bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenomic reconstruction reveals new insights into the evolution and biogeography of Atta leaf‐cutting ants (Hymenoptera: Formicidae)
Authors: Barrera Corina A. , Sosa‐Calvo Jeffrey , Schultz Ted R. , Rabeling Christian , Bacci Maurício
Published: September 2021

Atta Fabricius is an ecologically dominant leaf‐cutting ant genus, the major herbivore of the Neotropics, and an agricultural pest of great economic importance. Phylogenetic relationships within Atta have until now remained uncertain, and the delimitation and identification of a subset of Atta species are problematic. To address these phylogenetic uncertainties, we reconstruct the most comprehensive phylogenetic estimate to date of Atta by employing ultraconserved elements (UCEs). We recovered 2340 UCE loci from 224 Atta specimens, which include 14 out of the 15 identifiable species from across their geographic distributions, and 49 outgroup specimens. Our results strongly support the monophyly of Atta and of the four clades that coincide with the previously recognized subgenera Archeatta Gonçalves, Atta s.s. Emery, Epiatta Borgmeier, and Neoatta Gonçalves. The Archeatta clade contains three species occurring in North and Central America and the Caribbean and is the sister group of the remainder of all other Atta species. The Atta s.s. clade is composed of two species occupying North, Central, and South America. The Epiatta clade contains seven entirely South American species and the two species of the Neoatta clade occur in Central and South America. Divergence‐dating analyses identify a series of major events in the Miocene, such as the divergence of Acromyrmex Mayr and Atta 16.7 million years ago (Ma) and the crown‐group origin of Atta around 8.5 Ma. Extant Atta species evolved very recently, originating in the early Pleistocene, approximately 1.8–0.3 Ma (crown‐group ages). We provide the first evidence that Atta goiana Gonçalves belongs to the Epiatta clade and that Atta robusta Borgmeier is the species with the youngest crown‐group age of 0.3 Ma. The very young ages of Atta and its component species indicate a recent, rapid radiation. Biogeographic analyses suggest that the range of the most recent common ancestor of Atta consisted of the combined North/Central America and NW South America bioregions and that one daughter lineage subsequently dispersed into South America, rapidly diversifying in the newly formed Cerrado biome and Chaco, and further dispersing into the Atlantic Forest, Caatinga, and Pampas bioregions.
In search of TP53 mutational hot spots for Li‐Fraumeni syndrome in Asian populations
Authors: Lo Piccolo Luca , Jantrapirom Salinee , Moonmuang Sutpirat , Teeyakasem Pimpisa , Pasena Arnat , Suksakit Pathacha , Charoenkwan Pimlak , Pruksakorn Dumnoensun , Koonrungsesomboon Nut
Published: September 2021

Objective

Germline mutations of the TP53 tumour suppressor gene are the only known cause of the hereditary autosomal disorder called Li‐Fraumeni syndrome (LFS). However, little information is available about TP53 pathogenic variants in Asian LFS patients, making it difficult to provide precise genetic counselling with regard to long‐term cancer risk. We conducted a systematic review to gather relevant case–control studies exploring the association between TP53 polymorphisms and the incidence of cancer belonging to the LFS spectrum in Asian populations.

Method

Systematic review and meta‐analysis. The odds ratio was used as a summary effect measure to quantify the strength of the association between TP53 polymorphisms and cancer risk by means of random‐effects meta‐analysis.

Results

In total, 16 studies were included in this systematic review, with 13 studies (involving 10,645 cases and 28,288 controls) that enabled meta‐analysis. The majority of the studies focused on a single‐nucleotide variation at codon 72 in exon 4 (c.215C>G, p.Arg72Pro, rs1042522). Therefore, we tested either dominant, co‐dominant, recessive, or heterozygous models and found that the p.Arg72Pro was not significantly associated with increased cancer risk in any of the models.

Conclusion

We found the number of studies on cancers belonging to the LFS spectrum in Asia is very small. Thus, at the present time a meta‐analysis approach is somewhat useful to identify germline TP53 mutations as potential markers of hereditary cancer associated with LFS in Asian populations.
Response of canine thyroid carcinomas to radioiodine
Authors: Jegatheeson Selvi , Zuber Max , Woodward Andrew P. , Cannon Claire M.
Published: September 2021

Radioactive iodine (131I) has previously been reported to prolong survival in dogs with thyroid carcinoma. This study aimed to describe tumour response and progression‐free interval (PFI) in dogs with thyroid carcinomas treated with131I. Secondary aims were to describe overall survival time (OST) and prognostic factors. A bi‐institutional retrospective review of records identified 66 dogs with thyroid carcinoma treated with131I from January 2010 to April 2020. Response was described using RECIST or a subjective response assessment where specific tumour measurements were not available. Forty‐eight dogs (72.7%) were treatment naïve and 18 dogs (27.3%) had received prior therapy at the time of131I treatment. Objective responses were available for 34 dogs and subjective responses for 58 dogs. The overall response rate was 35.3% (four complete and eight partial responses). Improvement of clinical signs was seen in 76.2% of dogs (32/42). Kaplan–Meier‐estimated median PFI (95% confidence interval [CI]) was 301 (217–578) days and OST (95% CI) was 564 (421–865) days. Prior therapy was associated with a lower hazard for progression (hazard ratio [HR] 0.260 95% CI 0.123–0.548,p = .0004). Treatment of thyroid carcinoma using131I can effectively alleviate clinical signs and reduce disease burden in a proportion of dogs.
Subjective assessment of frequency distribution histograms and consequences on reference interval accuracy for small sample sizes: A computer‐simulated study
Authors: Coisnon Camille , Mitchell Mark A. , Rannou Benoit , Le Boedec Kevin
Published: September 2021

Background

Inaccuracy in estimating reference intervals (RIs) is a problem with small sample sizes.

Objectives

This study aimed to identify the most accurate statistical methods to estimate RIs based on sample size and population distribution shape. We also studied the accuracy of sample frequency distribution histograms to retrieve the original population distribution and compared strategies based on the histogram and goodness‐of‐fit test.

Methods

The statistical methods that best enhanced accuracy were determined for various sample sizes (n = 20‐60) and population distributions (Gaussian, log‐normal, and left‐skewed) were determined by repeated‐measures ANOVA and posthoc analyses. Frequency distribution histograms were built from 900 samples of five different sizes randomly extracted from six simulated populations. Three reviewers classified the population distributions from visual assessments of a sample histogram, and the classification error rate was calculated. RI accuracy was compared among the strategies based on the histograms and goodness‐of‐fit tests.

Results

The parametric, nonparametric, and robust methods enhanced lower reference limit estimation accuracy for Gaussian, log‐normal, and left‐skewed distributions, respectively. The parametric, nonparametric bootstrap, and nonparametric methods enhanced the upper limit estimation accuracy for Gaussian, log‐normal, and left‐skewed distributions, respectively. Regardless of sample size, sample histogram assessments properly classified the original population distribution 71% to 93.9% of the time, depending on the reviewers. In this study, the strategy based on histograms assessed by the statistician was significantly more precise and accurate than the strategy based on the goodness‐of‐fit test (P < 0.001).

Conclusions

A strategy based on histograms might enhance the accuracy of RI estimations. However, relevant inter‐reviewer variations in histogram interpretation were detected. Factors affecting inter‐reviewer variations should be further explored.
A Mixed-Method Examination of Coaches’ Interpersonal Emotion Regulation Toward Athletes
Authors: Kim Jeemin , Tamminen Katherine A. , Harris Constance , Sutherland Sara
Published: September 2021

Athletes often upregulate and downregulate pleasant or unpleasant emotions to feel or perform better (i.e., for hedonic or instrumental reasons). In addition to athletes regulating their own emotions, interpersonal emotion regulation (IER) also occurs in sports, wherein individuals attempt to regulate the emotions of others. Although previous research has examined IER between teammates, studies have rarely considered coaches’ efforts to regulate athletes’ emotions. The current mixed-method study explored coaches’ beliefs about athletes’ emotions and engagement in IER. Analysis of quantitative survey data (N = 208) and qualitative interview data (n = 10) from competitive level coaches (Mage = 44.0 ± 13.2 years) revealed that coaches perceived both benefits and detriments of various emotions, and coaches’ beliefs about emotions influenced the ways they attempted to regulate athletes’ emotions. Most coaches reported frequently engaging in affect-improving IER. Although the coaches generally opposed the idea of intentionally worsening athletes’ emotions, sometimes their feedback to athletes had the effect of worsening their emotions. Coaches also emphasized the need to consider athletes’ individual differences when engaging in IER. The current findings highlight the relevance of coaches’ IER, suggest several directions for future research, and offer useful considerations for coaches and coach education programs.
Adjusting Identities When Times Change: The Role of Self-Compassion
Authors: Kullman Sasha M. , Semenchuk Brittany N. , Schellenberg Benjamin J.I. , Ceccarelli Laura , Strachan Shaelyn M.
Published: September 2021

Adjusting identity standards may be preferable to relentless pursuit or abandonment of an identity when facing an identity-challenging life transition. Self-compassion (SC) can help people adjust to challenges. The authors examined whether SC was associated with identity adjustment, exercise, and the moderating effect of identity–behavior discrepancy in 279 women exercisers who reported reduced exercise in motherhood. Participants completed the Self-Compassion Scale and reported the extent of and reflected on their identity discrepant behavior (reduced exercise). Reactions to discrepancy (acceptance, shame, guilt, and rumination), correlates of identity adjustment (subjective well-being, autonomous motivation, controlled motivation, and role conflict), and exercise behavior were assessed. SC associated positively with acceptance, correlates of successful identity adjustment, and exercise behavior. SC associated negatively with shame, rumination, and correlates of unsuccessful adjustment. SC may help exercise-identifying women who exercise less after becoming mothers adaptively cope with this identity challenge and continue exercising.
Memory CD8
+
T cells mediate early pathogen-specific protection via localized delivery of chemokines and IFNγ to clusters of monocytes
Authors: Boutet Marie , Benet Zachary , Guillen Erik , Koch Caroline , M’Homa Soudja Saidi , Delahaye Fabien , Fooksman David , Lauvau Grégoire
Published: September 2021

Protection in vaccinated hosts occurs quickly upon pathogen-specific memory CD8
+
T cell–mediated activation of myeloid cells.
Bottom-up assembly of biomedical relevant fully synthetic extracellular vesicles
Authors: Staufer Oskar , Dietrich Franziska , Rimal Rahul , Schröter Martin , Fabritz Sebastian , Boehm Heike , Singh Smriti , Möller Martin , Platzman Ilia , Spatz Joachim Pius
Published: September 2021

Engineered synthetic extracellular vesicles optimize cellular signaling for wound closure.
Heterojunction structures for reduced noise in large-area and sensitive perovskite x-ray detectors
Authors: Zhou Ying , Zhao Liang , Ni Zhenyi , Xu Shuang , Zhao Jingjing , Xiao Xun , Huang Jinsong
Published: September 2021

Low-noise, sensitive, and large-area x-ray detectors with heterojunction structure show promise for low-dose x-ray imaging.
Atypical genomic cortical patterning in autism with poor early language outcome
Authors: Lombardo Michael V. , Eyler Lisa , Pramparo Tiziano , Gazestani Vahid H. , Hagler Donald J. , Chen Chi-Hua , Dale Anders M. , Seidlitz Jakob , Bethlehem Richard A. I. , Bertelsen Natasha , Barnes Cynthia Carter , Lopez Linda , Campbell Kathleen , Lewis Nathan E. , Pierce Karen , Courchesne Eric
Published: September 2021

Genomic patterning of the cerebral cortex is different in autism early language outcome subtypes.
Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs
Authors: Shen Jun , Xu Yingxi , Zhang Shuo , Lyu Shuzhen , Huo Yingying , Zhu Yaoyao , Tang Kejing , Mou Junli , Li Xinjie , Hoyle Dixie L. , Wang Min , Wang Jianxiang , Li Xin , Wang Zack Z. , Cheng Tao
Published: September 2021

Hypoxia enhances hematopoiesis with functional T cell potential from human pluripotent stem cells via arterial priming.
Tumor-draining lymph nodes: At the crossroads of metastasis and immunity
Authors: du Bois Haley , Heim Taylor A. , Lund Amanda W.
Published: September 2021

Tumors remodel their draining lymph nodes to simultaneously affect both metastatic potential and systemic immune surveillance.
Supplemental Material: Late Quaternary geochronologic record of soil formation and erosion: Effects of climate change on Mojave Desert hillslopes (Nevada, USA)
Authors: Persico Lyman , al. et
Published: September 2021

Additional environmental information about the field site and soil profile descriptions, and details on the methods used for field mapping and OSL, XRF, and laser diffraction analyses.
Supplemental Material: Unraveling the histories of Proterozoic shales through in situ Rb-Sr dating and trace element laser ablation analysis
Authors: Subarkah Darwinaji , al. et
Published: September 2021

Extended methods and dataset.
Study of the Influence of Different Methods of Taking into Account the Coulomb Interaction on Determining Asymptotic Normalization Coefficients within the Framework of Exactly Solvable Model
Authors: Blokhintsev L. D. , Savin D. A.
Published: September 2021

It is shown that the Schrödinger equation for the sum of the potential of a square well and the Coulomb potential of a uniformly charged sphere admits an analytical solution for arbitrary values of the orbital angular momentum. An explicit form of this solution has been found. Using the obtained solution, the influence of the Coulomb interaction for both point and distributed nuclear charges on the values of asymptotic normalization coefficients for various nuclear systems is investigated. It is shown that taking into account the non-point distribution of the nuclear charge has little effect on the calculated values of the asymptotic normalization coefficients, provided that the binding energy of the system is assumed to be fixed.
Neurodevelopment in normocephalic children with and without prenatal Zika virus exposure
Authors: Blackmon Karen , Evans Roberta , Fernandes Michelle , Landon Barbara , Noel Trevor , Macpherson Calum , Cudjoe Nikita , Burgen Kemi S , Punch Bianca , Krystosik Amy , Grossi-Soyster Elysse N , LaBeaud Angelle Desiree , Waechter Randall
Published: September 2021

Objective

Zika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls.

Design

Cohort study.

Setting

Public health centres in Grenada, West Indies.

Patients

384 mother–child pairs were enrolled during a period of active ZIKV transmission (April 2016–March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum.

Main outcome measures

The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child’s exposure status.

Results

A total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays.

Conclusions

Overall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.
WHO essential medicines for children 2011–2019: age-appropriateness of enteral formulations
Authors: Orubu Ebiowei Samuel F , Duncan Jennifer , Tuleu Catherine , Turner Mark A , Nunn Anthony
Published: September 2021

Introduction

The WHO Essential Medicine List for children (EMLc) is used for promoting access to medicines. The age-appropriateness of enteral (oral and rectal) formulations for children depend on their adaptability/flexibility to allow age-related or weight-related doses to be administered/prescribed and the child’s ability to swallow, as appropriate. There is scant information on the age-appropriateness of essential enteral medicines for children.

Objective

To evaluate the age-appropriateness of enteral essential medicines.

Materials and methods

Age-appropriateness of all enteral formulations indicated and recommended in the EMLc 3rd to 7th (2011–2019) editions were determined by assessing swallowability and/or dose adaptability for children under 12 years, stratified into five age groups.

Results

Enteral formulations in the EMLc were more age-appropriate for older children aged 6–11 years than for younger children. In the 3rd edition, for older children, 77%, n=342, of formulations were age-appropriate. For younger children, age-appropriateness decreased with age group: 34% in those aged 3–5 years, 30% in those aged 1–2 years, 22% among those aged 28 days to 11 months and 15% in those aged 0–27 days. Overall, similar proportions were found for the 7th edition. In contrast, the majority of medicines in the 7th list were age-appropriate in targeted diseases like HIV and tuberculosis.

Conclusion

Most recommended enteral essential medicines in EMLc 2011 and 2019 were not age-appropriate for children <6 years. Medicines which are not age-appropriate must be manipulated before administration, leading to potential issues of safety and efficacy. Evaluation of the age-appropriateness of formulations for medicines to be included in EMLc could improve access to better medicines for children in the future.
Persistent seropositivity in oophorectomy-resistant anti-NMDA receptor encephalitis
Authors: Tripathi Susmit , Michaelson Nara M , Segal Alan
Published: September 2021

To discuss (1) the significance of seropositivity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and (2) clinical decision making in oophorectomy resistant disease. Patient A (a 35-year-old woman) had high CSF and serum anti-NMDA antibody titres, a complicated hospital course, little improvement with first and second-line therapies, and remained with high CSF and serum antibody titres despite unilateral oophorectomy, requiring a nearly 13-month long hospitalisation. Conversely, patient B (a 29-year-old woman) had low CSF titres, seronegative disease and quickly recovered to her baseline with first line therapies and oophorectomy. Anti-NMDAR antibodies are themselves pathological, causing signalling dysfunction and internalisation of the NMDAR. Seropositivity with anti-NMDAR antibodies likely reflects leakage from the blood–brain barrier, with high serum titres being a downstream effect of high CSF titres. Empiric bilateral oophorectomies is controversial but appropriate on a case-by-case basis in extremely treatment-resistant NMDAR encephalitis given the possibility of antigenic microteratomas, which may not be detected on imaging or even bilateral ovarian biopsies.
Oesophagomediastinal fistula: a rare complication of tuberculosis
Authors: Nedkov Gambin Maurizio , Vella Sarah Marie , Vella Chantal , Schembri John
Published: September 2021

We report a case of a woman from Thailand, living in Malta, who was diagnosed with concomitant tuberculosis (TB) and HIV with depleted CD4 count. Her case was further complicated by the formation of a fistula between the mediastinal lymph nodes and the oesophagus, an unusual finding but for which she had many risk factors. The diagnosis was suspected on CT scan of the thorax and confirmed via upper gastrointestinal endoscopy. Following the commencement of both anti-TB and antiretroviral therapy, she suffered a lapse of immune reconstitution inflammatory syndrome but with aggressive medical management eventually made a full recovery without the need for surgical intervention.
Psychological burden of anaphylaxis and the fight for an EpiPen
Authors: Pradhan Sara
Published: September 2021

A university student with a background of atopy presented to her general practitioner (GP) 2 weeks following an episode of throat tightening and dizziness occurring after touching cashew nut to her lip. She took antihistamine medication immediately and went to sleep, fearing for her life. On waking, she felt astounded to be alive. Her symptoms resolved gradually over the following week. She waited 2 weeks for an appointment with her GP, who referred her to allergy clinic. Eight months later, she was still waiting for her clinic appointment, and was left fearing a future fatal reaction, having been provided with no interim treatment. Not all patients who have severe allergic reactions present to the emergency department. Living with the constant fear of anaphylaxis can be overwhelming for patients and their families, and it can negatively impact mental health. Therefore, we advise early allergy counselling and early EpiPen prescription.
Surgical management of a giant abdominal wall desmoid tumour
Authors: Patel Nandesh , Slivkova Ralitsa , James Sunil , Almond Max
Published: September 2021

Desmoid tumours are clonal fibroblastic proliferations in soft tissues, characterised by infiltrative growth and local recurrence, but not metastasis. Various treatment strategies for desmoid tumours exist, varying from observation, medical and systemic therapy to radiotherapy and surgery. A 25-year-old woman with a background of familial adenomatous polyposis was referred with an enlarging abdominal desmoid tumour measuring 40×40×40 cm despite repeated radiofrequency ablation, surgical debulking and hormone therapy. The patient had a two-stage operation. The first stage involved excision of the desmoid tumour with full-thickness abdominal wall. The abdominal wall was not closed, and a topical negative pressure seal was applied. After 2 days, she underwent the second stage: reconstruction of the abdominal wall defect with a large porcine mesh which was covered with anterolateral thigh flaps. Postoperative complications included ileus and a fall which required further surgery. The patient was discharged 1 month after the first operation. Abdominal MRI scans were performed at 3 and 7 months postdischarge and showed no recurrence of diseaseBackground
Remdesivir-associated bradycardia
Authors: Ching Patrick R , Lee Calvin
Published: September 2021

Remdesivir is an antiviral used for the treatment of COVID-19 requiring hospitalisation. Information on its cardiovascular safety profile is scarce. We report the case of a 37-year-old man with COVID-19 who developed bradycardia after receiving remdesivir. We recommend a baseline ECG for all patients prior to receiving remdesivir and continuous cardiac monitoring during treatment, especially among those with underlying cardiovascular disease, elderly and using β-blockers.
Validation of parsimonious prognostic models for patients infected with COVID-19
Authors: Harish Keerthi , Zhang Ben , Stella Peter , Hauck Kevin , Moussa Marwa M , Adler Nicole M , Horwitz Leora I , Aphinyanaphongs Yindalon
Published: September 2021

Objectives

Predictive studies play important roles in the development of models informing care for patients with COVID-19. Our concern is that studies producing ill-performing models may lead to inappropriate clinical decision-making. Thus, our objective is to summarise and characterise performance of prognostic models for COVID-19 on external data.

Methods

We performed a validation of parsimonious prognostic models for patients with COVID-19 from a literature search for published and preprint articles. Ten models meeting inclusion criteria were either (a) externally validated with our data against the model variables and weights or (b) rebuilt using original features if no weights were provided. Nine studies had internally or externally validated models on cohorts of between 18 and 320 inpatients with COVID-19. One model used cross-validation. Our external validation cohort consisted of 4444 patients with COVID-19 hospitalised between 1 March and 27 May 2020.

Results

Most models failed validation when applied to our institution’s data. Included studies reported an average validation area under the receiver–operator curve (AUROC) of 0.828. Models applied with reported features averaged an AUROC of 0.66 when validated on our data. Models rebuilt with the same features averaged an AUROC of 0.755 when validated on our data. In both cases, models did not validate against their studies’ reported AUROC values.

Discussion

Published and preprint prognostic models for patients infected with COVID-19 performed substantially worse when applied to external data. Further inquiry is required to elucidate mechanisms underlying performance deviations.

Conclusions

Clinicians should employ caution when applying models for clinical prediction without careful validation on local data.
Associations between community cultural engagement and life satisfaction, mental distress and mental health functioning using data from the UK Household Longitudinal Study (UKHLS): are associations moderated by area deprivation?
Authors: Mak Hei Wan , Coulter Rory , Fancourt Daisy
Published: September 2021

Objectives

The association between community cultural engagement and mental health and well-being is well established. However, little is known about whether such associations are influenced by area characteristics. This study therefore examined whether the association between engagement in community cultural assets (attendance at cultural events, visiting museums and heritage sites) and subsequent well-being (life satisfaction, mental distress and mental health functioning) is moderated by neighbourhood deprivation.

Design

Data were drawn from Understanding Society: The UK Household Longitudinal Study waves 2 and 5. Participating households’ addresses were geocoded into statistical neighbourhood zones categorised according to their level of area deprivation.

Setting

General population.

Participants

UK general adult population, with a total sample of 14 783.

Main outcome measures

Life satisfaction was measured with a seven-point scale (1: completely unsatisfied to 7: completely satisfied). Mental distress was measured using the General Health Questionnaire 12. Mental health functioning was measured using 12-item Short Form Health Survey (SF-12).

Results

Using Ordinary Least Squares (OLS) regression, we found that engagement in cultural assets was consistently and positively associated with subsequent life satisfaction and mental health functioning and negatively associated with mental distress. Importantly, such associations were independent of individuals’ demographic background, socioeconomic characteristics and regional location. The results also show that relationships between engagement in community cultural assets and well-being were stronger in more deprived areas.

Conclusions

This study shows that engagement in community cultural assets is associated with better well-being, with some evidence that individuals in areas of high deprivation potentially may benefit more from these engagements. Given that causal mechanisms were not tested, causal claims cannot be generated from the results. However, the results suggest that place-based funding schemes that involve investment in areas of higher deprivation to improve engagement rates should be explored further to see if they can help promote better well-being among residents.
Midline incisional hernia prophylaxis using synthetic mesh in an emergency or urgent gastrointestinal tract surgery: a protocol for multicentre randomised clinical trial
Authors: Tansawet Amarit , Numthavaj Pawin , Sumritpradit Preeda , Techapongsatorn Suphakarn , McKay Gareth , Attia John , Thakkinstian Ammarin
Published: September 2021

Introduction

Between 5% and 30% of abdominal incisions eventually result in incisional hernias (IHs) that can lead to severe complications and impaired quality of life. Unfortunately, IH repair is often unsuccessful; therefore, hernia prophylaxis is an important issue. The efficacy of mesh augmentation has been proven for hernia prophylaxis in high-risk patients, but no randomised clinical trial has evaluated prophylactic mesh placement in emergency/urgent gastrointestinal operations.

Methods and analysis

A multicentre, prospective randomised, open and patient–assessor blinded endpoint design will be conducted. A total of 470 patients will be enrolled and randomly allocated to retrorectus mesh augmentation with lightweight polypropylene mesh or primary suture closure. The primary outcome is IH occurrence within 24 months of follow-up, while other clinical outcomes are secondary endpoints. A cost-effectiveness analysis will be conducted from the societal and provider perspectives.

Ethics and dissemination

Ethics approval was obtained from Ramathibodi Hospital (MURA2020/1478) and Vajira Hospital (COA164/2563). The protocol is on the process of submission to the local ethics committee of the other study sites. Results will be submitted for publication in a peer-reviewed journal.

Trial registration number

TCTR20200924002.
Seasonality of adverse birth outcomes in women with and without HIV in a representative birth outcomes surveillance study in Botswana
Authors: Caniglia Ellen C , Abrams Jasmyn , Diseko Modiegi , Mayondi Gloria , Mabuta Judith , Makhema Joseph , Mmalane Mompati , Lockman Shahin , Bernstein Aaron , Zash Rebecca , Shapiro Roger
Published: September 2021

Introduction

Sub-Saharan Africa has the largest number of people with HIV, one of the most severe burdens of adverse birth outcomes globally and particular vulnerability to climate change. We examined associations between seasonality and adverse birth outcomes among women with and without HIV in a large geographically representative birth outcomes surveillance study in Botswana from 2015 to 2018.

Methods

We evaluated stillbirth, preterm delivery, very preterm delivery, small for gestational age (SGA), very SGA, and combined endpoints of any adverse or severe birth outcome. We estimated the risk of each outcome by month and year of delivery, and adjusted risks ratios (ARRs) of outcomes during the early wet (1 November–15 January), late wet (16 January–31 March) and early dry (1 April–15 July) seasons, compared with the late dry (16 July–31 October) season. Analyses were conducted overall and separately by HIV status.

Results

Among 73 178 women (24% with HIV), the risk of all adverse birth outcomes peaked in November–January and reached low points in September. Compared with the late dry season, the ARRs for any adverse birth outcome were 1.03 (95% CI 1.00 to 1.06) for the early dry season, 1.08 (95% CI 1.04 to 1.11) for the early wet season and 1.07 (95% CI 1.03 to 1.10) for the late wet season. Comparing the early wet season to the late dry season, we found that ARRs for stillbirth and very preterm delivery were higher in women with HIV (1.23, 95% CI 0.96 to 1.59, and 1.33, 95% CI 1.10 to 1.62, respectively) than in women without HIV (1.07, 95% CI 0.91 to 1.26, and 1.19, 95% CI 1.04 to 1.36, respectively).

Conclusions

We identified a modest association between seasonality and adverse birth outcomes in Botswana, which was greatest among women with HIV. Understanding seasonal patterns of adverse birth outcomes and the role of HIV status may allow for mitigation of their impact in the face of seasonal extremes related to climate change.
Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017
Authors: Lynn Ena , Cousins Gráinne , Lyons Suzi , Bennett Kathleen E
Published: September 2021

Objective

To examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017.

Design

Repeated cross-sectional study.

Setting

Drug poisoning deaths in Ireland.

Participants

National Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017.

Outcome measures

The primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004–2017), change points over time and average annual percentage changes (AAPCs) with 95% CI.

Results

Increased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3).

Conclusion

Drugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.
Electrophysiological ventricular substrate of stroke: a prospective cohort study in the Atherosclerosis Risk in Communities (ARIC) study
Authors: Johnson John A , Haq Kazi T , Lutz Katherine J , Peters Kyle K , Paternostro Kevin A , Craig Natalie E , Stencel Nathan W L , Hawkinson Lila F , Khayyat-Kholghi Maedeh , Tereshchenko Larisa G
Published: September 2021

Objectives

The goal of the study was to determine an association of cardiac ventricular substrate with thrombotic stroke (TS), cardioembolic stroke (ES) and intracerebral haemorrhage (ICH).

Design

Prospective cohort study.

Setting

The Atherosclerosis Risk in Communities (ARIC) study in 1987–1989 enrolled adults (45–64 years), selected as a probability sample from four US communities (Minneapolis, Minnesota; Washington, Maryland; Forsyth, North Carolina; Jackson, Mississippi). Visit 2 was in 1990–1992, visit 3 in 1993–1995, visit 4 in 1996–1998 and visit 5 in 2011–2013.

Participants

ARIC participants with analysable ECGs and no history of stroke were included (n=14 479; age 54±6 y; 55% female; 24% black). Ventricular substrate was characterised by cardiac memory, spatial QRS-T angle (QRS-Ta), sum absolute QRST integral (SAIQRST), spatial ventricular gradient magnitude (SVGmag), premature ventricular contractions (PVCs) and tachycardia-dependent intermittent bundle branch block (TD-IBBB) on 12-lead ECG at visits 1–5.

Outcome

Adjudicated TS included a first definite or probable thrombotic cerebral infarction, ES—a first definite or probable non-carotid cardioembolic brain infarction. Definite ICH was included if it was the only stroke event.

Results

Over a median 24.5 years follow-up, there were 899 TS, 400 ES and 120 ICH events. Cox proportional hazard risk models were adjusted for demographics, cardiovascular disease, risk factors, atrial fibrillation, atrial substrate and left ventricular hypertrophy. After adjustment, PVCs (HR 1.72; 95% CI 1.02 to 2.92), QRS-Ta (HR 1.15; 95% CI 1.03 to 1.28), SAIQRST (HR 1.20; 95% CI 1.07 to 1.34) and time-updated SVGmag (HR 1.19; 95% CI 1.08 to 1.32) associated with ES. Similarly, PVCs (HR 1.53; 95% CI 1.03 to 2.26), QRS-Ta (HR 1.08; 95% CI 1.01 to 1.16), SAIQRST (HR 1.07; 95% CI 1.01 to 1.14) and time-updated SVGmag (HR 1.11; 95% CI 1.04 to 1.19) associated with TS. TD-IBBB (HR 3.28; 95% CI 1.03 to 10.46) and time-updated SVGmag (HR 1.23; 95% CI 1.03 to 1.47) were associated with ICH.

Conclusions

PVC burden (reflected by cardiac memory) is associated with ischaemic stroke. Transient cardiac memory (likely through TD-IBBB) precedes ICH.
Assessing the capacity of symptom scores to predict COVID-19 positivity in Nigeria: a national derivation and validation cohort study
Authors: Elimian Kelly Osezele , Aderinola Olaolu , Gibson Jack , Myles Puja , Ochu Chinwe Lucia , King Carina , Okwor Tochi , Gaudenzi Giulia , Olayinka Adebola , Zaiyad Habib Garba , Ohonsi Cornelius , Ebhodaghe Blessing , Dan-Nwafor Chioma , Nwachukwu William , Abdus-salam Ismail Adeshina , Akande Oluwatosin Wuraola , Falodun Olanrewaju , Arinze Chinedu , Ezeokafor Chidiebere , Jafiya Abubakar , Ojimba Anastacia , Aremu John Tunde , Joseph Emmanuel , Bowale Abimbola , Mutiu Bamidele , Saka Babatunde , Jinadu Arisekola , Hamza Khadeejah , Ibeh Christian , Bello Shaibu , Asuzu Michael , Mba Nwando , Oladejo John , Ilori Elsie , Alfvén Tobias , Igumbor Ehimario , Ihekweazu Chikwe
Published: September 2021

Objectives

This study aimed to develop and validate a symptom prediction tool for COVID-19 test positivity in Nigeria.

Design

Predictive modelling study.

Setting

All Nigeria States and the Federal Capital Territory.

Participants

A cohort of 43 221 individuals within the national COVID-19 surveillance dataset from 27 February to 27 August 2020. Complete dataset was randomly split into two equal halves: derivation and validation datasets. Using the derivation dataset (n=21 477), backward multivariable logistic regression approach was used to identify symptoms positively associated with COVID-19 positivity (by real-time PCR) in children (≤17 years), adults (18–64 years) and elderly (≥65 years) patients separately.

Outcome measures

Weighted statistical and clinical scores based on beta regression coefficients and clinicians’ judgements, respectively. Using the validation dataset (n=21 744), area under the receiver operating characteristic curve (AUROC) values were used to assess the predictive capacity of individual symptoms, unweighted score and the two weighted scores.

Results

Overall, 27.6% of children (4415/15 988), 34.6% of adults (9154/26 441) and 40.0% of elderly (317/792) that had been tested were positive for COVID-19. Best individual symptom predictor of COVID-19 positivity was loss of smell in children (AUROC 0.56, 95% CI 0.55 to 0.56), either fever or cough in adults (AUROC 0.57, 95% CI 0.56 to 0.58) and difficulty in breathing in the elderly (AUROC 0.53, 95% CI 0.48 to 0.58) patients. In children, adults and the elderly patients, all scoring approaches showed similar predictive performance.

Conclusions

The predictive capacity of various symptom scores for COVID-19 positivity was poor overall. However, the findings could serve as an advocacy tool for more investments in resources for capacity strengthening of molecular testing for COVID-19 in Nigeria.
Cross-sectional association between long working hours and endoscopic gastritis: the Kangbuk Samsung Health Study
Authors: Mun Eunchan , Lee Yesung , Lee Woncheol , Park Soyoung
Published: September 2021

Objectives

This study aimed to determine the cross-sectional association between long working hours and gastritis diagnosed by endoscopy.

Design

Cross-sectional study.

Setting

Large university hospitals in Seoul and Suwon, South Korea.

Participants

Workers in formal employment who underwent a comprehensive health examination at the Kangbuk Samsung Hospital Total Healthcare Centre clinics in Seoul and Suwon, South Korea, between January 2011 and December 2018. Of the 386 488 participants, 168 391 full-time day workers met the inclusion criteria and were included in the analysis.

Primary outcome measure

Endoscopic gastritis.

Results

The participants were predominantly college graduates or above (88.9%), male (71.2%) and in their 30s (51.1%), and the median age was 36 (IQR 31–42). Approximately 93.2% of participants had positive endoscopic gastritis, and there was a significant association between working hours and positive findings of endoscopic gastritis. The multivariate fully adjusted prevalence ratio (PR) of endoscopic gastritis for participants working >55 hours per week compared with 35–40 hours per week was 1.011 (95% CI 1.007 to 1.015). Furthermore, endoscopic findings were classified into nine subtypes of gastritis, including superficial gastritis, erosive gastritis, atrophic gastritis, intestinal metaplasia and haemorrhagic gastritis increased with longer working hours (p for trends <0.05). Their PRs for participants working >55 hours per week compared with 35–40 hours per week were 1.019 (95% CI 1.012 to 1.026), 1.025 (95% CI 1.011 to 1.040), 1.017 (95% CI 1.008 to 1.027), 1.066 (95% CI 1.028 to 1.105) and 1.177 (95% CI 1.007 to 1.375), respectively.

Conclusions

Working over 55 hours per week was cross-sectionally associated with positive findings of endoscopic gastritis. The study findings indicated potentially increased risks of superficial gastritis, erosive gastritis, atrophic gastritis, intestinal metaplasia and haemorrhagic gastritis among workers with long working hours (>55 hours per week), supporting the need for further exploration via longitudinal studies.
Protocol for a multicentre, randomised, parallel-control, superiority trial comparing administration of clotting factor concentrates with a standard massive haemorrhage protocol in severely bleeding trauma patients: the FiiRST 2 trial (a 2020 EAST multicentre trial)
Authors: da Luz Luis Teodoro , Callum Jeannie , Beckett Andrew , Hucke Hans-Peter , Carroll Jo , Grewal Deep , Schwartz Bruce , Peng Henry , Engels Paul T , Parry Neil , Petrosoniak Andrew , Tien Homer , Nathens Avery B , Scales Damon , Karkouti Keyvan
Published: September 2021

Introduction

Acute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.

Methods and analysis

The factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.

Ethics and dissemination

The study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.

Trial registration number

NCT04534751, pre results.
Implementing person-centred outcome measures (PCOMs) into routine palliative care: A protocol for a mixed-methods process evaluation of The RESOLVE PCOM Implementation Strategy
Authors: Bradshaw Andy , Santarelli Martina , Khamis Assem M , Sartain Kathryn , Johnson Miriam , Boland Jason , Pearson Mark , Murtagh Fliss E M
Published: September 2021

Introduction

Person-centred outcome measures improve quality of care and patient outcomes but are used inconsistently in palliative care practice. To address this implementation gap, we developed the ‘RESOLVE Implementation Strategy’. This protocol describes a process evaluation to explore mechanisms through which this strategy does, or does not, support the implementation of outcome measures in routine palliative care practice.

Methods and analysis

Multistrand, mixed-methods process evaluation. Strand one will collect routine outcomes data (palliative Phase of Illness, Integrated Palliative care Outcomes Scale, Australia-modified Karnofsky Performance Status) to map the changes in use of outcome measures over 12 months (July 2021–July 2022). Strand two will collect survey data over the same 12-month period to explore how professionals’ understandings of, skills in using and ability to build organisational practices around, outcome measures change over time. Strand three will collect interview data to understand the mechanisms underpinning/affecting our implementation strategy. Thematic framework analysis and descriptive statistics will be used to analyse qualitative and quantitative data, respectively.

Ethics and dissemination

For strand one, ethical approval has been obtained (Cambridge REC, REF: 20/EE/0188). For strands two and three, ethical approval has been obtained from Hull York Medical School ethics committee (2105). Tailored feedback of study findings will be provided to participating sites. Abstracts and papers will be submitted to national/international conferences and peer-reviewed journals. Lay and policy briefings and newsletters will be shared through patient and public involvement and project networks, plus via the project website.