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1. Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease

Author

Mihaela I. Dregoesc, Helin Tercan, Adrian B. Țigu, Siroon Bekkering, Leo AB. Joosten, Mihai G. Netea, Rosanne C. van Deuren, Alexander Hoischen, Niels P. Riksen, and Adrian C. Iancu

Subjects
Health sciences, Cardiovascular medicine, Science
Abstract

Summary: Clonal hematopoiesis (CH) is a risk factor for atherosclerotic cardiovascular disease, but the impact of smaller clones and the effect on inflammatory parameters is largely unknown. Using ultrasensitive single-molecule molecular inversion probe sequencing, we evaluated the association between CH and a first major adverse cardiovascular event (MACE) in patients with angiographically documented stable coronary artery disease (CAD) and no history of acute ischemic events. CH was associated with an increased rate of MACE at four years follow-up. The size of the clone predicted MACE at an optimal cut-off value of 1.07% variant allele frequency (VAF). Mutation carriers had no change in monocytes subsets or cytokine production capacity but had higher levels of circulating tissue factor, matrilysin, and proteinase-activated receptor-1. Our study identified CH driver mutations with a VAF as small as 1.07% as a residual cardiovascular risk factor and identified potential biomarkers and therapeutic targets for patients with stable CAD.

Published
2024
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3. Diagnostic labels and advice for rotator cuff disease influence perceived need for shoulder surgery: an online randomised experiment

Author

Joshua R Zadro, Mary O’Keeffe, Giovanni E Ferreira, Adrian C Traeger, Andrew R Gamble, Richard Page, Robert D Herbert, Ian A Harris, and Christopher G Maher

Subjects
Rotator cuff, Shoulder pain, Subacromial impingement, Bursitis, Labelling, Advice, Therapeutics. Pharmacology, RM1-950
Abstract

Question: What are the effects of diagnostic labels and advice, and interactions between labels and advice, on perceived need for shoulder surgery for rotator cuff disease? Design: 2×2 factorial online randomised experiment. Participants: People with shoulder pain. Intervention: Participants read a scenario describing a patient with rotator cuff disease and were randomised to bursitis label plus guideline-based advice, bursitis label plus treatment recommendation, rotator cuff tear label plus guideline-based advice, and rotator cuff tear label plus treatment recommendation. Guideline-based advice included encouragement to stay active and positive prognostic information. Treatment recommendation stressed that treatment is needed for recovery. Outcome measures: Perceived need for surgery (primary outcome), imaging, an injection, a second opinion and to see a specialist; and perceived seriousness of the condition, recovery expectations, impact on work performance and need to avoid work. Results: A total of 2,024 responses (99.8% of 2,028 randomised) were analysed. Labelling as bursitis (versus rotator cuff tear) decreased perceived need for surgery (mean effect –0.5 on a 0-to-10 scale, 98.3% CI –0.7 to –0.2), imaging and to see a specialist, and perceived seriousness of the condition and need to avoid work. Guideline-based advice (versus treatment recommendation) decreased perceived need for surgery (mean effect –1.0, 98.3% CI –1.3 to –0.7), imaging, an injection, a second opinion and to see a specialist, and perceived seriousness of the condition and recovery expectations. There was little to no evidence of an advice label interaction for any outcome. Conclusion: Labels and advice influenced perceived need for surgery and other secondary outcomes in people with rotator cuff disease, with larger effects for advice. There was evidence of little or no interaction between labels and advice for any outcome, but the additive effect of labels and advice appeared large for some outcomes (eg, perceived need for imaging and perceived seriousness of the condition). Trial registration: ACTRN12621001370897.

Published
2022
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4. Low back pain of disc, sacroiliac joint, or facet joint origin: a diagnostic accuracy systematic reviewResearch in context

Author

Christopher S. Han, Mark J. Hancock, Sweekriti Sharma, Saurab Sharma, Ian A. Harris, Steven P. Cohen, John Magnussen, Chris G. Maher, and Adrian C. Traeger

Subjects
Diagnosis, Pathoanatomical, Low back pain, Reference standard, Index test, Medicine (General), R5-920
Abstract

Summary: Background: The accuracy of diagnostic tests available in primary care to identify the disc, sacroiliac joint, and facet joint as the source of low back pain is uncertain. Methods: Systematic review of diagnostic tests available in primary care. MEDLINE, CINAHL, and EMBASE were searched between March 2006 and 25th January 2023. Pairs of reviewers independently screened all studies, extracted data, and assessed risk of bias using QUADAS-2. Pooling was performed for homogenous studies. Positive likelihood ratios (+LR) ≥2 and negative likelihood ratios (−LR) ≤0.5 were considered informative. This review is registered with PROSPERO (CRD42020169828). Findings: We included 62 studies: 35 investigated the disc, 14 the facet joint, 11 the sacroiliac joint, and 2 investigated all three structures in patients with persistent low back pain. For risk of bias, the domain ‘reference standard’ scored worst, however approximately half the studies were of low risk of bias for every other domain. For the disc, pooling demonstrated MRI findings of disc degeneration and annular fissure resulted in informative +LRs: 2.53 (95% CI: 1.57–4.07) and 2.88 (95% CI: 2.02–4.10) and −LRs: 0.15 (95% CI: 0.09–0.24) and 0.24 (95% CI: 0.10–0.55) respectively. Pooled results for Modic type 1, Modic type 2, and HIZ on MRI, and centralisation phenomenon yielded informative +LRs: 10.00 (95% CI: 4.20–23.82), 8.03 (95% CI: 3.23–19.97), 3.10 (95% CI: 2.27–4.25), and 3.06 (95% CI: 1.44–6.50) respectively, but uninformative −LRs: 0.84 (95% CI: 0.74–0.96), 0.88 (95% CI: 0.80–0.96), 0.61 (95% CI: 0.48–0.77), and 0.66 (95% CI: 0.52–0.84) respectively. For the facet joint, pooling demonstrated facet joint uptake on SPECT resulted in informative +LRs: 2.80 (95% CI: 1.82–4.31) and −LRs: 0.44 (95% CI: 0.25–0.77). For the sacroiliac joint, a combination of pain provocation tests and absence of midline low back pain resulted in informative +LRs of 2.41 (95% CI: 1.89–3.07) and 2.44 (95% CI: 1.50–3.98) and −LRs of 0.35 (95% CI: 0.12–1.01) and 0.31 (95% CI: 0.21–0.47) respectively. Radionuclide imaging yielded an informative +LR 7.33 (95% CI: 1.42–37.80) but an uninformative −LR 0.74 (95% CI: 0.41–1.34). Interpretation: There are informative diagnostic tests for the disc, sacroiliac joint, and facet joint (only one test). The evidence suggests a diagnosis may be possible for some patients with low back pain, potentially guiding targeted and specific treatment approaches. Funding: There was no funding for this study.

Published
2023
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5. Missed pathological femoral neck fracture undergoes spontaneous healing

Author

Adrian C. Kong, MS, Stephanie D. Zarate, PAC, and Ana C. Belzarena, MD, MPH

Subjects
Pathological fracture, bone metastases, breast cancer, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Pathologic fractures are common complications of metastatic bone disease in patients with breast cancer. Fractures involving the proximal femur generally cause significant pain that is exacerbated by ambulation. Due to excessive stress on the weight-bearing hip joint, these fractures present a significant burden on the quality of life among patients. Here we describe a case of a 38-year-old female patient who was found to have a pathologic fracture of the proximal femur missed on imaging studies that underwent spontaneous union. Pathologic fractures rarely heal on their own, since a tumor at the fracture site interferes with bone healing and most fractures have to be managed with surgical intervention. Fractures can be missed on imaging studies in the setting of extensive metastatic disease. Physicians should be cognizant of this fact and maintain a high level of suspicion to recognize fractures with unusual presentations where patients may not present with the typical findings of acute onset of pain and inability to ambulate or bear weight.

Published
2022
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6. Nexplanon removal from intramuscular implantation in biceps: case report

Author

Adrian C. Kong, MS, Matthew N. Alfonso, MD, Dimas E. Pineda, BS, Michael S. Thorpe, MD, and Roberto A. Miki, MD

Subjects
Contraceptive implant, Nexplanon, Subfascial implant removal, Complication, Etonogestrel, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Contraceptive implant devices are relatively safe devices, but complications arise when implants become nonpalpable, and cannot be safely removed. In this case report, we describe the location of an implant in the subfascial plane of the upper arm, the diagnostic imaging findings we encountered during the workup, and the procedure necessary to remove it. We demonstrated that if the device is in close proximity to the fascia, it may be difficult to distinguish from the fascia on magnetic resonance imaging. Nonetheless, fluoroscopy and ultrasound easily distinguished the device from the surrounding tissue and allowed localization intraoperatively.

Published
2021
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7. Evolutionary profile of the family Calliphoridae, with notes on the origin of myiasis

Author

Mohamed G. Nasser, Eslam M. Hosni, Mohamed A. Kenawy, Sulaiman A. Alharbi, Hesham S. Almoallim, Magda H. Rady, Bouthaina A. Merdan, Adrian C. Pont, and Sara A. Al-Ashaal

Subjects
Blowflies, Conservative genes, Evolution, Data science, Phylogeny, Biology (General), QH301-705.5
Abstract

The family Calliphoridae is a group of heterogenous calyptrate flies with a worldwide distribution including species of ecological, veterinary, medical, and forensic importance. Notorious for their parasitic habits, the larvae of many blowflies are characterised – like some other dipteran larvae – by their ability to develop in animal flesh. When parasitism affects a living host, it is termed “myiasis”. This has led the Calliphoridae to be considered as a pivotal family in its relationship with a man. Nevertheless, even after more than 50 years of research, the phylogenetic relationships among calliphorid subfamilies together with the evolutionary origin of myiasis remain unclear. In order to elucidate these problems, we constructed three phylogenetic trees by using nucleotide sequence data from cytochrome oxidase subunit one (COI), representing a mitochondrial conservative gene, and nuclear 28S subunit of ribosomal RNA gene (28S rRNA) in order to interpret the evolutionary profile of myiasis in the family Calliphoridae. The sequenced data represented species associated with ectoparasitic life-styles, either saprophagy or facultative and obligate parasitism. A total number of 50 accessions were collected for 28S rRNA, 56 for COI, and 38 for combined sequences phylogeny. Molecular Evolutionary Genetics Analysis (MEGA) software was used to align 2197 nucleotide positions of 28S rRNA and 1500 nucleotide positions of COI with a gap opening penalties and gap extension penalties equalling 20 and 0.1 respectively. The results reveal the non-monophyly of the family Calliphoridae despite the stable monophyletic status of the Chrysomyinae, Luciliinae, and Auchmeromyiinae. Also, our findings recommend ranking the Toxotarsinae as a separate family. Furthermore, comparative analysis of the phylogenetic trees shows that the habit of obligatory myiasis originated independently more than five times. This strengthens our hypothesis that the origin of eating fresh meat is a case of convergent evolution that has taken place after speciation events millions of years ago. Finally, estimating the divergence dates between lineages from molecular sequences provides a better chance of understanding their evolutionary biology.

Published
2021
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8. Soil pore network response to freeze-thaw cycles in permafrost aggregates

Author

Erin C. Rooney, Vanessa L. Bailey, Kaizad F. Patel, Maria Dragila, Anil K. Battu, Alexander C. Buchko, Adrian C. Gallo, Jeffery Hatten, Angela R. Possinger, Odeta Qafoku, Loren.R. Reno, Michael SanClements, Tamas Varga, and Rebecca A. Lybrand

Subjects
Pore morphology, Pore connectivity, Freeze thaw, Microscale, Permafrost thaw, Arctic, Science
Abstract

Climate change in Arctic landscapes may increase freeze–thaw frequency within the active layer as well as newly thawed permafrost. Freeze-thaw is a highly disruptive process that can deform soil pores and alter the architecture of the soil pore network with varied impacts to water transport and retention, redox conditions, and microbial activity. Our objective was to investigate how freeze–thaw cycles impacted the pore network of newly thawed permafrost aggregates to improve understanding of what type of transformations can be expected from warming Arctic landscapes. We measured the impact of freeze–thaw on pore morphology, pore throat diameter distribution, and pore connectivity with X-ray computed tomography (XCT) using six permafrost aggregates with sizes of 2.5 cm3 from a mineral soil horizon (Bw; 28–50 cm depths) in Toolik, Alaska. Freeze-thaw cycles were performed using a laboratory incubation consisting of five freeze–thaw cycles (−10 °C to 20 °C) over five weeks. Our findings indicated decreasing spatial connectivity of the pore network across all aggregates with higher frequencies of singly connected pores following freeze–thaw. Water-filled pores that were connected to the pore network decreased in volume while the overall connected pore volumetric fraction was not affected. Shifts in the pore throat diameter distribution were mostly observed in pore throats ranges of 100 µm or less with no corresponding changes to the pore shape factor of pore throats. Responses of the pore network to freeze–thaw varied by aggregate, suggesting that initial pore morphology may play a role in driving freeze–thaw response. Our research suggests that freeze–thaw alters the microenvironment of permafrost aggregates during the incipient stage of deformation following permafrost thaw, impacting soil properties and function in Arctic landscapes undergoing transition.

Published
2022
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10. Updated international consensus report on the investigation and management of primary immune thrombocytopenia

Author

Drew Provan, Donald M. Arnold, James B. Bussel, Beng H. Chong, Nichola Cooper, Terry Gernsheimer, Waleed Ghanima, Bertrand Godeau, Tomás José González-López, John Grainger, Ming Hou, Caroline Kruse, Vickie McDonald, Marc Michel, Adrian C. Newland, Sue Pavord, Francesco Rodeghiero, Marie Scully, Yoshiaki Tomiyama, Raymond S. Wong, Francesco Zaja, and David J. Kuter

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.

Published
2019
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12. Codon-Optimization of Wild-Type Adeno-Associated Virus Capsid Sequences Enhances DNA Family Shuffling while Conserving Functionality

Author

Marti Cabanes-Creus, Samantha L. Ginn, Anais K. Amaya, Sophia H.Y. Liao, Adrian Westhaus, Claus V. Hallwirth, Patrick Wilmott, Jason Ward, Kimberley L. Dilworth, Giorgia Santilli, Arkadiusz Rybicki, Hiroyuki Nakai, Adrian J. Thrasher, Adrian C. Filip, Ian E. Alexander, and Leszek Lisowski

Subjects
Genetics, QH426-470, Cytology, QH573-671
Abstract

Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human gene therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with the aim of developing novel variants with enhanced tropism for specific human cell types, decreased human seroreactivity, and increased manufacturability. Selection strategies based on directed evolution rely on the generation of highly variable AAV capsid libraries using methods such as DNA-family shuffling, a technique reliant on stretches of high DNA sequence identity between input parental capsid sequences. This identity dependence for reassembly of shuffled capsids is inherently limiting and results in decreased shuffling efficiency as the phylogenetic distance between parental AAV capsids increases. To overcome this limitation, we have developed a novel codon-optimization algorithm that exploits evolutionarily defined codon usage at each amino acid residue in the parental sequences. This method increases average sequence identity between capsids, while enhancing the probability of retaining capsid functionality, and facilitates incorporation of phylogenetically distant serotypes into the DNA-shuffled libraries. This technology will help accelerate the discovery of an increasingly powerful repertoire of AAV capsid variants for cell-type and disease-specific applications. Keywords: AAV, library, directed evolution, codon optimization, DNA shuffling, capsid

Published
2019
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13. Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review

Author

Giovanni E Ferreira, Adrian C Traeger, Mary O’Keeffe, and Chris G Maher

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Question: What are staff and patients’ perceptions of physiotherapists working in the emergency department (ED)? Design: Systematic review of qualitative studies. Participants: Staff working in EDs and patients presenting to the ED and managed by ED physiotherapists. Outcome measures: Perceptions of ED staff and patients were synthesised using a three-stage thematic analysis consisting of extraction, grouping (codes), and abstraction of findings. Results: Eight studies, which had sought the perceptions of 138 patients and 122 ED staff members, were included. Three main themes emerged: role of physiotherapists in the ED, positive perceptions of ED physiotherapists, and concerns about physiotherapists in the ED. Patients and ED staff both considered physiotherapists to be experts in musculoskeletal care. The role of ED physiotherapists was seen as providing thorough patient education, non-pharmacological pain management and activity resumption, especially through exercise therapy. Having broad knowledge to assess and treat different health conditions was seen as facilitating the work of physiotherapists in the ED. Patients and ED staff felt that ED physiotherapists had good interpersonal communication skills. ED staff expressed concerns regarding the additional time that physiotherapists spent with patients. Some patients felt that performing exercises in the ED was inappropriate and painful. Conclusions: ED physiotherapists were mostly well accepted by patients and ED staff, and their work was perceived to improve the ED. Concerns included restricted availability, lack of awareness of the role undertaken by physiotherapists in the ED, and increased treatment time in some settings. [Ferreira GE, Traeger AC, O’Keeffe M, Maher CG (2018) Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review. Journal of Physiotherapy 64: 229–236] Key words: Emergency department, Physical therapy specialty, Emergency medicine, Primary contact physical therapy, Musculoskeletal pain

Published
2018
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14. S95021, a novel selective and pan-neutralizing anti interferon alpha (IFN-α) monoclonal antibody as a candidate treatment for selected autoimmune rheumatic diseases

Author

Fanny Duguet, Céline Ortega-Ferreira, Benjamin Fould, Hélène Darville, Sylvie Berger, Agnès Chomel, Grégory Leclerc, Kai Kisand, Liis Haljasmägi, Adrian C. Hayday, Emiko Desvaux, Emmanuel Nony, Philippe Moingeon, and Frédéric De Ceuninck

Subjects
Interferon-alpha, Biological therapy, Autoimmune diseases, Systemic lupus erythematosus, Primary Sjögren syndrome, Immunologic diseases. Allergy, RC581-607
Abstract

Increased interferon-α (IFN-α) production is a critical component in the pathophysiology of systemic lupus erythematosus (SLE) and other rheumatic autoimmune diseases. Herein, we report the characterization of S95021, a fully human IgG1 anti–IFN–α monoclonal antibody (mAb) as a novel therapeutic candidate for targeted patient populations. S95021 was expressed in CHOZN GS−/− cells, purified by chromatography and characterized by using electrophoresis, size exclusion chromatography and liquid chromatography-mass spectrometry. High purity S95021 was obtained as a monomeric entity comprising different charge variants mainly due to N-glycosylation. Surface plasmon resonance kinetics experiments showed strong association rates with all IFN-α subtypes and estimated KDs below picomolar values. Pan–IFN–α-binding properties were confirmed by immunoprecipitation assays and neutralization capacity with reporter HEK-Blue IFN-α/β cells. S95021 was IFN-α-selective and exhibited superior potency and broader neutralization profile when compared with the benchmark anti–IFN–α mAbs rontalizumab and sifalimumab. STAT-1 phosphorylation and the type I IFN gene signature induced in human peripheral blood mononuclear cells by recombinant IFN-α subtypes or plasmas from selected autoimmune patients were efficiently reduced by S95021 in a dose-dependent manner. Together, our results show that S95021 is a new potent, selective and pan IFN-α-neutralizing mAb. It is currently further evaluated as a valid therapeutic candidate in selected autoimmune diseases in which the IFN-α pro-inflammatory pathway is dysregulated.

Published
2021
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15. Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000–17

Author

Kirsten E Wiens, Paulina A Lindstedt, Brigette F Blacker, Kimberly B Johnson, Mathew M Baumann, Lauren E Schaeffer, Hedayat Abbastabar, Sr, Foad Abd-Allah, Ahmed Abdelalim, Ibrahim Abdollahpour, Kedir Hussein Abegaz, Ayenew Negesse Abejie, Lucas Guimarães Abreu, Michael R M Abrigo, Ahmed Abualhasan, Manfred Mario Kokou Accrombessi, Dilaram Acharya, Maryam Adabi, Abdu A Adamu, Oladimeji M Adebayo, Rufus Adesoji Adedoyin, Sr, Victor Adekanmbi, Olatunji O Adetokunboh, Sr, Beyene Meressa Adhena, Mohsen Afarideh, Sohail Ahmad, Keivan Ahmadi, Anwar E Ahmed, Muktar Beshir Ahmed, Rushdia Ahmed, Temesgen Yihunie Akalu, Fares Alahdab, Ziyad Al-Aly, Noore Alam, Sr, Samiah Alam, Genet Melak Alamene, Turki M Alanzi, Jacqueline Elizabeth Alcalde-Rabanal, Beriwan Abdulqadir Ali, Mehran Alijanzadeh, Vahid Alipour, Syed Mohamed Aljunid, Ali Almasi, Sr, Amir Almasi-Hashiani, Hesham M Al-Mekhlafi, Khalid A Altirkawi, Nelson Alvis-Guzman, Nelson J Alvis-Zakzuk, Saeed Amini, Sr, Arianna Maever L Amit, Sr, Catalina Liliana Andrei, Sr, Mina Anjomshoa, Amir Anoushiravani, Sr, Fereshteh Ansari, Carl Abelardo T Antonio, Benny Antony, Ernoiz Antriyandarti, Jalal Arabloo, Hany Mohamed Amin Aref, Sr, Olatunde Aremu, Bahram Armoon, Amit Arora, Sr, Krishna K Aryal, Afsaneh Arzani, Mehran Asadi-Aliabadi, Hagos Tasew Atalay, Seyyed Shamsadin Athari, Sr, Seyyede Masoume Athari, Sachin R Atre, Marcel Ausloos, Nefsu Awoke, Beatriz Paulina Ayala Quintanilla, Getinet Ayano, Martin Amogre Ayanore, Sr, Yared Asmare Aynalem IV, Samad Azari, Peter S Azzopardi, Ebrahim Babaee, Tesleem Kayode Babalola, Alaa Badawi, Sr, Mohan Bairwa, Shankar M Bakkannavar, Senthilkumar Balakrishnan, Ayele Geleto Bali, Maciej Banach, Sr, Joseph Adel Mattar Banoub, Sr, Aleksandra Barac, Till Winfried Bärnighausen, Huda Basaleem, Sanjay Basu, Vo Dinh Bay, Mohsen Bayati, Estifanos Baye, Neeraj Bedi, Mahya Mahya Beheshti Beheshti, Masoud Behzadifar, Meysam Behzadifar, Bayu Begashaw Bekele, Yaschilal Muche Belayneh, Michellr L Bell, Sr, Derrick A Bennett, Sr, Dessalegn Ajema Berbada, Robert S Bernstein, Anusha Ganapati Bhat, Sr, Krittika Bhattacharyya, Sr, Suraj Bhattarai, Soumyadeep Bhaumik, Zulfiqar A Bhutta, Ali Bijani, Boris Bikbov, Binyam Minuye Birihane IV, Raaj Kishore Biswas, Somayeh Bohlouli, Hunduma Amensisa Amensisa Bojia I, Soufiane Boufous, Oliver J Brady, Nicola Luigi Bragazzi, Andrey Nikolaevich Briko, Nikolay Ivanovich Briko, Gabrielle B Britton, Sharath Burugina Nagaraja, Sr, Reinhard Busse, Sr, Zahid A Butt, Luis LA Alberto Cámera, Sr, Ismael R Campos-Nonato, Sr, Jorge Cano, Josip Car, Rosario Cárdenas, Felix Carvalho, Sr, Carlos A Castañeda-Orjuela, Sr, Franz Castro, Wagaye Fentahun Chanie, Sr, Pranab Chatterjee, Vijay Kumar Chattu, Tesfaye Yitna Yitna Chichiabellu, Jr, Ken Lee Chin, Sr, Devasahayam J Christopher, Dinh-Toi Chu, Natalie Maria Cormier, Vera Marisa Costa, Carlos Culquichicon, Matiwos Soboka Daba, Giovanni Damiani, Sr, Lalit Dandona, Rakhi Dandona, Anh Kim Dang, Aso Mohammad Darwesh, Amira Hamed Darwish, Ahmad Daryani, Sr, Jai K Das, Rajat Das Gupta, Aditya Prasad Dash, Gail Davey, Claudio Alberto Dávila-Cervantes, Adrian C Davis, Sr, Dragos Virgil Davitoiu, Fernando Pio De la Hoz, Asmamaw Bizuneh Demis, Dereje Bayissa Demissie, Getu Debalkie Demissie, Gebre Teklemariam Demoz, Sr, Edgar Denova-Gutiérrez, Sr, Kebede Deribe, Sr, Assefa Desalew, Aniruddha Deshpande, Samath Dhamminda Dharmaratne, Preeti Dhillon, Meghnath Dhimal, Govinda Prasad Dhungana, Daniel Diaz, Sr, Isaac Oluwafemi Dipeolu, Shirin Djalalinia, Kerrie E Doyle, Eleonora Dubljanin, Bereket Duko, Andre Rodrigues Duraes, Mohammad Ebrahimi Kalan, Hisham Atan Edinur, Sr, Andem Effiong, Sr, Aziz Eftekhari, Nevine El Nahas, Iman El Sayed, Maysaa El Sayed Zaki, Maha El Tantawi, Teshome Bekele Elema I, Hala Rashad Elhabashy, Sr, Shaimaa I El-Jaafary, Hajer Elkout, Aisha Elsharkawy, Iqbal RF Elyazar, Aklilu Endalamaw, Daniel Adane Endalew, Sr, Sharareh Eskandarieh, Alireza Esteghamati, Sadaf Esteghamati, Sr, Arash Etemadi, Oluchi Ezekannagha, Mohammad Fareed, Roghiyeh Faridnia, Farshad Farzadfar, Mehdi Fazlzadeh, Valery L Feigin, Sr, Seyed-Mohammad Fereshtehnejad, Eduarda Fernandes, Irina Filip, Florian Fischer, Nataliya A Foigt, Morenike Oluwatoyin Folayan, Sr, Masoud Foroutan, Richard Charles Franklin, Takeshi Fukumoto, Mohamed M Gad, Reta Tsegaye Gayesa, Teshome Gebre, Sr, Ketema Bizuwork Gebremedhin, Gebreamlak Gebremedhn Gebremeskel, Sr, Hailay Abrha Gesesew, Kebede Embaye Gezae, Keyghobad Ghadiri, Sr, Ahmad Ghashghaee, Pramesh Raj Ghimire, Sr, Paramjit Singh Gill, Sr, Tiffany K Gill, Themba G G Ginindza, Nelson G M Gomes, Sameer Vali Gopalani, Alessandra C Goulart, Bárbara Niegia Garcia Goulart, Ayman Grada, Mohammed Ibrahim Mohialdeen Gubari, Harish Chander Gugnani, Sr, Davide Guido, Rafael Alves Guimarães, Yuming Guo, Sr, Rajeev Gupta, Nima Hafezi-Nejad, Dessalegn H Haile, Sr, Gessessew Bugssa Hailu, Arvin Haj-Mirzaian, Arya Haj-Mirzaian, Randah R Hamadeh, Samer Hamidi, Demelash Woldeyohannes Handiso, Hamidreza Haririan, Sr, Ninuk Hariyani, Ahmed I Hasaballah, Md Mehedi Hasan, Edris Hasanpoor, Amir Hasanzadeh, Hadi Hassankhani, Hamid Yimam Hassen, Mohamed I Hegazy, Behzad Heibati, Behnam Heidari, Delia Hendrie, Sr, Nathaniel J Henry, Claudiu Herteliu, Fatemeh Heydarpour, Hagos Degefa de Hidru I, Thomas R Hird, Chi Linh Hoang, Enayatollah Homaie Rad, Praveen Hoogar, Mohammad Hoseini, Naznin Hossain, Mostafa Hosseini, Mehdi Hosseinzadeh, Mowafa Househ, Mohamed Hsairi, Sr, Guoqing Hu, Mohammedaman Mama Hussen, Segun Emmanuel Ibitoye, Ehimario U Igumbor, Sr, Olayinka Stephen Ilesanmi, Milena D Ilic, Mohammad Hasan Imani-Nasab, Usman Iqbal, Seyed Sina Naghibi Irvani, Sheikh Mohammed Shariful Islam, Chinwe Juliana Iwu, Neda Izadi, Sr, Anelisa Jaca, Nader Jahanmehr, Mihajlo Jakovljevic, Amir Jalali, Achala Upendra Jayatilleke, Ravi Prakash Jha, Vivekanand Jha, John S Ji, Sr, Jost B Jonas, Jacek Jerzy Jozwiak, Ali Kabir, Zubair Kabir, Sr, Amaha Kahsay, Hamed Kalani, Tanuj Kanchan, Behzad Karami Matin, André Karch, Mohd Anisul Karim, Hamidreza Karimi-Sari, Surendra Karki, Amir Kasaeian, Gebremicheal Gebreslassie Kasahun, Yawukal chane Kasahun, Habtamu Kebebe Kasaye, Gebrehiwot G Kassa, Getachew Mullu Kassa, Gbenga A Kayode, Ali Kazemi Karyani, Mihiretu M Kebede, Peter Njenga Keiyoro, Abraham Getachew Kelbore, Sr, Andre Pascal Kengne, Sr, Daniel Bekele Ketema, Yousef Saleh Khader, Morteza Abdullatif Khafaie, Nauman Khalid, Rovshan Khalilov, Ejaz Ahmad Khan, Sr, Junaid Khan, Md Nuruzzaman Khan I, Muhammad Shahzeb Khan, Khaled Khatab, Sr, Amir M Khater, Mona M Khater, Maryam Khayamzadeh, Mohammad Khazaei, Salman Khazaei, Mohammad Hossein Khosravi, Jagdish Khubchandani, Ali Kiadaliri, Yun Jin Kim, Ruth W Kimokoti, Adnan Kisa, Sezer Kisa, Niranjan Kissoon, Sr, Shivakumar KM Marulasiddaiah M KMShivakumar, Sr, Sonali Kochhar, Tufa Kolola, Sr, Hamidreza Komaki, Soewarta Kosen, Parvaiz A Koul, Ai Koyanagi, Moritz U G Kraemer, Kewal Krishan, Nuworza Kugbey, G Anil Kumar, Manasi Kumar, Sr, Pushpendra Kumar, Vivek Kumar, Dian Kusuma, Carlo La Vecchia, Ben Lacey, Sheetal D Lad, Dharmesh Kumar Lal, Felix Lam, Faris Hasan Lami, Sr, Prabhat Lamichhane, Van Charles Lansingh, Savita Lasrado, Avula Laxmaiah, Paul H Lee, Sr, Kate E LeGrand, Mostafa Leili, Tsegaye Lolaso Lenjebo, Cheru Tesema Leshargie, Sr, Aubrey J Levine, Shanshan Li, Sr, Shai Linn, Shiwei Liu, Simin Liu, Rakesh Lodha, Joshua Longbottom, Jaifred Christian F Lopez, Hassan Magdy Abd El Razek, Muhammed Magdy Abd El Razek, D R Mahadeshwara Prasad, Phetole Walter Mahasha, Sr, Narayan B Mahotra, Azeem Majeed, Reza Malekzadeh, Sr, Deborah Carvalho Malta, Abdullah A Mamun, Sr, Navid Manafi, Sr, Ana Laura Manda, Narendar Dawani Dawanu Manohar, Mohammad Ali Mansournia, Chabila Christopher Mapoma, Joemer C Maravilla, Gabriel Martinez, Sr, Santi Martini, Francisco Rogerlândio Martins-Melo, Anthony Masaka, Benjamin Ballard Massenburg, Manu Raj Mathur, Benjamin K Mayala, Mohsen Mazidi, Colm McAlinden, Birhanu Geta Meharie, Man Mohan Mehndiratta, Sr, Kala M Mehta, Tefera C Chane Mekonnen, Gebrekiros Gebremichael Meles, Peter T N Memiah, Ziad A Memish, Sr, Walter Mendoza, Ritesh G Menezes, Seid Tiku Mereta, Tuomo J Meretoja, Sr, Tomislav Mestrovic, Bartosz Miazgowski, Kebadnew Mulatu Mihretie, Sr, Ted R Miller, GK Mini, Erkin M Mirrakhimov, Babak Moazen, Bahram Mohajer, Amjad Mohamadi-Bolbanabad, Dara K Mohammad, Karzan Abdulmuhsin Mohammad, Yousef Mohammad, Naser Mohammad Gholi Mezerji, Roghayeh Mohammadibakhsh, Noushin Mohammadifard, Jemal Abdu Mohammed, Sr, Shafiu Mohammed, Farnam Mohebi, Ali H Mokdad, Mariam Molokhia, Lorenzo Monasta, Yoshan Moodley, Sr, Catrin E Moore, Sr, Ghobad Moradi, Masoud Moradi, Mohammad Moradi-Joo, Maziar Moradi-Lakeh, Paula Moraga, Linda Morales, Ilais Moreno Velásquez, Abbas Mosapour, Simin Mouodi, Seyyed Meysam Mousavi, Miliva Mozaffor I, Kindie Fentahun Muchie, Sr, Getahun Fentaw Mulaw, Sr, Sandra B Munro, Moses K Muriithi, Christopher J L Murray, GVS Murthy, Kamarul Imran Musa, Ghulam Mustafa, Sr, Saravanan Muthupandian, Sr, Ashraf F Nabhan, Mehdi Naderi, Ahamarshan Jayaraman Nagarajan, Kovin S Naidoo, Gurudatta Naik, Farid Najafi, Vinay Nangia, Sr, Jobert Richie Nansseu, Bruno Ramos Nascimento, Sr, Javad Nazari, Duduzile Edith Ndwandwe, Sr, Ionut Negoi, Sr, Henok Biresaw Netsere Netsere, Sr, Josephine W Ngunjiri, Sr, Cuong Tat Nguyen, Huong Lan Thi Nguyen, Trang Huyen Nguyen, Dabere Nigatu, Solomon Gedlu Nigatu, Dina Nur Anggraini Ningrum, Chukwudi A Nnaji, Marzieh Nojomi, Vuong Minh Nong, Ole F Norheim, Sr, Jean Jacques Noubiap, Soraya Nouraei Motlagh, Bogdan Oancea, Okechukwu Samuel Ogah, Felix Akpojene Ogbo, In-Hwan Oh, Andrew T Olagunju, Tinuke O Olagunju, Bolajoko Olubukunola Olusanya, Jacob Olusegun Olusanya, Obinna E Onwujekwe, Sr, Eyal Oren, Doris V V Ortega-Altamirano, Sr, Osayomwanbo Osarenotor, Frank B Osei, Sr, Mayowa O Owolabi, Mahesh P A, Sr, Jagadish Rao Padubidri, Smita Pakhale, Sangram Kishor Patel, Angel J Paternina-Caicedo, Sr, Ashish Pathak, Sr, George C Patton, Deepak Paudel, Sr, Kebreab Paulos, Sr, Veincent Christian Filipino Pepito, Alexandre Pereira, Norberto Perico, Aslam Pervaiz, Julia Moreira Pescarini, Bakhtiar Piroozi, Meghdad Pirsaheb, Maarten J Postma, Hadi Pourjafar, Farshad Pourmalek, Sr, Akram Pourshams, Hossein Poustchi, Sergio I Prada, Sr, Narayan Prasad, Liliana Preotescu, Hedley Quintana, Navid Rabiee, Amir Radfar, Alireza Rafiei, Fakher Rahim, Afarin Rahimi-Movaghar, Vafa Rahimi-Movaghar, Mohammad Hifz Ur Rahman, Muhammad Aziz Rahman, SHAFIUR Rahman, Fatemeh Rajati, Sr, Saleem Muhammad Rana, Sr, Chhabi Lal Ranabhat, Davide Rasella, David Laith Rawaf, Salman Rawaf, Sr, Lal Rawal, Wasiq Faraz Rawasia, Vishnu Renjith, Andre M N Renzaho, Sr, Serge Resnikoff, Sr, Melese Abate Reta, Negar Rezaei, Mohammad sadegh Rezai, Seyed Mohammad Riahi, Ana Isabel Ribeiro, Jennifer Rickard, Sr, Maria Rios-Blancas, Leonardo Roever, Luca Ronfani, Elias Merdassa Roro, Sr, Jennifer M Ross, Enrico Rubagotti, Salvatore Rubino, Anas M Saad, Yogesh Damodar Sabde, Siamak Sabour, Ehsan Sadeghi, Sr, Yahya Safari, Roya Safari-Faramani, Rajesh Sagar, Amirhossein Sahebkar, Mohammad Ali Sahraian, S Mohammad Sajadi, Mohammad Reza Salahshoor, Nasir Salam, Sr, Payman Salamati, Hosni Salem, Marwa R Rashad Salem I, Yahya Salimi, Hamideh Salimzadeh, Abdallah M Samy, Juan Sanabria, Sr, Milena M Santric-Milicevic, Bruno Piassi Sao Jose, Sivan Yegnanarayana Iyer Saraswathy, Kaushik Sarkar, Sr, Abdur Razzaque Sarker, Nizal Sarrafzadegan I, Benn Sartorius, Brijesh Sathian, Thirunavukkarasu Sathish, Monika Sawhney, Sonia Saxena, Sr, David C Schwebel, Sr, Anbissa Muleta Senbeta IV, Subramanian Senthilkumaran, Sadaf G Sepanlou, Edson Serván-Mori, Sr, Hosein Shabaninejad, Azadeh Shafieesabet, Sr, Masood Ali Shaikh, Ali S Shalash, Sr, Seifadin Ahmed Shallo, Mehran Shams-Beyranvand, MohammadBagher Shamsi, Morteza Shamsizadeh, Mohammed Shannawaz, Kiomars Sharafi, Hamid Sharifi, Hatem Samir Shehata, Sr, Aziz Sheikh, B Suresh Kumar Shetty, Sr, Kenji Shibuya, Sr, Wondimeneh Shibabaw Shiferaw, Sr, Desalegn Markos Shifti, Mika Shigematsu, Jae Il Shin, Rahman Shiri, Sr, Reza Shirkoohi, Soraya Siabani, Tariq Jamal Siddiqi, Diego Augusto Santos Silva, Ambrish Singh, Jasvinder A Singh, Narinder Pal Singh, Virendra Singh, Malede Mequanent Sisay, Eirini Skiadaresi, Mohammad Reza Sobhiyeh, Sr, Anton Sokhan, Shahin Soltani, Ranjani Somayaji, Moslem Soofi, Muluken Bekele Sorrie, Sr, Ireneous N Soyiri, Chandrashekhar T Sreeramareddy, Agus Sudaryanto, Mu'awiyyah Babale Sufiyan, Sr, Hafiz Ansar Rasul Suleria, Marufa Sultana, Bruno Fokas Sunguya, Bryan L Sykes, Rafael Tabarés-Seisdedos, Takahiro Tabuchi, Degena Bahrey Tadesse, Jr, Ingan Ukur Tarigan, Aberash Abay Tasew, Yonatal Mesfin Tefera, Sr, Merhawi Gebremedhin Tekle, Mohamad-Hani Temsah, Berhe Etsay Tesfay I, Fisaha Haile Haile Tesfay, Belay Tessema, Zemenu Tadesse Tessema, Kavumpurathu Raman Thankappan, Nihal Thomas, Alemayehu Toma Toma, Sr, Roman Topor-Madry, Marcos Roberto Roberto Tovani-Palone, Eugenio Traini, Bach Xuan Tran, Khanh Bao Tran, Irfan Ullah, Bhaskaran Unnikrishnan, Muhammad Shariq Usman, Sr, Benjamin S Chudi Uzochukwu, Sr, Pascual R Valdez, Santosh Varughese, Sr, Francesco S Violante, Sr, Sebastian Vollmer, Sr, Feleke Gebremeskel W/hawariat, Sr, Yasir Waheed, Mitchell Taylor Wallin, Yafeng Wang, Yuan-Pang Wang, Marcia Weaver, Bedilu Girma Weji, Girmay Teklay Weldesamuel, Catherine A Welgan, Andrea Werdecker, Ronny Westerman, Sr, Taweewat Wiangkham, Charles Shey Wiysonge, Sr, Haileab Fekadu Wolde, Sr, Dawit Zewdu Wondafrash, Tewodros Eshete Wonde, Sr, Getasew Taddesse Worku, Sr, Ai-Min Wu, Gelin Xu, Ali Yadollahpour, Seyed Hossein Yahyazadeh Jabbari, Tomohide Yamada, Sr, Hiroshi Yatsuya, Alex Yeshaneh, Christopher Sabo Yilgwan, Mekdes Tigistu Yilma, Paul Yip, Sr, Engida Yisma, Naohiro Yonemoto, Sr, Seok-Jun Yoon, Mustafa Z Younis, Mahmoud Yousefifard, Hebat-Allah Salah A Yousof, Chuanhua Yu, Hasan Yusefzadeh, Siddhesh Zadey, Zoubida Zaidi, Sojib Bin Zaman, Mohammad Zamani, Hamed Zandian, Nejimu Biza Zepro, Taddese Alemu Zerfu, Yunquan Zhang, Xiu-Ju George Zhao, Arash Ziapour, Sanjay Zodpey, Sr, Yves Miel H Zuniga, Simon I Hay, and Robert C Reiner, Jr

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods: We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000–17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. Findings: While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000–7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910–68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation: To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Funding: Bill & Melinda Gates Foundation.

Published
2020
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17. Caregiving and mental health among workers: Longitudinal evidence from a large cohort of adults in Thailand

Author

Vasoontara Yiengprugsawan, Liana Leach, Janneke Berecki-Gisolf, Hal Kendig, David Harley, Sam-ang Seubsman, and Adrian C Sleigh

Subjects
Public aspects of medicine, RA1-1270, Social sciences (General), H1-99
Abstract

Background: As people in middle and lower income countries live longer, more people become sick, disabled, and frail and the demand for family caregiving grows. Thailand faces such challenges. This study investigates the relationship between caregiving and mental health among workers drawn from a large longitudinal cohort of Thai adults. Methods: Participants were drawn from the Thai Health-Risk Transition Study, a cohort study since 2005 of distance-learning adult Open University students residing nationwide. Caregiving status and binary psychological distress outcome (score 19–30 on Kessler 6) were recorded in 2009 and 2013 among cohort members who were paid workers at both years (n=33,972). Multivariate logistic regression was used to estimate the relationship between four-year longitudinal caregiving status and psychological distress in 2013, adjusting for potential covariates. Results: Longitudinal analyses revealed the transitional nature of care with 25% exiting and 10% entering the caring role during the four-year follow-up. Based on multivariate logistic regression, 2009–2013 caregiving status was significantly associated with psychological distress. Cohort members transitioning into caregiving and those who were caregivers in both 2009 and 2013 had a higher risk for psychological distress than non-caregivers (Adjusted Odds Ratios 1.40 [1.02–1.96] and 1.64 [1.16–2.33], respectively). Conclusion: Our findings provide evidence on caregiving and associated risk for psychological distress among working Thais. This adds to the limited existing literature in middle-income countries and highlights the potential pressure among caregivers in balancing work and care while preserving their own mental health. Keywords: Carers, Caregivers, Mental health, Work and health, Longitudinal data, Cohort study, Thailand

Published
2016
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18. Searching for photon-sector Lorentz violation using gravitational-wave detectors

Author

V. Alan Kostelecký, Adrian C. Melissinos, and Matthew Mewes

Subjects
Physics, QC1-999
Abstract

We study the prospects for using interferometers in gravitational-wave detectors as tools to search for photon-sector violations of Lorentz symmetry. Existing interferometers are shown to be exquisitely sensitive to tiny changes in the effective refractive index of light occurring at frequencies around and below the microhertz range, including at the harmonics of the frequencies of the Earth's sidereal rotation and annual revolution relevant for tests of Lorentz symmetry. We use preliminary data obtained by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2006–2007 to place constraints on coefficients for Lorentz violation in the photon sector exceeding current limits by about four orders of magnitude.

Published
2016
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19. Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author

Bolajoko O. Olusanya, Adrian C. Davis, Donald Wertlieb, Nem-Yun Boo, M.K.C. Nair, Ricardo Halpern, Hannah Kuper, Cecilia Breinbauer, Petrus J de Vries, Melissa Gladstone, Neal Halfon, Vijaya Kancherla, Mphelekedzeni C. Mulaudzi, Angelina Kakooza-Mwesige, Felix A. Ogbo, Jacob O. Olusanya, Andrew N. Williams, Scott M. Wright, Helena Manguerra, Alison Smith, Michelle Echko, Chad Ikeda, Angela Liu, Anoushka Millear, Katherine Ballesteros, Emma Nichols, Holly E. Erskine, Damian Santomauro, Zane Rankin, Mari Smith, Harvey A. Whiteford, Helen E. Olsen, and Nicholas J. Kassebaum

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The Sustainable Development Goals (SDGs) mandate systematic monitoring of the health and wellbeing of all children to achieve optimal early childhood development. However, global epidemiological data on children with developmental disabilities are scarce. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 provides a comprehensive assessment of prevalence and years lived with disability (YLDs) for development disabilities among children younger than 5 years in 195 countries and territories from 1990 to 2016. Methods: We estimated prevalence and YLDs for epilepsy, intellectual disability, hearing loss, vision loss, autism spectrum disorder, and attention deficit hyperactivity disorder. YLDs were estimated as the product of the prevalence estimate and the disability weight for each mutually exclusive disorder, corrected for comorbidity. We used DisMod-MR 2.1, a Bayesian meta-regression tool, on a pool of primary data derived from systematic reviews of the literature, health surveys, hospital and claims databases, cohort studies, and disease-specific registries. Findings: Globally, 52·9 million (95% uncertainty interval [UI] 48·7–57·3; or 8·4% [7·7–9·1]) children younger than 5 years (54% males) had developmental disabilities in 2016 compared with 53·0 million (49·0–57·1; or 8·9% [8·2–9·5]) in 1990. About 95% of these children lived in low-income and middle-income countries. YLDs among these children increased from 3·8 million (95% UI 2·8–4·9) in 1990 to 3·9 million (2·9–5·2) in 2016. These disabilities accounted for 13·3% of the 29·3 million YLDs for all health conditions among children younger than 5 years in 2016. Vision loss was the most prevalent disability, followed by hearing loss, intellectual disability, and autism spectrum disorder. However, intellectual disability was the largest contributor to YLDs in both 1990 and 2016. Although the prevalence of developmental disabilities among children younger than 5 years decreased in all countries (except for North America) between 1990 and 2016, the number of children with developmental disabilities increased significantly in sub-Saharan Africa (71·3%) and in North Africa and the Middle East (7·6%). South Asia had the highest prevalence of children with developmental disabilities in 2016 and North America had the lowest. Interpretation: The global burden of developmental disabilities has not significantly improved since 1990, suggesting inadequate global attention on the developmental potential of children who survived childhood as a result of child survival programmes, particularly in sub-Saharan Africa and south Asia. The SDGs provide a framework for policy and action to address the needs of children with or at risk of developmental disabilities, particularly in resource-poor countries. Funding: The Bill & Melinda Gates Foundation.

Published
2018
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20. Modelling of the workpiece geometry effects on Ti–6Al–4V linear friction welds

Author

Anthony R. McAndrew, Paul A. Colegrove, Adrian C. Addison, Bertrand C.D. Flipo, Michael J. Russell, and Lucie A. Lee

Subjects
Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Linear friction welding (LFW) is a solid-state joining process that is finding increasing interest from industry for the fabrication of titanium alloy (Ti–6Al–4V) preforms. Currently, the effects of the workpiece geometry on the thermal fields, material flow and interface contaminant removal during processing are not fully understood. To address this problem, two-dimensional (2D) computational models were developed using the finite element analysis (FEA) software DEFORM and validated with experiments. A key finding was that the width of the workpieces in the direction of oscillation (in-plane width) had a much greater effect on the experimental weld outputs than the cross-sectional area. According to the validated models, a decrease of the in-plane width increased the burn-off rate whilst decreasing the interface temperature, TMAZ thickness and the burn-off required to remove the interface contaminants from the weld into the flash. Furthermore, the experimental weld interface consisted of a Widmanstätten microstructure, which became finer as the in-plane width was reduced. These findings have significant, practical benefits and may aid industrialisation of the LFW process. Keywords: Linear friction welding, Modelling, Titanium

Published
2015
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22. Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice

Author

Adrian C. Lo, Zsuzsanna Callaerts-Vegh, Ana F. Nunes, Cecília M.P. Rodrigues, and Rudi D'Hooge

Subjects
Alzheimer's disease, APP/PS1, TUDCA, Learning and memory, Morris water maze, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by extracellular Aβ1–42 containing plaques, and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory deficits and cognitive disabilities start to occur as these hallmarks affect hippocampus and frontal cortex, regions highly involved in memory. Connective tissue growth factor (CTGF) expression, which is high in the vicinity of Aβ plaques and NFTs, was found to influence γ-secretase activity, the molecular crux in Aβ1–42 production. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that downregulates CTGF expression in hepatocytes and has been shown to possess therapeutic efficacy in neurodegenerative models. To investigate the possible in vivo therapeutic effects of TUDCA, we provided 0.4% TUDCA-supplemented food to APP/PS1 mice, a well-established AD mouse model. Six months of TUDCA supplementation prevented the spatial, recognition and contextual memory defects observed in APP/PS1 mice at 8 months of age. Furthermore, TUDCA-supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid deposition. These effects of TUDCA supplementation suggest a novel mechanistic route for Alzheimer therapeutics.

Published
2013
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23. Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease

Author

Peter Lohse, Sylke Maas, Pia Lohse, Adrian C. Sewell, Otto P. van Diggelen, and Dietrich Seidel

Subjects
lipid metabolism, lysosomal acid lipase, enzyme deficiency, genotype, mutation analysis, Biochemistry, QD415-436
Abstract

Human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) is essential for the intralysosomal metabolism of cholesteryl esters and triglycerides taken up by receptor-mediated endocytosis of lipoprotein particles. The key role of the enzyme in intracellular lipid homeostasis is illustrated by two lysosomal storage diseases inherited as autosomal recessive traits. Wolman disease, associated with deficient hLAL activity, leads to massive intracellular substrate accumulation and is always fatal in early infancy. Cholesteryl ester storage disease (CESD), in contrast, is characterized by very low levels of enzymic activity sufficient to allow survival of the affected patients into adulthood. In order to elucidate the underlying molecular defects in Wolman disease, we have characterized the hLAL gene in two female Wolman patients of German and Turkish origin by SSCP and DNA sequence analysis. Our results demonstrate that the German proband was compound heterozygous for an 8-bp deletion in exon 3 and a 2-bp deletion in exon 4 of the hLAL gene. These frameshift mutations lead to protein truncation at amino acid positions 24 and 116 and to complete loss of hydrolytic activity. The Turkish proband, in contrast, was homozygous for a G1064→T substitution in exon 10 of the hLAL gene which converts the completely conserved glycine (GGG) residue at position 321 of the mature enzyme to tryptophan (TGG). In vitro expression of the hLAL(Gly321→Trp) cDNA construct revealed that the amino acid replacement results in a more than 99% reduction of neutral lipid hydrolysis. The mutations provide new insights into the molecular basis of Wolman disease which is apparently more heterogeneous at the genetic level than cholesteryl ester storage disease.—Lohse, P., S. Maas, P. Lohse, A. C. Sewell, O. P. van Diggelen, and D. Seidel. Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease. J. Lipid Res. 1999. 40: 221–228.

Published
1999
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24. Accelerating topical formulation development for inflammatory \ud dermatoses; an ex vivo human skin culture model consistent with \ud clinical therapeutics

Author

Neil, Jessica E., Brown, Marc B., Lenn, Jon D., and Williams, Adrian C.

Abstract

Although animal models have been extensively used to evaluate human topical therapeutics, they exhibit marked physiological differences to human skin. Our objective was to develop a human ex vivo skin culture model to explore the pathophysiology of inflammatory dermatoses and for preclinical testing of potential therapeutic treatments. Ex vivo skin barrier integrity and metabolic activity was retained for 5 days and stimulation of T-helper cells (Th1), which produce proinflammatory cytokines, provided inflammatory responses similar to those reported from in vivo biopsy. Tissue responses to established therapies of pimecrolimus (Elidel) and clobetasol propionate (Dermovate) were evaluated using the human ex vivo skin culture, assessing pharmacodynamic changes in gene expression alongside the pharmacokinetics of drug penetration with both products showing time dependent efficacies. The translational utility of the human ex vivo skin culture model of inflammatory dermatoses was demonstrated through comparison with an in vivo clinical study, with similar reductions in inflammatory gene expression recorded for both drug treatments. Thus, this model can reduce, replace or refine animal testing and also mitigate the risk of failure in costly and time-consuming clinical trials associated with novel topical therapeutic development.

Published
2022

25. A new ex vivo skin model for mechanistic understanding of putative anti-inflammatory topical therapeutics

Author

M S, Jessica E Neil, Jon D, Lenn, Marc B, Brown, and Adrian C, Williams

Subjects
Anti-Inflammatory Agents, Humans, Psoriasis, Pharmaceutical Science, Dermatitis, Epidermis, Skin
Abstract

Several in vitro models have been designed as test systems for inflammatory skin conditions, commonly using cell-culture or reconstructed human epidermis approaches. However, these systems poorly recapitulate the physiology and, importantly, the metabolism and biochemical activity of skin in vivo, whereas ex vivo skin culture models can retain these features of the tissue. Our objective was to develop a human ex vivo skin culture model to explore the pathophysiology of inflammatory dermatoses and for preclinical testing of potential therapeutic treatments. Following exogenous stimulation, tissue integrity and ability to induce inflammatory gene expression was retained, and stimulant concentrations and duration was optimised to mimic published data from inflammatory clinical biopsies of dermatitis and psoriasis patients. The validity and utility of the model was demonstrated when challenged with 5 drugs including a corticosteroid and vitamin D3 analogue, where inflammatory biomarkers were regulated in a manner consistent with the drugs' reported in vivo mechanisms of action. This model retains important inflammatory gene signals observed in human inflammatory dermatoses for preclinical evaluation of novel therapeutics.

Published
2022

26. Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgeryCentral MessagePerspective

Author

Nigel E. Drury, PhD, FRCS(CTh), Carin van Doorn, MD, FRCS(CTh), Rebecca L. Woolley, MSc, Rebecca J. Amos-Hirst, MSc, Rehana Bi, BSc(Hons), Collette M. Spencer, BSc(Hons), Kevin P. Morris, MD, FRCPCH, James Montgomerie, MD, FRCA, John Stickley, BSc, Adrian Crucean, MD, Alicia Gill, MSc, Matt Hill, MSc, Ralf J.M. Weber, PhD, Lukas Najdekr, PhD, Andris Jankevics, PhD, Andrew D. Southam, PhD, Gavin R. Lloyd, PhD, Osama Jaber, MD, Imre Kassai, PhD, Giuseppe Pelella, MD, Natasha E. Khan, MD, FRCS(CTh), Phil Botha, PhD, FRCS(CTh), David J. Barron, MD, FRCS(CTh), Melanie Madhani, PhD, Warwick B. Dunn, PhD, Natalie J. Ives, MSc, Paulus Kirchhof, MD, Timothy J. Jones, MD, FRCS(CTh), Edmund D. Carver, Alistair J. Cranston, Fraser Harban, Vasco Laginha Rolo, Ritchie Marcus, Anthony Moriarty, Raju Reddy, Susanna N. Ritchie-McLean, Monica A. Stokes, Ayngara Thillaivasan, Nandlal Bhatia, Carol Bodlani, Wendy Lim, Joe Mellor, and Jutta Scheffczik

Subjects
clinical trial, cyanosis, myocardial protection, pediatric cardiac surgery, remote ischemic preconditioning, tetralogy of Fallot, Diseases of the circulatory (Cardiovascular) system, RC666-701, Surgery, RD1-811
Abstract

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Published
2024
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27. Cannabigerol as an anti-inflammatory agent altering the level of arachidonic acid derivatives in the colon tissue of rats subjected to a high-fat high-sucrose diet

Author

Klaudia Sztolsztener, Ewa Harasim-Symbor, Adrian Chabowski, and Karolina Konstantynowicz-Nowicka

Subjects
Cannabigerol, Inflammation, High-fat high-sucrose diet, Colon, Therapeutics. Pharmacology, RM1-950
Abstract

Fat and sugar overconsumption is the cause of increasing worldwide incidence of gastrointestinal tract in inflammatory conditions. The intestinal pre-inflammatory alterations are partially reversible, simultaneously inhibiting the predisposition to colitis. Searching for an effective pharmacotherapy for treating inflammatory conditions in the intestine is essential. This study aimed to investigate the effect of cannabigerol (CBG) on the inflammation state in the colon tissue of rats subjected to high-caloric diet. The experiment was conducted on male Wistar rats subjected to a standard or a high-fat high-sucrose diets for six weeks. For the last 14 days, half of rats from both groups received intragastrically cannabigerol solution (30 mg/kg of body mass). The ratio of n-6/n-3 PUFA, the activity of n-6 and n-3 PUFA, and arachidonic acid (AA) content in selected lipid fractions were determined by gas-liquid chromatography. Immunoblotting examined the expression of proteins involved in inflammation development. ELISA kits measured the content of arachidonic acid derivatives. CBG treatment reduced the n-6/n-3 PUFA ratio in TAG fraction and increased the n-3 PUFA pathway activity in almost all lipid fractions. Cannabigerol supplementation decreased AA concentration in PL and TAG. CBG also caused diminishments in the expression of cPLA2, COX-1, COX-2, and 12/15-LOX, which was indirectly correlated with a decreased LTB4 level and an increased LXA4 level. We concluded that cannabigerol has a protective influence on the development of inflammation in the colon tissue under lipid and sugar overload condition, thereby favoring cancer initiation and progression.

Published
2024
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28. Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data – The European Joint Programme HBM4EU

Author

Romuald Tagne-Fotso, Margaux Riou, Abdessattar Saoudi, Abdelkrim Zeghnoun, Hanne Frederiksen, Tamar Berman, Parisa Montazeri, Anna-Maria Andersson, Laura Rodriguez-Martin, Agneta Akesson, Marika Berglund, Pierre Biot, Argelia Castaño, Marie-Aline Charles, Emmanuelle Cocco, Elly Den Hond, Marie-Christine Dewolf, Marta Esteban-Lopez, Liese Gilles, Eva Govarts, Cedric Guignard, Arno C. Gutleb, Christina Hartmann, Tina Kold Jensen, Gudrun Koppen, Tina Kosjek, Nathalie Lambrechts, Rosemary McEachan, Amrit K. Sakhi, Janja Snoj Tratnik, Maria Uhl, Jose Urquiza, Marina Vafeiadi, An Van Nieuwenhuyse, Martine Vrijheid, Till Weber, Cécile Zaros, Elena Tarroja-Aulina, Lisbeth E. Knudsen, Adrian Covaci, Robert Barouki, Marike Kolossa-Gehring, Greet Schoeters, Sebastien Denys, Clemence Fillol, and Loïc Rambaud

Subjects
HBM4EU, Human biomonitoring (HBM), Bisphenol A (BPA), Human exposure, Vulnerable population, Standardized procedures, Environmental sciences, GE1-350
Abstract

Background: Bisphenol A (BPA; or 4,4′-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. Objective: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18–73 years (n = 4,226) and its determinants. Methods: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. Results: Total BPA was quantified in 85–100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA’s BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. Conclusion: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Published
2024
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29. Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study

Author

Anteneh Desalegn, Tessa Schillemans, Eleni Papadopoulou, Amrit K. Sakhi, Line S. Haug, Ida Henriette Caspersen, Andrea Rodriguez-Carrillo, Sylvie Remy, Greet Schoeters, Adrian Covaci, Michelle Laeremans, Mariana F Fernández, Susana Pedraza-Diaz, Tina Kold Jensen, Hanne Frederiksen, Agneta Åkesson, Bianca Cox, Shereen Cynthia D’Cruz, Loïc Rambaud, Margaux Riou, Marike Kolossa-Gehring, Antje Gerofke, Aline Murawski, Nina Vogel, Catherine Gabriel, Spyros Karakitsios, Nafsika Papaioannou, Dimosthenis Sarigiannis, Fabio Barbone, Valentina Rosolen, Sanna Lignell, Anna Karin Lindroos, Janja Snoj Tratnik, Anja Stajnko, Tina Kosjek, Žiga Tkalec, Lucia Fabelova, Lubica Palkovicova Murinova, Branislav Kolena, Sona Wimmerova, Tamás Szigeti, Szilvia Középesy, Annick van den Brand, Jan-Paul Zock, Beata Janasik, Wojciech Wasowicz, Annelies De Decker, Stefaan De Henauw, Eva Govarts, and Nina Iszatt

Subjects
Environmental sciences, GE1-350
Abstract

Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs

Published
2024
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30. Energy flexibility quantification of a tropical net-zero office building using physically consistent neural network-based model predictive control

Author

Wei Liang, Han Li, Sicheng Zhan, Adrian Chong, and Tianzhen Hong

Subjects
Grid-interactive efficient buildings, Energy flexibility, PV and BESS, Model predictive control (MPC), Physics-informed neural network (PINN), Energy industries. Energy policy. Fuel trade, HD9502-9502.5
Abstract

Building energy flexibility plays a critical role in demand-side management for reducing utility costs for building owners and sustainable, reliable, and smart grids. Realizing building energy flexibility in tropical regions requires solar photovoltaics and energy storage systems. However, quantifying the energy flexibility of buildings utilizing such technologies in tropical regions has yet to be explored, and a robust control sequence is needed for this scenario. Hence, this work presents a case study to evaluate the building energy flexibility controls and operations of a net-zero energy office building in Singapore. The case study utilizes a data-driven energy flexibility quantification workflow and employs a novel data-driven model predictive control (MPC) framework based on the physically consistent neural network (PCNN) model to optimize the building energy flexibility. To the best of our knowledge, this is the first instance that PCNN is applied to a mathematical MPC setting, and the stability of the system is formally proved. Three scenarios are evaluated and compared: the default regulated flat tariff, a real-time pricing mechanism, and an on-site battery energy storage system (BESS). Our findings indicate that incorporating real-time pricing into the MPC framework could be more beneficial to leverage building energy flexibility for control decisions than the flat-rate approach. Moreover, adding BESS to the on-site PV generation improved the building self-sufficiency and the PV self-consumption by 17% and 20%, respectively. This integration also addresses model mismatch issues within the MPC framework, thus ensuring a more reliable local energy supply. Future research can leverage the proposed PCNN-MPC framework for different data-driven energy flexibility quantification types.

Published
2024
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31. Evaluation of the photocatalytic activity of ZnO nanorods and nanoflowers grown from seed layers deposited by spin coating

Author

Antonia del Rocío López Guemez, Adrián Cordero García, José Luis Cervantes López, Hermicenda Pérez Vidal, and Laura Lorena Díaz Flores

Subjects
Óxido de zinc, Sol-gel, Crecimiento hidrotermal, Nanoestructuras, Fotocatálisis, Clay industries. Ceramics. Glass, TP785-869
Abstract

The increase in pollution, using photocatalytic materials to degrade organic pollutants remains in force. ZnO is the most used semiconductors for photocatalytic applications. The oriented growth of nanostructures on substrates or seed layers (SL) improves the physical and chemical properties compared to the bulk-grown material. In this work, the photocatalytic efficiency of ZnO nanorods and nanoflowers was evaluated, obtained by hydrothermal growth (HG) over SL deposited by the spin-coating technique (SCT). The characterizations results showed two types of growth: 1D nanostructures with a dimension in the range of 400–1000 nm and diameters of 70–100 nm, and 1D microstructures with approximate 5–11 μm length and diameters of 1–2 μm. However, in the 7 SL system, micro prisms were generated, which led to the formation of 3D nanostructures (micro flowers) of ZnO with a maximum of 6 μm in diameter. The system with 1D and 3D ZnO nanostructures, grown in 7 SL, was the most efficient methylene blue degradation. Achieving 100% transformation in 120 min, with a rate constant of 2.98 × 10−2 min−1. The results show that the SCT deposit combined with the sol–gel method and HG produces 1D and 3D structures with high potential in photocatalytic degradation. Resumen: El aumento de la contaminación, el empleo de materiales fotocatalíticos para degradar contaminantes orgánicos continúa vigente. El óxido de zinc (ZnO) es el semiconductor más utilizado para aplicaciones fotocatalíticas. El crecimiento orientado de nanoestructuras sobre capas semillas (SL) mejora las propiedades físicas y químicas comparado con el material crecido en bulto. En este trabajo se evaluó la eficiencia fotocatalítica de nanovarillas y nanoflores de ZnO obtenidas por crecimiento hidrotérmico (HG) sobre SL depositadas por la técnica spin coating (SCT). Los resultados de las caracterizaciones mostraron dos tipos de crecimiento: nanoestructuras 1D con dimensiones en el rango de 400 a 1.000 nm y diámetros de 70 a 100 nm, y microestructuras 1D con longitud aproximada de 5 a 11 μm y diámetros de 1 a 2 μm. Sin embargo, en el sistema de 7 SL se generaron microprismas orientados, generando nanoestructuras 3D (microflores) con un diámetro máximo de 6 μm. Este sistema fue el más eficiente en la degradación de azul de metileno. Degradando de 100% en 120 min, con una constante de velocidad de 2,98 x 10-2 min-1. Los resultados indican que la SCT combinada con el método sol-gel y el HG produce estructuras 1D y 3D con alto potencial de degradación fotocatalítica.

Published
2024
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32. Understanding the temperature induced aggregation of silica nanoparticles decorated with temperature-responsive polymers: can a small step in the chemical structure make a giant leap for a phase transition?

Author

Mansfield, Edward D. H., Filippov, Sergey K., de la Rosa, Victor R., Cook, Michael T., Grillo, Isabelle, Hoogenboom, Richard, Williams, Adrian C., and Khutoryanskiy, Vitaliy V.

Abstract

Temperature-responsive nanomaterials have gained increasing interest over the past decade due their ability to undergo conformational changes in situ, in response to a change in temperature. One class of temperature-responsive polymers are those with lower critical solution temperature, which phase separate in aqueous solution above a critical temperature. When these temperature-responsive polymers are grafted to a solid nanoparticle, a change in their surface properties occurs above this critical temperature, from hydrophilic to more hydrophobic, giving them a propensity to aggregate. This study explores the temperature induced aggregation of silica nanoparticles functionalised with two isomeric temperature-responsive polymers with lower critical solution temperature (LCST) behavior, namely poly(N-isopropyl acrylamide) (PNIPAM), and poly(2-n-propyl-2-oxazoline) (PNPOZ) with similar molecular weights (5000 Da) and grafting density. These nanoparticles exhibited striking differences in the temperature of aggregation, which is consistent with LCST of each polymer. Using a combination of small-angle neutron scattering (SANS) and dynamic light scattering (DLS), we probed subtle differences in the aggregation mechanism for PNIPAM- and PNPOZ-decorated silica nanoparticles. The nanoparticles decorated with PNIPAM and PNPOZ show similar aggregation mechanism that was independent of polymer structure, whereby aggregation starts by the formation of small aggregates. A further increase in temperature leads to interaction between these aggregates and results in full-scale aggregation and subsequent phase separation.

Published
2021

33. Codon-Optimization of Wild-Type Adeno-Associated Virus Capsid Sequences Enhances DNA Family Shuffling while Conserving Functionality

Author

Kimberley L. Dilworth, Adrian J. Thrasher, Arkadiusz Rybicki, Claus V. Hallwirth, Anais K. Amaya, Adrian C. Filip, Leszek Lisowski, Jason Ward, Sophia H.Y. Liao, Ian E. Alexander, Samantha L. Ginn, Patrick Wilmott, Hiroyuki Nakai, Giorgia Santilli, Marti Cabanes-Creus, and Adrian Westhaus

Subjects
0301 basic medicine, lcsh:QH426-470, viruses, Computational biology, Biology, medicine.disease_cause, DNA sequencing, Article, codon optimization, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetics, medicine, capsid, directed evolution, lcsh:QH573-671, Molecular Biology, Adeno-associated virus, DNA shuffling, Shuffling, lcsh:Cytology, library, AAV, Directed evolution, lcsh:Genetics, 030104 developmental biology, chemistry, Capsid, 030220 oncology & carcinogenesis, Codon usage bias, Molecular Medicine, DNA
Abstract

Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human gene therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with the aim of developing novel variants with enhanced tropism for specific human cell types, decreased human seroreactivity, and increased manufacturability. Selection strategies based on directed evolution rely on the generation of highly variable AAV capsid libraries using methods such as DNA-family shuffling, a technique reliant on stretches of high DNA sequence identity between input parental capsid sequences. This identity dependence for reassembly of shuffled capsids is inherently limiting and results in decreased shuffling efficiency as the phylogenetic distance between parental AAV capsids increases. To overcome this limitation, we have developed a novel codon-optimization algorithm that exploits evolutionarily defined codon usage at each amino acid residue in the parental sequences. This method increases average sequence identity between capsids, while enhancing the probability of retaining capsid functionality, and facilitates incorporation of phylogenetically distant serotypes into the DNA-shuffled libraries. This technology will help accelerate the discovery of an increasingly powerful repertoire of AAV capsid variants for cell-type and disease-specific applications. Keywords: AAV, library, directed evolution, codon optimization, DNA shuffling, capsid

Published
2019

34. Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review

Author

Adrian C Traeger, Mary O'Keeffe, Christopher G. Maher, and Giovanni E Ferreira

Subjects
musculoskeletal diseases, medicine.medical_specialty, Patients, Physical Therapy, Sports Therapy and Rehabilitation, Interpersonal communication, Positive perception, 03 medical and health sciences, 0302 clinical medicine, Professional Role, health services administration, medicine, Medical Staff, Hospital, Humans, 030212 general & internal medicine, Emergency Treatment, health care economics and organizations, business.industry, lcsh:RM1-950, Exercise therapy, Emergency department, Pain management, Physical Therapists, lcsh:Therapeutics. Pharmacology, Family medicine, Physical therapy, Thematic analysis, business, Emergency Service, Hospital, human activities, 030217 neurology & neurosurgery, Qualitative research, Patient education
Abstract

Question: What are staff and patients’ perceptions of physiotherapists working in the emergency department (ED)? Design: Systematic review of qualitative studies. Participants: Staff working in EDs and patients presenting to the ED and managed by ED physiotherapists. Outcome measures: Perceptions of ED staff and patients were synthesised using a three-stage thematic analysis consisting of extraction, grouping (codes), and abstraction of findings. Results: Eight studies, which had sought the perceptions of 138 patients and 122 ED staff members, were included. Three main themes emerged: role of physiotherapists in the ED, positive perceptions of ED physiotherapists, and concerns about physiotherapists in the ED. Patients and ED staff both considered physiotherapists to be experts in musculoskeletal care. The role of ED physiotherapists was seen as providing thorough patient education, non-pharmacological pain management and activity resumption, especially through exercise therapy. Having broad knowledge to assess and treat different health conditions was seen as facilitating the work of physiotherapists in the ED. Patients and ED staff felt that ED physiotherapists had good interpersonal communication skills. ED staff expressed concerns regarding the additional time that physiotherapists spent with patients. Some patients felt that performing exercises in the ED was inappropriate and painful. Conclusions: ED physiotherapists were mostly well accepted by patients and ED staff, and their work was perceived to improve the ED. Concerns included restricted availability, lack of awareness of the role undertaken by physiotherapists in the ED, and increased treatment time in some settings. [Ferreira GE, Traeger AC, O’Keeffe M, Maher CG (2018) Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review. Journal of Physiotherapy 64: 229–236] Key words: Emergency department, Physical therapy specialty, Emergency medicine, Primary contact physical therapy, Musculoskeletal pain

Published
2018

35. Hearing loss prevalence and years lived with disability, 1990–2019: findings from the Global Burden of Disease Study 2019

Author

Haile, Lydia M., Kamenov, Kaloyan, Briant, Paul S., Orji, Aislyn U., Steinmetz, Jaimie D., Pardhan, Shahina, GBD 2019 Hearing Loss Collaborators, Murray, Christopher J. L., Davis, Adrian C. J., Vos, Theo, and Chadha, Shelly

Subjects
otorhinolaryngologic diseases
Abstract

Background:\ud Hearing loss affects access to spoken language, which can affect cognition and development, and can negatively affect social wellbeing. We present updated estimates from the Global Burden of Disease (GBD) study on the prevalence of hearing loss in 2019, as well as the condition's associated disability.\ud Methods:\ud We did systematic reviews of population-representative surveys on hearing loss prevalence from 1990 to 2019. We fitted nested meta-regression models for severity-specific prevalence, accounting for hearing aid coverage, cause, and the presence of tinnitus. We also forecasted the prevalence of hearing loss until 2050.\ud Findings:\ud An estimated 1·57 billion (95% uncertainty interval 1·51–1·64) people globally had hearing loss in 2019, accounting for one in five people (20·3% [19·5–21·1]). Of these, 403·3 million (357·3–449·5) people had hearing loss that was moderate or higher in severity after adjusting for hearing aid use, and 430·4 million (381·7–479·6) without adjustment. The largest number of people with moderate-to-complete hearing loss resided in the Western Pacific region (127·1 million people [112·3–142·6]). Of all people with a hearing impairment, 62·1% (60·2–63·9) were older than 50 years. The Healthcare Access and Quality (HAQ) Index explained 65·8% of the variation in national age-standardised rates of years lived with disability, because countries with a low HAQ Index had higher rates of years lived with disability. By 2050, a projected 2·45 billion (2·35–2·56) people will have hearing loss, a 56·1% (47·3–65·2) increase from 2019, despite stable age-standardised prevalence.\ud Interpretation:\ud As populations age, the number of people with hearing loss will increase. Interventions such as childhood screening, hearing aids, effective management of otitis media and meningitis, and cochlear implants have the potential to ameliorate this burden. Because the burden of moderate-to-complete hearing loss is concentrated in countries with low health-care quality and access, stronger health-care provision mechanisms are needed to reduce the burden of unaddressed hearing loss in these settings.

Published
2021

36. Thiolated and PEGylated silica nanoparticle delivery to hair follicles

Author

Vitaliy V. Khutoryanskiy, Jamila H. Al Mahrooqi, and Adrian C. Williams

Subjects
Swine, Skin Absorption, Pharmaceutical Science, Nanoparticle, 02 engineering and technology, 030226 pharmacology & pharmacy, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, Drug Delivery Systems, 0302 clinical medicine, PEG ratio, Stratum corneum, medicine, Animals, Maleimide, Acne, Skin, integumentary system, Penetration (firestop), Silicon Dioxide, 021001 nanoscience & nanotechnology, medicine.disease, medicine.anatomical_structure, chemistry, Drug delivery, Biophysics, PEGylation, Nanoparticles, 0210 nano-technology, Hair Follicle
Abstract

Targeting drug delivery to hair follicles is valuable to treat conditions such as alopecia’s and acne, and this shunt route may also allow drug delivery to deeper skin layers and the systemic circulation by avoiding the intact stratum corneum. Here, we investigated the effects of nanoparticle surface chemistry on their delivery into hair follicles by synthesizing fluorescent thiolated silica nanoparticles and functionalizing with 750 Da and 5000 Da methoxypolyethylene glycol maleimide (PEG). The stability of the nanoparticles in skin homogenate was verified before tape stripping of porcine-dosed tissue showed the distribution of the free fluorescent dye and different nanoparticles in the skin. Analysis of microscopic images of the skin sections revealed penetration of nanoparticles functionalized with PEG into the appendages whereas thiolated nanoparticles stayed on the surface of the skin and were removed by tape stripping. Nanoparticles functionalized with PEG 5000 Da penetrated deeper into the hair follicles compared to counterparts functionalized with PEG 750 Da. PEGylation can thus enhance targeted delivery of nanoparticulates into hair follicles.

Published
2021

37. Enhancing neonatal thoracoscopic surgical training with rabbit model

Author

Adrian Chi Heng Fung, Patrick Ho Yu Chung, Ivy Hau Yee Chan, Eugene Chin Tung Lau, Jana Yim Hung Wo, and Kenneth Kak Yuen Wong

Subjects
Thoracoscopic, Neonatal surgery, Surgical training, Animal surgery, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: Thoracoscopy, which has an increasing role in the treatment of indexed neonatal surgical conditions, requires adequate training. To support this, the current study aimed to evaluate the feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons. Methods: Following didactic lectures and demonstrations, the participants were given hands-on opportunities to perform thoracoscopic procedures. The feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons were evaluated with pre-/post-course procedural confidence scores and a questionnaire. Results: This study included 13 paediatric surgeons—2 (15 %) males and 11 (85 %) females—who were evenly distributed. There were four basic surgical trainees, five higher surgical trainees and four fellows in paediatric surgery (mean surgical practice experience: 4.5 ± 3.7 years). Most had experience assisting paediatric (70 %) and neonatal (62 %) thoracoscopic surgery. Only 30 % had experience as the chief surgeon of paediatric thoracoscopic surgery, with none on neonates. Significant improvement was seen in procedural confidence as the assistant and chief surgeon of all procedures post-workshop. The surgeons rated the model positively. Conclusion: The procedural confidence level of paediatric surgeons improved significantly after workshop participation. This realistic and easily reproducible model can help perfect thoracoscopic skills. Therefore, its integration into paediatric surgical training would promote surgical skill proficiency and could improve surgeons’ confidence in neonate operations.

Published
2024
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38. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
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39. Residential energy transition and chronic respiratory diseases

Author

Hongcheng Wei, Qiurun Yu, Danrong Chen, Mingzhi Zhang, Quanquan Guan, Bo Hang, Antoine M. Snijders, Adrian Covaci, and Yankai Xia

Subjects
Science (General), Q1-390
Abstract

Obtaining clean energy is of prime importance for planetary health and sustainable development. We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases. Using data from the Global Health Observatory and Global Burden of Diseases, Injuries, and Risk Factors Study, we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale. In the China Health and Retirement Longitudinal Study, we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use, residential energy transition, duration of solid fuel use, and the risk of chronic respiratory diseases. Despite great progress, huge disparities in access to clean energy persist globally. Residential energy transition was associated with a lower risk of chronic respiratory diseases. In the period of 2011–2013, compared with persistent solid fuel users, both participants who switched from solid to clean fuels (adjusted risk ratio [RR] 0.78, 95% confidence interval [CI] 0.62–0.98) and persistent clean fuel users (adjusted RR 0.71, 95% CI 0.57–0.89) had significantly lower risk of chronic respiratory diseases (p

Published
2024
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40. Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients

Author

Lucas Panneel, Paulien Cleys, Giulia Poma, Yu Ait Bamai, Philippe G. Jorens, Adrian Covaci, and Antonius Mulder

Subjects
Endocrine disrupting chemicals, Neonatal exposome, Neonatal intensive care unit, Plastic medical devices, Premature neonates, Environmental sciences, GE1-350
Abstract

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4–10 samples per patient) born at

Published
2024
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41. Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment

Author

Žiga Tkalec, Jean-Philippe Antignac, Nicole Bandow, Frederic M. Béen, Lidia Belova, Jos Bessems, Bruno Le Bizec, Werner Brack, German Cano-Sancho, Jade Chaker, Adrian Covaci, Nicolas Creusot, Arthur David, Laurent Debrauwer, Gaud Dervilly, Radu Corneliu Duca, Valérie Fessard, Joan O. Grimalt, Thierry Guerin, Baninia Habchi, Helge Hecht, Juliane Hollender, Emilien L. Jamin, Jana Klánová, Tina Kosjek, Martin Krauss, Marja Lamoree, Gwenaelle Lavison-Bompard, Jeroen Meijer, Ruth Moeller, Hans Mol, Sophie Mompelat, An Van Nieuwenhuyse, Herbert Oberacher, Julien Parinet, Christof Van Poucke, Robert Roškar, Anne Togola, Jurij Trontelj, and Elliott J. Price

Subjects
High-resolution mass spectrometry, Effect-based methods, Sampling strategies, Chemical exposure, Chemical risk assessment, Effect-directed analysis, Environmental sciences, GE1-350
Abstract

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

Published
2024
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42. Predicting differences in angler beliefs, threat perceptions, and actions in British Columbia's rainbow trout and steelhead fisheries

Author

Shannon D. Bower, Amanda Jeanson, Jessica A. Robichaud, Morgan L. Piczak, Nathan Young, Adrian Clarke, Andy J. Danylchuk, and Steven J. Cooke

Subjects
Fish conservation, Rainbow trout, Recreational fisheries, Steelhead, Threat perception, Environmental sciences, GE1-350
Abstract

Anglers are a diverse population whose behaviours and perspectives are influenced by a myriad of factors including knowledge, expertise, management actions, and regulations. We examine similarities and differences in behaviours and perspectives amongst freshwater anglers of rainbow trout and steelhead (Oncorhynchus mykiss) in British Columbia, Canada, using an online survey. Findings from the survey suggest that subgroups or “types” of anglers are identifiable by differences in their behaviours and perspectives according to geographic area, gear type, fishery, and frequency of fishing activities. Our results indicate that angler types share many of the same motivations for engaging in fishing behaviours and similar concerns regarding threats to their preferred fishery; however, differences were evident across types of issues related to angler behaviour, as well as views on fisheries management. Overall, we argue that understanding fishery-scale angler heterogeneity can benefit fisheries management by highlighting areas of agreement and disagreement and encouraging tailored communications and relationship-building with important angler subgroups.

Published
2024
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43. Planarian toxicity fluorescent assay: a rapid and cheap pre-screening tool for potential skin irritants

Author

Wing Man Lau, Vitaliy V. Khutoryanskiy, Syed Ibrahim Shah, and Adrian C. Williams

Subjects
0301 basic medicine, Pharmacology, Toxicology, medicine.disease_cause, Fluorescence, 03 medical and health sciences, chemistry.chemical_compound, Benzalkonium chloride, 0302 clinical medicine, In vivo, Toxicity Tests, medicine, Animals, Skin, biology, Planarians, General Medicine, biology.organism_classification, Planaria, Acute toxicity, 030104 developmental biology, chemistry, Planarian, 030220 oncology & carcinogenesis, Toxicity, Irritants, Dipropylene glycol, Biological Assay, Irritation, medicine.drug
Abstract

Here we report a new planarian (Dugesia lugubris) fluorescent assay as a rapid and cheap pre-screening tool to predict strong skin irritants. Our aim was to provide a simple and cost-effective in vivo method that avoided use of higher vertebrates. Adapting previously reported methods for planaria mobility alongside an acute toxicity assay, different irritants at five concentrations (0.1%, 0.05%, 0.025%, 0.01% and 0.005% w/v) were tested but both methods failed to discriminate the irritation potential of the test compounds. Therefore, a new alternative fluorescence assay was developed, hypothesising that increasing damage from the irritant to the planarian outer protective membrane will increase accumulation of sodium fluorescein in the flatworm. Fourteen test chemicals were selected representing strong, moderate, mild and non-irritants. In general, results showed increasing sodium fluorescein accumulation within planaria following acute exposure to increasingly strong skin irritants; on exposure to the strong irritants, benzalkonium chloride, citronellal, methyl palmitate, 1-bromohexane and carvacrol, fluorescence within the planaria was significantly greater (P < 0.05) than the negative controls and the common non-irritants PEG-400, dipropylene glycol and isopropyl alcohol; fluorescence values of planaria tested with negative controls and non-irritants were not significantly different. For all test compounds, Fluorescence Intensity of the planaria was compared with literature Primary Irritation Index data and generated a statistically significant (P < 0.005) Pearson correlation (r) of 0.87. Thus, the planarian fluorescent assay is a promising tool for rapid early testing of potential strong skin irritants, and non-irritants, and avoids use of higher vertebrate models.

Published
2020

44. Impact of very early antiretroviral therapy during acute HIV infection on long-term immunovirological outcomes

Author

Paula Suanzes, Jordi Navarro, Ariadna Rando-Segura, Patricia Álvarez-López, Jorge García, Vicente Descalzo, Arnau Monforte, Maider Arando, Lucía Rodríguez, Bibiana Planas, Joaquín Burgos, Adrian Curran, María José Buzón, and Vicenç Falcó

Subjects
HIV infection, Acute HIV infection, Immune recovery, CD4+/CD8+ ratio, Antiretroviral treatment, Early treatment, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. Methods: Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL]

Published
2023
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45. Right versus left fully robotic live donor nephrectomy and open kidney transplantation: Does the laterality of the donor kidney really matter?

Author

Brianna Ruch, Deki Tsering, Chandra Bhati, Dhiren Kumar, Muhammad Saeed, Seung Duk Lee, Aamir Khan, Daisuke Imai, David Bruno, Marlon Levy, Adrian Cotterell, and Amit Sharma

Subjects
Robotics, Laparoscopy, Donor nephrectomy, Complication, Renal transplant, Outcome, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Objective: Robotic-assisted live donor nephrectomy (LDN) is being gradually adopted across transplant centers. The left donor kidney is preferred over right due to anatomical factors and ease of procurement. We aimed to study donor and recipient outcomes after robotic procurement and subsequent open implantation of right and left kidneys. Methods: All fully robotic LDNs and their corresponding open kidney transplants performed at our center between February 2016 and December 2021 were retrospectively analyzed. Results: Out of 196 robotic LDN (49 [right] vs. 147 [left]), 10 (5.1%) donors had intra-operative events (6.1% [right] vs. 4.8% [left], p=0.71). None of the LDN required conversion to open surgery. The operative times were comparable for the two groups. Nausea (13.3%) was the most common post-operative complication. There was no mortality in either LDN group. Herein, we report our outcomes on 156 recipients (39 right and 117 left allografts) excluding robotic implants, exports, and pediatric recipients. There were no significant differences between right and left kidney recipients with respect to 1-year post-transplant patient survival (100.0% vs. 98.1%, p=0.45) or graft survival (93.9% vs. 97.1%, p=0.11), or delayed graft function (7.7% vs. 5.1%, p=0.55). Conclusion: Non-hand-assisted robotic live donor nephrectomies can be safely performed with excellent outcomes. Right LDN was not associated with higher incidence of complications compared to left LDN. Open implantation of robotically procured right renal allografts was not associated with higher risk of recipient complications.

Published
2023
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46. A systematic review highlights the need to improve the quality and applicability of trials of physical therapy interventions for low back pain

Author

James H. McAuley, Edel O'Hagan, Adrian C Traeger, Matthew K Bagg, Hopin Lee, Steven J. Kamper, John Booth, Thiago Folly, Matthew D. Jones, and Aidan G Cashin

Subjects
Adult, medicine.medical_specialty, Quality Assurance, Health Care, Epidemiology, media_common.quotation_subject, Psychological intervention, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Bias, law, Intervention (counseling), Medicine, Humans, Quality (business), 030212 general & internal medicine, Physical Therapy Modalities, media_common, Aged, Data Management, Randomized Controlled Trials as Topic, Evidence-Based Medicine, business.industry, Evidence-based medicine, Middle Aged, Low back pain, Test (assessment), Intention to Treat Analysis, Physical therapy, Etiology, medicine.symptom, business, Low Back Pain, 030217 neurology & neurosurgery
Abstract

Objective To review and assess the methodological quality of randomised controlled trials that test physical therapy interventions for low back pain. Study Design and Setting Systematic review of trials of physical therapy interventions to prevent or treat low back pain (of any duration or type) in participants of any age indexed on the Physiotherapy Evidence Database (PEDro). Existing PEDro scale ratings were used to evaluate methodology quality. Results This review identified 2215 trials. The majority of trials were for adults (n=2136, 96.4%), low back pain without specific aetiology (n=1863, 84.1%), and chronic duration (n=947, 42.8%). The quality of trials improved over time, however most were at risk of bias. Less than half of the trials concealed allocation to intervention (n=813, 36.7%), used intention-to-treat principles (n=778, 35.1%), blinded assessors (n=810, 36.6%), participants (n=174, 7.9%) and therapists (n=39, 1.8%). These findings did not vary by type of therapy. Conclusion The majority of trials that test physical therapy interventions for low back pain have methodological limitations that could bias treatment effect estimates. Greater attention to simple methodological features, such as allocation concealment and the reporting of intention-to-treat effects, would improve the quality of trials testing physical therapy interventions for low back pain.

Published
2020

47. Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Author

Kaptoge, Stephen, Di Angelantonio, Emanuele, Moore, Carmel, Walker, Matthew, Armitage, Jane, Ouwehand, Willem H, Roberts, David J, Danesh, John, Thompson, Simon G, Donovan, Jenny, Ford, Ian, Henry, Rachel, Hunt, Beverley J, le Huray, Bridget, Mehenny, Susan, Miflin, Gail, Green, Jane, Stredder, Mike, Watkins, Nicholas A, McDermott, Alan, Ronaldson, Clive, Thomson, Claire, Tolkien, Zoe, Williamson, Lorna, Allan, David, Sambrook, Jennifer, Hammerton, Tracey, Bruce, David, Choudry, Fizzah, Ghvaert, Cedric, Jonston, Kirstie, Kelly, Anne, King, Andrew, Mo, Alfred, Page, Lizanne, Richardson, Penny, Senior, Peter, Umrania, Yagnesh, Wong, Henna, Burchell, Brendan, Gallacher, John, Murphy, Gavin, Newland, Adrian C, Wheatley, Keith, Greaves, Michael, Turner, Marc, Aziz, Tahir, Brain, Richard, Davies, Christine, Turner, Ruth, Wakeman, Paula, Dent, Alison, Wakeman, Alan, Anthony, Ben, Bland, Desmond, Parrondo, Willem H, Vincent, Helen, Weatherill, Candy, Forsyth, Andrea, Butterfield, Carol, Wright, Tracey, Ellis, Karen, Johnston, Kristie, Poynton, Pat, Brooks, Carolyn, Martin, Emma, Littler, Lara, Williamson, Lindsay, Blair, Donna, Ackerley, Karen, Woods, Lynn, Stanley, Sophie, Walsh, Gemma, Franklin, Gayle, Howath, Cheryl, Sharpe, Sarah, Smith, Deborah, Botham, Lauren, Williams, Caroline, Alexander, Claire, Sowerbutts, Gareth, Furnival, Diane, Thake, Michael, Patel, Shilpa, Roost, Carolyn, Sowerby, Sandra, Appleton, Mary Joy, Bays, Eileen, Bowyer, Geoff, Clarkson, Steven, Halson, Stuart, Holmes, Kate, Humphreys, Gareth, Parvin-Cooper, Lee, Towler, Jason, Addy, Joanne, Barrass, Patrica, Stennett, Louise, Burton, Susan, Dingwell, Hannah, Clarke, Victoria, Potton, Maria, Bolton, Thomas, Daynes, Michael, Spackman, Sarah, Walker, Michael, Momodu, Abudu, Fenton, James, King, Adam, Muhammad, Omer, Oates, Nicholas, Peakman, Tim, Ryan, Christine, Spreckley, Kristian, Stubbins, Craig, Williams, Joanna, Brannan, James, Mochon, Cedric, Taylor, Samantha, Warren, Kimberly, and Mant, Jonathan

Subjects
R1
Abstract

Background: \ud The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments.\ud \ud Methods: \ud The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed.\ud \ud Findings: \ud Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p

Published
2019

48. Family Help With Medication Management: A Predictive Marker for Early Readmission

Author

Adrian C. Garofoli, David A. Foley, Jenna M. Larock, and Magali P. Disdier Moulder

Subjects
medicine.medical_specialty, Hospital readmission, lcsh:R5-920, Predictive marker, Medication history, business.industry, Odds ratio, 030204 cardiovascular system & hematology, medicine.disease, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Ambulatory care, Heart failure, Emergency medicine, medicine, 030212 general & internal medicine, Prospective cohort study, business, lcsh:Medicine (General)
Abstract

Objectives: To identify aspects of medication management that are associated with a greater risk of hospital readmission. Patients and Methods: We conducted a prospective cohort study, with a thorough medication history and reconciliation performed at admission and discharge. Patients 18 years or older (N=258) were prospectively enrolled on admission to a cardiology service at a tertiary care hospital from September 1, 2011, through July 31, 2012. All patients received their hospital and outpatient care within our institution, which minimized loss to follow-up. Readmission rates within 30 days and 6 months after discharge were recorded and used to investigate associations with specific characteristics related to medication regimen and management. Nominal logistic fit tests were used to establish associations with risk factors. Results: A higher risk of readmission within 30 days after discharge was seen with heart failure diagnosis (P=.003) and with increased severity of comorbid conditions based on Charlson score (P=.02). Patients whose family managed their medications entirely had a higher risk of readmission at 30 days (odds ratio, 2.92; 95% CI, 1.25-5.6; P=.01) and at 6 months (odds ratio, 3.54; 95% CI, 1.70-7.65; P

Published
2017

50. Contributors

Author

Anderson, Kenneth C., primary, Arber, Daniel A., additional, Arnold, Donald M., additional, Bain, Barbara J., additional, Béné, Marie Christine, additional, Bevan, David H., additional, Bock, Oliver, additional, Boles, Jeremiah C., additional, Bouma, Gerben, additional, Boyd, Scott D., additional, Buckley, Shannon M., additional, Büsche, Guntram, additional, Czader, Magdalena, additional, Daniels, Geoff, additional, Davies, Faith E., additional, Delaunay, Jean, additional, Erber, Wendy N., additional, Escolar, Gines, additional, Ferguson, David J.P., additional, Gordon-Smith, Edward C., additional, Green, Ralph, additional, Grove, Carolyn S., additional, Hall, Georgina W., additional, Heddle, Nancy M., additional, Horny, Hans-Peter, additional, Hurley, Carolyn Katovich, additional, Kelton, John G., additional, Key, Nigel S., additional, Kreipe, Hans H., additional, Kvasnicka, Hans M., additional, Layton, D. Mark, additional, MacCallum, Peter K., additional, May, Alison, additional, McCullough, Jeffrey, additional, Moonim, Mufaddal T., additional, Moore, Jane C., additional, Nazi, Ishac, additional, Newland, Adrian C., additional, Norström, Eva, additional, Orazi, Attilio, additional, Perry, David J., additional, Pippard, Martin J., additional, Porwit, Anna, additional, Posch, Phillip E., additional, Provan, Drew, additional, Renella, Raffaele, additional, Roper, David R., additional, Rosenquist, Richard, additional, Sørensen, Benny, additional, Thein, Swee Lay, additional, Thrasher, Adrian J., additional, van der Walt, Jon D., additional, Verfaillie, Catherine, additional, White, James G., additional, Wickramasinghe, Sunitha N., additional, Wilkins, Bridget S., additional, Wood, William G., additional, and Zini, Gina, additional

Published
2011
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