32 results on '"Mark, Sullivan"'
Search Results
2. Order Set Usage is Associated With Lower Hospital Mortality in Patients With Sepsis
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Christopher R. Dale, MD, MPH, Shelley Schoepflin Sanders, MD, Shu Ching Chang, PhD, Omar Pandhair, MD, Naomi G. Diggs, MD, MBA, Whitney Woodruff, MPH, David N. Selander, MD, MBA, Nicholas M. Mark, MD, Sarah Nurse, MHA, RN, Mark Sullivan, MD, MPH, Liga Mezaraups, MHA, RN, and D. Shane O’Mahony, MD
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Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
IMPORTANCE:. The Surviving Sepsis Campaign recommends standard operating procedures for patients with sepsis. Real-world evidence about sepsis order set implementation is limited. OBJECTIVES:. To estimate the effect of sepsis order set usage on hospital mortality. DESIGN:. Retrospective cohort study. SETTING AND PARTICIPANTS:. Fifty-four acute care hospitals in the United States from December 1, 2020 to November 30, 2022 involving 104,662 patients hospitalized for sepsis. MAIN OUTCOMES AND MEASURES:. Hospital mortality. RESULTS:. The sepsis order set was used in 58,091 (55.5%) patients with sepsis. Initial mean sequential organ failure assessment score was 0.3 lower in patients for whom the order set was used than in those for whom it was not used (2.9 sd [2.8] vs 3.2 [3.1], p < 0.01). In bivariate analysis, hospital mortality was 6.3% lower in patients for whom the sepsis order set was used (9.7% vs 16.0%, p < 0.01), median time from emergency department triage to antibiotics was 54 minutes less (125 interquartile range [IQR, 68–221] vs 179 [98–379], p < 0.01), and median total time hypotensive was 2.1 hours less (5.5 IQR [2.0–15.0] vs 7.6 [2.5–21.8], p < 0.01) and septic shock was 3.2% less common (22.0% vs 25.4%, p < 0.01). Order set use was associated with 1.1 fewer median days of hospitalization (4.9 [2.8–9.0] vs 6.0 [3.2–12.1], p < 0.01), and 6.6% more patients discharged to home (61.4% vs 54.8%, p < 0.01). In the multivariable model, sepsis order set use was independently associated with lower hospital mortality (odds ratio 0.70; 95% CI, 0.66–0.73). CONCLUSIONS AND RELEVANCE:. In a cohort of patients hospitalized with sepsis, order set use was independently associated with lower hospital mortality. Order sets can impact large-scale quality improvement efforts.
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- 2023
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3. The WIRE study a phase II, multi-arm, multi-centre, non-randomised window-of-opportunity clinical trial platform using a Bayesian adaptive design for proof-of-mechanism of novel treatment strategies in operable renal cell cancer – a study protocol
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Stephan Ursprung, Helen Mossop, Ferdia A. Gallagher, Evis Sala, Richard Skells, Jamal A. N. Sipple, Thomas J. Mitchell, Anita Chhabra, Kate Fife, Athena Matakidou, Gemma Young, Amanda Walker, Martin G. Thomas, Mireia Crispin Ortuzar, Mark Sullivan, Andrew Protheroe, Grenville Oades, Balaji Venugopal, Anne Y. Warren, John Stone, Tim Eisen, James Wason, Sarah J. Welsh, and Grant D. Stewart
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Clinical trial protocol [MeSH] ,Clear cell renal cell carcinoma [MeSH] ,Phase II clinical trial [MeSH] ,Bayesian adaptive trial ,Olaparib [MeSH] ,Cediranib [MeSH] ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Window-of-opportunity trials, evaluating the engagement of drugs with their biological target in the time period between diagnosis and standard-of-care treatment, can help prioritise promising new systemic treatments for later-phase clinical trials. Renal cell carcinoma (RCC), the 7th commonest solid cancer in the UK, exhibits targets for multiple new systemic anti-cancer agents including DNA damage response inhibitors, agents targeting vascular pathways and immune checkpoint inhibitors. Here we present the trial protocol for the WIndow-of-opportunity clinical trial platform for evaluation of novel treatment strategies in REnal cell cancer (WIRE). Methods WIRE is a Phase II, multi-arm, multi-centre, non-randomised, proof-of-mechanism (single and combination investigational medicinal product [IMP]), platform trial using a Bayesian adaptive design. The Bayesian adaptive design leverages outcome information from initial participants during pre-specified interim analyses to determine and minimise the number of participants required to demonstrate efficacy or futility. Patients with biopsy-proven, surgically resectable, cT1b+, cN0–1, cM0–1 clear cell RCC and no contraindications to the IMPs are eligible to participate. Participants undergo diagnostic staging CT and renal mass biopsy followed by treatment in one of the treatment arms for at least 14 days. Initially, the trial includes five treatment arms with cediranib, cediranib + olaparib, olaparib, durvalumab and durvalumab + olaparib. Participants undergo a multiparametric MRI before and after treatment. Vascularised and de-vascularised tissue is collected at surgery. A ≥ 30% increase in CD8+ T-cells on immunohistochemistry between the screening and nephrectomy is the primary endpoint for durvalumab-containing arms. Meanwhile, a reduction in tumour vascular permeability measured by K trans on dynamic contrast-enhanced MRI by ≥30% is the primary endpoint for other arms. Secondary outcomes include adverse events and tumour size change. Exploratory outcomes include biomarkers of drug mechanism and treatment effects in blood, urine, tissue and imaging. Discussion WIRE is the first trial using a window-of-opportunity design to demonstrate pharmacological activity of novel single and combination treatments in RCC in the pre-surgical space. It will provide rationale for prioritising promising treatments for later phase trials and support the development of new biomarkers of treatment effect with its extensive translational agenda. Trial registration ClinicalTrials.gov: NCT03741426 / EudraCT: 2018–003056-21 .
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- 2021
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4. Pharmacokinetics of oral moxidectin in individuals with Onchocerca volvulus infection.
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Beesan Tan, Nicholas Opoku, Simon K Attah, Kwablah Awadzi, Annette C Kuesel, Janis Lazdins-Helds, Craig Rayner, Victoria Ryg-Cornejo, Mark Sullivan, and Lawrence Fleckenstein
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundOnchocerciasis ("river blindness"), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus and transmitted to humans through repeated bites by infective blackflies of the genus Simulium. Moxidectin was approved by the United States Food and Drug Administration in 2018 for the treatment of onchocerciasis in people at least 12 years of age. The pharmacokinetics of orally administered moxidectin in 18- to 60-year-old men and women infected with Onchocerca volvulus were investigated in a single-center, ivermectin-controlled, double-blind, randomized, single-ascending-dose, ascending severity of infection study in Ghana.Methodology/principal findingsParticipants were randomized to either a single dose of 2, 4 or 8 mg moxidectin or ivermectin. Pharmacokinetic samples were collected prior to dosing and at intervals up to 12 months post-dose from 33 and 34 individuals treated with 2 and 4 mg moxidectin, respectively and up to 18 months post-dose from 31 individuals treated with 8 mg moxidectin. Moxidectin plasma concentrations were determined using high-performance liquid chromatography with fluorescence detection. Moxidectin plasma AUC0-∞ (2 mg: 26.7-31.7 days*ng/mL, 4 mg: 39.1-60.0 days*ng/mL, 8 mg: 99.5-129.0 days*ng/mL) and Cmax (2mg, 16.2 to17.3 ng/mL, 4 mg: 33.4 to 35.0 ng/mL, 8 mg: 55.7 to 74.4 ng/mL) were dose-proportional and independent of severity of infection. Maximum plasma concentrations were achieved 4 hours after drug administration. The mean terminal half-lives of moxidectin were 20.6, 17.7, and 23.3 days at the 2, 4 and 8 mg dose levels, respectively.Conclusion/significanceWe found no relationship between severity of infection (mild, moderate or severe) and exposure parameters (AUC0-∞ and Cmax), T1/2 and Tmax for moxidectin. Tmax, volume of distribution (V/F) and oral clearance (CL/F) are similar to those in healthy volunteers from Europe. From a pharmacokinetic perspective, moxidectin is an attractive long-acting therapeutic option for the treatment of human onchocerciasis.
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- 2022
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5. Designing an Optimal LSST Deep Drilling Program for Cosmology with Type Ia Supernovae
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Philippe Gris, Nicolas Regnault, Humna Awan, Isobel Hook, Saurabh W. Jha, Michelle Lochner, Bruno Sanchez, Dan Scolnic, Mark Sullivan, Peter Yoachim, and The LSST Dark Energy Science Collaboration
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Cosmological parameters ,Astrophysics ,QB460-466 - Abstract
The Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST) is forecast to collect a large sample of Type Ia supernovae (SNe Ia) expected to be instrumental in unveiling the nature of dark energy. The feat, however, requires accurately measuring the two components of the Hubble diagram, distance modulus and redshift. Distance is estimated from SN Ia parameters extracted from light-curve fits, where the average quality of light curves is primarily driven by survey parameters. An optimal observing strategy is thus critical for measuring cosmological parameters with high accuracy. We present in this paper a three-stage analysis to assess the impact of the deep drilling (DD) strategy parameters on three critical aspects of the survey: redshift completeness, the number of well-measured SNe Ia, and cosmological measurements. We demonstrate that the current DD survey plans (internal LSST simulations) are characterized by a low completeness ( z ∼ 0.55–0.65), and irregular and low cadences (several days), which dramatically decrease the size of the well-measured SN Ia sample. We propose a method providing the number of visits required to reach higher redshifts. We use the results to design a set of optimized DD surveys for SN Ia cosmology taking full advantage of spectroscopic resources for host galaxy redshift measurements. The most accurate cosmological measurements are achieved with deep rolling surveys characterized by a high cadence (1 day), a rolling strategy (at least two seasons of observation per field), and ultradeep ( z ≳ 0.8) and deep ( z ≳ 0.6) fields. A deterministic scheduler including a gap recovery mechanism is critical to achieving a high-quality DD survey.
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- 2023
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6. Erratum: 'Spectra of Hydrogen-poor Superluminous Supernovae from the Palomar Transient Factory' (2018, ApJ, 855, 2)
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Robert M. Quimby, Annalisa De Cia, Avishay Gal-Yam, Giorgos Leloudas, Ragnhild Lunnan, Daniel A. Perley, Paul M. Vreeswijk, Lin Yan, Joshua S. Bloom, S. Bradley Cenko, Jeff Cooke, Richard Ellis, Alexei V. Filippenko, Mansi M. Kasliwal, Io K. W. Kleiser, Shrinivas R. Kulkarni, Thomas Matheson, Peter E. Nugent, Yen-Chen Pan, Jeffrey M. Silverman, Assaf Sternberg, Mark Sullivan, and Ofer Yaron
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Astrophysics ,QB460-466 - Published
- 2023
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7. Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer
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Michelle Wilson, Naveen S Vasudev, Grant D Stewart, Adebanji Adeyoju, Jon Cartledge, Michael Kimuli, Shibendra Datta, Damian Hanbury, David Hrouda, Grenville Oades, Poulam Patel, Naeem Soomro, Mark Sullivan, Jeff Webster, Peter J Selby, and Rosamonde E Banks
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Medicine - Abstract
Objectives To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis.Design Multicentre prospective observational cohort study.Setting and participants Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected.Outcomes Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival.Results Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC.Conclusions Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.
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- 2020
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8. Digital Pathology Transformation in a Supraregional Germ Cell Tumour Network
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Richard Colling, Andrew Protheroe, Mark Sullivan, Ruth Macpherson, Mark Tuthill, Jacqueline Redgwell, Zoe Traill, Angus Molyneux, Elizabeth Johnson, Niveen Abdullah, Andrea Taibi, Nikki Mercer, Harry R. Haynes, Anthony Sackville, Judith Craft, Joao Reis, Gabrielle Rees, Maria Soares, Ian S. D. Roberts, Darrin Siiankoski, Helen Hemsworth, Derek Roskell, Sharon Roberts-Gant, Kieron White, Jens Rittscher, Jim Davies, Lisa Browning, and Clare Verrill
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digital ,pathology ,testis ,germ cell ,Medicine (General) ,R5-920 - Abstract
Background: In this article we share our experience of creating a digital pathology (DP) supraregional germ cell tumour service, including full digitisation of the central laboratory. Methods: DP infrastructure (Philips) was deployed across our hospital network to allow full central digitisation with partial digitisation of two peripheral sites in the supraregional testis germ cell tumour network. We used a survey-based approach to capture the quantitative and qualitative experiences of the multidisciplinary teams involved. Results: The deployment enabled case sharing for the purposes of diagnostic reporting, second opinion, and supraregional review. DP was seen as a positive step forward for the departments involved, and for the wider germ cell tumour network, and was completed without significant issues. Whilst there were challenges, the transition to DP was regarded as worthwhile, and examples of benefits to patients are already recognised. Conclusion: Pathology networks, including highly specialised services, such as in this study, are ideally suited to be digitised. We highlight many of the benefits but also the challenges that must be overcome for such clinical transformation. Overall, from the survey, the change was seen as universally positive for our service and highlights the importance of engagement of the whole team to achieve success.
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- 2021
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9. Isolation and Quantification of Metabolite Levels in Murine Tumor Interstitial Fluid by LC/MS
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Mark Sullivan, Caroline Lewis, and Alexander Muir
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Biology (General) ,QH301-705.5 - Abstract
Cancer is a disease characterized by altered metabolism, and there has been renewed interest in understanding the metabolism of tumors. Even though nutrient availability is a critical determinant of tumor metabolism, there has been little systematic study of the nutrients directly available to cancer cells in the tumor microenvironment. Previous work characterizing the metabolites present in the tumor interstitial fluid has been restricted to the measurement of a small number of nutrients such as glucose and lactate in a limited number of samples. Here we adapt a centrifugation-based method of tumor interstitial fluid isolation readily applicable to a number of sample types and a mass spectrometry-based method for the absolute quantitation of many metabolites in interstitial fluid samples. In this method, tumor interstitial fluid (TIF) is analyzed by liquid chromatography-mass spectrometry (LC/MS) using both isotope dilution and external standard calibration to derive absolute concentrations of targeted metabolites present in interstitial fluid. The use of isotope dilution allows for accurate absolute quantitation of metabolites, as other methods of quantitation are inadequate for determining nutrient concentrations in biological fluids due to matrix effects that alter the apparent concentration of metabolites depending on the composition of the fluid in which they are contained. This method therefore can be applied to measure the absolute concentrations of many metabolites in interstitial fluid from diverse tumor types, as well as most other biological fluids, allowing for characterization of nutrient levels in the microenvironment of solid tumors.
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- 2019
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10. Identification of variant HIV envelope proteins with enhanced affinities for precursors to anti-gp41 broadly neutralizing antibodies.
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Hong Zhu, Elizabeth Mathew, Sara M Connelly, Jeffrey Zuber, Mark Sullivan, Michael S Piepenbrink, James J Kobie, and Mark E Dumont
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Medicine ,Science - Abstract
HIV envelope protein (Env) is the sole target of broadly neutralizing antibodies (BNAbs) that are capable of neutralizing diverse strains of HIV. While BNAbs develop spontaneously in a subset of HIV-infected patients, efforts to design an envelope protein-based immunogen to elicit broadly neutralizing antibody responses have so far been unsuccessful. It is hypothesized that a primary barrier to eliciting BNAbs is the fact that HIV envelope proteins bind poorly to the germline-encoded unmutated common ancestor (UCA) precursors to BNAbs. To identify variant forms of Env with increased affinities for the UCA forms of BNAbs 4E10 and 10E8, which target the Membrane Proximal External Region (MPER) of Env, libraries of randomly mutated Env variants were expressed in a yeast surface display system and screened using fluorescence activated cell sorting for cells displaying variants with enhanced abilities to bind the UCA antibodies. Based on analyses of individual clones obtained from the screen and on next-generation sequencing of sorted libraries, distinct but partially overlapping sets of amino acid substitutions conferring enhanced UCA antibody binding were identified. These were particularly enriched in substitutions of arginine for highly conserved tryptophan residues. The UCA-binding variants also generally exhibited enhanced binding to the mature forms of anti-MPER antibodies. Mapping of the identified substitutions into available structures of Env suggest that they may act by destabilizing both the initial pre-fusion conformation and the six-helix bundle involved in fusion of the viral and cell membranes, as well as providing new or expanded epitopes with increased accessibility for the UCA antibodies.
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- 2019
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11. Social media as a data resource for #monkseal conservation.
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Mark Sullivan, Stacie Robinson, and Charles Littnan
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Medicine ,Science - Abstract
The prevalence of social media platforms that share photos and videos could prove useful for wildlife research and conservation programs. When social media users post pictures and videos of animals, near real-time data like individual identification, sex, location, or other information are made accessible to scientists. These data can help inform researchers about animal occurrence, behavior, or threats to survival. The endangered Hawaiian monk seal (Neomonachus schauinslandi) population has only 1,400 seals remaining in the wild. A small but growing population of seals has recently reestablished itself in the human-populated main Hawaiian Islands. While this population growth raises concerns about human-seal interactions it also provides the opportunity to capitalize on human observations to enhance research and conservation activities. We measured the potential utility of non-traditional data sources, in this case Instagram, to supplement current population monitoring of monk seals in the main Hawaiian Islands. We tracked all Instagram posts with the identifier #monkseal for a one-year period and assessed the photos for biological and geographical information, behavioral concerns, human disturbance and public perceptions. Social media posts were less likely to provide images suitable for individual seal identification (16.5%) than traditional sighting reports (79.9%). However, social media enhanced the ability to detect human-seal interactions or animal disturbances: 22.1%, of the 2,392 Instagram posts examined showed people within 3 meters of a seal, and 17.8% indicated a disturbance to the animal, meanwhile only 0.64% of traditional reports noted a disturbance to the animal. This project demonstrated that data obtained through social media posts have value to monk seal research and management strategies beyond traditional data collection, and further development of social media platforms as data resources is warranted. Many conservation programs may benefit from similar work using social media to supplement the research and conservation activities they are undertaking.
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- 2019
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12. Creative use of the priority review voucher by public and not-for-profit actors delivers the first new FDA-approved treatment for river blindness in 20 years.
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Piero L Olliaro, Annette C Kuesel, Christine M Halleux, Mark Sullivan, and John C Reeder
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Published
- 2018
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13. High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study
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Christopher J. Boos, Kyo Bye, Luke Sevier, Josh Bakker-Dyos, David R. Woods, Mark Sullivan, Tom Quinlan, and Adrian Mellor
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heart rate variability ,high altitude ,cardiac patch ,acute mountain sickness ,non-linear ,rating of perceived exertion ,Physiology ,QP1-981 - Abstract
Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA.Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200–0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4–12 beats) and long-term (α2, 13–64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6–20 RPE scale.Results: All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO2 and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased (p < 0.05). RPE inversely correlated with SD1/SD2 (r = -0.31; p = 0.002), SampEn (r = -0.22; p = 0.03), HFnu (r = -0.27; p = 0.007) and positively correlated with LF (r = 0.24; p = 0.02), LF/HF (r = 0.24; p = 0.02), α1 (r = 0.32; p = 0.002) and α2 (r = 0.21; p = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS.Conclusion: Non-linear HRV is more sensitive to the effects of HA than time and frequency domain indices. HA leads to a compensatory decrease in nocturnal HRV and complexity, which is influenced by the RPE measured at the end of the previous day. HRV failed to predict AMS development.
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- 2018
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14. Developing product quality standards for wheelchairs used in less-resourced environments
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Anand Mhatre, Daniel Martin, Matt McCambridge, Norman Reese, Mark Sullivan, Don Schoendorfer, Eric Wunderlich, Chris Rushman, Dave Mahilo, and Jon Pearlman
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International Society of Wheelchair Professionals ,less-resourced environments ,literature review ,wheelchairs ,wheelchair standards ,wheelchair testing ,World Health Organization ,Vocational rehabilitation. Employment of people with disabilities ,HD7255-7256 ,Communities. Classes. Races ,HT51-1595 - Abstract
Background: Premature failures of wheelchairs in less-resourced environments (LREs) may be because of shortcomings in product regulation and quality standards. The standards published by the International Organization for Standardization (ISO) specify wheelchair tests for durability, safety and performance, but their applicability to products used in the rugged conditions of LREs is unclear. Because of this, wheelchair-related guidelines published by the World Health Organization recommended developing more rigorous durability tests for wheelchairs. Objectives: This study was performed to identify the additional tests needed for LREs. Methods: First, a literature review of the development of ISO test standards, wheelchair standards testing studies and wheelchair evaluations in LREs was performed. Second, expert advice from members of the Standards Working Group of the International Society of Wheelchair Professionals (ISWP) was compiled and reviewed. Results: A total of 35 articles were included in the literature review. Participation from LREs was not observed in the ISO standards development. As per wheelchair testing study evidence, wheelchair models delivered in LREs did not meet the minimum standards requirement. Multiple part failures and repairs were observed with reviewed field evaluation studies. ISWP experts noted that several testing factors responsible for premature failures with wheelchair parts are not included in the standards and accordingly provided advice for additional test development. Conclusion: The study findings indicate the need to develop a wide range of tests, with specific tests for measuring corrosion resistance of the entire wheelchair, rolling resistance of castors and rear wheels, and durability of whole wheelchair and castor assemblies.
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- 2017
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15. Monitoring Global Croplands with Coarse Resolution Earth Observations: The Global Agriculture Monitoring (GLAM) Project.
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Inbal Becker-Reshef, Christopher Justice, Mark Sullivan, Eric F. Vermote, Compton J. Tucker, Assaf Anyamba, Jennifer Small, Edwin W. Pak, Edward J. Masuoka, Jeff Schmaltz, Matthew C. Hansen, Kyle Pittman, Charon Birkett, Derrick Williams, Curt Reynolds, and Bradley Doorn
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- 2010
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16. Digital library of the Caribbean: a user-centric model for technology development in collaborative digitization projects.
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Mark Sullivan and Marilyn N. Ochoa
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- 2009
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17. From the air: the photographic record of Florida's lands.
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Stephanie C. Haas, Erich Kesse, Mark Sullivan, Randall Renner, and Joe Aufmuth
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- 2005
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18. INRstar: computerised decision support software for anticoagulation management in primary care
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Robert Jones, Mark Sullivan, and David Barrett
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anticoagulation management ,atrial fibrillation ,computerised decision support software ,INRstar ,warfarin ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Computerised decision support software (CDSS) for anticoagulation management has become established practice in the UK, offering significant advantages for patients and clinicians over traditional methods of dose calculation. The New GMS Contract has been partly responsible for this shift of management from secondary to primary care, in which INRstar has been the market leader for many years. In September 2004, INRstar received the John Perry Prize, awarded by the PHCSG for excellence and innovation in medical applications of information technology.
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- 2005
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19. Quasi-Cubes: Exploiting Approximations in Multidimensional Databases.
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Daniel Barbará and Mark Sullivan
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- 1997
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20. Non-immunogenicity of overlapping gag peptides pulsed on autologous cells after vaccination of HIV infected individuals.
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Henrik N Kløverpris, Akil Jackson, Amanda Handley, Peter Hayes, Jill Gilmour, Lynn Riddell, Fabian Chen, Mark Atkins, Marta Boffito, Bruce D Walker, Jim Ackland, Mark Sullivan, and Philip Goulder
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Medicine ,Science - Abstract
HIV Gag-specific CD4+ and CD8+ T-cell responses are important for HIV immune control. Pulsing overlapping Gag peptides on autologous lymphocytes (OPAL) has proven immunogenic and effective in reducing viral loads in multiple pigtail macaque studies, warranting clinical evaluation.We performed a phase I, single centre, placebo-controlled, double-blinded and dose-escalating study to evaluate the safety and preliminary immunogenicity of a novel therapeutic vaccine approach 'OPAL-HIV-Gag(c)'. This vaccine is comprised of 120 15mer peptides, overlapping by 11 amino acids, spanning the HIV Gag C clade sequence proteome, pulsed on white blood cells enriched from whole blood using a closed system, followed by intravenous reinfusion. Patients with undetectable HIV viral loads (
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- 2013
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21. A randomised, placebo-controlled, first-in-human study of a novel clade C therapeutic peptide vaccine administered ex vivo to autologous white blood cells in HIV infected individuals.
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Akil Jackson, Henrik N Kløverpris, Marta Boffito, Amanda Handley, Mark Atkins, Peter Hayes, Jill Gilmour, Lynn Riddel, Fabian Chen, Melanie Bailey-Tippets, Bruce Walker, Jim Ackland, Mark Sullivan, and Philip Goulder
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Medicine ,Science - Abstract
Preclinical studies of overlapping 15mer peptides, spanning SIV, SHIV or HIV, pulsed on autologous PBMC ex vivo have demonstrated high level, virus-specific T cell responses and viral suppression in non-human primates (NHP). Opal-HIV-Gag(c) consists of 120 synthetic 15mer peptides spanning Clade C, consensus Gag, manufactured to current good manufacturing practice; having been evaluated in a good laboratory practice toxicology study in Macaca mulatta. We evaluated the safety and preliminary immunogenicity of such peptides administered intravenously after short-duration ex vivo incubation, to HIV-positive adults on suppressive antiretroviral therapy.A first-in-human, placebo-controlled, double-blind, dose escalation study was conducted. Twenty-three patients with virus suppressed by antiretroviral therapy were enrolled in four groups 12 mg (n = 6), 24 mg (n = 6), 48 mg (n = 2) or matching placebo (n = 8). Treatment was administered intravenously after bedside enrichment of 120 mL whole blood for white cells using a closed system (Sepax S-100 device), with ex vivo peptide admixture (or diluent alone) and 37°C incubation for one hour prior to reinfusion. Patients received 4 administrations at monthly intervals followed by a 12-week observation post-treatment. Opal-HIV-Gag(c) was reasonably tolerated at doses of 12 and 24 mg. There was an increased incidence of temporally associated pyrexia, chills, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c) recipients compared to placebo. The study was terminated early, after two patients were recruited to the 48 mg cohort; a serious adverse event of hypotension, tachycardia secondary to diarrhoea occurred following a single product administration. An infectious cause for the event could not be identified, leaving the possibility of immunologically mediated product reaction.A serious, potentially life-threatening event of hypotension led to early, precautionary termination of the study. In the absence of a clearly defined mechanism or ability to predict such occurrence, further development of Opal-HIV-Gag(c) will not be undertaken in the current form.ClinicalTrials.gov NCT01123915; EudraCT: 2008-005142-23.
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- 2013
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22. Laparoscopic Cytoreductive Nephrectomy: A Three-Center Retrospective Analysis.
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Christopher Blick, Simon Bott, Asif Muneer, Neil J. Barber, Richard Hindley, Christopher Eden, and Mark Sullivan
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KIDNEY surgery ,POSTOPERATIVE care ,METASTASIS ,BLOOD loss estimation ,HOSPITAL care - Abstract
AbstractIntroduction:Metastatic renal cell carcinoma is associated with a poor prognosis. Given the current lack of effective systemic therapies and data suggesting a survival benefit from cytoreductive nephrectomy (CRN) before systemic therapy, we have retrospectively analyzed the experience of laparoscopic cytoreductive nephrectomy (LCRN) in three U.K. centers. The focus of this study was to assess the peri- and postoperative safety and hence feasibility of LCRN in the United Kingdom.Patients and Methods:Twenty-five patients with metastatic renal cell carcinoma deemed suitable for systemic therapy underwent LCRN in three U.K. centers over a 4-year period.Results:The tumors ranged from 3.4 cm in diameter to 12 cm. Operating times ranged from 89 (minimum) to 310 minutes (maximum), median 175 minutes. The median amount of blood loss was 150 mL, and hence the transfusion rate was low with only one patient requiring on-table transfusion and two patients requiring additional blood before discharge. Hospital stay ranged between 2.5 and 11 days; median postoperative stay was 3 days.Conclusions:In our initial experience, LCRN seems safe and feasible with low morbidity and a good perioperative outcome. [ABSTRACT FROM AUTHOR]
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- 2010
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23. Digital library of the Caribbean: a user-centric model for technology development in collaborative digitization projects.
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Mark Sullivan and Marilyn N. Ochoa
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- 2009
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24. Exaggerated Pain Behavior: By What Standard?
- Author
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Mark Sullivan
- Published
- 2004
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25. The renal tolerance of low-dose adefovir dipivoxil by lamivudine-resistant individuals co-infected with hepatitis B and HIV.
- Author
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Heidi Hannon, Corinne Isnard Bagnis, Yves Benhamou, Hélène Beaufils, Mark Sullivan, Carol Brosgart, Hassan Izzedine, Thierry Poynard, and Gilbert Deray
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DRUG administration ,HEPATITIS viruses ,HERPESVIRUS diseases ,PROTEINURIA - Abstract
Background. Adefovir (ADV), an orally administered nucleotide analogue active against hepadnaviruses, retroviruses and herpes viruses was shown to be effective in HIV-infected patients, but the prevalence of nephrotoxicity with doses of 60-120 mg/day was considered unacceptable. Recently, lower doses of ADV were shown to be effective for the treatment of HIV-1 patients with chronic lamivudine (LAM)-resistant hepatitis B. Methods. In a cohort of 35 patients infected with both HIV-1 and LAM-resistant hepatitis B virus, we investigated the renal tolerance of a once-daily dose of ADV 10 mg over 52 weeks. Their mean baseline creatinine clearance was within the normal range (105 ± 3 ml/min/1.73 m
2 ). No patient had significant changes in renal function or electrolyte balance secondary to ADV treatment. Results. Transient increases in serum creatinine, which resolved by the end of the study were noted in two patients and three developed proteinuria, which was felt to be unrelated to ADV treatment. The cohort's mean serum phosphate level, 2.45 ± 0.09 mg/dl at baseline, did not change significantly under treatment (2.66 ± 0.12 mg/dl at week 52, P = NS). Conclusions. Our study shows that ADV dosed at 10 mg/day for the treatment of LAM-resistant chronic hepatitis B in patients co-infected with HIV is not associated with renal tubular dysfunction or a significant change in renal function. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
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26. An Intravenous Medication Safety System: Preventing High-Risk Medication Errors at the Point of Care.
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Irene Hatcher, Mark Sullivan, James Hutchinson, Susan Thurman, and F. A Gaffney
- Subjects
- *
NURSE administrators , *DRUG administration , *NURSING , *MEDICATION errors , *MEDICAL errors - Abstract
Improving medication safety at the point of careparticularly for high-risk drugsis a major concern of nursing administrators. The medication errors most likely to cause harm are administration errors related to infusion of high-risk medications. An intravenous medication safety system is designed to prevent high-risk infusion medication errors and to capture continuous quality improvement data for best practice improvement. Initial testing with 50 systems in 2 units at Vanderbilt University Medical Center revealed that, even in the presence of a fully mature computerized prescriber order-entry system, the new safety system averted 99 potential infusion errors in 8 months. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
27. The Volumetric Rate of Calcium-rich Transients in the Local Universe.
- Author
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Chris Frohmaier, Mark Sullivan, Kate Maguire, and Peter Nugent
- Subjects
- *
CALCIUM isotopes , *GALAXY clusters , *GLOBULAR clusters , *CONSTRAINTS (Physics) , *TRANSIENTS (Dynamics) - Abstract
We present a measurement of the volumetric rate of “calcium-rich” optical transients in the local universe, using a sample of three events from the Palomar Transient Factory (PTF). This measurement builds on a detailed study of the PTF transient detection efficiencies and uses a Monte Carlo simulation of the PTF survey. We measure the volumetric rate of calcium-rich transients to be higher than previous estimates: events yr−1 Mpc−3. This is equivalent to 33%–94% of the local volumetric Type Ia supernova rate. This calcium-rich transient rate is sufficient to reproduce the observed calcium abundances in galaxy clusters, assuming an asymptotic calcium yield per calcium-rich event of ∼0.05 . We also study the PTF detection efficiency of these transients as a function of position within their candidate host galaxies. We confirm as a real physical effect previous results that suggest that calcium-rich transients prefer large physical offsets from their host galaxies. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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28. Environmental Dependence of Type Ia Supernova Luminosities from a Sample without a Local–Global Difference in Host Star Formation.
- Author
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Young-Lo Kim, Mathew Smith, Mark Sullivan, and Young-Wook Lee
- Subjects
TYPE I supernovae ,STELLAR luminosity function ,STAR formation ,STELLAR populations ,STELLAR mass ,COSMOLOGICAL principle - Abstract
It is established that there is a dependence of the luminosity of type Ia supernovae (SNe Ia) on environment: SNe Ia in young, star-forming, metal-poor stellar populations appear fainter after light-curve shape corrections than those in older, passive, metal-rich environments. This is accounted for in cosmological studies using a global property of the SN host galaxy, typically the host galaxy stellar mass. However, recent low-redshift studies suggest that this effect manifests itself most strongly when using the local star formation rate (SFR) at the SN location, rather than the global SFR or the stellar mass of the host galaxy. At high-redshift, such local SFRs are difficult to determine; here, we show that an equivalent local correction can be made by restricting the SN Ia sample in globally star-forming host galaxies to a low-mass host galaxy subset (≤10
10 M☉ ). Comparing this sample of SNe Ia (in locally star-forming environments) to those in locally passive host galaxies, we find that SNe Ia in locally star-forming environments are 0.081 ± 0.018 mag fainter (4.5σ), consistent with the result reported by Rigault et al., but our conclusion is based on a sample ∼5 times larger over a wider redshift range. This is a larger difference than when splitting the SN Ia sample based on global host galaxy SFR or host galaxy stellar mass. This method can be used in ongoing and future high-redshift SN surveys, where local SN Ia environments are difficult to determine. [ABSTRACT FROM AUTHOR]- Published
- 2018
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- View/download PDF
29. Type Ibn Supernovae Show Photometric Homogeneity and Spectral Diversity at Maximum Light.
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Griffin Hosseinzadeh, Curtis McCully, D. Andrew Howell, Iair Arcavi, Kelsey I. Clubb, Alexei V. Filippenko, WeiKang Zheng, Alessandra Corsi, David Sand, Ori D. Fox, G. H. Marion, Morgan Fraser, Cosimo Inserra, Stephen Smartt, Ken W. Smith, Russ Laher, Frank Masci, Jason Surace, Umaa Rebbapragada, and Mark Sullivan
- Subjects
TYPE I supernovae ,ASTRONOMICAL photometry ,HOMOGENEITY ,SPECTRAL sensitivity ,CIRCUMSTELLAR matter - Abstract
Type Ibn supernovae (SNe) are a small yet intriguing class of explosions whose spectra are characterized by low-velocity helium emission lines with little to no evidence for hydrogen. The prevailing theory has been that these are the core-collapse explosions of very massive stars embedded in helium-rich circumstellar material (CSM). We report optical observations of six new SNe Ibn: PTF11rfh, PTF12ldy, iPTF14aki, iPTF15ul, SN 2015G, and iPTF15akq. This brings the sample size of such objects in the literature to 22. We also report new data, including a near-infrared spectrum, on the Type Ibn SN 2015U. In order to characterize the class as a whole, we analyze the photometric and spectroscopic properties of the full Type Ibn sample. We find that, despite the expectation that CSM interaction would generate a heterogeneous set of light curves, as seen in SNe IIn, most Type Ibn light curves are quite similar in shape, declining at rates around 0.1 mag day
−1 during the first month after maximum light, with a few significant exceptions. Early spectra of SNe Ibn come in at least two varieties, one that shows narrow P Cygni lines and another dominated by broader emission lines, both around maximum light, which may be an indication of differences in the state of the progenitor system at the time of explosion. Alternatively, the spectral diversity could arise from viewing-angle effects or merely from a lack of early spectroscopic coverage. Together, the relative light curve homogeneity and narrow spectral features suggest that the CSM consists of a spatially confined shell of helium surrounded by a less dense extended wind. [ABSTRACT FROM AUTHOR]- Published
- 2017
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30. ON THE EARLY-TIME EXCESS EMISSION IN HYDROGEN-POOR SUPERLUMINOUS SUPERNOVAE.
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Paul M. Vreeswijk, Giorgos Leloudas, Avishay Gal-Yam, Annalisa De Cia, Daniel A. Perley, Robert M. Quimby, Roni Waldman, Mark Sullivan, Lin Yan, Eran O. Ofek, Christoffer Fremling, Francesco Taddia, Jesper Sollerman, Stefano Valenti, Iair Arcavi, D. Andrew Howell, Alexei V. Filippenko, S. Bradley Cenko, Ofer Yaron, and Mansi M. Kasliwal
- Subjects
EMISSION spectroscopy ,SUPERNOVAE ,LIGHT curves ,MAGNETARS ,RADIOACTIVE decay - Abstract
We present the light curves of the hydrogen-poor superluminous supernovae (SLSNe I) PTF 12dam and iPTF 13dcc, discovered by the (intermediate) Palomar Transient Factory. Both show excess emission at early times and a slowly declining light curve at late times. The early bump in PTF 12dam is very similar in duration (∼10 days) and brightness relative to the main peak (2–3 mag fainter) compared to that observed in other SLSNe I. In contrast, the long-duration (>30 days) early excess emission in iPTF 13dcc, whose brightness competes with that of the main peak, appears to be of a different nature. We construct bolometric light curves for both targets, and fit a variety of light-curve models to both the early bump and main peak in an attempt to understand the nature of these explosions. Even though the slope of the late-time decline in the light curves of both SLSNe is suggestively close to that expected from the radioactive decay of
56 Ni and56 Co, the amount of nickel required to power the full light curves is too large considering the estimated ejecta mass. The magnetar model including an increasing escape fraction provides a reasonable description of the PTF 12dam observations. However, neither the basic nor the double-peaked magnetar model is capable of reproducing the light curve of iPTF 13dcc. A model combining a shock breakout in an extended envelope with late-time magnetar energy injection provides a reasonable fit to the iPTF 13dcc observations. Finally, we find that the light curves of both PTF 12dam and iPTF 13dcc can be adequately fit with the model involving interaction with the circumstellar medium. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
31. RAPIDLY RISING TRANSIENTS IN THE SUPERNOVA—SUPERLUMINOUS SUPERNOVA GAP.
- Author
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Iair Arcavi, William M. Wolf, D. Andrew Howell, Lars Bildsten, Giorgos Leloudas, Delphine Hardin, Szymon Prajs, Daniel A. Perley, Gilad Svirski, Avishay Gal-Yam, Boaz Katz, Curtis McCully, S. Bradley Cenko, Chris Lidman, Mark Sullivan, Stefano Valenti, Pierre Astier, Cristophe Balland, Ray G. Carlberg, and Alex Conley
- Subjects
SUPERNOVAE ,GAMMA rays ,LUMINOSITY ,LUMINOUS flux ,STELLAR luminosity function - Abstract
We present observations of four rapidly rising (t
rise ≈ 10 days) transients with peak luminosities between those of supernovae (SNe) and superluminous SNe (Mpeak ≈ −20)—one discovered and followed by the Palomar Transient Factory (PTF) and three by the Supernova Legacy Survey. The light curves resemble those of SN 2011kl, recently shown to be associated with an ultra-long-duration gamma-ray burst (GRB), though no GRB was seen to accompany our SNe. The rapid rise to a luminous peak places these events in a unique part of SN phase space, challenging standard SN emission mechanisms. Spectra of the PTF event formally classify it as an SN II due to broad Hα emission, but an unusual absorption feature, which can be interpreted as either high velocity Hα (though deeper than in previously known cases) or Si ii (as seen in SNe Ia), is also observed. We find that existing models of white dwarf detonations, CSM interaction, shock breakout in a wind (or steeper CSM), and magnetar spin down cannot readily explain the observations. We consider the possibility that a “Type 1.5 SN” scenario could be the origin of our events. More detailed models for these kinds of transients and more constraining observations of future such events should help to better determine their nature. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
32. SEARCH FOR PRECURSOR ERUPTIONS AMONG TYPE IIB SUPERNOVAE.
- Author
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Nora L. Strotjohann, Eran O. Ofek, Avishay Gal-Yam, Mark Sullivan, Shrinivas R. Kulkarni, Nir J. Shaviv, Christoffer Fremling, Mansi M. Kasliwal, Peter E. Nugent, Yi Cao, Iair Arcavi, Jesper Sollerman, Alexei V. Filippenko, Ofer Yaron, Russ Laher, and Jason Surace
- Subjects
SUPERNOVAE ,STARS ,KINETIC energy ,COMPACT objects (Astronomy) ,CATACLYSMIC variable stars - Abstract
The progenitor stars of several Type IIb supernovae (SNe) show indications of extended hydrogen envelopes. These envelopes might be the outcome of luminous energetic pre-explosion events, so-called precursor eruptions. We use the Palomar Transient Factory (PTF) pre-explosion observations of a sample of 27 nearby SNe IIb to look for such precursors during the final years prior to the SN explosion. No precursors are found when combining the observations in 15-day bins, and we calculate the absolute-magnitude-dependent upper limit on the precursor rate. At the 90% confidence level, SNe IIb have on average <0.86 precursors as bright as an absolute R-band magnitude of −14 in the final 3.5 years before the explosion and <0.56 events over the final year. In contrast, precursors among SNe IIn have a ≳5 times higher rate. The kinetic energy required to unbind a low-mass stellar envelope is comparable to the radiated energy of a few-weeks-long precursor that would be detectable for the closest SNe in our sample. Therefore, mass ejections, if they are common in such SNe, are radiatively inefficient or have durations longer than months. Indeed, when using 60-day bins, a faint precursor candidate is detected prior to SN 2012cs (∼2% false-alarm probability). We also report the detection of the progenitor of SN 2011dh that does not show detectable variability over the final two years before the explosion. The suggested progenitor of SN 2012P is still present, and hence is likely a compact star cluster or an unrelated object. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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