bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical sensitivity of red blood cells improves in individuals with hemochromatosis following venesection therapy
Authors: Richardson Kieran J. , McNamee Antony P. , Simmonds Michael J. 
Published: September 2020

AbstractBackgroundIndividuals with hereditary hemochromatosis (HH) receive frequent blood withdrawals (ie, venesections) as part of their primary treatment to assist in normalizing blood iron levels. It remains unclear whether this source of blood is suitable for use in blood product development, as current data indicate that red blood cell (RBC) deformability, both before and after shear stress exposure, is impaired in individuals with HH, relative to healthy controls. Given that venesection therapy is known to significantly reduce circulating iron levels in individuals with HH, the current study examined whether venesection therapy is effective at improving RBC mechanical properties, both before and after shear stress exposure, in individuals with HH.Study Design and MethodsBlood samples were initially collected from untreated HH patients (age, 61 ± 9 years; 14% female) undergoing their first venesection, and then again during their second (approx. 9 weeks later) and third (approx. 16 weeks later) venesections. RBC deformability was measured at each time point with a commercial ektacytometer. Moreover, to determine cell responses to mechanical stimuli, the mechanical sensitivity of blood samples was determined at each time point.ResultsThe salient findings indicate that venesection therapy used for managing plasma ferritin concentration significantly improves the cellular deformability of RBC in individuals with HH. Further, the sensitivity of RBC to supraphysiological mechanical stress is decreased (ie, improved) in a dose‐response fashion with routine venesection.ConclusionWhile cellular mechanics of RBC from individuals with HH are impaired when untreated, venesection therapy significantly improves cellular properties of RBC, supporting the use of venesections in blood product development from individuals with well‐managed HH.
SARS‐CoV‐2 neutralization and serology testing of COVID‐19 convalescent plasma from donors with nonsevere disease
Authors: Gniadek Thomas J. , Thiede Joshua M. , Matchett William E. , Gress Abigail R. , Pape Kathryn A. , Fiege Jessica K. , Jenkins Marc K. , Menachery Vineet D. , Langlois Ryan A. , Bold Tyler D. 
Published: September 2020

AbstractBackgroundThe transfer of passive immunity with convalescent plasma is a promising strategy for treatment and prevention of COVID‐19, but donors with a history of nonsevere disease are serologically heterogenous. The relationship between SARS‐Cov‐2 antigen–binding activity and neutralization activity in this population of donors has not been defined.Study Design and MethodsConvalescent plasma units from 47 individuals with a history of nonsevere COVID‐19 were assessed for antigen‐binding activity of using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS‐CoV‐2 targets. These results were compared with functional neutralization activity using a fluorescent reporter strain of SARS‐CoV‐2 in a microwell assay.ResultsPositive correlations of varying strength (Spearman r = 0.37‐0.52) between antigen binding and viral neutralization were identified. Donors age 48 to 75 years had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75%‐82%) for those with the highest levels of neutralization.ConclusionThe strength of the relationship between antigen‐binding activity and neutralization varies depending on the clinical assay used. Units in the highest tertile of binding activity for each assay are predominantly comprised of those with the greatest neutralization activity.
Trade in intangibles and the global trade imbalance
Authors: Fu Xiaolan , Ghauri Pervez 
Published: September 2020

AbstractThe emergence of intangibles has brought significant challenges for our understanding of capitalism and international trade. This paper develops a framework for the measurement of global trade that integrates trade in intangibles and trade in goods and services to analyse the global trade imbalance. Through in‐depth discussions of the five modes through which trade in tangibles are carried out, it develops an integrated framework for the measurement of international trade. Applying this framework to the estimation of trade imbalance of a group of the world's top innovative countries, we see significant adjustments of their trade balance. The overall trade deficit of the United States reduces by nearly half of its size from USD763 billion to 390 billion in 2015, the year for which we have the latest trade in value‐added data. The paper argues that the true picture of global trade imbalance is of much smaller scale than the traditional trade statistics suggest. Policy responses to rebalance should be discussed using a framework that fully incorporates different types of trade activities in the twenty‐first century. Implications of the new conundrum of globalisation are also discussed.
Shortened immunotherapy dose‐escalation saves time, but is it safe? A case‐control study comparing the rates of adverse reactions between conventional and fast‐escalation subcutaneous immunotherapy protocols during the induction phase
Authors: Herrmann Ina , Loft Klaus E. , Olivry Thierry 
Published: September 2020

BackgroundAllergen immunotherapy (AIT) is the only intervention believed to change the course of atopic diseases. As dogs appear to have fewer severe adverse events (AEs) compared to people receiving AIT, a prolonged dose‐escalation induction phase might not be needed.ObjectivesTo report the incidence and characteristics of AEs induced by a fast‐escalation subcutaneous immunotherapy (f‐SCIT) protocol compared to a conventional (c‐SCIT) regimen.AnimalsOne hundred dogs treated with either f‐ SCIT (Centre 1, 50 dogs) or c‐SCIT (Centre 2, 50 dogs).Methods and materialsA case‐control study retrospectively evaluating AEs during the induction of AIT. We determined the incidence and type of AEs in each SCIT group; we also assessed factors such as self‐limitation and the need for AE‐associated protocol changes.ResultsTwelve of 100 dogs (12%) developed a SCIT‐attributable AE during the induction phase, with one dog having a local and 11 having systemic reactions (nine Grade I, two Grade II, none of grades III or IV). Dogs treated with the f‐SCIT had a significantly higher rate of AEs (11 of 50; 22%) compared to those receiving the c‐SCIT (one of 50; 2%). Most of the AEs (10 of 11; 91%) in the f‐SCIT group were mild and self‐limiting.Conclusions and clinical importanceThe induction phase of f‐SCIT is simpler, and the maintenance phase is reached faster than that of the c‐SCIT. Despite its higher rate of AEs than with the c‐SCIT regimen, the majority of f‐SCIT‐associated AEs were mild and self‐limiting. Whether or not this f‐SCIT protocol leads to a faster time‐to‐efficacy needs to be determined.
Preexercise Cycling Protocol Alters Pacing Behavior in Competitive Time Trials
Authors: Konings Marco J. , Hettinga Florentina J. 
Published: September 2020

Purpose: The behavior of an opponent has been shown to alter pacing and performance. To advance our understanding of the impact of perceptual stimuli such as an opponent on pacing and performance, this study examined the effect of a preexercise cycling protocol on exercise regulation with and without an opponent. Methods: Twelve trained cyclists performed 4 experimental, self-paced 4-km time-trial conditions on an advanced cycle ergometer in a randomized, counterbalanced order. Participants started the time trial in rested state (RS) or performed a 10-min cycling protocol at 67% peak power output (CP) before the time trial. During the time trials, participants had to ride alone (NO) or against a virtual opponent (OP). The experimental conditions were (1) RS-NO, (2) RS-OP, (3) CP-NO, and (4) CP-OP. Repeated-measures analyses of variance (P < .05) were used to examine differences in pacing and performance in terms of power output. Results: A faster pace was adopted in the first kilometer during RS-OP (318 [72] W) compared with RS-NO (291 [81] W; P = .03), leading to an improved finishing time during RS-OP compared with RS-NO (P = .046). No differences in either pacing or performance were found between CP-NO and CP-OP. Conclusions: The evoked response by the opponent to adopt a faster initial pace in the 4-km time trial disappeared when cyclists had to perform a preceding cycling protocol. The outcomes of this study highlight that perceived exertion alters the responsiveness to perceptual stimuli of cyclists during competition.
Minor salivary gland transplantation for severe dry eye disease due to cicatrising conjunctivitis: multicentre long-term outcomes of a modified technique
Authors: Vazirani Jayesh , Bhalekar Swapnil , Amescua Guillermo , Singh Swati , Basu Sayan 
Published: September 2020

Aim
To report the clinical outcomes of autologous minor salivary gland transplantation (MSGT) for the treatment of severe dry eye disease caused by cicatrising conjunctivitis.

Methods
This was a retrospective case series of patients undergoing MSGT at four different centres from 2016 to 2018. The technical modifications included en bloc harvesting of a 20 mm×15 mm mucosa–gland–muscle complex and fixation of the glands to the superior bulbar surface anchored to the superior rectus muscle. The primary outcome measure was improvement in best-corrected visual acuity (BCVA). Secondary outcome measures were change in Schirmer test scores and grades of conjunctival and corneal fluorescein staining, grades of corneal neovascularisation, opacification and keratinisation.

Results
21 eyes of 19 patients underwent MSGT, with a median follow-up duration of 3 years. The median BCVA improved from a baseline value of 20/500 to 20/125 at 1 year (p=0.0004) and 20/80 at 3 years (p=0.0002) after surgery. The proportion of cases with BCVA ≥20/200 improved from 38% at baseline to 67% at 1 year (p=0.0294), 78% at 2 years (p=0.0227) and 93% at 3 years (p=0.0015) after surgery. There was a significant improvement (p<0.0036) in Schirmer scores, conjunctival and corneal staining scores as well as grades of corneal neovascularisation and opacification after surgery. There were no serious sight-threatening complications in the transplanted eyes or at the donor site.

Conclusions
Long-term improvement in the visual acuity, ocular surface environment, and keratopathy was noted after MSGT performed in severely dry eyes using a modified technique.
The impact of demonetisation on the utilisation of hospital services, patient outcomes and finances: a multicentre observational study from India
Authors: George Tarun K , Peter John Victor , Jeyaseelan Lakshmanan , Yadav Bijesh , Patole Shalom , Koshy Roshine Mary , Joseph Prabhu , P Balasubramanian , Nair Aravindan , Zachariah Anand , George Krupa , Abraham Georgi , Venkatesh Balasubramanian 
Published: September 2020

BackgroundThis study assessed trends in healthcare utilisation in relation to the implementation of an economic policy in India wherein 500 and 1000 rupee notes were demonetised.MethodsIn this ambidirectional observational study of private not-for-profit hospitals, data on hospital outpatient and inpatient numbers, surgeries, emergency department (ED) visits, obstetric admissions and mortality were obtained for pre-demonetisation (September/October 2016), early (November/December 2016) and late demonetisation (January/February 2017), and post-demonetisation periods (March/April 2017) and compared with the control period (2015–2016) from 11 centres (three tertiary hospitals; eight secondary). A Bayesian regression analysis was performed to adjust for seasonal (winter) effect. Monthly financial data, including the proportion of cash versus non-cash transactions, were collected.FindingsOverall, at the pooled all-hospital level, Bayesian analysis showed non-significant increase in outpatients (535.4, 95% CI −7097 to 8116) and decrease in deaths (–6.3 per 1000 inpatients, 95% CI −15.45 to 2.75) and a significant decrease in inpatients (−145.6, 95% CI −286.4 to −10.63) during demonetisation. Analysis at the level of secondary and tertiary hospitals showed a variable effect. For individual hospitals, after adjusting for the seasonal effect, some hospitals observed a significant reduction in outpatient (n=2) and inpatient (n=3) numbers, ED visits (n=4) and mortality (n=2) during demonetisation, while others reported significantly increased outpatient numbers (n=3) and ED visits (n=2). Deliveries remained unchanged during demonetisation in the hospitals that provided the service. There was no significant reduction in hospital incomes during demonetisation. In tertiary hospitals, there was a significant increase in non-cash component of transactions from 35% to 60% (p=0.02) that persisted beyond the demonetisation period.ConclusionsThe effect of demonetisation on healthcare utilisation was variable. Some hospitals witnessed a significant reduction in utilisation in some areas, while others reported increased utilisation. There was an increase in non-cash transactions that persisted beyond the period of demonetisation.
Allocating resources to support universal health coverage: development of a geographical funding formula in Malawi
Authors: McGuire Finn , Revill Paul , Twea Pakwanja , Mohan Sakshi , Manthalu Gerald , Smith Peter C. 
Published: September 2020

BackgroundUniversal health coverage (UHC) requires that local health sector institutions—such as local authorities—are properly funded to fulfil their service delivery commitments. In this study, we examine how formula funding can align sub-national resource allocations with national priorities. This is illustrated by outlining alternative options for using mathematical formula to guide the allocation of national drug and service delivery budgets to district councils in Malawi in 2018/2019.MethodsWe use demographic, epidemiological and health sector budget data with information on implementation constraints to construct three variant allocation formulae. The first gives an equal per capita allocation to each district, and is included as a baseline to compare alternatives. The second allocates funds to districts using estimates of the resources required to provide Malawi’s essential health package of priority cost-effective interventions to the full population in need of each intervention. The third adjusts these estimates to reflect a practicable level of attainable coverage for each intervention, based on the current configurations of health services and demand for interventions.FindingsCompared with current district allocations, not underpinned by an explicit formula, the formulae presented in this study suggest sizeable shifts in the allocations received by many districts. In some cases, the magnitude of these shifts exceed 50% reductions or doubling of district budgets. The large shifts illustrate inequities in the current system of budget allocation and the potential improvements possible.ConclusionThe use of mathematical formulae can guide the efficient and equitable allocation of healthcare funds to local health authorities. The formulae developed were facilitated by the existence of an explicit package of priority interventions. The approach can be replicated in wide range of countries seeking to achieve UHC.
Mental health in the UK during the COVID-19 pandemic: cross-sectional analyses from a community cohort study
Authors: Jia Ru , Ayling Kieran , Chalder Trudie , Massey Adam , Broadbent Elizabeth , Coupland Carol , Vedhara Kavita 
Published: September 2020

ObjectivesPrevious pandemics have resulted in significant consequences for mental health. Here, we report the mental health sequelae of the COVID-19 pandemic in a UK cohort and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the first wave of data collection, which examined short-term consequences for mental health, as reported during the first 4–6 weeks of social distancing measures being introduced.DesignCross-sectional online survey.SettingCommunity cohort study.ParticipantsN=3097 adults aged ≥18 years were recruited through a mainstream and social media campaign between 3 April 2020 and 30 April 2020. The cohort was predominantly female (n=2618); mean age 44 years; 10% (n=296) from minority ethnic groups; 50% (n=1559) described themselves as key workers and 20% (n=649) identified as having clinical risk factors putting them at increased risk of COVID-19.Main outcome measuresDepression, anxiety and stress scores.ResultsMean scores for depression (x- =7.69, SD=6.0), stress (x- =6.48, SD=3.3) and anxiety (x- = 6.48, SD=3.3) significantly exceeded population norms (all p<0.0001). Analysis of non-modifiable factors hypothesised to be associated with mental health outcomes indicated that being younger, female and in a recognised COVID-19 risk group were associated with increased stress, anxiety and depression, with the final multivariable models accounting for 7%–14% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54%–57% of total variance.ConclusionsIncreased psychological morbidity was evident in this UK sample and found to be more common in younger people, women and in individuals who identified as being in recognised COVID-19 risk groups. Public health and mental health interventions able to ameliorate perceptions of risk of COVID-19, worry about COVID-19 loneliness and boost positive mood may be effective.
Povidone iodine treatment is deleterious to human ocular surface conjunctival cells in culture
Authors: Swift William , Bair Jeffrey A , Chen Wanxue , Li Michael , Lie Sole , Li Dayu , Yang Menglu , Shatos Marie A , Hodges Robin R , Kolko Miriam , Utheim Tor P , Scott Wendell , Dartt Darlene A 
Published: September 2020

ObjectiveTo determine the effect of povidone iodine (PI), an antiseptic commonly used prior to ocular surgery, on viability of mixed populations of conjunctival stratified squamous and goblet cells, purified conjunctival goblet cells and purified conjunctival stromal fibroblasts in primary culture.Methods and analysisMixed population of epithelial cells (stratified squamous and goblet cells), goblet cells and fibroblasts were grown in culture from pieces of human conjunctiva using either supplemented DMEM/F12 or RPMI. Cell type was evaluated by immunofluorescence microscopy. Cells were treated for 5 min with phosphate-buffered saline (PBS); 0.25%, 2.5%, 5% or 10% PI in PBS; or a positive control of 30% H2O2. Cell viability was determined using Alamar Blue fluorescence and a live/dead kit using calcein/AM and ethidium homodimer-1 (EH-1).ResultsMixed populations of epithelial cells, goblet cells and fibroblasts were characterised by immunofluorescence microscopy. As determined with Alamar Blue fluorescence, all concentrations of PI significantly decreased the number of cells from all three preparation types compared with PBS. As determined by calcein/EH-1 viability test, mixed populations of cells and fibroblasts were less sensitive to PI treatment than goblet cells. All concentrations of PI, except for 0.25% used with goblet cells, substantially increased the number of dead cells for all cell populations. The H2O2control also significantly decreased the number and viability of all three types of cells in both tests.ConclusionWe conclude that PI, which is commonly used prior to ocular surgeries, is detrimental to human conjunctival stratified squamous cells, goblet cells and fibroblasts in culture.
Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals
Authors: Mantovani Alessandro , Petracca Graziana , Beatrice Giorgia , Tilg Herbert , Byrne Christopher D , Targher Giovanni 
Published: September 2020

ObjectiveFollow-up studies have shown that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident diabetes, but currently, it is uncertain whether this risk changes with increasing severity of NAFLD. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.DesignWe systematically searched PubMed, Scopus and Web of Science databases from January 2000 to June 2020 using predefined keywords to identify observational studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by imaging techniques or biopsy. Meta-analysis was performed using random-effects modelling.Results33 studies with 501 022 individuals (30.8% with NAFLD) and 27 953 cases of incident diabetes over a median of 5 years (IQR: 4.0–19 years) were included. Patients with NAFLD had a higher risk of incident diabetes than those without NAFLD (n=26 studies; random-effects HR 2.19, 95% CI 1.93 to 2.48;I2=91.2%). Patients with more ‘severe’ NAFLD were also more likely to develop incident diabetes (n=9 studies; random-effects HR 2.69, 95% CI 2.08 to 3.49;I2=69%). This risk markedly increased across the severity of liver fibrosis (n=5 studies; random-effects HR 3.42, 95% CI 2.29 to 5.11;I2=44.6%). All risks were independent of age, sex, adiposity measures and other common metabolic risk factors. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.ConclusionThis updated meta-analysis shows that NAFLD is associated with a ~2.2-fold increased risk of incident diabetes. This risk parallels the underlying severity of NAFLD.
Do socioeconomic and birth order gradients in child maltreatment differ by immigrant status?
Authors: Kenny Kathleen S , Pulver Ariel , O’Campo Patricia , Guttmann Astrid , Urquia Marcelo L 
Published: September 2020

BackgroundWhile literature has documented strong gradients in child maltreatment (CM) by socioeconomic status and family composition in the general population, how these patterns extend to immigrants remain inconclusive. Using population-based administrative data, we examined, for the first time, whether gradients in CM by neighbourhood income and childbirth order vary by immigrant status.MethodsWe used linked hospitalisation, emergency department visits, small-area income, birth and death records with an official Canadian immigration database to create a retrospective cohort of all 1 240 874 children born from 2002 to 2012 in Ontario, Canada, followed from 0 to 5 years. We estimated rate ratios of CM among immigrants and non-immigrants using modified Poisson regression.ResultsCM rates were 1.6 per 100 children among non-immigrants and 1.0 among immigrants. CM was positively associated with neighbourhood deprivation. The adjusted rate ratio (ARR) of CM in the lowest neighbourhood income quintile versus the highest quintile was 1.57 (95% CI 1.49 to 1.66) for non-immigrants and 1.33 (95% CI 1.15 to 1.54) for immigrants. The socioeconomic gradient disappeared when restricted to children of immigrant mothers arrived at 25+ years and in analyses excluding emergency department visits. Compared to a first child, the ARR of CM for a fourth or higher-order child was 1.75 (95% CI 1.63 to 1.89) among non-immigrants and 0.57 (95% CI 0.44 to 0.74) among immigrants.ConclusionsImmigrants exhibited lower CM rates than non-immigrants across neighbourhood income quintiles and differences were greatest in more deprived neighbourhoods. The contrasting birth order gradients between immigrants and non-immigrants require further investigation.