical), Retinopathy, Electroretinography
Abstract

Purpose Mer tyrosine kinase-retinitis pigmentosa (MERTK-RP) causes a primary defect in the retinal pigment epithelium, which subsequently affects rod and cone photoreceptors. The study aims to identify the most appropriate MERTK-RP biomarkers to measure disease progression for deciding the optimum therapeutic trial intervention time. Materials and methods Patients' data from baseline (BL) and last follow-up (LFU) were reviewed. Best corrected visual acuity (BCVA), spectral domain-optical coherence tomography (SD-OCT), ultra-widefield fundus autofluorescence (UWF-FAF) patterns, kinetic perimetry (KP), and electroretinography (ERG) parameters were analyzed. Results Five patients were included with the mean age of 17.7 ± 14.4 years old (6.7-42.3) at BL and mean BCVA follow-up of 8.4 ± 5.1 years. Mean BCVA at BL and LFU were 0.84 ± 0.86 LogMAR and 1.14 ± 0.86 LogMAR, respectively. The BCVA decline rate was 0.05 ± 0.03 LogMAR units/year. Ellipzoid zones (EZ) were measurable in eight eyes with mean BL length of 1293.75 ± 421.07 µm and reduction of 140.95 ± 69.28 µm/year and mean BL CMT of 174.2 ± 37.52 µm with the rate of 11.2 ± 12.77 µm declining/year. Full-field ERG (ffERG) and pattern ERG (pERG) were barely recordable. UWF-FAF showed central macular hyper-autofluorescence (hyperAF). KP (III4e and V4e) was normal in two eyes, restricted nasally in four eyes, superior wedge defect in two eyes and undetectable in two eyes. The four restricted nasally KPs became worse, while the others stayed almost unchanged. Conclusions This cohort showed early visual loss, moderately rapid EZ reduction and macular hyperAF. EZ, CMT, and BCVA were consistently reduced. Relative rapid decline in these biomarkers reflecting visual function suggests an early and narrow timespan for intervention.

Published
2021

24. BNA Bank celebrates grand opening of downtown Tupelo location

Author

McCluskey, Caleb

Subjects
Banks (Finance), Business, Business, regional
Abstract

TUPELO -- Bankers and officials from across Northeast Mississippi gathered to celebrate the grand opening of New Albany-based BNA Bank's newest location in Tupelo with a ribbon cutting, Wednesday morning. [...]

Published
2022

25. On the Importance of Domain Model Configuration for Automated Planning Engines

Author

Thomas Leo McCluskey, Frank Hutter, Mauro Vallati, and Lukáš Chrpa

Subjects
Online and offline, Computer science, business.industry, Distributed computing, Knowledge engineering, 020207 software engineering, 0102 computer and information sciences, 02 engineering and technology, Domain model, Modular design, 01 natural sciences, Software, Computational Theory and Mathematics, 010201 computation theory & mathematics, Artificial Intelligence, Automated planning and scheduling, 0202 electrical engineering, electronic engineering, information engineering, Domain knowledge, Macro, business
Abstract

The development of domain-independent planners within the AI planning community is leading to “off-the-shelf” technology that can be used in a wide range of applications. Moreover, it allows a modular approach—in which planners and domain knowledge are modules of larger software applications—that facilitates substitutions or improvements of individual modules without changing the rest of the system. This approach also supports the use of reformulation and configuration techniques, which transform how a model is represented in order to improve the efficiency of plan generation. In this article, we investigate how the performance of domain-independent planners is affected by domain model configuration, i.e. the order in which elements are ordered in the model, particularly in the light of planner comparisons. We then introduce techniques for the online and offline configuration of domain models, and we analyse the impact of domain model configuration on other reformulation approaches, such as macros.

Published
2021

26. Biomarkers of coagulation, endothelial function, and fibrinolysis in critically ill patients with COVID‐19: A single‐center prospective longitudinal study

Author

Juneja, Ganeem K., Castelo, Matthew, Yeh, Calvin H., Cerroni, Samantha E., Hansen, Bettina E., Chessum, James E., Abraham, Joel, Cani, Erblin, Dwivedi, Dhruva J., Fraser, Douglas D., Slessarev, Marat, Martin, Claudio, McGilvray, Scott, Gross, Peter L., Liaw, Patricia C., Weitz, Jeffrey I., Kim, Paul Y., Trigatti, Bernardo, Fox-Robichaud, Alison, Werstuck, Geoff, Kretz, Colin A., Karkouti, Keyvan, McCluskey, Stuart, and dos Santos, Claudia

Subjects
Adult, Oncology, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, coronavirus, 030204 cardiovascular system & hematology, Lung injury, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, law, Internal medicine, Plasminogen Activator Inhibitor 1, Fibrinolysis, medicine, Humans, Longitudinal Studies, Prospective Studies, Prospective cohort study, thrombosis, SARS-CoV-2, business.industry, COVID-19, biomarkers, Hematology, Intensive care unit, 3. Good health, chemistry, Tissue Plasminogen Activator, Plasminogen activator inhibitor-1, Biomarker (medicine), fibrinolysis, Original Article, observational study, Fibrin Clot Lysis Time, business, Plasminogen activator, Blood drawing
Abstract

Background Immunothrombosis and coagulopathy in the lung microvasculature may lead to lung injury and disease progression in coronavirus disease 2019 (COVID‐19). We aim to identify biomarkers of coagulation, endothelial function, and fibrinolysis that are associated with disease severity and may have prognostic potential. Methods We performed a single‐center prospective study of 14 adult COVID‐19(+) intensive care unit patients who were age‐ and sex‐matched to 14 COVID‐19(−) intensive care unit patients, and healthy controls. Daily blood draws, clinical data, and patient characteristics were collected. Baseline values for 10 biomarkers of interest were compared between the three groups, and visualized using Fisher's linear discriminant function. Linear repeated‐measures mixed models were used to screen biomarkers for associations with mortality. Selected biomarkers were further explored and entered into an unsupervised longitudinal clustering machine learning algorithm to identify trends and targets that may be used for future predictive modelling efforts. Results Elevated D‐dimer was the strongest contributor in distinguishing COVID‐19 status; however, D‐dimer was not associated with survival. Variable selection identified clot lysis time, and antigen levels of soluble thrombomodulin (sTM), plasminogen activator inhibitor‐1 (PAI‐1), and plasminogen as biomarkers associated with death. Longitudinal multivariate k‐means clustering on these biomarkers alone identified two clusters of COVID‐19(+) patients: low (30%) and high (100%) mortality groups. Biomarker trajectories that characterized the high mortality cluster were higher clot lysis times (inhibited fibrinolysis), higher sTM and PAI‐1 levels, and lower plasminogen levels. Conclusions Longitudinal trajectories of clot lysis time, sTM, PAI‐1, and plasminogen may have predictive ability for mortality in COVID‐19.

Published
2021

27. Uveal Melanoma and Secondary Angle-Closure Crisis: A Case Report and Literature Review

Author

John A. Grigg, Tuan Anh Hoang, Peter McCluskey, and Tung Thanh Hoang

Subjects
medicine.medical_specialty, secondary angle closure, medicine.diagnostic_test, genetic structures, serous retinal detachment, business.industry, Retinal detachment, Case Report, Ciliary body melanoma, RE1-994, medicine.disease, Malignancy, Serous Retinal Detachment, eye diseases, Posterior segment of eyeball, Ophthalmology, Gonioscopy, medicine, Optic nerve, sense organs, uveal melanoma, business, Spindle Cell Melanoma
Abstract

A 66-years-old Vietnamese healthy female patient presented with prolonged severe right ocular pain and complete vision loss in that eye. Anterior segment assessment including gonioscopy identified angle-closure configuration. A suspected ciliary body melanoma was seen through the pupil. Posterior segment examination revealed a large tumor mass and 360° retinal detachment (kissing configuration). An ultrasound examination was consistent with a uveal tumor. The painful, blind right eye with a tumor mass was enucleated. Histopathology confirmed a type A uveal spindle cell melanoma associated with total serous retinal detachment without evidence of tumor necrosis, epithelioid cells, scleral, or optic nerve infiltration. There was no evidence of metastasis after 1-year of follow-up. It is critically important to differentiate primary and secondary angle closure, especially in cases with life-threatening ocular malignancy as uveal melanoma.

Published
2021

28. Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results

Author

Meghan Cifrino, Lakshmi Nayak, Jennifer Stefanik, Wenya Linda Bi, Christine McCluskey, Thomas Graillon, Ian F. Dunn, Patrick Y. Wen, David A. Reardon, Deborah LaFrankie, Keith L. Ligon, Alona Muzikansky, Joseph Driver, Ugonma Chukwueke, David Meredith, Andrew D. Cherniack, Rameen Beroukhim, Ricardo McFaline-Figueroa, Ossama Al-Mefty, Christina Taubert, Sandro Santagata, Samantha E Hoffman, Lisa Doherty, Mikael L. Rinne, Raymond Y. Huang, Sarah C. Gaffey, E. Antonio Chiocca, Yvonne Y. Li, Eudocia Q. Lee, and Ziming Du

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Tumor-infiltrating lymphocytes, medicine.medical_treatment, Phases of clinical research, Immunotherapy, medicine.disease, Meningioma, Radiation therapy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Blocking antibody, Toxicity, Medicine, Neurology (clinical), Nivolumab, business
Abstract

Background Programmed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy. Methods Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale. Results Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO. Conclusion Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.

Published
2021

29. Evaluation of the nursing care plan in a thyroidectomy surgical case

Author

Emma McCluskey

Subjects
Nursing care, Nursing care plan, Work (electrical), Nursing, business.industry, medicine.medical_treatment, Thyroidectomy, Medicine, Quality of care, business, Veterinary Nurses
Abstract

Veterinary nurses work closely with their patients to deliver a high quality of care. This care is implemented using nursing care plans (NCPs). This article aims to evaluate the use of a nursing care plan and its value in practice as well as enhancing nurses' understanding of them. Within this article the author will be discussing the actual and potential problems and implementing the nursing interventions in a nursing care plan pre, post surgery and at discharge in a thyroidectomy case. Veterinary nurses play an important role in making sure the NCP is successful and patients receive the best quality of care. This article evaluates the benefits and disadvantages of NCPs to determine whether they are useful for nursing care of surgical cases.

Published
2021

30. Addressing Sexuality Among People Living With Chronic Disease and Disability: A Systematic Mixed Methods Review of Knowledge, Attitudes, and Practices of Health Care Professionals

Author

Emma Power, Sandra Lever, Margaret McGrath, Annie McCluskey, and Michelle Anne Low

Subjects
Health Knowledge, Attitudes, Practice, 030506 rehabilitation, medicine.medical_specialty, Health Personnel, medicine.medical_treatment, MEDLINE, Scopus, Physical Therapy, Sports Therapy and Rehabilitation, Human sexuality, PsycINFO, 03 medical and health sciences, 0302 clinical medicine, Health care, medicine, Humans, Disabled Persons, Competence (human resources), Rehabilitation, business.industry, Data extraction, Family medicine, Chronic Disease, 0305 other medical science, business, Psychology, Sexuality, 030217 neurology & neurosurgery
Abstract

Objective To systematically review health care professionals’ practices and attitudes toward addressing sexuality with people who are living with chronic disease and disability. Data Sources Scopus, PubMed, PsycINFO, Cumulative Index to Nursing and Allied Health, Allied and Complementary Medicine Database, and MEDLINE were searched to August 2020 for English language publications. Reference lists of relevant publications were also searched. Study Selection Eligible studies reported on knowledge, attitudes, and behaviors of health care professionals about addressing sexuality in the context of chronic disease and disability. The search yielded 2492 records; 187 full texts were assessed for eligibility and 114 documents were included (103 unique studies). Study quality was rated using the Mixed Methods Appraisal Tool. Data Extraction Characteristics of included studies were recorded independently by 2 authors. Differences were resolved through discussion or by a third author. Data Synthesis A sequential, exploratory mixed studies approach was used for synthesis. Pooled analysis showed that 14.2% (95% CI, 10.6-18.9 [I2=94.8%, P Conclusion Despite recognizing the value of sexuality to health and well-being, most health professionals regardless of clinical context fail to routinely include assessment of sexuality in their practice. Professionals have limited knowledge and confidence when addressing sexuality and experience significant discomfort when raising this topic with people living with chronic disease and disability. Multicomponent implementation programs are needed to improve health professionals’ knowledge, competence, and comfort when addressing sexuality for people living with chronic disease and disability.

Published
2021

31. Altering the rehabilitation environment to improve stroke survivor activity: A Phase II trial

Author

Sandy Middleton, Michael Nilsson, Peter W New, Heidi Janssen, Jannette M. Blennerhassett, Steven G Faux, Julie Bernhardt, Leonid Churilov, Michael Pollack, Neil J. Spratt, Louise Ada, and Annie McCluskey

Subjects
030506 rehabilitation, medicine.medical_specialty, medicine.medical_treatment, Phase (combat), rehabilitation, recovery, 03 medical and health sciences, Patient safety, 0302 clinical medicine, Physical medicine and rehabilitation, Activities of Daily Living, Animals, Humans, Medicine, Survivors, Stroke, Environmental enrichment, Rehabilitation, business.industry, activity, Stroke Rehabilitation, clinical trial, Cognition, medicine.disease, stroke, Clinical trial, Clinical research, Neurology, environmental enrichment, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

Background Environmental enrichment involves organization of the environment and provision of equipment to facilitate engagement in physical, cognitive, and social activities. In animals with stroke, it promotes brain plasticity and recovery. Aims To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment. Methods A nonrandomized cluster trial with blinded measurement involving people with stroke ( n = 193) in four rehabilitation units was carried out. Feasibility was operationalized as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at three months, by an assessor blinded to group. Results The experimental group ( n = 91) spent 7% (95% CI −14 to 0) less time inactive, 9% (95% CI 0–19) more time physically, and 6% (95% CI 2–10) more time socially active than the control group ( n = 102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or three months or in clinical outcomes at three months. Conclusions This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes three months after stroke do not provide justification for an efficacy trial.

Published
2021

32. Blood Cell Salvage and Autotransfusion Does Not Worsen Oncologic Outcomes Following Liver Transplantation with Incidental Hepatocellular Carcinoma: A Propensity Score-Matched Analysis

Author

Stuart A. McCluskey, Peter Yoon, Tommy Ivanics, Hala Muaddi, Marco P. A. W. Claasen, Christopher R Shubert, Gonzalo Sapisochin, Bettina E. Hansen, and Surgery

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Hazard ratio, Intraoperative Blood Cell Salvage, Liver transplantation, medicine.disease, Gastroenterology, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Oncology, Surgical oncology, 030220 oncology & carcinogenesis, Internal medicine, Hepatocellular carcinoma, Propensity score matching, medicine, 030211 gastroenterology & hepatology, Surgery, business, Autotransfusion
Abstract

Background: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes. Objective: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA. Methods: Patients undergoing LT (January 2001–October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan–Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death. Results: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52–3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28–25.30, p = 0.40). Conclusions: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.

Published
2021

33. Low maternal vitamin A intake increases the incidence of teratogen induced congenital diaphragmatic hernia in mice

Author

Timothy R. A. Dalmer, Robin D. Clugston, Juan F Garcia Rivas, Tianna G Clarke, Sydney A McCluskey, and Ayanna W. Rocke

Subjects
0301 basic medicine, Vitamin, medicine.drug_class, Physiology, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Pregnancy, 030225 pediatrics, Medicine, Animals, Retinoid, Risk factor, Vitamin A, Fetus, Mice, Inbred BALB C, business.industry, Incidence, Congenital diaphragmatic hernia, medicine.disease, Basic Science Article, Teratology, Diet, 030104 developmental biology, Posterolateral diaphragmatic hernia, Teratogens, chemistry, Pediatrics, Perinatology and Child Health, Etiology, Female, business, Hernias, Diaphragmatic, Congenital
Abstract

Background Congenital diaphragmatic hernia (CDH) is a severe birth defect associated with high perinatal mortality and long-term morbidity. The etiology of CDH is poorly understood although abnormal retinoid signaling has been proposed to contribute to abnormal diaphragm development. Existing epidemiological data suggest that inadequate dietary vitamin A intake is a risk factor for developing CDH. Methods Using a mouse model of teratogen-induced CDH, the objective of this study was to test the hypothesis that low maternal vitamin A intake contributes to abnormal diaphragm development. To test this hypothesis, we optimized a model of altered maternal dietary vitamin A intake and a teratogenic model of CDH in mice that recapitulates the hallmark features of posterolateral diaphragmatic hernia in humans. Results Our data uniquely show that low maternal dietary vitamin A intake and marginal vitamin A status increases the incidence of teratogen-induced CDH in mice. Conclusion Low dietary vitamin A intake and marginal vitamin A status lead to an increased incidence of teratogen-induced CDH in mice, highlighting the importance of adequate dietary vitamin A intake and CDH risk. Impact This study describes and validates a mouse model of altered maternal and fetal vitamin A status. This study links existing epidemiological data with a mouse model of teratogen-induced congenital diaphragmatic hernia, highlighting the importance of low maternal vitamin A intake as a risk factor for the development of congenital diaphragmatic hernia. This study supports the Retinoid Hypothesis, which posits that the etiology of congenital diaphragmatic hernia is linked to abnormal retinoid signaling in the developing diaphragm.

Published
2021

34. Heterogeneity in Bleeding Tendency and Arthropathy Development in Individuals with Hemophilia

Author

Aisling M. Rehill, James S. O’Donnell, Seán McCluskey, Roger J. S. Preston, and Michael Dockal

Subjects
Bleeding episodes, business.industry, Hemorrhage, Hematology, 030204 cardiovascular system & hematology, Bleed, Hemophilia A, medicine.disease, Bioinformatics, Recombinant factor viii, Review article, 03 medical and health sciences, Joint disease, 0302 clinical medicine, Coagulation, Arthropathy, medicine, Humans, Joint Diseases, Age of onset, Cardiology and Cardiovascular Medicine, business, 030215 immunology
Abstract

People with hemophilia (PWH) have an increased tendency to bleed, often into their joints, causing debilitating joint disease if left untreated. To reduce the incidence of bleeding events, PWH receive prophylactic replacement therapy with recombinant factor VIII (FVIII) or FIX. Bleeding events in PWH are typically proportional to their plasma FVIII or IX levels; however, in many PWH, bleeding tendency and the likelihood of developing arthropathy often varies independently of endogenous factor levels. Consequently, many PWH suffer repeated bleeding events before correct dosing of replacement factor can be established. Diagnostic approaches to define an individual's bleeding tendency remain limited. Multiple modulators of bleeding phenotype in PWH have been proposed, including the type of disease-causing variant, age of onset of bleeding episodes, plasma modifiers of blood coagulation or clot fibrinolysis pathway activity, interindividual differences in platelet reactivity, and endothelial anticoagulant activity. In this review, we summarize current knowledge of established factors modulating bleeding tendency and discuss emerging concepts of additional biological elements that may contribute to variable bleeding tendency in PWH. Finally, we consider how variance in responses to new gene therapies may also necessitate consideration of patient-specific tailoring of treatment. Cumulatively, these studies highlight the need to reconsider the current “one size fits all” approach to treatment regimens for PWH and consider therapies guided by the bleeding phenotype of each individual PWH at the onset of therapy. Further characterization of the biological bases of bleeding heterogeneity in PWH, combined with the development of novel diagnostic assays to identify those factors that modulate bleeding risk in PWH, will be required to meet these aspirations.

Published
2021

35. Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda

Author

Jeffrey N. Martin, P. Richard Harrigan, David R. Bangsberg, Nicholas Musinguzi, Brian T. Foley, Peter W. Hunt, Yap Boum, Simone H. Kigozi, Mwebesa Bwana, Jonathan M. Carlson, Mary Carrington, Zabrina L. Brumme, Kimia Kamelian, Suzanne M. McCluskey, Conrad Muzoora, Jessica E. Haberer, Guinevere Q. Lee, and Mark J. Siedner

Subjects
0301 basic medicine, Immunology, Integrase inhibitor, HIV Infections, HIV Integrase, Human leukocyte antigen, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cabotegravir, Acquired immunodeficiency syndrome (AIDS), Drug Resistance, Viral, Genotype, medicine, Humans, Immunology and Allergy, Uganda, HIV Integrase Inhibitors, 030212 general & internal medicine, Genotyping, Africa South of the Sahara, Retrospective Studies, biology, business.industry, medicine.disease, Virology, Integrase, 030104 developmental biology, Infectious Diseases, chemistry, Mutation, Dolutegravir, HIV-1, biology.protein, business
Abstract

OBJECTIVE Dolutegravir (DTG) is now a preferred component of first-line antiretroviral therapy (ART). However, prevalence data on natural resistance to integrase inhibitors [integrase strand transfer inhibitors (INSTIs)] in circulating non-subtype B HIV-1 in sub-Saharan Africa is scarce. Our objective is to report prevalence of pre-treatment integrase polymorphisms associated with resistance to INSTIs in an ART-naive cohort with diverse HIV-1 subtypes. DESIGN We retrospectively examined HIV-1 integrase sequences from Uganda. METHODS Plasma samples were derived from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, reflecting enrollment from 2002 to 2010, prior to initiation of ART. HIV-1 integrase was amplified using nested-PCR and Sanger-sequenced (HXB2 4230-5093). Stanford HIVdb v8.8 was used to infer clinically significant INSTI-associated mutations. Human leukocyte antigen (HLA) typing was performed for all study participants. RESULTS Plasma samples from 511 ART-naive individuals (subtype: 48% A1, 39% D) yielded HIV-1 integrase genotyping results. Six out of 511 participants (1.2%) had any major INSTI-associated mutations. Of these, two had E138T (subtype A1), three had E138E/K (subtype D), and one had T66T/I (subtype D). No participants had mutations traditionally associated with high levels of INSTI resistance. HLA genotypes A∗02:01/05/14, B∗44:15, and C∗04:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure. CONCLUSION We detected no HIV-1 polymorphisms associated with high levels of DTG resistance in Uganda in the pre-DTG era. Our results support widespread implementation of DTG but careful monitoring of patients on INSTI with virologic failure is warranted to determine if unique mutations predict failure for non-B subtypes of HIV-1.

Published
2021

36. Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator)

Author

Emily P. Hyle, Stephen B. Calderwood, Edward T. Ryan, Camille N. Kotton, Jacob E. Lazarus, Sayon Dutta, Nesli Basgoz, Tyler S. Brown, Caitlin M Dugdale, Jacob E. Lemieux, Louise C. Ivers, Sandra B Nelson, Jennifer L. Reedy, Amy L. Miller, Rochelle P. Walensky, Kristen Hysell, Howard M. Heller, Erica S. Shenoy, John S. Albin, Miriam B Barshak, David M. Rubins, Rocío M. Hurtado, Andrea L. Ciaranello, David C. Hooper, Dustin McEvoy, Suzanne M. McCluskey, Hang Lee, and Kimon C. Zachary

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Isolation (health care), business.industry, Incidence (epidemiology), 030106 microbiology, Logistic regression, Clinical decision support system, Discontinuation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Calculator, law, Health care, Emergency medicine, Medicine, 030212 general & internal medicine, business
Abstract

Background Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. Methods We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. Results Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44–.63]; P Conclusions CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Published
2021

37. Does conventional energy pricing induce innovation in renewable energy? New evidence from a nonlinear approach

Author

Syed Badruddoza, Jill J. McCluskey, and Modhurima D. Amin

Subjects
Economics and Econometrics, Energy pricing, Electricity generation, Country level, business.industry, Negative binomial distribution, Economics, Monetary economics, Development, Crude oil, business, Control function, Renewable energy
Abstract

This article theoretically and empirically studies the association between research and development investments in renewable energy (RE) and oil prices at the country level. We find a positive and robust association between patent counts for RE and price of crude oil using a panel of 46 countries for 1991–2013 in a fixed‐effects hurdle Negative Binomial control function framework. Results suggest that net conventional energy importing countries are more likely to invest in RE when oil prices increase. Countries with more electricity production, less emissions, and greater energy utilization generate more RE patents per year. JEL CLASSIFICATION Q13; Q42; Q55

Published
2021

38. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 1

Author

Rupesh Agrawal, Ilaria Testi, Sarakshi Mahajan, Yew Sen Yuen, Aniruddha Agarwal, Onn Min Kon, Talin Barisani-Asenbauer, John H. Kempen, Amod Gupta, Douglas A. Jabs, Justine R. Smith, Quan Dong Nguyen, Carlos Pavesio, Vishali Gupta, Mamta Agarwal, Manisha Agarwal, Ashutosh Aggarwal, Kanika Aggarwal, Mukesh Agrawal, Hassan Al-Dhibi, Sofia Androudi, Fatma Asyari, Manohar Babu Balasundaram, Kalpana Babu Murthy, Edoardo Baglivo, Alay Banker, Reema Bansal, Soumyava Basu, Digamber Behera, Jyotirmay Biswas, Bahram Bodaghi, Ester Carreño, Laure Caspers, Soon Phaik Chee, Romi Chhabra, Luca Cimino, Luz Elena Concha del Rio, Emmett T. Cunningham, Andrè Luiz Land Curi, Dipankar Das, Janet Davis, Marc DeSmet, Ekaterina Denisova, Alastair K. Denniston, Marie-Hélène Errera, Alejandro Fonollosa, Amala George, Debra A. Goldstein, Yan Guex Crosier, Dinesh Visva Gunasekeran, Avinash Gurbaxani, Alessandro Invernizzi, Hazlita M. Isa, Shah Md. Islam, Nicholas Jones, Deeksha Katoch, Moncef Khairallah, Amit Khosla, Michal Kramer, Amitabh Kumar, Atul Kumar, Rina La Distia Nora, Richard Lee, Careen Lowder, Saurabh Luthra, Padmamalini Mahendradas, Dorine Makhoul, Shahana Mazumdar, Peter McCluskey, Salil Mehta, Elisabetta Miserocchi, Manabu Mochizuki, Oli S. Mohamed, Cristina Muccioli, Marion R. Munk, Somasheila Murthy, Shishir Narain, Heloisa Nascimento, Piergiorgio Neri, Myhanh Nguyen, Annabelle A. Okada, Pinar Ozdal, Alan Palestine, Francesco Pichi, Dhananjay Raje, S.R. Rathinam, Andres Rousselot, Ariel Schlaen, Shobha Sehgal, H. Nida Sen, Aman Sharma, Kusum Sharma, Samir S. Shoughy, Nirbhai Singh, Ramandeep Singh, Masoud Soheilian, Sudharshan Sridharan, Jennifer E. Thorne, Christoph Tappeiner, Stephen Teoh, Maria Sofia Tognon, Ilknur Tugal-Tutkun, Mudit Tyagi, Harvey Uy, Daniel Vitor Vasconcelos Santos, Natasa Vidovic Valentincic, Mark Westcott, Ryoji Yanai, Bety Yanez Alvarez, Rahman Zahedur, and Manfred Zierhut

Subjects
0303 health sciences, medicine.medical_specialty, Tuberculosis, business.industry, MEDLINE, Modified delphi, Ocular tuberculosis, medicine.disease, eye diseases, 03 medical and health sciences, Ophthalmology, Choroiditis, 0302 clinical medicine, 030221 ophthalmology & optometry, medicine, Tuberculoma, Intensive care medicine, business, Uveitis, Ocular inflammation, 030304 developmental biology
Abstract

Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Published
2021

39. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 2

Author

Rupesh Agrawal, Ilaria Testi, Baharam Bodaghi, Talin Barisani-Asenbauer, Peter McCluskey, Aniruddha Agarwal, John H. Kempen, Amod Gupta, Justine R. Smith, Marc D. de Smet, Yew Sen Yuen, Sarakshi Mahajan, Onn Min Kon, Quan Dong Nguyen, Carlos Pavesio, Vishali Gupta, Mamta Agarwal, Manisha Agarwal, Ashutosh Aggarwal, Kanika Aggarwal, Mukesh Agrawal, Hassan Al-Dhibi, Sofia Androudi, Fatma Asyari, Manohar Babu Balasundaram, Kalpana Babu Murthy, Edoardo Baglivo, Alay Banker, Reema Bansal, Soumyava Basu, Digamber Behera, Jyotirmay Biswas, Ester Carreño, Laure Caspers, Soon Phaik Chee, Romi Chhabra, Luca Cimino, Luz Elena Concha del Rio, Emmett T. Cunningham, Andrè Luiz Land Curi, Dipankar Das, Janet Davis, Marc DeSmet, Ekaterina Denisova, Alastair K. Denniston, Marie-Hélène Errera, Alejandro Fonollosa, Amala George, Debra A. Goldstein, Yan Guex Crosier, Dinesh Visva Gunasekeran, Avinash Gurbaxani, Alessandro Invernizzi, Hazlita M. Isa, Shah M.d. Islam, Nicholas Jones, Deeksha Katoch, Moncef Khairallah, Amit Khosla, Michal Kramer, Amitabh Kumar, Atul Kumar, Rina La Distia Nora, Richard Lee, Careen Lowder, Saurabh Luthra, Padmamalini Mahendradas, Dorine Makhoul, Shahana Mazumdar, Salil Mehta, Elisabetta Miserocchi, Manabu Mochizuki, Oli S. Mohamed, Cristina Muccioli, Marion R. Munk, Somasheila Murthy, Shishir Narain, Heloisa Nascimento, Piergiorgio Neri, Myhanh Nguyen, Annabelle A. Okada, Pinar Ozdal, Alan Palestine, Francesco Pichi, Dhananjay Raje, S.R. Rathinam, Andres Rousselot, Ariel Schlaen, Shobha Sehgal, H. Nida Sen, Aman Sharma, Kusum Sharma, Samir S. Shoughy, Nirbhai Singh, Ramandeep Singh, Masoud Soheilian, Sudharshan Sridharan, Jennifer E. Thorne, Christoph Tappeiner, Stephen Teoh, Maria Sofia Tognon, Ilknur Tugal-Tutkun, Mudit Tyagi, Harvey Uy, Daniel Vitor Vasconcelos Santos, Natasa Vidovic Valentincic, Mark Westcott, Ryoji Yanai, Bety Yanez Alvarez, Rahman Zahedur, Manfred Zierhut, and Zheng Xian

Subjects
First episode, 0303 health sciences, medicine.medical_specialty, Tuberculosis, business.industry, Retinal vasculitis, education, MEDLINE, Retrospective cohort study, Eye infection, medicine.disease, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Internal medicine, 030221 ophthalmology & optometry, medicine, Intermediate uveitis, business, Uveitis, 030304 developmental biology
Abstract

Topic The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). Clinical Relevance The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Methods Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Results Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. Discussion The COTS consensus guidelines were generated based on the evidence from published literature, specialists’ opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Published
2021

40. Recommendations for the management of childhood juvenile idiopathic arthritis‐type chronic anterior uveitis

Author

Diana Conrad, Janet M Matthews, Sophia Zagora, Peter McCluskey, Davinder Singh-Grewal, Jane M. Wells, Rachael L Niederer, Justine R. Smith, Mei Ling Tay-Kearney, and Anthony J. Hall

Subjects
medicine.medical_specialty, genetic structures, business.industry, Australia, Delphi method, Outcome measures, Glaucoma, Arthritis, medicine.disease, Uveitis, Anterior, Arthritis, Juvenile, Cataract, eye diseases, Uveitis, Ophthalmology, medicine, Chronic anterior uveitis, Humans, Juvenile, Child, Intensive care medicine, business, Juvenile rheumatoid arthritis
Abstract

Importance Australian- and New Zealand-based, uveitis-specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)-type chronic anterior uveitis. Background Historically, the visual prognosis of JIA-type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States. Design This work involved a consensus survey and a panel meeting. Participants The Australian and New Zealand JIA-Uveitis Working Group (29 ophthalmologists) participated in the work. Methods The Delphi technique was used to achieve consensus. Main outcome measures This work yielded consensus statements. Results The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non-corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA-type uveitis. Conclusions and relevance Recommendations of the Australian and New Zealand JIA-Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA.

Published
2021

41. Telehealth in an acute ophthalmic setting during <scp>COVID</scp> ‐19 lock‐down

Author

Catriona Downie, Elisa E Cornish, Danny Lam, Sophia Zagora, and Peter McCluskey

Subjects
Adult, Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Record locking, Eye Diseases, Coronavirus disease 2019 (COVID-19), MEDLINE, Comorbidity, Telehealth, Epidemiology, Disease Transmission, Infectious, medicine, Humans, Intensive care medicine, SARS-CoV-2, business.industry, COVID-19, Middle Aged, medicine.disease, Telemedicine, Ophthalmology, Acute Disease, Communicable Disease Control, Female, business, Disease transmission
Published
2020

42. Bobath therapy is inferior to task-specific training and not superior to other interventions in improving lower limb activities after stroke: a systematic review

Author

Karl Schurr, Katharine Scrivener, Simone Dorsch, Roberta B. Shepherd, Sarah Tyson, Petra L. Graham, Zheng Cao, and Annie McCluskey

Subjects
Adult, medicine.medical_specialty, Strength training, Psychological intervention, Physical Therapy, Sports Therapy and Rehabilitation, Lower limb activities, walking, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), Humans, Medicine, physical therapy, 030212 general & internal medicine, Stroke, Balance (ability), Proprioception, business.industry, lcsh:RM1-950, Stroke Rehabilitation, Bobath, medicine.disease, stroke, Exercise Therapy, lcsh:Therapeutics. Pharmacology, Lower Extremity, Facilitation, Physical therapy, lower limb, business, 030217 neurology & neurosurgery
Abstract

Question In adults with stroke, does Bobath therapy improve lower limb activity performance, strength or co-ordination when compared with no intervention or another intervention? Design Systematic review of randomised trials with meta-analyses. Participants Adults after stroke. Intervention Bobath therapy compared with another intervention or no intervention. Outcome measures Lower limb activity performance (eg, sit to stand, walking, balance), lower limb strength and lower limb co-ordination. Trial quality was assessed using the PEDro scale. Results Twenty-two trials were included in the review and 17 in the meta-analyses. The methodological quality of the trials varied, with PEDro scale scores ranging from 2 to 8 out of 10. No trials compared Bobath therapy to no intervention. Meta-analyses estimated the effect of Bobath therapy on lower limb activities compared with other interventions, including: task-specific training (nine trials), combined interventions (four trials), proprioceptive neuromuscular facilitation (one trial) and strength training (two trials). The pooled data indicated that task-specific training has a moderately greater benefit on lower limb activities than Bobath therapy (SMD 0.48), although the true magnitude of the benefit may be substantially larger or smaller than this estimate (95% CI 0.01 to 0.95). Bobath therapy did not clearly improve lower limb activities more than a combined intervention (SMD −0.06, 95% CI −0.73 to 0.61) or strength training (SMD 0.35, 95% CI −0.37 to 1.08). In one study, Bobath therapy was more effective than proprioceptive neuromuscular facilitation for improving standing balance (SMD −1.40, 95% CI −1.92 to −0.88), but these interventions did not differ on any other outcomes. Bobath therapy did not improve strength or co-ordination more than other interventions. Conclusions Bobath therapy was inferior to task-specific training and not superior to other interventions, with the exception of proprioceptive neuromuscular facilitation. Prioritising Bobath therapy over other interventions is not supported by current evidence. Registration PROSPERO CRD42019112451.

Published
2020

43. Viral Ocular Infections

Author

Peter McCluskey, Maria Cabrera-Aguas, Stephanie L Watson, and Pauline Khoo

Subjects
business.industry, Viral Ocular Infections, Immunology, Medicine, business
Published
2022

44. Investigating Unhealthy Alcohol Use As an Independent Risk Factor for Increased COVID-19 Disease Severity: Observational Cross-sectional Study

Author

Connor McCluskey, Niranjan S. Karnik, Yousaf Ilyas, Robert A. Balk, Dale L. Smith, Randy A. Boley, Majid Afshar, Ali Keshavarzian, Sameer Bhalla, and Brihat Sharma

Subjects
medicine.medical_specialty, Cross-sectional study, substance use, Health Informatics, Disease, mechanical ventilation, Severity of Illness Index, unhealthy alcohol use, Odds, Risk Factors, Internal medicine, Severity of illness, medicine, Humans, Risk factor, Uncategorized, Original Paper, SARS-CoV-2, business.industry, substance misuse, Public Health, Environmental and Occupational Health, COVID-19, Odds ratio, Emergency department, acute respiratory distress syndrome, Cross-Sectional Studies, Observational study, business
Abstract

Background Unhealthy alcohol use (UAU) is known to disrupt pulmonary immune mechanisms and increase the risk of acute respiratory distress syndrome in patients with pneumonia; however, little is known about the effects of UAU on outcomes in patients with COVID-19 pneumonia. To our knowledge, this is the first observational cross-sectional study that aims to understand the effect of UAU on the severity of COVID-19. Objective We aim to determine if UAU is associated with more severe clinical presentation and worse health outcomes related to COVID-19 and if socioeconomic status, smoking, age, BMI, race/ethnicity, and pattern of alcohol use modify the risk. Methods In this observational cross-sectional study that took place between January 1, 2020, and December 31, 2020, we ran a digital machine learning classifier on the electronic health record of patients who tested positive for SARS-CoV-2 via nasopharyngeal swab or had two COVID-19 International Classification of Disease, 10th Revision (ICD-10) codes to identify patients with UAU. After controlling for age, sex, ethnicity, BMI, smoking status, insurance status, and presence of ICD-10 codes for cancer, cardiovascular disease, and diabetes, we then performed a multivariable regression to examine the relationship between UAU and COVID-19 severity as measured by hospital care level (ie, emergency department admission, emergency department admission with ventilator, or death). We used a predefined cutoff with optimal sensitivity and specificity on the digital classifier to compare disease severity in patients with and without UAU. Models were adjusted for age, sex, race/ethnicity, BMI, smoking status, and insurance status. Results Each incremental increase in the predicted probability from the digital alcohol classifier was associated with a greater odds risk for more severe COVID-19 disease (odds ratio 1.15, 95% CI 1.10-1.20). We found that patients in the unhealthy alcohol group had a greater odds risk to develop more severe disease (odds ratio 1.89, 95% CI 1.17-3.06), suggesting that UAU was associated with an 89% increase in the odds of being in a higher severity category. Conclusions In patients infected with SARS-CoV-2, UAU is an independent risk factor associated with greater disease severity and/or death.

Published
2022
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45. Bacterial Eye Infections

Author

Peter McCluskey, Pauline Khoo, Maria Cabrera-Aguas, and Stephanie L Watson

Subjects
medicine.medical_specialty, business.industry, medicine, Eye infection, business, Dermatology
Published
2022

46. Fungal Ocular Infections

Author

Pauline Khoo, Maria Cabrera-Aguas, Peter McCluskey, and Stephanie L Watson

Subjects
medicine.medical_specialty, business.industry, Ocular Infections, medicine, business, Dermatology
Published
2022

47. Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2

Author

Jason Roy, Alessandro Sette, Natalie Bruiners, Sunanda Gaur, Rahul Ukey, Deborah McCluskey, Pankaj K. Mishra, Maria Laura Gennaro, Abraham Pinter, Hridesh Mishra, Alberta Onyuka, Daniela Weiskopf, and Fei Chen

Subjects
COVID-19 Vaccines, Ad26.COV2.S, T cell, Antibodies, Viral, Neutralizing antibodies, Article, Viral vector, mRNA-1273, Pandemic, Correspondence, medicine, Humans, RNA, Messenger, Antibody binding, Neutralizing antibody, Antigen-specific B cells, B cell, Antigen-specific T cells, biology, Ad26COVS1, business.industry, SARS-CoV-2, Immunogenicity, Vaccination, COVID-19, General Medicine, Immunity, Humoral, medicine.anatomical_structure, Immunology, biology.protein, Medicine, BNT162b2, mRNA Vaccines, Antibody, business
Abstract

Background Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. Main body We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class 5 months earlier on average. After controlling for the time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Conclusions A dichotomy exists between the humoral and cellular responses elicited by the two vaccine classes. Testing only for humoral responses to compare the durability of SARS-CoV-2 vaccine-induced responses, as typically performed for public health and research purposes, is insufficient.

Published
2022

48. Volume IV The DUNE far detector single-phase technology

Author

L. Di Giulio, J. Martin-Albo, S. Ravat, W. Mu, D. Marfatia, T. Kosc, D. Autiero, Poonam Mehta, A. Borkum, N. McConkey, G. Karagiorgi, Robert Wilson, L. M. Cremaldi, Stephen P. Gent, T. Young, Julián Félix, D. MacFarland, Andrew Smith, M. Manrique Plata, J. Freestone, D. Rivera, B. Stillwell, Marco Verzocchi, A. Lambert, Orlando L. G. Peres, K. Gollwitzer, E. Kemp, G. Yang, I. Kreslo, F. Varanini, M. Chalifour, A. Holin, S. J. Patton, R. J. Nichol, Giovanni Bellettini, V. A. Kudryavtsev, M. Sorel, E. Church, S. Kasai, H. O. Back, A. Lister, S. Santana, C. Mariani, Carlos Escobar, J. C. Freeman, Kaushik De, M. J. Rodriguez Alonso, M. A. Acero, A. Christensen, G. S. Varner, S. Sacerdoti, D. Shooltz, Seodong Shin, M. Santos-Maldonado, T. Schaffer, Jeremy Wolcott, J. Vasel, J. A. Gonzalez-Cuevas, J. Franc, C. Mossey, Jonas Rademacker, G. P. Zeller, Joshua Barrow, John Marshall, Alessandro Thea, H. A. Tanaka, W. C. Louis, E. Hazen, Armin Karcher, D. Smargianaki, Christopher L. Marshall, M. Soderberg, A. C. Weber, Christopher J. Milne, E. Brianne, A. Aranda-Fernandez, J. Calcutt, K. Warburton, M. Nalbandyan, Dave Sankey, J. Asaadi, F. Diaz, E. Valencia, B. Kirby, A. Bross, K. Koehler, M. A. Uchida, Y. Bezawada, D. Warner, C. E. Thorn, Srubabati Goswami, Z. Williams, Gregory Iles, A. Friedland, K. M. Heeger, V. P. Luzio, G. C. Blazey, J. Barranco Monarca, Carl Grace, A. M. Gago, E. James, M. Newcomer, H. W. Sobel, Roberto Gutiérrez, C. Vignoli, R. Hatcher, M. Zhao, F. Cavalier, M. A. Hernandez Morquecho, N. Poonthottathil, Ara Ioannisian, W. Metcalf, T. Wongjirad, H. T. Rakotondramanana, D. Cherdack, M. A. Ramirez Delgado, R. Diurba, G. Christodoulou, S. Calvez, T. Durkin, H. Y. Wei, M. Muether, S. Roy, A. Caminata, A. Scarpelli, Christopher Brew, Pavel Snopok, Y. Rigaut, L. Escudero Sanchez, K. Kothekar, W. Flanagan, V. Papadimitriou, S. J. Brice, Nicolas Lurkin, M. V. Diwan, Andrew White, S. Berkman, H. Muramatsu, Z. Pavlovic, A. A. Machado, Christian Farnese, A. Mastbaum, Alfredo G. Cocco, G. Zhu, S. Centro, S. Henry, J. Rout, P. de Jong, H. Carranza, Milos Lokajicek, K. Nishimura, A. Delbart, N. J. C. Spooner, C. McGrew, E. Pantic, Mario Campanelli, David Cussans, B. T. Fleming, K. Negishi, F. Spagliardi, J. Nesbit, André Rubbia, Akitaka Ariga, Marvin L Marshak, F. Pietropaolo, F. D. M. Blaszczyk, T. Hasegawa, Kate Scholberg, O. Gogota, R. Poling, Simon Jones, A. Tonazzo, M. P. Andrews, R. Petti, S. Bertolucci, M. Bonesini, A. F. Moor, C. Barnes, A. S. Hesam, S. H. Kettell, M. Bongrand, M. R. While, D. J. Payne, C. Gotti, A. Chiriacescu, Paul Keener, Leigh H. Whitehead, James Stewart, A. Mazzacane, L. W. Koerner, T. Rehak, C. Andreopoulos, F. Terranova, Jaroslaw Pasternak, E. Raguzin, L. C. J. Rice, J. L. Bazo Alba, S. Li, J. Hartnell, M. Potekhin, N. Moggi, D. J. Summers, J. Berger, L. Cremonesi, Katsuya Yonehara, T. E. Coan, Claire Shepherd-Themistocleous, B. Radics, Karol Hennessy, S. Söldner-Rembold, C. S. Lin, L. Greenler, B. Guo, Frank Filthaut, R. B. Patterson, E. Pennacchio, E. Zhivun, C. Cuesta, T. Loew, G. Prior, D. Duchesneau, Lina Necib, S. Rescia, W. Gu, Andrés Castillo, N. Kazaryan, O. G. Miranda, C. Patrick, Robert Shrock, José W. F. Valle, J. Reichenbacher, D. A. Sanders, John F. Beacom, S. Tufanli, S. Ventura, Riccardo Papaleo, J. Zennamo, A. De Roeck, M. Calin, P. Ding, Alessandro Menegolli, B. V. K. S. Potukuchi, T. Le, T. Wachala, L. O. Arnold, J. R. Macier, A. M. Teklu, E. Blucher, L. Hertel, F. W. Sippach, S. Childress, T. Miao, P. Fernandez Menendez, J. Han, R. Gandrajula, C. Y. Chi, Marzio Nessi, Aldo Penzo, Ina Sarcevic, Kendall Mahn, Jorge Molina, F. Bonini, Eric W. Hoppe, M. Groh, Barry King, R. Mazza, Keith Rielage, Patrick Dunne, M. Mellinato, D. Lorca, R. Guenette, F. Bento Neves, L. Pickering, Manuel Alejandro Segura Delgado, J. J. Russell, H. R. Gallagher, J. Zuklin, Steven Gardiner, P. Madigan, D. Douglas, Daniel Gastler, S. Manly, P. Hamilton, L. Montaño Zetina, R. G. Van de Water, S. Dennis, M. Tenti, N. Dokania, Kim Siyeon, E. Fernandez-Martinez, P. P. Koller, D. Whittington, T. Li, M. C. Sanchez, S. Biagi, C. Sarasty, Juraj Bracinik, A. N. Khotjantsev, N. Tsverava, Yasaman Farzan, M. Tzanov, J. G. Boissevain, J. Smolik, Andrew Brandt, J. Hoff, D. A. Harris, C. Distefano, Ornella Palamara, H. S. Budd, Alastair Grant, A. K. Giri, Thorsten Lux, C. E. Lane, J. Marteau, Irakli Lomidze, E. Kearns, Zviad Tsamalaidze, L. S. Gomez Fajardo, H. da Motta, J. S. Real, Sukalyan Chattopadhyay, B. Viren, J. Mousseau, Ihn Sik Seong, C. M. Sutera, A. C. Ezeribe, F. Ferraro, Marco Adinolfi, Nikolaos Simos, A. Stuart, D. Brailsford, N. Solomey, Laura Manenti, L. V. Gomez Bermeo, Andrea Zani, Kristian Harder, Timothy M. Shaw, J. Hewes, Sandro Palestini, D. Braga, D. Garcia-Gamez, J. Stock, S. Bolognesi, D. Belver, Laura Paulucci, J. Ahmed, Narendra Sahu, Sandip Pakvasa, L. Pasqualini, D. Mladenov, M. Kordosky, S. Zucchelli, L. Stanco, M. Torti, B. Jargowsky, E. Smith, C. J. Solano Salinas, N.V. Mokhov, D. Vanegas Forero, C. Jesús-Valls, Andrew Blake, L. Jiang, F. Andrianala, W. Ketchum, Matthaeus Leitner, K. Fahey, Marco Pallavicini, Bindu A. Bambah, K. Francis, M. H. Shaevitz, N. Barros, I. Caro Terrazas, R. Itay, G. Sirri, H. Steiner, Laura Dominé, S. Lockwitz, G. Savage, N. Bostan, J. A. Nowak, A. Scarff, Konstantinos Manolopoulos, R. K. Plunkett, B. Morgan, A. Rafique, Cari L. Johnson, M. Parvu, L. Patrizii, James A. Anderson, L. Corwin, A. Hourlier, S. L. Mufson, S. Martynenko, V. J. Guarino, B. Carlus, D. Boyden, F. Marinho, David Delepine, J. Bremer, Paola Sala, P. Cotte, J.V. Dawson, G. Mandrioli, O. Goodwin, Jitendra Kumar, Ph. Lebrun, J. Soto-Oton, K. K. Guthikonda, Evgueni Goudzovski, Gabriella Carini, S. Gao, M. Dabrowski, Sudarshan Paramesvaran, G. Pessina, S. Davini, R. L. Talaga, Francesco Gonnella, A. Joglekar, G. Sinev, S. Gwon, A. Surdo, M. O. Wascko, R. Bajou, Pedro A. N. Machado, Massimo Rossella, G. S. Davies, I. De Bonis, K. S. McFarland, C. T. Macias, T. Alion, O. V. Mineev, M. Bishai, R. Northrop, Chao Zhang, R. Van Berg, L. Di Noto, Kam-Biu Luk, J. Chaves, J. Wang, K. Qi, W. E. Sondheim, Sergei Striganov, B. Paulos, Janice L. Thompson, M. Rai, P. N. Ratoff, T. Kutter, D. Totani, J. A. B. Coelho, F. Stocker, T. Gamble, J. J. Grudzinski, I. Gil-Botella, T. Yang, Wayne A. Barkhouse, C. E. Tull, H. Mendez, Z. Ghorbani-Moghaddam, Y.-J. Jwa, F. Cavanna, F. Kamiya, V. Basque, R. Sipos, V. Bellini, C. Alt, Sandhya Choubey, B. Abi, A. Mefodiev, V. A. Kostelecky, A. L. Renshaw, Giuseppe Benedetto Cerati, S. Balasubramanian, M. Biassoni, D. Pershey, J. Maricic, K. Lande, A. Muir, L.S. Rochester, A. Papanestis, A. Aurisano, F. Bay, R. Nandakumar, T. L. Usher, Bo Yu, A. V. Waldron, A. Filkins, Y. Cui, P. A. Rodrigues, Daijin Kim, G.D. Barr, Junwei Huang, V. De Romeri, H.E. Rogers, Andrea Dell'Acqua, A. Cervera Villanueva, Robert Svoboda, Yu. Onishchuk, T. Hamernik, A. P. Furmanski, M. Wetstein, P.T. Smith, G. Brunetti, Mariam Tórtola, Matthew L Strait, G. Barenboim, P. Guzowski, J. D. Eisch, N. Gallice, D. Newhart, A. J. Roeth, H. Berns, E. Granados, A. Weinstein, A. Falcone, D. Caratelli, L. Bellantoni, Wei Wu, J. Mills, A. Hackenburg, D. Caiulo, Chia-Chan Chang, Dave M Newbold, C. K. Jung, F. Krennrich, G. Testera, S. Rosauro-Alcaraz, A. Sitraka, L. Bagby, J. M. LoSecco, S. Tariq, C. Mauger, J. J. Back, J. Yu, R. Acciarri, B. Behera, P. Lasorak, Karol Lang, Irina Mocioiu, H. Schellman, Han Wang, Sergey A. Kulagin, A. Bashyal, Beatriz B. Siffert, C. N. Booth, L. Zambelli, M. T. Graham, A. Mann, Rakesh Kumar, Y. Xiao, Gregory J Pawloski, T. Prakash, Arsen Khvedelidze, A.S. Dyshkant, Paolo Carniti, C. Rubbia, M. Reggiani-Guzzo, M. M. Khabibullin, D. Wenman, S. C. Timm, R. Sharma, R. Saakyan, Marcelo M. Guzzo, P. Baesso, M. Pozzato, T. R. Junk, C. Morris, A. Cervelli, A. Heavey, Grzegorz Deptuch, M. Á. García-Peris, B. Bhuyan, M. Kabirnezhad, Pierre Baldi, M. Mooney, E. Tyley, A. 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Molina Bueno, Science and Technology Facilities Council (STFC), Abi, B, Acciarri, R, Acero, M, Adamov, G, Adams, D, Adinolfi, M, Ahmad, Z, Ahmed, J, Alion, T, Monsalve, S, Alt, C, Anderson, J, Andreopoulos, C, Andrews, M, Andrianala, F, Andringa, S, Ankowski, A, Antonova, M, Antusch, S, Aranda-Fernandez, A, Ariga, A, Arnold, L, Arroyave, M, Asaadi, J, Aurisano, A, Aushev, V, Autiero, D, Azfar, F, Back, H, Back, J, Backhouse, C, Baesso, P, Bagby, L, Bajou, R, Balasubramanian, S, Baldi, P, Bambah, B, Barao, F, Barenboim, G, Barker, G, Barkhouse, W, Barnes, C, Barr, G, Monarca, J, Barros, N, Barrow, J, Bashyal, A, Basque, V, Bay, F, Alba, J, Beacom, J, Bechetoille, E, Behera, B, Bellantoni, L, Bellettini, G, Bellini, V, Beltramello, O, Belver, D, Benekos, N, Neves, F, Berger, J, Berkman, S, Bernardini, P, Berner, R, Berns, H, Bertolucci, S, Betancourt, M, Bezawada, Y, Bhattacharjee, M, Bhuyan, B, Biagi, S, Bian, J, Biassoni, M, Biery, K, Bilki, B, Bishai, M, Bitadze, A, Blake, A, Siffert, 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Conrad, J, Convery, M, Corwin, L, Cotte, P, Cremaldi, L, Cremonesi, L, Crespo-Anadon, J, Cristaldo, E, Cross, R, Cuesta, C, Cui, Y, Cussans, D, Dabrowski, M, Motta, H, Peres, L, David, Q, Davies, G, Davini, S, Dawson, J, De, K, Almeida, R, Debbins, P, Bonis, I, Decowski, M, Gouvea, A, Holanda, P, Astiz, I, Deisting, A, Jong, P, Delbart, A, Delepine, D, Delgado, M, Dell'Acqua, A, Lurgio, P, Neto, J, Demuth, D, Dennis, S, Densham, C, Deptuch, G, Roeck, A, Romeri, V, Vries, J, Dharmapalan, R, Dias, M, Diaz, F, Diaz, J, Domizio, S, Giulio, L, Ding, P, Noto, L, Distefano, C, Diurba, R, Diwan, M, Djurcic, Z, Dokania, N, Dolinski, M, Domine, L, Douglas, D, Drielsma, F, Duchesneau, D, Duffy, K, Dunne, P, Durkin, T, Duyang, H, Dvornikov, O, Dwyer, D, Dyshkant, A, Eads, M, Edmunds, D, Eisch, J, Emery, S, Ereditato, A, Escobar, C, Sanchez, L, Evans, J, Ewart, E, Ezeribe, A, Fahey, K, Falcone, A, Farnese, C, Farzan, Y, Felix, J, Fernandez-Martinez, E, Menendez, P, Ferraro, F, Fields, L, Filkins, A, Filthaut, F, Fitzpatrick, R, Flanagan, W, Fleming, B, Flight, R, Fowler, J, Fox, W, Franc, J, Francis, K, Franco, D, Freeman, J, Freestone, J, Fried, J, Friedland, A, Fuess, S, Furic, I, Furmanski, A, Gago, A, Gallagher, H, Gallego-Ros, A, Gallice, N, Galymov, V, Gamberini, E, Gamble, T, Gandhi, R, Gandrajula, R, Gao, S, Garcia-Gamez, D, Garcia-Peris, M, Gardiner, S, Gastler, D, Ge, G, Gelli, B, Gendotti, A, Gent, S, Ghorbani-Moghaddam, Z, Gibin, D, Gil-Botella, I, Girerd, C, Giri, A, Gnani, D, Gogota, O, Gold, M, Gollapinni, S, Gollwitzer, K, Gomes, R, Bermeo, L, Fajardo, L, Gonnella, F, Gonzalez-Cuevas, J, Goodman, M, Goodwin, O, Goswami, S, Gotti, C, Goudzovski, E, Grace, C, Graham, M, Gramellini, E, Gran, R, Granados, E, Grant, A, Grant, C, Gratieri, D, Green, P, Green, S, Greenler, L, Greenwood, M, Greer, J, Griffith, C, Groh, M, Grudzinski, J, Grzelak, K, Gu, W, Guarino, V, Guenette, R, Guglielmi, A, Guo, B, Guthikonda, K, Gutierrez, R, Guzowski, P, Guzzo, M, Gwon, S, Habig, A, Hackenburg, A, Hadavand, H, Haenni, R, Hahn, A, Haigh, J, Haiston, J, Hamernik, T, Hamilton, P, Han, J, Harder, K, Harris, D, Hartnell, J, Hasegawa, T, Hatcher, R, Hazen, E, Heavey, A, Heeger, K, Hennessy, K, Henry, S, Morquecho, M, Herner, K, Hertel, L, Hesam, A, Hewes, J, Pichardo, A, Hill, T, Hillier, S, Himmel, A, Hoff, J, Hohl, C, Holin, A, Hoppe, E, Horton-Smith, G, Hostert, M, Hourlier, A, Howard, B, Howell, R, Huang, J, Hugon, J, Iles, G, Iliescu, A, Illingworth, R, Ioannisian, A, Itay, R, Izmaylov, A, James, E, Jargowsky, B, Jediny, F, Jesus-Valls, C, Ji, X, Jiang, L, Jimenez, S, Jipa, A, Joglekar, A, Johnson, C, Johnson, R, Jones, B, Jones, S, Jung, C, Junk, T, Jwa, Y, Kabirnezhad, M, Kaboth, A, Kadenko, I, Kamiya, F, Karagiorgi, G, Karcher, A, Karolak, M, Karyotakis, Y, Kasai, S, Kasetti, S, Kashur, L, Kazaryan, N, Kearns, E, Keener, P, Kelly, K, Kemp, E, Ketchum, W, Kettell, S, Khabibullin, M, Khotjantsev, A, Khvedelidze, A, Kim, D, King, B, Kirby, B, Kirby, M, Klein, J, Koehler, K, Koerner, L, Kohn, S, Koller, P, Kordosky, M, Kosc, T, Kose, U, Kostelecky, V, Kothekar, K, Krennrich, F, Kreslo, I, Kudenko, Y, Kudryavtsev, V, Kulagin, S, Kumar, J, Kumar, R, Kuruppu, C, Kus, V, Kutter, T, Lambert, A, Lande, K, Lane, C, Lang, K, Langford, T, Lasorak, P, Last, D, Lastoria, C, Laundrie, A, Lawrence, A, Lazanu, I, Lazur, R, Le, T, Learned, J, Lebrun, P, Miotto, G, Lehnert, R, De Oliveira, M, Leitner, M, Leyton, M, Li, L, Li, S, Li, T, Li, Y, Liao, H, Lin, C, Lin, S, Lister, A, Littlejohn, B, Liu, J, Lockwitz, S, Loew, T, Lokajicek, M, Lomidze, I, Long, K, Loo, K, Lorca, D, Lord, T, Losecco, J, Louis, W, Luk, K, Luo, X, Lurkin, N, Lux, T, Luzio, V, Macfarland, D, Machado, A, Machado, P, Macias, C, Macier, J, Maddalena, A, Madigan, P, Magill, S, Mahn, K, Maio, A, Maloney, J, Mandrioli, G, Maneira, J, Manenti, L, Manly, S, Mann, A, Manolopoulos, K, Plata, M, Marchionni, A, Marciano, W, Marfatia, D, Mariani, C, Maricic, J, Marinho, F, Marino, A, Marshak, M, Marshall, C, Marshall, J, Marteau, J, Martin-Albo, J, Martinez, N, Caicedo, D, Martynenko, S, Mason, K, Mastbaum, A, Masud, M, Matsuno, S, Matthews, J, Mauger, C, Mauri, N, Mavrokoridis, K, Mazza, R, Mazzacane, A, Mazzucato, E, Mccluskey, E, Mcconkey, N, Mcfarland, K, Mcgrew, C, Mcnab, A, Mefodiev, A, Mehta, P, Melas, P, Mellinato, M, Mena, O, Menary, S, Mendez, H, Menegolli, A, Meng, G, Messier, M, Metcalf, W, Mewes, M, Meyer, H, Miao, T, Michna, G, Miedema, T, Migenda, J, Milincic, R, Miller, W, Mills, J, Milne, C, Mineev, O, Miranda, O, Miryala, S, Mishra, C, Mishra, S, Mislivec, A, Mladenov, D, Mocioiu, I, Moffat, K, Moggi, N, Mohanta, R, Mohayai, T, Mokhov, N, Molina, J, Bueno, L, Montanari, A, Montanari, C, Montanari, D, Zetina, L, Moon, J, Mooney, M, Moor, A, Moreno, D, Morgan, B, Morris, C, Mossey, C, Motuk, E, Moura, C, Mousseau, J, Mu, W, Mualem, L, Mueller, J, Muether, M, Mufson, S, Muheim, F, Muir, A, Mulhearn, M, Muramatsu, H, Murphy, S, Musser, J, Nachtman, J, Nagu, S, 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A., Adamov, G., Adams, D., Adinolfi, M., Ahmad, Z., Ahmed, J., Alion, T., Monsalve, S. Alonso, Alt, C., Anderson, J., Andreopoulos, C., Andrews, M., Andrianala, F., Andringa, S., Ankowski, A., Antonova, M., Antusch, S., Aranda-Fernandez, A., Ariga, A., Arnold, L. O., Arroyave, M. A., Asaadi, J., Aurisano, A., Aushev, V., Autiero, D., Azfar, F., Back, H., Back, J. J., Backhouse, C., Baesso, P., Bagby, L., Bajou, R., Balasubramanian, S., Baldi, P., Bambah, B., Barao, F., Barenboim, G., Barker, G., Barkhouse, W., Barnes, C., Barr, G., Monarca, J. Barranco, Barros, N., Barrow, J. L., Bashyal, A., Basque, V., Bay, F., Alba, J. Bazo, Beacom, J. F., Bechetoille, E., Behera, B., Bellantoni, L., Bellettini, G., Bellini, V., Beltramello, O., Belver, D., Benekos, N., Neves, F. Bento, Berger, J., Berkman, S., Bernardini, P., Berner, R. 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Cervera, Chalifour, M., Chang, C., Chardonnet, E., Chatterjee, A., Chattopadhyay, S., Chaves, J., Chen, H., Chen, M., Chen, Y., Cherdack, D., Chi, C., Childress, S., Chiriacescu, A., Cho, K., Choubey, S., Christensen, A., Christian, D., Christodoulou, G., Church, E., Clarke, P., Coan, T. E., Cocco, A. G., Coelho, J., Conley, E., Conrad, J., Convery, M., Corwin, L., Cotte, P., Cremaldi, L., Cremonesi, L., Crespo-Anadón, J. I., Cristaldo, E., Cross, R., Cuesta, C., Cui, Y., Cussans, D., Dabrowski, M., Motta, H. Da, Peres, L. Da Silva, David, Q., Davies, G. S., Davini, S., Dawson, J., De, K., Almeida, R. M. De, Debbins, P., Bonis, I. De, Decowski, M., Gouvea, A. De, Holanda, P. C. De, Astiz, I. L. De Icaza, Deisting, A., Jong, P. De, Delbart, A., Delepine, D., Delgado, M., Dell'Acqua, A., Lurgio, P. De, Neto, J. R. De Mello, Demuth, D. M., Dennis, S., Densham, C., Deptuch, G., Roeck, A. De, Romeri, V. De, Vries, J. De, Dharmapalan, R., Dias, M., Diaz, F., Diaz, J., Domizio, S. Di, Giulio, L. Di, Ding, P., Noto, L. Di, Distefano, C., Diurba, R., Diwan, M., Djurcic, Z., Dokania, N., Dolinski, M., Domine, L., Douglas, D., Drielsma, F., Duchesneau, D., Duffy, K., Dunne, P., Durkin, T., Duyang, H., Dvornikov, O., Dwyer, D., Dyshkant, A., Eads, M., Edmunds, D., Eisch, J., Emery, S., Ereditato, A., Escobar, C., Sanchez, L. Escudero, Evans, J. J., Ewart, E., Ezeribe, A. C., Fahey, K., Falcone, A., Farnese, C., Farzan, Y., Felix, J., Fernandez-Martinez, E., Menendez, P. Fernandez, Ferraro, F., Fields, L., Filkins, A., Filthaut, F., Fitzpatrick, R. S., Flanagan, W., Fleming, B., Flight, R., Fowler, J., Fox, W., Franc, J., Francis, K., Franco, D., Freeman, J., Freestone, J., Fried, J., Friedland, A., Fuess, S., Furic, I., Furmanski, A. P., Gago, A., Gallagher, H., Gallego-Ros, A., Gallice, N., Galymov, V., Gamberini, E., Gamble, T., Gandhi, R., Gandrajula, R., Gao, S., Garcia-Gamez, D., García-Peris, M. Á., Gardiner, S., Gastler, D., Ge, G., Gelli, B., Gendotti, A., Gent, S., Ghorbani-Moghaddam, Z., Gibin, D., Gil-Botella, I., Girerd, C., Giri, A., Gnani, D., Gogota, O., Gold, M., Gollapinni, S., Gollwitzer, K., Gomes, R. A., Bermeo, L. Gomez, Fajardo, L. S. Gomez, Gonnella, F., Gonzalez-Cuevas, J., Goodman, M. C., Goodwin, O., Goswami, S., Gotti, C., Goudzovski, E., Grace, C., Graham, M., Gramellini, E., Gran, R., Granados, E., Grant, A., Grant, C., Gratieri, D., Green, P., Green, S., Greenler, L., Greenwood, M., Greer, J., Griffith, C., Groh, M., Grudzinski, J., Grzelak, K., Gu, W., Guarino, V., Guenette, R., Guglielmi, A., Guo, B., Guthikonda, K., Gutierrez, R., Guzowski, P., Guzzo, M. M., Gwon, S., Habig, A., Hackenburg, A., Hadavand, H., Haenni, R., Hahn, A., Haigh, J., Haiston, J., Hamernik, T., Hamilton, P., Han, J., Harder, K., Harris, D. A., Hartnell, J., Hasegawa, T., Hatcher, R., Hazen, E., Heavey, A., Heeger, K. M., Hennessy, K., Henry, S., Morquecho, M. Hernandez, Herner, K., Hertel, L., Hesam, A. S., Hewes, J., Pichardo, A. Higuera, Hill, T., Hillier, S. J., Himmel, A., Hoff, J., Hohl, C., Holin, A., Hoppe, E., Horton-Smith, G. A., Hostert, M., Hourlier, A., Howard, B., Howell, R., Huang, J., Hugon, J., Iles, G., Iliescu, A. M., Illingworth, R., Ioannisian, A., Itay, R., Izmaylov, A., James, E., Jargowsky, B., Jediny, F., Jesús-Valls, C., Ji, X., Jiang, L., Jiménez, S., Jipa, A., Joglekar, A., Johnson, C., Johnson, R., Jones, B., Jones, S., Jung, C., Junk, T., Jwa, Y., Kabirnezhad, M., Kaboth, A., Kadenko, I., Kamiya, F., Karagiorgi, G., Karcher, A., Karolak, M., Karyotakis, Y., Kasai, S., Kasetti, S. P., Kashur, L., Kazaryan, N., Kearns, E., Keener, P., Kelly, K. J., Kemp, E., Ketchum, W., Kettell, S., Khabibullin, M., Khotjantsev, A., Khvedelidze, A., Kim, D., King, B., Kirby, B., Kirby, M., Klein, J., Koehler, K., Koerner, L. W., Kohn, S., Koller, P. P., Kordosky, M., Kosc, T., Kose, U., Kostelecky, V., Kothekar, K., Krennrich, F., Kreslo, I., Kudenko, Y., Kudryavtsev, V., Kulagin, S., Kumar, J., Kumar, R., Kuruppu, C., Kus, V., Kutter, T., Lambert, A., Lande, K., Lane, C. E., Lang, K., Langford, T., Lasorak, P., Last, D., Lastoria, C., Laundrie, A., Lawrence, A., Lazanu, I., Lazur, R., Le, T., Learned, J., Lebrun, P., Miotto, G. Lehmann, Lehnert, R., de Oliveira, M. Leigui, Leitner, M., Leyton, M., Li, L., Li, S., Li, T., Li, Y., Liao, H., Lin, C., Lin, S., Lister, A., Littlejohn, B. R., Liu, J., Lockwitz, S., Loew, T., Lokajicek, M., Lomidze, I., Long, K., Loo, K., Lorca, D., Lord, T., Losecco, J., Louis, W. C., Luk, K., Luo, X., Lurkin, N., Lux, T., Luzio, V. P., Macfarland, D., Machado, A., Machado, P., Macias, C., Macier, J., Maddalena, A., Madigan, P., Magill, S., Mahn, K., Maio, A., Maloney, J. A., Mandrioli, G., Maneira, J. C., Manenti, L., Manly, S., Mann, A., Manolopoulos, K., Plata, M. Manrique, Marchionni, A., Marciano, W., Marfatia, D., Mariani, C., Maricic, J., Marinho, F., Marino, A. D., Marshak, M., Marshall, C., Marshall, J., Marteau, J., Martin-Albo, J., Martinez, N., Caicedo, D. A. Martinez, Martynenko, S., Mason, K., Mastbaum, A., Masud, M., Matsuno, S., Matthews, J., Mauger, C., Mauri, N., Mavrokoridis, K., Mazza, R., Mazzacane, A., Mazzucato, E., Mccluskey, E., Mcconkey, N., Mcfarland, K. S., Mcgrew, C., Mcnab, A., Mefodiev, A., Mehta, P., Melas, P., Mellinato, M., Mena, O., Menary, S., Mendez, H., Menegolli, A., Meng, G., Messier, M., Metcalf, W., Mewes, M., Meyer, H., Miao, T., Michna, G., Miedema, T., Migenda, J., Milincic, R., Miller, W., Mills, J., Milne, C., Mineev, O., Miranda, O. G., Miryala, S., Mishra, C., Mishra, S., Mislivec, A., Mladenov, D., Mocioiu, I., Moffat, K., Moggi, N., Mohanta, R., Mohayai, T. A., Mokhov, N., Molina, J. A., Bueno, L. Molina, Montanari, A., Montanari, C., Montanari, D., Zetina, L. M. Montano, Moon, J., Mooney, M., Moor, A., Moreno, D., Morgan, B., Morris, C., Mossey, C., Motuk, E., Moura, C. A., Mousseau, J., Mu, W., Mualem, L., Mueller, J., Muether, M., Mufson, S., Muheim, F., Muir, A., Mulhearn, M., Muramatsu, H., Murphy, S., Musser, J., Nachtman, J., Nagu, S., Nalbandyan, M., Nandakumar, R., Naples, D., Narita, S., Navas-Nicolás, D., Nayak, N., Nebot-Guinot, M., Necib, L., Negishi, K., Nelson, J. K., Nesbit, J., Nessi, M., Newbold, D., Newcomer, M., Newhart, D., Nichol, R., Niner, E., Nishimura, K., Norman, A., Northrop, R., Novella, P., Nowak, J. A., Oberling, M., Campo, A. Olivares Del, Olivier, A., Onel, Y., Onishchuk, Y., Ott, J., Pagani, L., Pakvasa, S., Palamara, O., Palestini, S., Paley, J. M., Pallavicini, M., Palomares, C., Pantic, E., Paolone, V., Papadimitriou, V., Papaleo, R., Papanestis, A., Paramesvaran, S., Parke, S., Parsa, Z., Parvu, M., Pascoli, S., Pasqualini, L., Pasternak, J., Pater, J., Patrick, C., Patrizii, L., Patterson, R. B., Patton, S., Patzak, T., Paudel, A., Paulos, B., Paulucci, L., Pavlovic, Z., Pawloski, G., Payne, D., Pec, V., Peeters, S. J., Penichot, Y., Pennacchio, E., Penzo, A., Peres, O. L., Perry, J., Pershey, D., Pessina, G., Petrillo, G., Petta, C., Petti, R., Piastra, F., Pickering, L., Pietropaolo, F., Pillow, J., Plunkett, R., Poling, R., Pons, X., Poonthottathil, N., Pordes, S., Potekhin, M., Potenza, R., Potukuchi, B. V., Pozimski, J., Pozzato, M., Prakash, S., Prakash, T., Prince, S., Prior, G., Pugnere, D., Qi, K., Qian, X., Raaf, J., Raboanary, R., Radeka, V., Rademacker, J., Radics, B., Rafique, A., Raguzin, E., Rai, M., Rajaoalisoa, M., Rakhno, I., Rakotondramanana, H., Rakotondravohitra, L., Ramachers, Y., Rameika, R., Delgado, M. Ramirez, Ramson, B., Rappoldi, A., Raselli, G., Ratoff, P., Ravat, S., Razafinime, H., Real, J., Rebel, B., Redondo, D., Reggiani-Guzzo, M., Rehak, T., Reichenbacher, J., Reitzner, S. D., Renshaw, A., Rescia, S., Resnati, F., Reynolds, A., Riccobene, G., Rice, L. C., Rielage, K., Rigaut, Y., Rivera, D., Rochester, L., Roda, M., Rodrigues, P., Alonso, M. Rodriguez, Rondon, J. Rodriguez, Roeth, A., Rogers, H., Rosauro-Alcaraz, S., Rossella, M., Rout, J., Roy, S., Rubbia, A., Rubbia, C., Russell, B., Russell, J., Ruterbories, D., Saakyan, R., Sacerdoti, S., Safford, T., Sahu, N., Sala, P., Samios, N., Sanchez, M., Sanders, D. A., Sankey, D., Santana, S., Santos-Maldonado, M., Saoulidou, N., Sapienza, P., Sarasty, C., Sarcevic, I., Savage, G., Savinov, V., Scaramelli, A., Scarff, A., Scarpelli, A., Schaffer, T., Schellman, H., Schlabach, P., Schmitz, D., Scholberg, K., Schukraft, A., Segreto, E., Sensenig, J., Seong, I., Sergi, A., Sergiampietri, F., Sgalaberna, D., Shaevitz, M., Shafaq, S., Shamma, M., Sharma, H. R., Sharma, R., Shaw, T., Shepherd-Themistocleous, C., Shin, S., Shooltz, D., Shrock, R., Simard, L., Simos, N., Sinclair, J., Sinev, G., Singh, J., Singh, V., Sipos, R., Sippach, F., Sirri, G., Sitraka, A., Siyeon, K., Smargianaki, D., Smith, A., Smith, E., Smith, P., Smolik, J., Smy, M., Snopok, P., Nunes, M. Soare, Sobel, H., Soderberg, M., Salinas, C. J. Solano, Söldner-Rembold, S., Solomey, N., Solovov, V., Sondheim, W. E., Sorel, M., Soto-Oton, J., Sousa, A., Soustruznik, K., Spagliardi, F., Spanu, M., Spitz, J., Spooner, N. J., Spurgeon, K., Staley, R., Stancari, M., Stanco, L., Steiner, H., Stewart, J., Stillwell, B., Stock, J., Stocker, F., Stokes, T., Strait, M., Strauss, T., Striganov, S., Stuart, A., Summers, D., Surdo, A., Susic, V., Suter, L., Sutera, C., Svoboda, R., Szczerbinska, B., Szelc, A., Talaga, R., Tanaka, H., Oregui, B. Tapia, Tapper, A., Tariq, S., Tatar, E., Tayloe, R., Teklu, A., Tenti, M., Terao, K., Ternes, C. A., Terranova, F., Testera, G., Thea, A., Thompson, J. L., Thorn, C., Timm, S., Tonazzo, A., Torti, M., Tortola, M., Tortorici, F., Totani, D., Toups, M., Touramanis, C., Trevor, J., Trzaska, W. H., Tsai, Y. T., Tsamalaidze, Z., Tsang, K., Tsverava, N., Tufanli, S., Tull, C., Tyley, E., Tzanov, M., Uchida, M. A., Urheim, J., Usher, T., Vagins, M., Vahle, P., Valdiviesso, G., Valencia, E., Vallari, Z., Valle, J. W., Vallecorsa, S., Berg, R. Van, de Water, R. G. Van, Forero, D. Vanega, Varanini, F., Vargas, D., Varner, G., Vasel, J., Vasseur, G., Vaziri, K., Ventura, S., Verdugo, A., Vergani, S., Vermeulen, M. A., Verzocchi, M., de Souza, H. Vieira, Vignoli, C., Vilela, C., Viren, B., Vrba, T., Wachala, T., Waldron, A. V., Wallbank, M., Wang, H., Wang, J., Wang, Y., Warburton, K., Warner, D., Wascko, M., Waters, D., Watson, A., Weatherly, P., Weber, A., Weber, M., Wei, H., Weinstein, A., Wenman, D., Wetstein, M., While, M. R., White, A., Whitehead, L. H., Whittington, D., Wilking, M. J., Wilkinson, C., Williams, Z., Wilson, F., Wilson, R. J., Wolcott, J., Wongjirad, T., Wood, K., Wood, L., Worcester, E., Worcester, M., Wret, C., Wu, W., Xiao, Y., Yang, G., Yang, T., Yershov, N., Yonehara, K., Young, T., Yu, B., Yu, J., Zalesak, J., Zambelli, L., Zamorano, B., Zani, A., Zazueta, L., Zeller, G., Zennamo, J., Zeug, K., Zhang, C., Zhao, M., Zhivun, E., Zhu, G., Zimmerman, E. D., Zito, M., Zucchelli, S., Zuklin, J., Zutshi, V., Zwaska, R., Abi B., Acciarri R., Acero M.A., Adamov G., Adams D., Adinolfi M., Ahmad Z., Ahmed J., Alion T., Monsalve S.A., Alt C., Anderson J., Andreopoulos C., Andrews M., Andrianala F., Andringa S., Ankowski A., Antonova M., Antusch S., Aranda-Fernandez A., Ariga A., Arnold L.O., Arroyave M.A., Asaadi J., Aurisano A., Aushev V., Autiero D., Azfar F., Back H., Back J.J., Backhouse C., Baesso P., Bagby L., Bajou R., Balasubramanian S., Baldi P., Bambah B., Barao F., Barenboim G., Barker G., Barkhouse W., Barnes C., Barr G., Monarca J.B., Barros N., Barrow J.L., Bashyal A., Basque V., Bay F., Alba J.B., Beacom J.F., Bechetoille E., Behera B., Bellantoni L., Bellettini G., Bellini V., Beltramello O., Belver D., Benekos N., Neves F.B., Berger J., Berkman S., Bernardini P., Berner R.M., Berns H., Bertolucci S., Betancourt M., Bezawada Y., Bhattacharjee M., Bhuyan B., Biagi S., Bian J., Biassoni M., Biery K., Bilki B., Bishai M., Bitadze A., Blake A., Siffert B.B., Blaszczyk F., Blazey G., Blucher E., Boissevain J., Bolognesi S., Bolton T., Bonesini M., Bongrand M., Bonini F., Booth A., Booth C., Bordoni S., Borkum A., Boschi T., Bostan N., Bour P., Boyd S., Boyden D., Bracinik J., Braga D., Brailsford D., Brandt A., Bremer J., Brew C., Brianne E., Brice S.J., Brizzolari C., Bromberg C., Brooijmans G., Brooke J., Bross A., Brunetti G., Buchanan N., Budd H., Caiulo D., Calafiura P., Calcutt J., Calin M., Calvez S., Calvo E., Camilleri L., Caminata A., Campanelli M., Caratelli D., Carini G., Carlus B., Carniti P., Terrazas I.C., Carranza H., Castillo A., Castromonte C., Cattadori C., Cavalier F., Cavanna F., Centro S., Cerati G., Cervelli A., Villanueva A.C., Chalifour M., Chang C., Chardonnet E., Chatterjee A., Chattopadhyay S., Chaves J., Chen H., Chen M., Chen Y., Cherdack D., Chi C., Childress S., Chiriacescu A., Cho K., Choubey S., Christensen A., Christian D., Christodoulou G., Church E., Clarke P., Coan T.E., Cocco A.G., Coelho J., Conley E., Conrad J., Convery M., Corwin L., Cotte P., Cremaldi L., Cremonesi L., Crespo-Anadon J.I., Cristaldo E., Cross R., Cuesta C., Cui Y., Cussans D., Dabrowski M., Motta H.D., Peres L.D.S., David Q., Davies G.S., Davini S., Dawson J., De K., Almeida R.M.D., Debbins P., Bonis I.D., Decowski M., Gouvea A.D., Holanda P.C.D., Astiz I.L.D.I., Deisting A., Jong P.D., Delbart A., Delepine D., Delgado M., Dell'acqua A., Lurgio P.D., Neto J.R.D.M., Demuth D.M., Dennis S., Densham C., Deptuch G., Roeck A.D., Romeri V.D., Vries J.D., Dharmapalan R., Dias M., Diaz F., Diaz J., Domizio S.D., Giulio L.D., Ding P., Noto L.D., Distefano C., Diurba R., Diwan M., Djurcic Z., Dokania N., Dolinski M., Domine L., Douglas D., Drielsma F., Duchesneau D., Duffy K., Dunne P., Durkin T., Duyang H., Dvornikov O., Dwyer D., Dyshkant A., Eads M., Edmunds D., Eisch J., Emery S., Ereditato A., Escobar C., Sanchez L.E., Evans J.J., Ewart E., Ezeribe A.C., Fahey K., Falcone A., Farnese C., Farzan Y., Felix J., Fernandez-Martinez E., Menendez P.F., Ferraro F., Fields L., Filkins A., Filthaut F., Fitzpatrick R.S., Flanagan W., Fleming B., Flight R., Fowler J., Fox W., Franc J., Francis K., Franco D., Freeman J., Freestone J., Fried J., Friedland A., Fuess S., Furic I., Furmanski A.P., Gago A., Gallagher H., Gallego-Ros A., Gallice N., Galymov V., Gamberini E., Gamble T., Gandhi R., Gandrajula R., Gao S., Garcia-Gamez D., Garcia-Peris M.A., Gardiner S., Gastler D., Ge G., Gelli B., Gendotti A., Gent S., Ghorbani-Moghaddam Z., Gibin D., Gil-Botella I., Girerd C., Giri A., Gnani D., Gogota O., Gold M., Gollapinni S., Gollwitzer K., Gomes R.A., Bermeo L.G., Fajardo L.S.G., Gonnella F., Gonzalez-Cuevas J., Goodman M.C., Goodwin O., Goswami S., Gotti C., Goudzovski E., Grace C., Graham M., Gramellini E., Gran R., Granados E., Grant A., Grant C., Gratieri D., Green P., Green S., Greenler L., Greenwood M., Greer J., Griffith C., Groh M., Grudzinski J., Grzelak K., Gu W., Guarino V., Guenette R., Guglielmi A., Guo B., Guthikonda K., Gutierrez R., Guzowski P., Guzzo M.M., Gwon S., Habig A., Hackenburg A., Hadavand H., Haenni R., Hahn A., Haigh J., Haiston J., Hamernik T., Hamilton P., Han J., Harder K., Harris D.A., Hartnell J., Hasegawa T., Hatcher R., Hazen E., Heavey A., Heeger K.M., Hennessy K., Henry S., Morquecho M.H., Herner K., Hertel L., Hesam A.S., Hewes J., Pichardo A.H., Hill T., Hillier S.J., Himmel A., Hoff J., Hohl C., Holin A., Hoppe E., Horton-Smith G.A., Hostert M., Hourlier A., Howard B., Howell R., Huang J., Hugon J., Iles G., Iliescu A.M., Illingworth R., Ioannisian A., Itay R., Izmaylov A., James E., Jargowsky B., Jediny F., Jesus-Valls C., Ji X., Jiang L., Jimenez S., Jipa A., Joglekar A., Johnson C., Johnson R., Jones B., Jones S., Jung C., Junk T., Jwa Y., Kabirnezhad M., Kaboth A., Kadenko I., Kamiya F., Karagiorgi G., Karcher A., Karolak M., Karyotakis Y., Kasai S., Kasetti S.P., Kashur L., Kazaryan N., Kearns E., Keener P., Kelly K.J., Kemp E., Ketchum W., Kettell S., Khabibullin M., Khotjantsev A., Khvedelidze A., Kim D., King B., Kirby B., Kirby M., Klein J., Koehler K., Koerner L.W., Kohn S., Koller P.P., Kordosky M., Kosc T., Kose U., Kostelecky V., Kothekar K., Krennrich F., Kreslo I., Kudenko Y., Kudryavtsev V., Kulagin S., Kumar J., Kumar R., Kuruppu C., Kus V., Kutter T., Lambert A., Lande K., Lane C.E., Lang K., Langford T., Lasorak P., Last D., Lastoria C., Laundrie A., Lawrence A., Lazanu I., Lazur R., Le T., Learned J., Lebrun P., Miotto G.L., Lehnert R., De Oliveira M.L., Leitner M., Leyton M., Li L., Li S., Li T., Li Y., Liao H., Lin C., Lin S., Lister A., Littlejohn B.R., Liu J., Lockwitz S., Loew T., Lokajicek M., Lomidze I., Long K., Loo K., Lorca D., Lord T., Losecco J., Louis W.C., Luk K., Luo X., Lurkin N., Lux T., Luzio V.P., MacFarland D., MacHado A., MacHado P., MacIas C., MacIer J., Maddalena A., Madigan P., Magill S., Mahn K., Maio A., Maloney J.A., Mandrioli G., Maneira J.C., Manenti L., Manly S., Mann A., Manolopoulos K., Plata M.M., Marchionni A., Marciano W., Marfatia D., Mariani C., Maricic J., Marinho F., Marino A.D., Marshak M., Marshall C., Marshall J., Marteau J., Martin-Albo J., Martinez N., Caicedo D.A.M., Martynenko S., Mason K., Mastbaum A., Masud M., Matsuno S., Matthews J., Mauger C., Mauri N., Mavrokoridis K., Mazza R., Mazzacane A., Mazzucato E., McCluskey E., McConkey N., McFarland K.S., McGrew C., McNab A., Mefodiev A., Mehta P., Melas P., Mellinato M., Mena O., Menary S., Mendez H., Menegolli A., Meng G., Messier M., Metcalf W., Mewes M., Meyer H., Miao T., Michna G., Miedema T., Migenda J., Milincic R., Miller W., Mills J., Milne C., Mineev O., Miranda O.G., Miryala S., Mishra C., Mishra S., Mislivec A., Mladenov D., Mocioiu I., Moffat K., Moggi N., Mohanta R., Mohayai T.A., Mokhov N., Molina J.A., Bueno L.M., Montanari A., Montanari C., Montanari D., Zetina L.M.M., Moon J., Mooney M., Moor A., Moreno D., Morgan B., Morris C., Mossey C., Motuk E., Moura C.A., Mousseau J., Mu W., Mualem L., Mueller J., Muether M., Mufson S., Muheim F., Muir A., Mulhearn M., Muramatsu H., Murphy S., Musser J., Nachtman J., Nagu S., Nalbandyan M., Nandakumar R., Naples D., Narita S., Navas-Nicolas D., Nayak N., Nebot-Guinot M., Necib L., Negishi K., Nelson J.K., Nesbit J., Nessi M., Newbold D., Newcomer M., Newhart D., Nichol R., Niner E., Nishimura K., Norman A., Northrop R., Novella P., Nowak J.A., Oberling M., Campo A.O.D., Olivier A., Onel Y., Onishchuk Y., Ott J., Pagani L., Pakvasa S., Palamara O., Palestini S., Paley J.M., Pallavicini M., Palomares C., Pantic E., Paolone V., Papadimitriou V., Papaleo R., Papanestis A., Paramesvaran S., Parke S., Parsa Z., Parvu M., Pascoli S., Pasqualini L., Pasternak J., Pater J., Patrick C., Patrizii L., Patterson R.B., Patton S., Patzak T., Paudel A., Paulos B., Paulucci L., Pavlovic Z., Pawloski G., Payne D., Pec V., Peeters S.J., Penichot Y., Pennacchio E., Penzo A., Peres O.L., Perry J., Pershey D., Pessina G., Petrillo G., Petta C., Petti R., Piastra F., Pickering L., Pietropaolo F., Pillow J., Plunkett R., Poling R., Pons X., Poonthottathil N., Pordes S., Potekhin M., Potenza R., Potukuchi B.V., Pozimski J., Pozzato M., Prakash S., Prakash T., Prince S., Prior G., Pugnere D., Qi K., Qian X., Raaf J., Raboanary R., Radeka V., Rademacker J., Radics B., Rafique A., Raguzin E., Rai M., Rajaoalisoa M., Rakhno I., Rakotondramanana H., Rakotondravohitra L., Ramachers Y., Rameika R., Delgado M.R., Ramson B., Rappoldi A., Raselli G., Ratoff P., Ravat S., Razafinime H., Real J., Rebel B., Redondo D., Reggiani-Guzzo M., Rehak T., Reichenbacher J., Reitzner S.D., Renshaw A., Rescia S., Resnati F., Reynolds A., Riccobene G., Rice L.C., Rielage K., Rigaut Y., Rivera D., Rochester L., Roda M., Rodrigues P., Alonso M.R., Rondon J.R., Roeth A., Rogers H., Rosauro-Alcaraz S., Rossella M., Rout J., Roy S., Rubbia A., Rubbia C., Russell B., Russell J., Ruterbories D., Saakyan R., Sacerdoti S., Safford T., Sahu N., Sala P., Samios N., Sanchez M., Sanders D.A., Sankey D., Santana S., Santos-Maldonado M., Saoulidou N., Sapienza P., Sarasty C., Sarcevic I., Savage G., Savinov V., Scaramelli A., Scarff A., Scarpelli A., Schaffer T., Schellman H., Schlabach P., Schmitz D., Scholberg K., Schukraft A., Segreto E., Sensenig J., Seong I., Sergi A., Sergiampietri F., Sgalaberna D., Shaevitz M., Shafaq S., Shamma M., Sharma H.R., Sharma R., Shaw T., Shepherd-Themistocleous C., Shin S., Shooltz D., Shrock R., Simard L., Simos N., Sinclair J., Sinev G., Singh J., Singh V., Sipos R., Sippach F., Sirri G., Sitraka A., Siyeon K., Smargianaki D., Smith A., Smith E., Smith P., Smolik J., Smy M., Snopok P., Nunes M.S., Sobel H., Soderberg M., Salinas C.J.S., Soldner-Rembold S., Solomey N., Solovov V., Sondheim W.E., Sorel M., Soto-Oton J., Sousa A., Soustruznik K., Spagliardi F., Spanu M., Spitz J., Spooner N.J., Spurgeon K., Staley R., Stancari M., Stanco L., Steiner H., Stewart J., Stillwell B., Stock J., Stocker F., Stokes T., Strait M., Strauss T., Striganov S., Stuart A., Summers D., Surdo A., Susic V., Suter L., Sutera C., Svoboda R., Szczerbinska B., Szelc A., Talaga R., Tanaka H., Oregui B.T., Tapper A., Tariq S., Tatar E., Tayloe R., Teklu A., Tenti M., Terao K., Ternes C.A., Terranova F., Testera G., Thea A., Thompson J.L., Thorn C., Timm S., Tonazzo A., Torti M., Tortola M., Tortorici F., Totani D., Toups M., Touramanis C., Trevor J., Trzaska W.H., Tsai Y.T., Tsamalaidze Z., Tsang K., Tsverava N., Tufanli S., Tull C., Tyley E., Tzanov M., Uchida M.A., Urheim J., Usher T., Vagins M., Vahle P., Valdiviesso G., Valencia E., Vallari Z., Valle J.W., Vallecorsa S., Berg R.V., De Water R.G.V., Forero D.V., Varanini F., Vargas D., Varner G., Vasel J., Vasseur G., Vaziri K., Ventura S., Verdugo A., Vergani S., Vermeulen M.A., Verzocchi M., De Souza H.V., Vignoli C., Vilela C., Viren B., Vrba T., Wachala T., Waldron A.V., Wallbank M., Wang H., Wang J., Wang Y., Warburton K., Warner D., Wascko M., Waters D., Watson A., Weatherly P., Weber A., Weber M., Wei H., Weinstein A., Wenman D., Wetstein M., While M.R., White A., Whitehead L.H., Whittington D., Wilking M.J., Wilkinson C., Williams Z., Wilson F., Wilson R.J., Wolcott J., Wongjirad T., Wood K., Wood L., Worcester E., Worcester M., Wret C., Wu W., Xiao Y., Yang G., Yang T., Yershov N., Yonehara K., Young T., Yu B., Yu J., Zalesak J., Zambelli L., Zamorano B., Zani A., Zazueta L., Zeller G., Zennamo J., Zeug K., Zhang C., Zhao M., Zhivun E., Zhu G., Zimmerman E.D., Zito M., Zucchelli S., Zuklin J., Zutshi V., and Zwaska R.

Subjects
Technology, 530 Physics, media_common.quotation_subject, Neutrino oscillations, liquid Argon TPC, DUNE technical design report, single phase LArTPC, Electrons, FREE-ELECTRONS, 01 natural sciences, 7. Clean energy, 09 Engineering, 030218 nuclear medicine & medical imaging, Standard Model, 03 medical and health sciences, neutrino, 0302 clinical medicine, LIQUID ARGON, 0103 physical sciences, Grand Unified Theory, High Energy Physics, Aerospace engineering, Instrumentation, Instruments & Instrumentation, Mathematical Physics, media_common, Physics, Science & Technology, 02 Physical Sciences, 010308 nuclear & particles physics, business.industry, Detector, Lıquıd Argonfree, Nuclear & Particles Physics, Symmetry (physics), Universe, Long baseline neutrino experiment, CP violation, Antimatter, Neutrino, business, Event (particle physics)
Abstract

This document was prepared by the DUNE collaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. The DUNE collaboration also acknowledges the international, national, and regional funding agencies supporting the institutions who have contributed to completing this Technical Design Report., The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. Central to achieving DUNE's physics program is a far detector that combines the many tens-of-kiloton fiducial mass necessary for rare event searches with sub-centimeter spatial resolution in its ability to image those events, allowing identification of the physics signatures among the numerous backgrounds. In the single-phase liquid argon time-projection chamber (LArTPC) technology, ionization charges drift horizontally in the liquid argon under the influence of an electric field towards a vertical anode, where they are read out with fine granularity. A photon detection system supplements the TPC, directly enhancing physics capabilities for all three DUNE physics drivers and opening up prospects for further physics explorations. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume IV presents an overview of the basic operating principles of a single-phase LArTPC, followed by a description of the DUNE implementation. Each of the subsystems is described in detail, connecting the high-level design requirements and decisions to the overriding physics goals of DUNE., Fermi Research Alliance, LLC (FRA) DE-AC02-07CH11359

Published
2020

49. Volume I. Introduction to DUNE

Author

E. Hazen, Armin Karcher, D. Smargianaki, Christopher L. Marshall, K. Spurgeon, M. Gold, C. Vignoli, C. J. Solano Salinas, M. J. Wilking, K. Kothekar, G. Sirri, Evgueni Goudzovski, H. Mendez, W. Flanagan, V. Papadimitriou, D. Redondo, S. R. Mishra, Y.-J. Jwa, G. Petrillo, M. Spanu, Xiaolu Ji, O. V. Mineev, M. Bishai, S. Menary, L. Molina Bueno, P. C. de Holanda, H. Berns, A. Gendotti, A. M. Szelc, R. Gandhi, A. Himmel, M. Rajaoalisoa, P. Bour, N. Kazaryan, L. Mualem, Gareth J. Barker, C. Cattadori, S. Ravat, W. Mu, D. Marfatia, T. Miedema, Kendall Mahn, Jorge Molina, Filippo Resnati, S. Magill, E. Niner, D. Autiero, Poonam Mehta, John Evans, J. S. Díaz, P. Novella, J. Fowler, G. Karagiorgi, S. J. M. Peeters, William J. Marciano, S. Bordoni, James Mueller, J. Martín-Albo, W. Fox, K. Grzelak, C. Hohl, R. Haenni, S. Alonso Monsalve, B. Howard, G. Ge, Alexander Tapper, Thomas Strauss, Silvia Pascoli, B. Stillwell, A. Lambert, A. Holin, K. V. Tsang, J. Maneira, R.A. Rameika, Juraj Bracinik, C. Wret, M. Tenti, Alberto Cervelli, Sukalyan Chattopadhyay, Laura Dominé, K. Herner, Hem Raj Sharma, S. Kasai, A. Higuera Pichardo, M. Betancourt, A. Scarff, R. Northrop, M. V. Diwan, D. J. Payne, C. Gotti, M. A. Vermeulen, R. M. Berner, J. J. De Vries, S. Shafaq, Yu. G. Kudenko, L. Pickering, B. Bhuyan, C. Kuruppu, Janet Conrad, D. Brailsford, R. Van Berg, J. Chaves, B. Paulos, R. Sipos, E. Pennacchio, F. W. Sippach, T. Li, S. Striganov, Laura Paulucci, S. Manly, P. Hamilton, R. G. Van de Water, R. Nandakumar, B. Szczerbinska, D. Cherdack, H. Carranza, Milos Lokajicek, K. Nishimura, E. Kearns, A. C. Ezeribe, J. Hoff, A. McNab, A. Stuart, G. Vasseur, C. Petta, M. Wetstein, M. M. Khabibullin, A. Bitadze, Yichen Li, G. Brunetti, L. Suter, L. Pasqualini, S. Martynenko, Ph. Lebrun, B. Morgan, L. Patrizii, A. Guglielmi, D. Wenman, S. C. Timm, R. Sharma, R. Saakyan, R. Gran, C. McGrew, C. Andreopoulos, A. Mann, F. Terranova, C. Cuesta, O. G. Miranda, C. 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B., Patton, S., Patzak, T., Paudel, A., Paulos, B., Paulucci, L., Pavlovic, Z., Pawloski, G., Payne, D., Pec, V., Peeters, S. J., Penichot, Y., Pennacchio, E., Penzo, A., Peres, O. L., Perry, J., Pershey, D., Pessina, G., Petrillo, G., Petta, C., Petti, R., Piastra, F., Pickering, L., Pietropaolo, F., Pillow, J., Plunkett, R., Poling, R., Pons, X., Poonthottathil, N., Pordes, S., Potekhin, M., Potenza, R., Potukuchi, B. V., Pozimski, J., Pozzato, M., Prakash, S., Prakash, T., Prince, S., Prior, G., Pugnere, D., Qi, K., Qian, X., Raaf, J., Raboanary, R., Radeka, V., Rademacker, J., Radics, B., Rafique, A., Raguzin, E., Rai, M., Rajaoalisoa, M., Rakhno, I., Rakotondramanana, H., Rakotondravohitra, L., Ramachers, Y., Rameika, R., Delgado, M. Ramirez, Ramson, B., Rappoldi, A., Raselli, G., Ratoff, P., Ravat, S., Razafinime, H., Real, J., Rebel, B., Redondo, D., Reggiani-Guzzo, M., Rehak, T., Reichenbacher, J., Reitzner, S. 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A., Terranova, F., Testera, G., Thea, A., Thompson, J. L., Thorn, C., Timm, S., Tonazzo, A., Torti, M., Tortola, M., Tortorici, F., Totani, D., Toups, M., Touramanis, C., Trevor, J., Trzaska, W. H., Tsai, Y. T., Tsamalaidze, Z., Tsang, K., Tsverava, N., Tufanli, S., Tull, C., Tyley, E., Tzanov, M., Uchida, M. A., Urheim, J., Usher, T., Vagins, M., Vahle, P., Valdiviesso, G., Valencia, E., Vallari, Z., Valle, J. W., Vallecorsa, S., Berg, R. Van, de Water, R. G. Van, Forero, D. Vanega, Varanini, F., Vargas, D., Varner, G., Vasel, J., Vasseur, G., Vaziri, K., Ventura, S., Verdugo, A., Vergani, S., Vermeulen, M. A., Verzocchi, M., de Souza, H. Vieira, Vignoli, C., Vilela, C., Viren, B., Vrba, T., Wachala, T., Waldron, A. V., Wallbank, M., Wang, H., Wang, J., Wang, Y., Warburton, K., Warner, D., Wascko, M., Waters, D., Watson, A., Weatherly, P., Weber, A., Weber, M., Wei, H., Weinstein, A., Wenman, D., Wetstein, M., While, M. R., White, A., Whitehead, L. H., Whittington, D., Wilking, M. J., Wilkinson, C., Williams, Z., Wilson, F., Wilson, R. J., Wolcott, J., Wongjirad, T., Wood, K., Wood, L., Worcester, E., Worcester, M., Wret, C., Wu, W., Xiao, Y., Yang, G., Yang, T., Yershov, N., Yonehara, K., Young, T., Yu, B., Yu, J., Zalesak, J., Zambelli, L., Zamorano, B., Zani, A., Zazueta, L., Zeller, G., Zennamo, J., Zeug, K., Zhang, C., Zhao, M., Zhivun, E., Zhu, G., Zimmerman, E. D., Zito, M., Zucchelli, S., Zuklin, J., Zutshi, V., and Zwaska, R.

Subjects
detector: technology, deep underground detector [neutrino], 530 Physics, Physics::Instrumentation and Detectors, Data management, media_common.quotation_subject, far detector, Long baseline neutrino experiment CP violation, 01 natural sciences, 030218 nuclear medicine & medical imaging, Neutrino oscillations. Neutrino Detectors. CP violation. Matter stability, design [detector], 03 medical and health sciences, neutrino, neutrino: deep underground detector, 0302 clinical medicine, near detector, 0103 physical sciences, Deep Underground Neutrino Experiment, ddc:610, Neutrino oscillation, Instrumentation, detector: design, Mathematical Physics, activity report, media_common, 010308 nuclear & particles physics, business.industry, Detector, Volume (computing), Modular design, time projection chamber: liquid argon, Universe, technology [detector], liquid argon [time projection chamber], Systems engineering, High Energy Physics::Experiment, Neutrino oscillations, DUNE technical design report, executive summary, detector technologies, data management, Neutrino, business
Abstract

Journal of Instrumentation 15(08), T08008 (1-228) (2020). doi:10.1088/1748-0221/15/08/T08008, The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology., Published by Inst. of Physics, London

Published
2020

50. Current ophthalmology practice patterns for syphilitic uveitis

Author

Genevieve, F Oliver, Roy, M Stathis, João, M Furtado, Tiago, E Arantes, Peter, J McCluskey, Janet, M Matthews, Justine, R Smith, Accorinti, M, Adan, A, Agarwal, A, Alieldin, R, Allegri, P, Alvarez, C, Androudi, S, Arevalo, Jf, Aubin, Mj, Babu, K, Barisani-Asenbauer, T, Barron, Z, Basu, S, Biswas, J, Bodaghi, B, Bursztyn, M, Jose Capella, M, Caspers, L, Chee, Sp, Cimino, L, Colombero, D, Concha Del Rio LE, Curi, All, Dacey, M, Das, D, Davis, J, Edwar, L, Errera, Mh, Finamor, Lp, Fonollosa, A, Fortin, E, Fraser-Bell, S, Funk, M, Garcia-Serrano, Jl, Garweg, J, Garza-Leon, M, George, A, Goldstein, D, Goto, H, Gottlieb, C, Guedes, M, Guex-Crosier, Y, Gurbaxani, A, Henry, C, Hooper, C, Hovland, T, Hwang, Ys, Invernizzi, A, Isa, H, Jodar-Marquez, M, Kansupada, K, Kawali, A, Kempen, Jh, Khairallah, M, Krag, S, Kuijpers, R, Laithwaite, J, Lee, St, Lefebvre, P, Lehoang, P, Lobo, Am, Mahendradas, P, Mccluskey, P, Mili-Boussen, I, Mochizuki, M, Moschos, M, Nascimento, H, Nguyen, J, Nguyen, Qd, O'Keefe, G, Oli Mohamed, S, Ozdal, P, Menendez Padron MI, Palestine, A, Paroli, Mp, Pavesio, C, Pichi, F, Pleyer, U, Przezdziecka-Dolyk, J, Rao, N, Rathinam, S, Ribeiro, M, Roy, M, O P, Sabat, Sandhu, Hs, Sittivarakul, W, Smith, J, Smith, W, Somkijrungroj, T, Sood, A, Suelves, A, Tay-Kearney, Ml, Teuchner, B, Thorne, J, Trittibach, P, Tugal-Tutkun, I, Unzueta-Medina, Ja, Santos Valadares ED, Van Os, L, Wells, J, Alvarez, By, Young, S, Zierhut, M., and Surgical clinical sciences

Subjects
Adult, Male, syphilis, Penicillins, EYE, Eye Infections, Bacterial, Uveitis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Copyright policy, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Practice Patterns, Physicians', Referral and Consultation, Societies, Medical, Retrospective Studies, Medicine(all), Practice patterns, business.industry, Middle Aged, medicine.disease, infection, Sensory Systems, Anti-Bacterial Agents, Syphilis Serodiagnosis, 3. Good health, Ophthalmology, inflammation, eye, uveitis, 030221 ophthalmology & optometry, Optometry, Female, Syphilis, business
Abstract

BackgroundSyphilitic uveitis is re-emerging alongside the systemic infection. In July 2017, an international group of uveitis-specialised ophthalmologists formed the International Ocular Syphilis Study Group to define current practice patterns.Methods103 Study Group members based in 35 countries completed a 25-item questionnaire focused on case load, clinical presentations, use and interpretation of investigations, treatment and clinical indicators of poor prognosis.ResultsMembers managed a mean of 6.1 patients with syphilitic uveitis in clinics that averaged 707 annual cases of uveitis (0.9%); 53.2% reported increasing numbers over the past decade. Patients presented to more members (40.2%) during secondary syphilis. Uveitis was usually posterior (60.8%) or pan (22.5%); complications included optic neuropathy, macular oedema and posterior synechiae. All members diagnosed syphilitic uveitis using serological tests (simultaneous or sequential testing algorithms), and 97.0% routinely checked for HIV co-infection. Cerebrospinal fluid (CSF) analysis was ordered by 90.2% of members, and 92.7% took uveitis plus Venereal Disease Research Laboratory test (VDRL) or fluorescent treponemal antibody absorption test (FTA-ABS) to indicate neurosyphilis. Patients were commonly co-managed with infectious disease physicians, and treated with penicillin for at least 10–14 days, plus corticosteroid. Features predicting poor outcome included optic neuropathy (86.3%) and initial misdiagnosis (63.7%). Reasons for delayed diagnosis were often practitioner-related. 82.5% of members tested every patient they managed with uveitis for syphilis.ConclusionThis comprehensive report by an international group of uveitis-specialised ophthalmologists provides a current approach for the management of syphilitic uveitis.

Published
2019

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