Publications by authors named "James Smith"

1,371 Publications

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Understanding inequalities in COVID-19 outcomes following hospital admission for people with intellectual disability compared to the general population: a matched cohort study in the UK.

BMJ Open 2021 10 4;11(10):e052482. Epub 2021 Oct 4.

Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.

Objectives: This study explores the hospital journey of patients with intellectual disabilities (IDs) compared with the general population after admission for COVID-19 during the first wave of the pandemic (when demand on inpatient resources was high) to identify disparities in treatment and outcomes.

Design: Matched cohort study; an ID cohort of 506 patients were matched based on age, sex and ethnicity with a control group using a 1:3 ratio to compare outcomes from the International Severe Acute Respiratory and emerging Infections Consortium WHO Clinical Characterisation Protocol UK.

Setting: Admissions for COVID-19 from UK hospitals; data on symptoms, severity, access to interventions, complications, mortality and length of stay were extracted.

Interventions: Non-invasive respiratory support, intubation, tracheostomy, ventilation and admission to intensive care units (ICU).

Results: Subjective presenting symptoms such as loss of taste/smell were less frequently reported in ID patients, whereas indicators of more severe disease such as altered consciousness and seizures were more common. Controls had higher rates of cardiovascular risk factors, asthma, rheumatological disorder and smoking. ID patients were admitted with higher respiratory rates (median=22, range=10-48) and were more likely to require oxygen therapy (35.1% vs 28.9%). Despite this, ID patients were 37% (95% CI 13% to 57%) less likely to receive non-invasive respiratory support, 40% (95% CI 7% to 63%) less likely to receive intubation and 50% (95% CI 30% to 66%) less likely to be admitted to the ICU while in hospital. They had a 56% (95% CI 17% to 102%) increased risk of dying from COVID-19 after they were hospitalised and were dying 1.44 times faster (95% CI 1.13 to 1.84) compared with controls.

Conclusions: There have been significant disparities in healthcare between people with ID and the general population during the COVID-19 pandemic, which may have contributed to excess mortality in this group.
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http://dx.doi.org/10.1136/bmjopen-2021-052482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491000PMC
October 2021

Primary care and the climate and ecological emergency.

Br J Gen Pract 2021 Oct 30;71(711):439. Epub 2021 Sep 30.

Greener Practice Bristol, Bristol; RCGP Severn Faculty Climate and Sustainability Champion, Bristol; Salaried GP, Charlotte Keel Medical Practice, Easton, Bristol.

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http://dx.doi.org/10.3399/bjgp21X717077DOI Listing
October 2021

Effects of Charcoal Rot on Soybean Seed Composition in Soybean Genotypes That Differ in Charcoal Rot Resistance under Irrigated and Non-Irrigated Conditions.

Plants (Basel) 2021 Aug 29;10(9). Epub 2021 Aug 29.

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 308 Harvard Street, SE, Minneapolis, MN 55455, USA.

Charcoal rot is a major disease of soybean () caused by and results in significant loss in yield and seed quality. The effects of charcoal rot on seed composition (seed protein, oil, and fatty acids), a component of seed quality, is not well understood. Therefore, the objective of this research was to investigate the impact of charcoal rot on seed protein, oil, and fatty acids in different soybean genotypes differing in their charcoal rot susceptibility under irrigated and non-irrigated conditions. Two field experiments were conducted in 2012 and 2013 in Jackson, TN, USA. Thirteen genotypes differing in charcoal rot resistance (moderately resistant and susceptible) were evaluated. Under non-irrigated conditions, moderately resistant genotypes showed either no change or increased protein and oleic acid but had lower linolenic acid. Under non-irrigated conditions, most of the susceptible genotypes showed lower protein and linolenic acid but higher oleic acid. Most of the moderately resistant genotypes had higher protein than susceptible genotypes under irrigated and non-irrigated conditions but lower oil than susceptible genotypes. The different responses among genotypes for protein, oil, oleic acid, and linolenic acid observed in each year may be due to both genotype tolerance to drought and environmental conditions, especially heat differences in each year (2012 was warmer than 2013). This research showed that the increases in protein and oleic acid and the decrease in linolenic acid may be a possible physiological mechanism underlying the plant's responses to the charcoal rot infection. This research further helps scientists understand the impact of irrigated and non-irrigated conditions on seed nutrition changes, using resistant and susceptible genotypes.
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http://dx.doi.org/10.3390/plants10091801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470747PMC
August 2021

Sperm deoxyribonucleic acid fragmentation: predictors, fertility outcomes, and assays among infertile males.

F S Rep 2021 Sep 19;2(3):282-288. Epub 2021 Jun 19.

Duke University School of Medicine, Durham, North Carolina.

Objective: To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays.

Design: Secondary analysis.

Setting: Nine US-based fertility centers.

Patients: Infertile men (N = 147) with sperm concentration ≤15 × 10/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency.

Interventions: At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months.

Main Outcome Measures: The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations.

Results: The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19).

Conclusions: Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.
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http://dx.doi.org/10.1016/j.xfre.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441563PMC
September 2021

Predicting downed woody material carbon stocks in forests of the conterminous United States.

Sci Total Environ 2021 Sep 3;803:150061. Epub 2021 Sep 3.

USDA Forest Service, Northern Research Station, 271 Mast Road, Durham, NH 03824, USA. Electronic address:

Downed woody material (DWM) is a unique part of the forest carbon cycle serving as a pool between living biomass and subsequent atmospheric emission or transference to other forest pools. Thus, DWM is an individually defined pool in national greenhouse gas inventories. The diversity of DWM carbon drivers (e.g., decay, tree mortality, or wildfire) and associated high spatial variability make this a difficult-to-predict component of forest ecosystems. Using the now fully established nationwide inventory of DWM across the United States (US), we developed models, which substantially improved predictions of stand-level DWM carbon density relative to the current national-reporting model ('previous' model, here). The previous model was developed from published DWM carbon densities prior to the NFI DWM inventory. Those predictions were tested using NFI DWM carbon densities resulting in a poor fit to the data (coefficient of determination, or R = 0.03). We present new random forest (RF) and stochastic gradient boosted (SGB) regression models to prediction DWM carbon density on all NFI plots and spatially on all forest land pixels. We evaluated various biotic and abiotic regression predictors, and the most important were standing dead trees, long-term annual precipitation, and long-term maximum summer temperature. A RF model scored best for expanding predictions to NFI plots (R = 0.31), while an SGB model was identified for DWM carbon predictions based on purely spatial data (i.e., NFI-plot-independent, with R = 0.23). The new RF model predicts conterminous US DWM carbon stocks to be 15% lower than the previous model and 2% higher than NFI data expanded according to inventory design-based inference. The new NFI data-driven models not only improve the predictions of DWM carbon density on all plots, they also provide flexibility in extending these predictions beyond the NFI to make spatially explicit and spatially continuous estimates of DWM carbon on all forest land in the US.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150061DOI Listing
September 2021

The global climate and health agenda: Australia must do more.

Health Promot J Austr 2021 Sep 6. Epub 2021 Sep 6.

School of Health & Social Development, Faculty of Health, Deakin University, Melbourne, Australia.

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http://dx.doi.org/10.1002/hpja.529DOI Listing
September 2021

Cation complexation by mucoid Pseudomonas aeruginosa extracellular polysaccharide.

PLoS One 2021 2;16(9):e0257026. Epub 2021 Sep 2.

School of Food Science & Nutrition, University of Leeds, Leeds, United Kingdom.

Mucoid Pseudomonas aeruginosa is a prevalent cystic fibrosis (CF) lung colonizer, producing an extracellular matrix (ECM) composed predominantly of the extracellular polysaccharide (EPS) alginate. The ECM limits antimicrobial penetration and, consequently, CF sufferers are prone to chronic mucoid P. aeruginosa lung infections. Interactions between cations with elevated concentrations in the CF lung and the anionic EPS, enhance the structural rigidity of the biofilm and exacerbates virulence. In this work, two large mucoid P. aeruginosa EPS models, based on β-D-mannuronate (M) and β-D-mannuronate-α-L-guluronate systems (M-G), and encompassing thermodynamically stable acetylation configurations-a structural motif unique to mucoid P. aeruginosa-were created. Using highly accurate first principles calculations, stable coordination environments adopted by the cations have been identified and thermodynamic stability quantified. These models show the weak cross-linking capability of Na+ and Mg2+ ions relative to Ca2+ ions and indicate a preference for cation binding within M-G blocks due to the smaller torsional rearrangements needed to reveal stable binding sites. The geometry of the chelation site influences the stability of the resulting complexes more than electrostatic interactions, and the results show nuanced chemical insight into previous experimental observations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257026PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412252PMC
September 2021

The relationship of plasma antioxidant levels to semen parameters: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial.

J Assist Reprod Genet 2021 Aug 28. Epub 2021 Aug 28.

Department of Reproductive Endocrinology and Infertility, Duke University School of Medicine, Durham, NC, USA.

Purpose: The understanding of the role of plasma antioxidant levels in male fertility in the USA is limited. In a secondary analysis of the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial, we sought to determine whether serum levels of vitamin E (α-tocopherol), zinc, and selenium were correlated with semen parameters and couple fertility outcomes.

Methods: This study is a secondary analysis of the MOXI clinical trial. The primary endpoints in this secondary analysis include semen parameters, and DNA fragmentation and clinical outcomes including pregnancy and live birth. Analyses were completed using Wilcoxon's rank-sum test and linear regression models.

Results: At baseline, the analysis included plasma labs for vitamin E (n = 131), selenium (n = 124), and zinc (n = 128). All baseline plasma values were in the normal ranges. There was no association between selenium, zinc, or vitamin E levels and semen parameters or DNA fragmentation. Baseline antioxidant levels in the male partners did not predict pregnancy or live birth among all couples. Among those randomized to placebo, baseline male antioxidant levels did not differ between those couples with live birth and those that did not conceive or have a live birth.

Conclusions: Among men attending fertility centers in the USA, who have sufficient plasma antioxidant levels of zinc, selenium, or vitamin E, no association was observed between vitamins and semen parameters or clinical outcomes in couples with male infertility. Higher levels of antioxidants among men with circulating antioxidants in the normal range do not appear to confer benefit on semen parameters or male fertility.
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http://dx.doi.org/10.1007/s10815-021-02301-2DOI Listing
August 2021

Participation by conflict-affected and forcibly displaced communities in humanitarian healthcare responses: A systematic review.

J Migr Health 2020 9;1-2:100026. Epub 2020 Dec 9.

Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Community participation in health responses in humanitarian crises is increasingly promoted by humanitarian actors to support adoption of measures that are relevant and effective to local needs. Our aim was to understand the role of community participation in humanitarian health responses for conflict-affected populations (including forcibly displaced populations) in low- and middle-income countries and the barriers and facilitators to community participation in healthcare responses.

Methods: Using a systematic review methodology, following the PRISMA protocol, we searched four bibliographic databases for publications reporting peer-reviewed primary research. Studies were selected if they reported how conflict-affected populations were involved in healthcare responses in low- and middle-income settings, and associated changes in healthcare responses or health outcomes. We applied descriptive thematic synthesis and assessed study quality using study design-specific appraisal tools.

Results: Of 18,247 records identified through the database searching, 18 studies met our inclusion criteria. Various types of community participation were observed, with participation mostly involved in implementing interventions rather than framing problems or designing solutions. Most studies on community participation focused on changes in health services (access, utilisation, quality), community acceptability and awareness, and ownership and sustainability. Key barriers and facilitators to community participation included political will at national and local level, ongoing armed conflict, financial and economic factors, socio-cultural dynamics of communities, design of humanitarian responses, health system factors, and health knowledge and beliefs. Included studies were of mixed quality and the overall strength of evidence was weak. More generally there was limited critical engagement with concepts of participation.

Conclusion: This review highlights the need for more research on more meaningful community participation in healthcare responses in conflict-affected communities, particularly in framing problems and creating solutions. More robust research is also required linking community participation with longer-term individual and health system outcomes, and that critically engages in constructs of community participation.
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http://dx.doi.org/10.1016/j.jmh.2020.100026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352176PMC
December 2020

Modeling Hepatitis C Elimination Among People Who Inject Drugs in New Hampshire.

JAMA Netw Open 2021 Aug 2;4(8):e2119092. Epub 2021 Aug 2.

Tuck School of Business at Dartmouth, Hanover, New Hampshire.

Importance: The success of direct-acting antiviral therapies for chronic hepatitis C virus (HCV) infection led the World Health Organization to set elimination targets by 2030. For the United States to achieve these benchmarks, public health responses must target high-risk populations, such as people who inject drugs (PWID), a group with high rates of HCV incidence and low rates of treatment uptake.

Objective: To evaluate potential improvements in the HCV care cascade among PWID, focusing on improved testing, treatment uptake, and access to harm reduction.

Design, Setting, And Participants: This decision analytic model used a differential equation-based dynamic transmission model based on data from New Hampshire, an illustrative state with a large number of PWID and limited HCV treatment infrastructure. Surveillance data through 2020 was used for model parameterization, and the final analysis was conducted in May 2021.

Main Outcomes And Measures: Model forecasts of chronic HCV cases and advanced-stage HCV outcomes from 2022 to 2045.

Results: A total of 6 scenarios were tested: (1) the base case, (2) improved harm reduction, (3) improved testing, (4) improved treatment, (5) improved testing and treatment, and (6) improved testing, treatment, and harm reduction. All scenarios with improved testing, treatment uptake, and/or access to harm reduction were associated with decreases in forecasted HCV prevalence and HCV-associated mortality compared with the base case. Improving harm reduction, testing, and treatment individually were forecast to reduce prevalence of HCV in 2045 from 69.7% in the base case to 62.8%, 45.7%, and 35.5%, respectively. Combining treatment and testing improvements was associated with a 2045 prevalence of 0.3%; adding harm reduction improvements was associated with further reductions in prevalence forecasts (to 0.2%), with fewer total treatments (10 960 vs 13 219 from 2022-2045).

Conclusions And Relevance: In this modeling study, no single intervention was projected to achieve World Health Organization HCV elimination targets. Scenarios with improvements in both testing and treatment were associated with a prevalence of less than 3% by 2030 and achieved elimination targets. Adding improvements in harm reduction was associated with faster reductions in prevalence and fewer treatments.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.19092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335578PMC
August 2021

Identification and Confirmation of Loci Associated With Canopy Wilting in Soybean Using Genome-Wide Association Mapping.

Front Plant Sci 2021 14;12:698116. Epub 2021 Jul 14.

Department of Crop, Soil, and Environmental Sciences, University of Arkansas, Fayetteville, AR, United States.

Drought causes significant soybean [ (L.) Merr.] yield losses each year in rain-fed production systems of many regions. Genetic improvement of soybean for drought tolerance is a cost-effective approach to stabilize yield under rain-fed management. The objectives of this study were to confirm previously reported soybean loci and to identify novel loci associated with canopy wilting (CW) using a panel of 200 diverse maturity group (MG) IV accessions. These 200 accessions along with six checks were planted at six site-years using an augmented incomplete block design with three replications under irrigated and rain-fed treatments. Association mapping, using 34,680 single nucleotide polymorphisms (SNPs), identified 188 significant SNPs associated with CW that likely tagged 152 loci. This includes 87 SNPs coincident with previous studies that likely tagged 68 loci and 101 novel SNPs that likely tagged 84 loci. We also determined the ability of genomic estimated breeding values (GEBVs) from previous research studies to predict CW in different genotypes and environments. A positive relationship ( ≤ 0.05;0.37 ≤ r ≤ 0.5) was found between observed CW and GEBVs. In the vicinity of 188 significant SNPs, 183 candidate genes were identified for both coincident SNPs and novel SNPs. Among these 183 candidate genes, 57 SNPs were present within genes coding for proteins with biological functions involved in plant stress responses. These genes may be directly or indirectly associated with transpiration or water conservation. The confirmed genomic regions may be an important resource for pyramiding favorable alleles and, as candidates for genomic selection, enhancing soybean drought tolerance.
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http://dx.doi.org/10.3389/fpls.2021.698116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317169PMC
July 2021

Factors Influencing the Decision for Fresh vs Cryopreserved Microdissection Testicular Sperm Extraction for Non-Obstructive Azoospermia.

Urology 2021 Jul 29. Epub 2021 Jul 29.

University of Southern California Institute of Urology, Los Angeles, CA. Electronic address:

Objective: To determine reproductive urologists' (RU) practice patterns for microdissection testicular sperm extraction (microTESE) and factors associated with use of fresh vs frozen microTESE for non-obstructive azoospermia.

Materials And Methods: We electronically surveyed Society for Study of Male Reproduction members with a 21-item questionnaire. Our primary outcomes were to determine RU preference for fresh or frozen microTESE and to understand barriers to performing microTESE. Pearson's chi-square and Fisher's exact tests were used to analyze categorical outcomes and candidate predictor variables. Firth logistic regression was performed to identify the predictors for preferring and performing fresh vs frozen microTESE.

Results: A total of 208 surveys were sent with 76 responses. Most (63.0%) primarily perform frozen microTESE for non-obstructive azoospermia, while 37.0% primarily perform fresh. However, in an ideal practice, 59.3% prefer fresh microTESE, 22.2% prefer frozen microTESE, and 18.5% had no preference. MicroTESE is performed most often (61.1%) at surgical centers not affiliated with a fertility practice. The most commonly reported barriers for both fresh and frozen microTESE are cost (42.6%), scheduling (33.3%), and andrologist unavailability (16.7%). There are no statistically significant differences between these barriers and performing fresh vs frozen microTESE. On multivariable analysis, reproductive endocrinology and infertility-based surgical center (OR 22.9; 95% CI 1.1-467.2; P = 0.04) and professional fee $2,500-$4,999 (OR 20.7; 95% CI 1.27-337.9; P = 0.03) are significant predictors of performing fresh microTESE.

Conclusion: Frozen microTESE is performed more commonly than fresh, despite most RU preferring fresh microTESE in an ideal setting. Both fresh and frozen microTESE have a role in reproductive care. Barriers to performing fresh microTESE include cost, scheduling and andrologist availability.
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http://dx.doi.org/10.1016/j.urology.2021.07.016DOI Listing
July 2021

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

Fertil Steril 2021 Jul 26. Epub 2021 Jul 26.

University of Southern California, Institute of Urology, Los Angeles, California. Electronic address:

Objective: To compare racial differences in male fertility history and treatment.

Design: Retrospective review of prospectively collected data.

Setting: North American reproductive urology centers.

Patient(s): Males undergoing urologist fertility evaluation.

Intervention(s): None.

Main Outcome Measure(s): Demographic and reproductive Andrology Research Consortium data.

Result(s): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%).

Conclusion(s): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.
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http://dx.doi.org/10.1016/j.fertnstert.2021.06.029DOI Listing
July 2021

Male vitamin D status and male factor infertility.

Fertil Steril 2021 Oct 18;116(4):973-979. Epub 2021 Jul 18.

Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina.

Objective: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility.

Design: Secondary analysis of a randomized, controlled trial.

Setting: Nine fertility centers in the United States.

Patient(s): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency.

Intervention(s): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6.

Main Outcome Measure(s): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates.

Result(s): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3).

Conclusion(s): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.
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http://dx.doi.org/10.1016/j.fertnstert.2021.06.035DOI Listing
October 2021

A higher-level nuclear phylogenomic study of the carrot family (Apiaceae).

Am J Bot 2021 07 21;108(7):1252-1269. Epub 2021 Jul 21.

Royal Botanic Gardens Kew, Richmond, Surrey, TW9 3AE, UK.

Premise: The carrot family (Apiaceae) comprises 466 genera, which include many well-known crops (e.g., aniseed, caraway, carrots, celery, coriander, cumin, dill, fennel, parsley, and parsnips). Higher-level phylogenetic relationships among subfamilies, tribes, and other major clades of Apiaceae are not fully resolved. This study aims to address this important knowledge gap.

Methods: Target sequence capture with the universal Angiosperms353 probe set was used to examine phylogenetic relationships in 234 genera of Apiaceae, representing all four currently recognized subfamilies (Apioideae, Azorelloideae, Mackinlayoideae, and Saniculoideae). Recovered nuclear genes were analyzed using both multispecies coalescent and concatenation approaches.

Results: We recovered hundreds of nuclear genes even from old and poor-quality herbarium specimens. Of particular note, we placed with strong support three incertae sedis genera (Platysace, Klotzchia, and Hermas); all three occupy isolated positions, with Platysace resolved as sister to all remaining Apiaceae. We placed nine genera (Apodicarpum, Bonannia, Grafia, Haplosciadium, Microsciadium, Physotrichia, Ptychotis, Tricholaser, Xatardia) that have never previously been included in any molecular phylogenetic study.

Conclusions: We provide support for the maintenance of the four existing subfamilies of Apiaceae, while recognizing that Hermas, Klotzschia, and the Platysace clade may each need to be accommodated in additional subfamilies (pending improved sampling). The placement of the currently apioid genus Phlyctidocarpa can be accommodated by the expansion of subfamily Saniculoideae, although adequate morphological synapomorphies for this grouping are yet to be defined. This is the first phylogenetic study of the Apiaceae using high-throughput sequencing methods and represents an unprecedented evolutionary framework for the group.
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http://dx.doi.org/10.1002/ajb2.1701DOI Listing
July 2021

Bridging boundaries: Health promotion leadership in the context of Health-In-All-Policies.

Health Promot J Austr 2021 Jul 16;32(3):369-371. Epub 2021 Jul 16.

Centre for Health-in-All-Policies Research Translation, South Australian Health and Medical Research Institute, Adelaide, Australia.

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http://dx.doi.org/10.1002/hpja.519DOI Listing
July 2021

Too much theory and not enough practice? The challenge of implementation science application in healthcare practice.

J Eval Clin Pract 2021 Jul 15. Epub 2021 Jul 15.

Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia.

Background: Implementation science (IS) should contribute to maintaining high standards of care across healthcare systems and enhancing care practices. However, despite the evident need for greater and more rapid uptake and integration of evidence in practice, IS design and methodology fall short of the needs of effective translation.

Aim: In this paper we examine what it is about IS that makes it so appealing for effective uptake of interventions in routine practice, and yet so difficult to achieve. We propose a number of ways that implementation scientists could build mutual relationships with healthcare practitioners and other stakeholders including public members to ensure greater shared care practices, and highlight the value of IS training, collaborative educational events, and co-designed research.

Discussion: More consideration should be given to IS applications in healthcare contexts. Implementation scientists can make a valuable contribution by mobilizing theory and improving practice. However, goals for an evidence-based system may be more appropriately achieved through greater outreach and collaboration, with methods that are flexible to support rapid implementation in complex adaptive systems. Collective learning and mutual trust can be cultivated by embedding researchers into healthcare services while offering greater opportunities for practitioners to learn about, and engage in, implementation research.

Conclusion: To bridge the worlds of healthcare practice and IS, researchers could be more consistent in the relationships they build with professionals and the public, communicating through a shared language and co-joining practical approaches to effective implementation. This will build capacity for improved collaboration and foster respectful, interdisciplinary relationships.
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http://dx.doi.org/10.1111/jep.13600DOI Listing
July 2021

Michelle's Story: The Complexity of Patient Care in a Family Medicine Residency Clinic.

Ann Fam Med 2021 Jul-Aug;19(4):362-364

Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, Minnesota.

Family medicine covers all ages and specializes in chronic disease management as well as acute care medicine. As the health of the population continues to grow in complexity, treating patients appropriately and efficiently is imperative to improving health outcomes and managing health care costs. Family medicine physicians are uniquely poised to provide this type of care. A patient story plus a look at the patients seen over the course of a day within a family medicine residency clinic explores the complexity of care and the ability of family medicine physicians to provide the necessary care. Taking a close look at who comes through our door on a particular day highlights 3 points: primary care physicians are seeing patients with an increasing complexity of needs, our society is witnessing an extreme increase in patients suffering with mental health problems and substance use disorders, and addressing social determinants of health must be part of the solution.
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http://dx.doi.org/10.1370/afm.2652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282289PMC
October 2021

Communicating assemblies of biomimetic nanocapsules.

Nanoscale 2021 Jul;13(26):11343-11348

Stephenson Institute for Renewable Energy and Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.

Communication assemblies between biomimetic nanocapsules in a 3D closed system with self-regulating and self-organization functionalities were demonstrated for the first time. Two types of biomimetic nanocapsules, TiO2/polydopamine capsules and SiO2/polyelectrolytes capsules with different stimuli-responsive properties were prepared and leveraged to sense the external stimulus, transmit chemical signaling, and autonomic communication-controlled release of active cargos. The capsules have clear core-shell structures with average diameters of 30 nm and 25 nm, respectively. The nitrogen adsorption-desorption isotherms and thermogravimetric analysis displayed their massive pore structures and encapsulation capacity of 32% of glycine pH buffer and 68% of benzotriazole, respectively. Different from the direct release mode of the single capsule, the communication assemblies show an autonomic three-stage release process with a "jet lag" feature, showing the internal modulation ability of self-controlled release efficiency. The control overweight ratios of capsules influences on communication-release interaction between capsules. The highest communication-release efficiency (89.6% of benzotriazole) was achieved when the weight ratio of TiO2/polydopamine/SiO2/polyelectrolytes capsules was 5 : 1 or 10 : 1. Communication assemblies containing various types of nanocapsules can autonomically perform complex tasks in a biomimetic fashion, such as cascaded amplification and multidirectional communication platforms in bioreactors.
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http://dx.doi.org/10.1039/d1nr03170hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265773PMC
July 2021

Revealing nuclear receptor hub modules from Basal-like breast cancer expression networks.

PLoS One 2021 23;16(6):e0252901. Epub 2021 Jun 23.

School of Food Science & Nutrition, Faculty of Environment, University of Leeds, Leeds, United Kingdom.

Nuclear receptors are a class of transcriptional factors. Together with their co-regulators, they regulate development, homeostasis, and metabolism in a ligand-dependent manner. Their ability to respond to environmental stimuli rapidly makes them versatile cellular components. Their coordinated activities regulate essential pathways in normal physiology and in disease. Due to their complexity, the challenge remains in understanding their direct associations in cancer development. Basal-like breast cancer is an aggressive form of breast cancer that often lacks ER, PR and Her2. The absence of these receptors limits the treatment for patients to the non-selective cytotoxic and cytostatic drugs. To identify potential drug targets it is essential to identify the most important nuclear receptor association network motifs in Basal-like subtype progression. This research aimed to reveal the transcriptional network patterns, in the hope to capture the underlying molecular state driving Basal-like oncogenesis. In this work, we illustrate a multidisciplinary approach of integrating an unsupervised machine learning clustering method with network modelling to reveal unique transcriptional patterns (network motifs) underlying Basal-like breast cancer. The unsupervised clustering method provides a natural stratification of breast cancer patients, revealing the underlying heterogeneity in Basal-like. Identification of gene correlation networks (GCNs) from Basal-like patients in both the TCGA and METABRIC databases revealed three critical transcriptional regulatory constellations that are enriched in Basal-like. These represent critical NR components implicated in Basal-like breast cancer transcription. This approach is easily adaptable and applicable to reveal critical signalling relationships in other diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252901PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221501PMC
June 2021

Embedding Usage Sensors in Point-of-Use Water Treatment Devices: Sensor Design and Application in Limpopo, South Africa.

Environ Sci Technol 2021 07 16;55(13):8955-8964. Epub 2021 Jun 16.

Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Health benefits from point-of-use (POU) water treatment devices come only with consistent use. Embedded sensors can measure the consistency of POU-device use and can provide insights about improving it. We demonstrate both potentials with data from SmartSpouts: accelerometer-based sensors embedded in spigot handles that record the duration and timing of use. In the laboratory, most sensor readings correlated well (>0.98) with manually timed water withdrawals. In the field, SmartSpouts measured >60,000 water withdrawals across 232 households in Limpopo, South Africa. Sensors proved critical to understanding consistent use; surveys overestimated it by 53 percentage points. Sensor data showed when households use POU devices (evening peaks and delayed weekend routines) and user preferences (safe storage over filters). We demonstrate analytically and with data that (i) consistent use (e.g., 7 continuous days) is extremely sensitive to single-day use prevalence and (ii) use prevalence affects the performance of contact-time-based POU devices, exemplified with silver tablets. Deployed SmartSpouts had limitations, including memory overflows and confounding device relocation with water withdrawal. Nevertheless, SmartSpouts provided useful and objective data on the prevalence of single-day and consistent use. Considerably less expensive than alternatives, SmartSpouts enable an order of magnitude increase in how many POU-device sensors can be deployed.
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http://dx.doi.org/10.1021/acs.est.0c08683DOI Listing
July 2021

Phylogenetics and comparative plastome genomics of two of the largest genera of angiosperms, Piper and Peperomia (Piperaceae).

Mol Phylogenet Evol 2021 Oct 13;163:107229. Epub 2021 Jun 13.

Department of Biological Sciences, Boise State University, 1910 University Drive, Boise, ID 83725-1515, USA. Electronic address:

Biological radiations provide unique opportunities to understand the evolution of biodiversity. One such radiation is the pepper plant family Piperaceae, an early-diverging and mega-diverse lineage that could serve as a model to study the diversification of angiosperms. However, traditional genetic markers lack sufficient variation for such studies, and testing hypotheses on poorly resolved phylogenetic frameworks becomes challenging. Limited genomic data is available for Piperaceae, which contains two of the largest genera of angiosperms, Piper (>2100 species) and Peperomia (>1300 species). To address this gap, we used genome skimming to assemble and annotate whole plastomes (152-161kbp) and >5kbp nuclear ribosomal DNA region from representatives of Piper and Peperomia. We conducted phylogenetic and comparative genomic analyses to study plastome evolution and investigate the role of hybridization in this group. Plastome phylogenetic trees were well resolved and highly supported, with a hard incongruence observed between plastome and nuclear phylogenetic trees suggesting hybridization in Piper. While all plastomes of Piper and Peperomia had the same gene content and order, there were informative structural differences between them. First, ycf1 was more variable and longer in Piper than Peperomia, extending well into the small single copy region by thousands of base pairs. We also discovered previously unknown structural variation in 14 out of 25 Piper taxa, tandem duplication of the trnH-GUG gene resulting in an expanded large single copy region. Other early-diverging angiosperms have a duplicated trnH-GUG, but the specific rearrangement we found is unique to Piper and serves to refine knowledge of relationships among early-diverging angiosperms. Our study demonstrates that genome skimming is an efficient approach to produce plastome assemblies for comparative genomics and robust phylogenies of species-rich plant genera.
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http://dx.doi.org/10.1016/j.ympev.2021.107229DOI Listing
October 2021

Performance characteristics of platelet autoantibody testing for the diagnosis of immune thrombocytopenia using strict clinical criteria.

Br J Haematol 2021 Jul 9;194(2):439-443. Epub 2021 Jun 9.

McMaster Centre for Transfusion Research, Department of Medicine, McMaster University, Hamilton, ON, Canada.

Misclassification of immune thrombocytopenia (ITP) is common, which might undermine the value of platelet autoantibody testing. We determined the sensitivity and specificity of platelet autoantibody testing using the direct antigen capture assay for anti-glycoprotein (GP) IIb/IIIa or anti-GPIbIX in patients with 'definite ITP', defined as those with a documented treatment response. Sensitivity of platelet autoantiboody testing increased from 48·3% [95% confidence interval (CI) 43·5-53·2] for all ITP patients to 64·7% (95% CI 54·6-73·9) for definite ITP patients. Specificity was unchanged [75·3% (95% CI 67·5-82·1)]. High optical density values (>0·8) improved the specificity of platelet autoantibody testing but lowered sensitivity. In patients with a high pretest probability, platelet autoantibodies can aid in the diagnosis of ITP and may be most prevalent in certain patient subsets.
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http://dx.doi.org/10.1111/bjh.17566DOI Listing
July 2021

Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia.

N Engl J Med 2021 08 9;385(8):720-728. Epub 2021 Jun 9.

From the Departments of Medicine (A.B., D.M.A., T.E.W., J.W.S., Z.A.A.A.M., A.S., J.G.K., I.N.) and Pathology and Molecular Medicine (A.B., T.E.W.), Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, the Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB (T.P., J.M.S.), the Department of Hematology/Oncology, Centre Hospitalier de l'Université de Montreal, Montreal (N.B.), and the Department of Hematology/Oncology, Hôpital Régional de Saint-Jérôme, St. Jerome, QC (M.-C.L.) - all in Canada.

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).
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http://dx.doi.org/10.1056/NEJMoa2107051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362588PMC
August 2021

Resolving species boundaries in a recent radiation with the Angiosperms353 probe set: the Lomatium packardiae/L. anomalum clade of the L. triternatum (Apiaceae) complex.

Am J Bot 2021 07 8;108(7):1217-1233. Epub 2021 Jun 8.

Department of Biological Sciences, Boise State University, Boise, ID, 83725, USA.

Premise: Speciation not associated with morphological shifts is challenging to detect unless molecular data are employed. Using Sanger-sequencing approaches, the Lomatium packardiae/L. anomalum subcomplex within the larger Lomatium triternatum complex could not be resolved. Therefore, we attempt to resolve these boundaries here.

Methods: The Angiosperms353 probe set was employed to resolve the ambiguity within Lomatium triternatum species complex using 48 accessions assigned to L. packardiae, L. anomalum, or L. triternatum. In addition to exon data, 54 nuclear introns were extracted and were complete for all samples. Three approaches were used to estimate evolutionary relationships and define species boundaries: STACEY, a Bayesian coalescent-based species tree analysis that takes incomplete lineage sorting into account; ASTRAL-III, another coalescent-based species tree analysis; and a concatenated approach using MrBayes. Climatic factors, morphological characters, and soil variables were measured and analyzed to provide additional support for recovered groups.

Results: The STACEY analysis recovered three major clades and seven subclades, all of which are geographically structured, and some correspond to previously named taxa. No other analysis had full agreement between recovered clades and other parameters. Climatic niche and leaflet width and length provide some predictive ability for the major clades.

Conclusions: The results suggest that these groups are in the process of incipient speciation and incomplete lineage sorting has been a major barrier to resolving boundaries within this lineage previously. These results are hypothesized through sequencing of multiple loci and analyzing data using coalescent-based processes.
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http://dx.doi.org/10.1002/ajb2.1676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362113PMC
July 2021

Genome sequencing in congenital cataracts improves diagnostic yield.

Hum Mutat 2021 Sep 15;42(9):1173-1183. Epub 2021 Jun 15.

Eye Genetics Research Unit, The Children's Hospital at Westmead, Save Sight Institute, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.

Congenital cataracts are one of the major causes of childhood-onset blindness around the world. Genetic diagnosis provides benefits through avoidance of unnecessary tests, surveillance of extraocular features, and genetic family information. In this study, we demonstrate the value of genome sequencing in improving diagnostic yield in congenital cataract patients and families. We applied genome sequencing to investigate 20 probands with congenital cataracts. We examined the added value of genome sequencing across a total cohort of 52 probands, including 14 unable to be diagnosed using previous microarray and exome or panel-based approaches. Although exome or genome sequencing would have detected the variants in 35/52 (67%) of the cases, specific advantages of genome sequencing led to additional diagnoses in 10% (5/52) of the overall cohort, and we achieved an overall diagnostic rate of 77% (40/52). Specific benefits of genome sequencing were due to detection of small copy number variants (2), indels in repetitive regions (2) or single-nucleotide variants (SNVs) in GC-rich regions (1), not detectable on the previous microarray, exome sequencing, or panel-based approaches. In other cases, SNVs were identified in cataract disease genes, including those newly identified since our previous study. This study highlights the additional yield of genome sequencing in congenital cataracts.
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http://dx.doi.org/10.1002/humu.24240DOI Listing
September 2021

Molecular properties affecting the hydration of acid-base clusters.

Phys Chem Chem Phys 2021 Jun;23(23):13106-13114

Department of Chemistry, University of California, Irvine, California 92617, USA.

In the atmosphere, water in all phases is ubiquitous and plays important roles in catalyzing atmospheric chemical reactions, participating in cluster formation and affecting the composition of aerosol particles. Direct measurements of water-containing clusters are limited because water is likely to evaporate before detection, and therefore, theoretical tools are needed to study hydration in the atmosphere. We have studied thermodynamics and population dynamics of the hydration of different atmospherically relevant base monomers as well as sulfuric acid-base pairs. The hydration ability of a base seems to follow in the order of gas-phase base strength whereas hydration ability of acid-base pairs, and thus clusters, is related to the number of hydrogen binding sites. Proton transfer reactions at water-air interfaces are important in many environmental and biological systems, but a deeper understanding of their mechanisms remain elusive. By studying thermodynamics of proton transfer reactions in clusters containing up to 20 water molecules and a base molecule, we found that that the ability of a base to accept a proton in a water cluster is related to the aqueous-phase basicity. We also studied the second deprotonation reaction of a sulfuric acid in hydrated acid-base clusters and found that sulfate formation is most favorable in the presence of dimethylamine. Molecular properties related to the proton transfer ability in water clusters are discussed.
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http://dx.doi.org/10.1039/d1cp01704gDOI Listing
June 2021

Orthoplastic management of open tibial fractures in children : a consecutive five-year series from a paediatric major trauma centre.

Bone Joint J 2021 Jun;103-B(6):1160-1167

Bristol Royal Hospital for Children, Bristol, UK.

Aims: Open tibial fractures are limb-threatening injuries. While limb loss is rare in children, deep infection and nonunion rates of up to 15% and 8% are reported, respectively. We manage these injuries in a similar manner to those in adults, with a combined orthoplastic approach, often involving the use of vascularised free flaps. We report the orthopaedic and plastic surgical outcomes of a consecutive series of patients over a five-year period, which includes the largest cohort of free flaps for trauma in children to date.

Methods: Data were extracted from medical records and databases for patients with an open tibial fracture aged < 16 years who presented between 1 May 2014 and 30 April 2019. Patients who were transferred from elsewhere were excluded, yielding 44 open fractures in 43 patients, with a minimum follow-up of one year. Management was reviewed from the time of injury to discharge. Primary outcome measures were the rate of deep infection, time to union, and the Modified Enneking score.

Results: The mean age of the patients was 9.9 years (2.8 to 15.8), and 28 were male (64%). A total of 30 fractures (68%) involved a motor vehicle collision, and 34 (77%) were classified as Gustilo Anderson (GA) grade 3B. There were 17 (50%) GA grade 3B fractures, which were treated with a definitive hexapod fixator, and 33 fractures (75%) were treated with a free flap, of which 30 (91%) were scapular/parascapular or anterolateral thigh (ALT) flaps. All fractures united at a median of 12.3 weeks (interquartile range (IQR) 9.6 to 18.1), with increasing age being significantly associated with a longer time to union (p = 0.005). There were no deep infections, one superficial wound infection, and the use of 20 fixators (20%) was associated with a pin site infection. The median Enneking score was 90% (IQR 87.5% to 95%). Three patients had a bony complication requiring further surgery. There were no flap failures, and eight patients underwent further plastic surgery.

Conclusion: The timely and comprehensive orthoplastic care of open tibial fractures in this series of patiemts aged < 16 years resulted in 100% union and 0% deep infection, with excellent patient-reported functional outcomes. Cite this article:  2021;103-B(6):1160-1167.
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http://dx.doi.org/10.1302/0301-620X.103B6.BJJ-2020-2085.R1DOI Listing
June 2021

Demonstrating trustworthiness when collecting and sharing genomic data: public views across 22 countries.

Genome Med 2021 May 25;13(1):92. Epub 2021 May 25.

Centre for Law and Genetics, University of Tasmania, Hobart, 7001, Australia.

Background: Public trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.

Methods: We analyse the 'Your DNA, Your Say' online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.

Results: Providing transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data-endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.

Conclusions: Our findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
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http://dx.doi.org/10.1186/s13073-021-00903-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147072PMC
May 2021

Implications of critical race theory for Aboriginal and Torres Strait Islander men's health.

Lancet Glob Health 2021 06;9(6):e756

Wellbeing and Preventable Chronic Diseases Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0815, Australia; Freemasons Centre for Male Health and Wellbeing, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0815, Australia.

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http://dx.doi.org/10.1016/S2214-109X(21)00100-5DOI Listing
June 2021
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