bluuebunny/crossref_metadata_2025 huggingface dataset:
Study design and baseline characteristics of Shenzhen ageing-related disorder cohort in China
Authors: Liu Li , Liu Wei , Nie Lulin , Guo Zhiwei , Luo Yi , Chen Weihong , Liu Weimin , Zhu Feiqi , Wang Lu , Zhang Jiafei , Wang Xian , Li Tian , Gao Erwei , Zhou Li , He Kaiwu , Huang Yidan , Yuan Chunjie , Zhu Qingqing , Ye Fang , Yu Xingchen , Yuan Jing , Liu Jianjun
Published: June 2020

Purpose

The Shenzhen ageing-related disorder cohort was designed to detect the associations of lifestyle, environmental and genetic factors with major ageing-related disorders, especially neurological and mental disorders.

Participants

The cohort was a community-dwelling prospective study of 9411 elderly adults aged 60 to 92 years from 51 community health service centres in Luohu district of Shenzhen, China. The baseline data were collected between 2017 and 2018, including demographics and socioeconomics, lifestyles, medical history, family history of major non-communicable chronic disease, environmental exposures, clinical analysis of blood and urine, clinical imaging measurements, anthropometric measures and neurological function and mental health assessments. Blood and urinary samples were collected at baseline. All participants will be followed for physiological and psychological disorders and updated lifestyle and environmental exposures every 5 years.

Findings to date

The mean age of the participants was 67.73 years at baseline, and 42.74% were males. The prevalences of individuals with unhealthy conditions were as follows: overweight/obesity (54.38%), hypertension (58.24%), diabetes mellitus (22.30%), dyslipidaemia (75.69%), chronic bronchitis (1.45%), myocardial infarction (0.55%), coronary heart disease (5.69%), stroke (1.10%), cancer (2.18%), arthritis (5.04%), Alzheimer’s disease (0.18%), Parkinson’s disease (0.23%), brain injury (5.75%), cognitive impairment (5.39%) and depression status (3.28%). The mean scores for the Lawton-Brody Activities of Daily Living Scale and the Social Support Rate Scale were 14.15 and 39.54, respectively.

Future plans

2000 new entrants from Luohu district will be recruited every year until 2028. The data collection is expected to be ended at the end of 2030. The data will be used to assess the causality of ageing-related disorders, especially neurological and mental disorders through integrating environmental, genetic and lifestyle factors. The data sets generated and/or analysed during the current study are not publicly available at this stage, but are available from the corresponding author on reasonable request.
Standardised patient encounters to improve quality of counselling for pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) in Kenya: study protocol of a cluster randomised controlled trial
Authors: Larsen Anna , Wilson Kate S , Kinuthia John , John-Stewart G , Richardson BA , Pintye Jillian , Abuna Felix , Lagat Harison , Owens Tamara , Kohler Pamela
Published: June 2020

Introduction

Adolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) demonstration projects observe that AGYW uptake and adherence to PrEP during risk periods is suboptimal. Judgemental interactions with healthcare workers (HCW) and inadequate counselling can be barriers to PrEP use among AGYW. Improving HCW competency and communication to support PrEP delivery to AGYW requires new strategies.

Methods and analysis

PrEP Implementation for Young Women and Adolescents Program-standardised patient (PrIYA-SP) is a cluster randomised trial of a standardised patient actor (SP) training intervention designed to improve HCW adherence to PrEP guidelines and communication skills. We purposively selected 24 clinics offering PrEP services under fully programmatic conditions in Kisumu County, Kenya. At baseline, unannounced SP ‘mystery shoppers’ present to clinics portraying AGYW in common PrEP scenarios for a cross-sectional assessment of PrEP delivery. Twelve facilities will be randomised to receive a 2-day training intervention, consisting of lectures, role-playing with SPs and group debriefing. Unannounced SPs will repeat the assessment in all 24 sites following the intervention. The primary outcome is quality of PrEP counselling, including adherence to national guidelines and communication skills, scored on a checklist by SPs blinded to intervention assignment. An intention-to-treat (ITT) analysis will evaluate whether the intervention resulted in higher scores within intervention compared with control facilities, adjusted for baseline SP scores and accounting for clustering by facility. We hypothesise that the intervention will improve quality of PrEP counselling compared with standard of care. Results from this study will inform guidelines for PrEP delivery to AGYW in low-resource settings and offer a potentially scalable strategy to improve service delivery for this high-risk group.

Ethics and dissemination

The protocol was approved by institutional review boards at Kenyatta National Hospital and University of Washington. An external advisory committee monitors social harms. Results will be disseminated through peer-reviewed journals and presentations.

Trial registration number

NCT03875950
Effect of early cryoprecipitate transfusion versus standard care in women who develop severe postpartum haemorrhage (ACROBAT) in the UK: a protocol for a pilot cluster randomised trial
Authors: Green Laura , Daru Jahnavi , Dodds Julie , Gonzalez Carreras Francisco Jose , Lanz Doris , Zamora Javier , Pardo Llorente Maria del Carmen , Pérez Pérez Teresa , Sweeney Lorna , Thangaratinam Shakila , Thomas Amy , Khan Khalid Saeed
Published: June 2020

Introduction

The incidence of severe postpartum haemorrhage (PPH) that requires blood transfusion is on the increase. Fibrinogen levels have been shown to drop early and significantly during PPH, which is associated with worse outcomes. Early fibrinogen replacement could potentially improve outcomes. No studies have investigated the clinical impact of early cryoprecipitate transfusion in PPH. Prior to performing a full-scale trial, a pilot study is needed to determine feasibility of the intervention and recruitment.

Methods

ACROBAT is a cluster-randomised pilot study with a qualitative evaluation. Four large London maternity units are randomised to either the intervention or control group. The intervention group will adapt their major obstetric haemorrhage procedures to administer cryoprecipitate early for primary PPH. The control group will retain their standard of care.

We include women at >24 weeks gestation who are actively bleeding within 24 hours of delivery and for whom transfusion of red blood cells (RBCs) has been started. We exclude women who decline blood transfusions in advance or have inherited Factor XIII or fibrinogen deficiency. Due to the emergency nature of the intervention, informed consent for administering the intervention is waived.

The primary objective is to assess the feasibility of administering cryoprecipitate within 90 min of RBC request, as compared with standard treatment where cryoprecipitate is given later or not at all. Secondary objectives include the feasibility of recruitment and data collection, reasons for and barriers to consent, preliminary maternal clinical outcomes, identification of the optimal infrastructure pathways for study delivery, and acceptability of the intervention and outcomes.

Ethics and dissemination

The trial has approvals from the London—Brighton & Sussex Research Ethics Committee (ref. 18/LO/2062), the Confidentiality Advisory Group (ref. 18/CAG/0199) and Health Research Authority (IRAS number 237959). Data analysis and publication of manuscripts will start in Q3 2020.

Trial registration number

ISRCTN12146519.
Ankle osteoarthritis and its association with severe ankle injuries, ankle surgeries and health-related quality of life in recently retired professional male football and rugby players: a cross-sectional observational study
Authors: Paget Liam D. A. , Aoki Haruhito , Kemp Simon , Lambert Mike , Readhead Clint , Stokes Keith A , Viljoen Wayne , Reurink Gustaaf , Tol Johannes L , Kerkhoffs Gino M M J , Gouttebarge Vincent
Published: June 2020

Objectives

To determine (1) the prevalence of ankle osteoarthritis (OA) among former professional football and rugby players, (2) assess the association between ankle injuries or ankle surgeries with ankle OA, and (3) compare the mental and physical quality of life (QoL) between former professional football and rugby players with and without OA.

Methods

We conducted a questionnaire-based observational study with a cross-sectional design. Former professional football and rugby players were recruited by the Football Players Worldwide and the International Rugby Players. Information concerning ankle OA, sustained ankle injuries and ankle surgeries was gathered (medical record or most recent medical professional). Health-related QoL was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) physical and mental health scores.

Results

Overall, 553 former professional football (n=401) and rugby (n=152) players were enrolled in the study (response rate of 56%). Ankle OA prevalence among former professional football and rugby players was 9.2% and 4.6%, respectively. Football players were more likely to suffer from ankle OA following every ankle injury and/or surgery. Football and rugby players with ankle OA had similar PROMIS physical and mental health scores to the norm for the general population.

Conclusion

Former professional football and rugby players had higher ankle OA prevalence than the general population (3.4%). Football players are more likely to suffer from ankle OA following every ankle injury and/or surgery. No clinically relevant difference was seen for physical or mental health-related QoL among football and rugby players. Preventive measures for ankle injuries are recommended.
Patient feedback for safety improvement in primary care: results from a feasibility study
Authors: Hernan Andrea L , Giles Sally J , Beks Hannah , McNamara Kevin , Kloot Kate , Binder Marley J , Versace Vincent
Published: June 2020

Objectives

Patient involvement in safety improvement is a developing area of research. The aim of this study was to investigate the feasibility of a patient feedback on safety intervention in primary care. Specifically, the intervention acceptability, fidelity, implementation enablers and barriers, scalability, and process of systematically collecting safety data were examined.

Design, setting and participants

Mixed-methods feasibility trial with six purposively selected Australian primary care practices.

Intervention

The intervention comprised an iterative process with a cycle of measurement, learning, feedback, action planning and implementation period of 6 months.

Primary and secondary outcomes

Qualitative and quantitative data relating to feasibility measures (acceptability, fidelity, enablers, barriers, scalability and process of collecting safety data) were collected and analysed.

Results

A total of n=1750 patients provided feedback on safety. There was a statistically significant increase in mean patient safety scores indicating improved safety (4.30–4.37, p=0.002). Staff deemed the intervention acceptable, with minor recommendations for improvement. Intervention fidelity was high and implementation enablers were attributed to the intervention structure and framework, use of intuitive problem-solving approaches, and multidisciplinary team involvement. Practice-based safety interventions resulted in sustainable and measurable changes to systems for safety, such as increased access to care and improved patient information accuracy.

Conclusions

The findings indicate that this innovative patient feedback on safety intervention is feasible for scale-up to a larger effectiveness trial and further spread into policy and practice. This intervention complements existing safety improvement strategies and activities, and integrates into current patient feedback service requirements for Australian primary care. Further research is needed to examine the intervention effects on safety incident reduction.
Improving transitions from acute care to home among complex older adults using the LACE Index and care coordination
Authors: Charles Lesley , Jensen Lisa , Torti Jacqueline M I , Parmar Jasneet , Dobbs Bonnie , Tian Peter George Jaminal
Published: June 2020

Background

Improving transitions in care is a major focus of healthcare planning. The objective of this study was to determine the improvement in transitions from an intervention identifying complex older adult patients in acute care and supporting their discharge into the community.

Methods

This was a quality assurance study evaluating an intervention on high-risk patients admitted in an acute care hospital. In phase 1, theLength of Stay,Acuity of the Admission,Charlson Comorbidity Index Score, andEmergency Department Use (LACE Index) was selected to assess a patient’s risk for readmission and a standard discharge protocol was developed. In phase 2, the intervention was implemented: (1) all patients were screened for the risk of readmission using the LACE Index; and (2) the high-risk patients were provided care coordination including follow-up phone calls focused on medications, equipment and homecare services. Emergency department (ED) revisits and hospital readmissions were measured.

Results

The LACE Index identified 433/1621 (27%) patients at high risk for readmission. Care coordination was achieved within 72 hours in 79% of patients. The 433 high-risk patients receiving the intervention, compared with a group without intervention (n=231), had lower lengths of stay (12.7 days vs 16.6 days); similar 7-day ED revisits (10.6% vs 10.8%) and 30-day ED revisits (30.5% vs 33.3%); lower 90-day readmissions (39.3% vs 44.6%); and lower 6-month readmissions (50.9% vs 58.4%). The 7-day and 30-day readmissions were similar in both groups.

Conclusions

Identifying complex patients at high risk for readmission and supporting them during transitions from acute care to home potentially decreases lengths of hospital stay and prevents short-term ED revisits and long-term readmissions.
Positron emission tomography imaging in cardiovascular disease
Authors: Tarkin Jason M , Ćorović Andrej , Wall Christopher , Gopalan Deepa , Rudd James HF
Published: June 2020

Positron emission tomography (PET) imaging is useful in cardiovascular disease across several areas, from assessment of myocardial perfusion and viability, to highlighting atherosclerotic plaque activity and measuring the extent of cardiac innervation in heart failure. Other important roles of PET have emerged in prosthetic valve endocarditis, implanted device infection, infiltrative cardiomyopathies, aortic stenosis and cardio-oncology. Advances in scanner technology, including hybrid PET/MRI and total body PET imaging, as well as the development of novel PET tracers and cardiac-specific postprocessing techniques using artificial intelligence will undoubtedly continue to progress the field.
DNA damage repair pathway alterations in metastatic clear cell renal cell carcinoma and implications on systemic therapy
Authors: Ged Yasser , Chaim Joshua L , DiNatale Renzo G , Knezevic Andrea , Kotecha Ritesh R , Carlo Maria I , Lee Chung-Han , Foster Ashley , Feldman Darren R , Teo Min Yuen , Iyer Gopakumar , Chan Timothy , Patil Sujata , Motzer Robert J , Hakimi A Ari , Voss Martin H
Published: June 2020

Background

Loss-of-function alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may determine benefit from immune-oncology (I/O) agents as shown in colon cancer. However, biologic significance and relevance to I/O in metastatic clear cell RCC (ccRCC) are unknown.

Methods

Genomic data and treatment outcomes were retrospectively collected for patients with metastatic ccRCC. Tumor and germline DNA were subject to targeted next generation sequencing across >400 genes of interest, including 34 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) deleterious DDR gene alterations present (Del DDR); (2) wild-type (WT) and variants of unknown significance (VUS) DDR gene alterations present (WT/VUS DDR). Association between DDR status and therapeutic benefit was investigated separately for I/O and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy.

Results

Del DDR were detected in 43/229 patients (19%). The most frequently altered genes wereCHEK2andATM. Clonality analysis was performed in 27 somatic DDR mutations and 17 were clonal (63%). For patients with I/O treatment, Del DDR status was associated with superior overall survival (log-rank p=0.049); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Del DDR was 0.41 (95% CI: 0.14–1.14; p=0.09). No association was seen with VEGF-TKI treatment (log-rank p=0.903).

Conclusion

Del DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Loss-of-function events in these genes may affect outcome with I/O therapy in metastatic RCC, and these hypothesis-generating results deserve further study.
Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy
Authors: Murray-Brown William , Wilsdon Tom D , Weedon Helen , Proudman Susanna , Sukumaran Shawgi , Klebe Sonja , Walker Jennifer G , Smith Malcolm D , Wechalekar Mihir D
Published: June 2020

Background

Immune checkpoint inhibitors (ICIs) are associated with rheumatic and musculoskeletal immune-related adverse events (irAEs) in 5%–20% of patients. Currently, patients refractory to corticosteroids and conventional disease-modifying antirheumatic drugs (cDMARD) are treated with biological DMARDs (bDMARDs) targeting tumor necrosis factor α (TNFα) and interleukin-6, although without a clear biological rationale. Synovial tissue (ST) biopsy presents a valuable opportunity to investigate irAE pathogenesis and appropriately stratify bDMARD use in refractory irAE patients.

Case presentation

We provide the first report of comparative, parallel ST and synovial fluid (SF) analyses of severe, cDMARD-refractory, seronegative polyarthritis, classified as a grade 3 irAE occurring in response to nivolumab treatment for metastatic squamous cell lung cancer, in comparison with ST and SF from patients with untreated rheumatoid arthritis (RA). We investigated immunohistochemical labeling of ST cytokine expression as a biological rationale for selecting therapy. Flow cytometric analysis of lymphocytes from ST, SF and blood collected before and after synovial biopsy-guided therapy, in comparison with RA, were evaluated for insights into the immunopathogenesis of irAE. Immunolabeling of ST demonstrated an excess of TNFα cytokine expression. Subsequent treatment with infliximab resulted in resolution of inflammatory symptoms and a significant reduction in C reactive protein levels. Flow cytometric analysis of synovial infiltrates indicated absence of programmed cell death protein-1 (PD-1) receptor positivity despite cessation of nivolumab approximately 200 days prior to the analyzes.

Conclusions

A deeper understanding of the immunopathogenetic basis of immune activation in irAEs is required in order to select therapy that is likely to be the most effective. This is the first report investigating parallel blood, ST and SF in ICI-induced severe rheumatic irAE. Use of a bDMARD directed by the dominant inflammatory cytokine achieved resolution of synovitis while maintaining cancer remission.
Targeting the coding sequence: opposing roles in regulating classical and non-classical MHC class I molecules by miR-16 and miR-744
Authors: Friedrich Michael , Vaxevanis Christoforos K , Biehl Katharina , Mueller Anja , Seliger Barbara
Published: June 2020

Background

To control gene expression, microRNAs (miRNAs) are of key importance and their deregulation is associated with the development and progression of various cancer types. In this context, a discordant messenger RNA/protein expression pointing to extensive post-transcriptional regulation of major histocompatibility complex (MHC) class I molecules was already shown. However, only a very limited number of miRNAs targeting these molecules have yet been identified. Despite an increasing evidence of coding sequence (CDS)-located miRNA binding sites, there exists so far, no detailed study of the interaction of miRNAs with the CDS of MHC class I molecules.

Methods

Using an MS2-tethering approach in combination with small RNA sequencing, a number of putative miRNAs binding to the CDS of human leukocyte antigen (HLA)-G were identified. These candidate miRNAs were extensively screened for their effects in the HLA-G-positive JEG3 cell line. Due to the high sequence similarity between HLA-G and classical MHC class I molecules, the impact of HLA-G candidate miRNAs on HLA class I surface expression was also analyzed. The Cancer Genome Atlas data were used to correlate candidate miRNAs and HLA class I gene expression.

Results

Transfection of candidate miRNAs revealed that miR-744 significantly downregulates HLA-G protein levels. In contrast, overexpression of the candidate miRNAs miR-15, miR-16, and miR-424 sharing the same seed sequence resulted in an unexpected upregulation of HLA-G. Comparable results were obtained for classical MHC class I members after transfection of miRNA mimics into HEK293T cells. Analyses of The Cancer Genome Atlas data sets for miRNA and MHC class I expression further validated the results.

Conclusions

Our data expand the knowledge about MHC class I regulation and showed for the first time an miRNA-dependent control of MHC class I antigens mediated by the CDS. CDS-located miRNA binding sites could improve the general use of miRNA-based therapeutic approaches as these sites are highly independent of structural variations (e.g. mutations) in the gene body. Surprisingly, miR-16 family members promoted MHC class I expression potentially in a gene activation-like mechanism.
Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients
Authors: Fan Yanbin , Tan Dandan , Song Danyu , Zhang Xu , Chang Xingzhi , Wang Zhaoxia , Zhang Cheng , Chan Sophelia Hoi-Shan , Wu Qixi , Wu Liwen , Wang Shuang , Yan Hui , Ge Lin , Yang Haipo , Mao Bing , Bönnemann Carsten , Liu Jingying , Wang Suxia , Yuan Yun , Wu Xiru , Zhang Hong , Xiong Hui
Published: June 2020

Background

LMNA-related muscular dystrophy is caused by mutations in LMNA gene. We aimed to identify genetic variations and clinical features in a large cohort of Chinese patients with LMNA mutations in an attempt to establish genotype-phenotype correlation.

Methods

The clinical presentations of patients with LMNA-related muscular dystrophy were recorded using retrospective and prospective cohort study. LMNA mutation analysis was performed by Sanger sequencing or next-generation sequencing. Mosaicism was detected by personal genome machine amplicon deep sequencing for mosaicism.

Results

Eighty-four patients were identified to harbour LMNA mutations. Forty-one of those were diagnosed with LMNA-related congenital muscular dystrophy (L-CMD), 32 with Emery-Dreifuss muscular dystrophy (EDMD) and 11 with limb-girdle muscular dystrophy type 1B (LGMD1B). We identified 21 novel and 29 known LMNA mutations. Two frequent mutations were identified: c.745C>T and c.1357C>T. A correlation between the location of mutation and the clinical phenotype was observed: mutations affecting the head and coil 2A domains mainly occurred in L-CMD, while the coil 2B and Ig-like domains mainly related to EDMD and LGMD1B. We found somatic mosaicism in one parent of four probands. Muscle biopsies revealed 11 of 20 biopsied L-CMD exhibited inflammatory changes, and muscle cell ultrastructure showed abnormal nuclear morphology.

Conclusions

Our detailed clinical and genetic analysis of 84 patients with LMNA-related muscular dystrophy expands clinical spectrum and broadens genetic variations caused by LMNA mutations. We identified 21 novel and 29 known LMNA mutations and found two frequent mutations. A correlation between the location of mutation and the clinical severity was observed. Preliminary data suggested that low-dose corticosteroid treatment may be effective.
Defining the phenotypical spectrum associated with variants in TUBB2A
Authors: Brock Stefanie , Vanderhasselt Tim , Vermaning Sietske , Keymolen Kathelijn , Régal Luc , Romaniello Romina , Wieczorek Dagmar , Storm Tim Matthias , Schaeferhoff Karin , Hehr Ute , Kuechler Alma , Krägeloh-Mann Ingeborg , Haack Tobias B , Kasteleijn Esmee , Schot Rachel , Mancini Grazia Maria Simonetta , Webster Richard , Mohammad Shekeeb , Leventer Richard J , Mirzaa Ghayda , Dobyns William B , Bahi-Buisson Nadia , Meuwissen Marije , Jansen Anna C , Stouffs Katrien
Published: June 2020

Background

Variants in genes belonging to the tubulin superfamily account for a heterogeneous spectrum of brain malformations referred to as tubulinopathies. Variants in TUBB2A have been reported in 10 patients with a broad spectrum of brain imaging features, ranging from a normal cortex to polymicrogyria, while one patient has been reported with progressive atrophy of the cerebellar vermis.

Methods

In order to further refine the phenotypical spectrum associated with TUBB2A, clinical and imaging features of 12 patients with pathogenic TUBB2A variants, recruited via the international network of the authors, were reviewed.

Results

We report 12 patients with eight novel and one recurrent variants spread throughout the TUBB2A gene but encoding for amino acids clustering at the protein surface. Eleven patients (91.7%) developed seizures in early life. All patients suffered from intellectual disability, and 11 patients had severe motor developmental delay, with 4 patients (36.4 %) being non-ambulatory. The cerebral cortex was normal in five individuals and showed dysgyria of variable severity in seven patients. Associated brain malformations were less frequent in TUBB2A patients compared with other tubulinopathies. None of the patients had progressive cerebellar atrophy.

Conclusion

The imaging phenotype associated with pathogenic variants in TUBB2A is highly variable, ranging from a normal cortex to extensive dysgyria with associated brain malformations. For recurrent variants, no clear genotype–phenotype correlations could be established, suggesting the role of additional modifiers.
Novel loss-of-function mutation in HERC2 is associated with severe developmental delay and paediatric lethality
Authors: Elpidorou Marilena , Best Sunayna , Poulter James A , Hartill Verity , Hobson Emma , Sheridan Eamonn , Johnson Colin A
Published: June 2020

Background

The HERC2 gene encodes a 527 kDa E3 ubiquitin protein ligase that has key roles in cell cycle regulation, spindle formation during mitosis, mitochondrial functions and DNA damage responses. It has essential roles during embryonic development, particularly for neuronal and muscular functions. To date, missense mutations in HERC2 have been associated with an autosomal recessive neurodevelopmental disorder with some phenotypical similarities to Angelman syndrome, and a homozygous deletion spanning HERC2 and OCA2 causing a more severe neurodevelopmental phenotype.

Methods and results

We ascertained a consanguineous family with a presumed autosomal recessive severe neurodevelopmental disorder that leads to paediatric lethality. In affected individuals, we identified a homozygous HERC2 frameshift variant that results in a premature stop codon and complete loss of HERC2 protein. Functional characterisation of this variant in fibroblasts, from one living affected individual, revealed impaired mitochondrial network and function as well as disrupted levels of known interacting proteins such as XPA.

Conclusion

This study extends the genotype–phenotype correlation for HERC2 variants to include a distinct lethal neurodevelopmental disorder, highlighting the importance of further characterisation for HERC2-related disorders.
UKCGG Consensus Group guidelines for the management of patients with constitutionalTP53pathogenic variants
Authors: Hanson Helen , Brady Angela F , Crawford Gillian , Eeles Rosalind A , Gibson Sarah , Jorgensen Mette , Izatt Louise , Sohaib Aslam , Tischkowitz Marc , Evans D Gareth
Published: June 2020

Constitutional pathogenic variants inTP53are associated with Li-Fraumeni syndrome or the more recently described heritableTP53-related cancer syndrome and are associated with increased lifetime risks of a wide spectrum of cancers. Due to the broad tumour spectrum, surveillance for this patient group has been limited. To date, the only recommendation in the UK has been for annual breast MRI in women; however, more recently, a more intensive surveillance protocol including whole-body MRI (WB-MRI) has been recommended by International Expert Groups. To address the gap in surveillance for this patient group in the UK, the UK Cancer Genetics Group facilitated a 1-day consensus meeting to discuss a protocol for the UK. Using a preworkshop survey followed by structured discussion on the day, we achieved consensus for a UK surveillance protocol forTP53carriers to be adopted by UK Clinical Genetics services. The key recommendations are for annual WB-MRI and dedicated brain MRI from birth, annual breast MRI from 20 years in women and three-four monthly abdominal ultrasound in children along with review in a dedicated clinic.
Haploinsufficiency of theNF1gene is associated with protection against diabetes
Authors: Kallionpää Roope A , Peltonen Sirkku , Leppävirta Jussi , Pöyhönen Minna , Auranen Kari , Järveläinen Hannu , Peltonen Juha
Published: June 2020

Background

The hereditary predisposition to diabetes is only partially explained by genes identified so far. Neurofibromatosis type 1 (NF1) is a rare monogenic dominant syndrome caused by aberrations of theNF1gene. Here, we used a cohort of 1410 patients with NF1 to study the association of theNF1gene with type 1 (T1D) and type 2 diabetes (T2D).

Methods

A total of 1410 patients were confirmed to fulfil the National Institutes of Health diagnostic criteria for NF1 by individually reviewing their medical records. The patients with NF1 were compared with 14 017 controls matched for age, sex and area of residence as well as 1881 non-NF1 siblings of the patients with NF1. Register-based information on purchases of antidiabetic medication and hospital encounters related to diabetes were retrieved. The Cox proportional hazards model was used to calculate the relative risk for diabetes in NF1.

Results

Patients with NF1 showed a lower rate of T2D when compared with a 10-fold control cohort (HR 0.27, 95% CI 0.17 to 0.43) or with their siblings without NF1 (HR 0.28, 95% CI 0.16 to 0.47). The estimates remained practically unchanged after adjusting the analyses for history of obesity and dyslipidaemias. The rate of T1D in NF1 was decreased although statistically non-significantly (HR 0.58, 95% CI 0.27 to 1.25).

Conclusion

Haploinsufficiency of theNF1gene may protect against T2D and probably T1D. SinceNF1negatively regulates the Ras signalling pathway, the results suggest that the Ras pathway may be involved in the pathogenesis of diabetes.
Revisiting the equity debate in COVID-19: ICU is no panacea
Authors: Ballantyne Angela , Rogers Wendy A , Entwistle Vikki , Towns Cindy
Published: June 2020

Throughout March and April 2020, debate raged about how best to allocate limited intensive care unit (ICU) resources in the face of a growing COVID-19 pandemic. The debate was dominated by utility-based arguments for saving the most lives or life-years. These arguments were tempered by equity-based concerns that triage based solely on prognosis would exacerbate existing health inequities, leaving disadvantaged patients worse off. Central to this debate was the assumption that ICU admission is a valuable but scarce resource in the pandemic context.

In this paper, we argue that the concern about achieving equity in ICU triage is problematic for two reasons. First, ICU can be futile and prolong or exacerbate suffering rather than ameliorate it. This may be especially true in patients with COVID-19 with emerging data showing that most who receive access to a ventilator will still die. There is no value in admitting patients with poor prognostic indicators to ICU to meet an equity target when intensive critical care is contrary to their best interests. Second, the focus on ICU admission shifts focus away from important aspects of COVID-19 care where there is greater opportunity for mitigating suffering and enhancing equitable care.

We propose that the focus on equity concerns during the pandemic should broaden to include providing all people who need it with access to the highest possible standard of end-of-life care. This requires attention to culturally safe care in the following interlinked areas: palliative care, communication and decision support and advanced care planning.
Role for machine learning in sex-specific prediction of successful electrical cardioversion in atrial fibrillation?
Authors: Vinter Nicklas , Frederiksen Anne Sofie , Albertsen Andi Eie , Lip Gregory Y H , Fenger-Grøn Morten , Trinquart Ludovic , Frost Lars , Møller Dorthe Svenstrup
Published: June 2020

Objective

Electrical cardioversion is frequently performed to restore sinus rhythm in patients with persistent atrial fibrillation (AF). However, AF recurs in many patients and identifying the patients who benefit from electrical cardioversion is difficult. The objective was to develop sex-specific prediction models for successful electrical cardioversion and assess the potential of machine learning methods in comparison with traditional logistic regression.

Methods

In a retrospective cohort study, we examined several candidate predictors, including comorbidities, biochemistry, echocardiographic data, and medication. The outcome was successful cardioversion, defined as normal sinus rhythm immediately after the electrical cardioversion and no documented recurrence of AF within 3 months after. We used random forest and logistic regression models for sex-specific prediction.

Results

The cohort comprised 332 female and 790 male patients with persistent AF who underwent electrical cardioversion. Cardioversion was successful in 44.9% of the women and 49.9% of the men. The prediction errors of the models were high for both women (41.0% for machine learning and 48.8% for logistic regression) and men (46.0% for machine learning and 44.8% for logistic regression). Discrimination was modest for both machine learning (0.59 for women and 0.56 for men) and logistic regression models (0.60 for women and 0.59 for men), although the models were well calibrated.

Conclusions

Sex-specific machine learning and logistic regression models showed modest predictive performance for successful electrical cardioversion. Identifying patients who will benefit from cardioversion remains challenging in clinical practice. The high recurrence rate calls for thoroughly informed shared decision-making for electrical cardioversion.
Price and expenditure elasticity of cigarette demand in El Salvador: a household-level analysis and simulation of a tax increase
Authors: Paraje Guillermo , Araya Daniel , De Paz Adonay , Nargis Nigar
Published: June 2020

Background

In El Salvador, 8.8% of adults 15 years and older smoke cigarettes. Little is known about the sensitivity of cigarette consumption among the adults in El Salvador to tax and price increases and income growth.

Methods

Elasticities are estimated using Deaton’s Almost Ideal Demand System model applied to data from the National Household Income and Expenditure Survey 2005/2006 for the total population and separately for income groups. The estimates are then used to simulate the effects of a proposed change in tobacco tax policy on cigarette consumption and tax revenue.

Findings

The estimated price elasticities (−0.77 for the total population) are within the range of price elasticity estimates available for low and middle-income countries. Given the estimated elasticities, a tobacco tax increase is expected to reduce the number of smokers (by almost 20%) and increase tobacco tax revenue (by more than 50%).

Conclusions

Increasing tobacco taxes has the potential to decrease consumption in El Salvador and raise fiscal revenues. The tobacco tax burden in El Salvador is one of the lowest in Latin America and the social costs of tobacco consumption largely exceed the tobacco tax revenues. An increase in tobacco tax could significantly decrease the number of smokers and reduce the burden of tobacco-related diseases and deaths.
Characterization of backwater valves in sanitary sewer laterals and associated failures in a Canadian context
Authors: Dusolt S. , Binns A. , McBean E. , Gharabaghi B. , Sandink D.
Published: June 2020

Backwater valves in sanitary sewer laterals have become a primary mechanism for reducing the risk of basement flooding in residential homes. Despite widespread reliance on these devices to prevent sewer back-up, the performance of backwater valves during significant rainfall events is mostly unknown. Using a questionnaire-based approach followed by an in-field site visit, this paper identifies installation and maintenance as the two key factors that lead to potential failures of backwater valves. Among the results discussed, failures were linked to a general lack of knowledge on backwater valve devices and the maintenance procedures required to ensure adequate performance.
Disturbing to restore? Effects of mounding on understory communities on seismic lines in treed peatlands
Authors: Echiverri Laureen F.I. , Macdonald S. Ellen , Nielsen Scott E.
Published: June 2020

In peatlands, microtopography strongly affects understory plant communities. Disturbance can result in a loss of microtopographic variation, primarily through the loss of hummocks. To address this, mounding treatments can be used to restore microtopography. We examined the effects of mounding on the understory vegetation on seismic lines in wooded fens. Seismic lines are deforested linear corridors (∼3 to 8 m wide) created for oil and gas exploration. Our objectives were to compare the recovery of understory communities on unmounded and mounded seismic lines and determine how recovery varies with microtopographic position. Recovery was evident in the unmounded seismic lines, with higher shrub and total understory cover at the “tops” of the small, natural hummocks than at lower microtopographic positions — much like the trends in adjacent treed fens. In contrast, mounding treatments that artificially created hummocks on seismic lines significantly changed understory communities. Mounded seismic lines had higher forb cover, much lower bryophyte cover, less variation along the microtopographic gradient, and community composition less similar to that of the reference sites than unmounded seismic lines due to higher abundance of marsh-associated species. Our results suggest that mounding narrow seismic lines can be detrimental to the recovery of the understory communities in treed peatlands.
Oddity in nonrelativistic, strong gravity
Authors: Ergen Mert , Hamamcı Efe , Van den Bleeken Dieter
Published: June 2020

We consider the presence of odd powers of the speed of light c in the covariant nonrelativistic expansion of General Relativity (GR). The term of order c in the relativistic metric is a vector potential that contributes at leading order in this expansion and describes strong gravitational effects outside the (post-)Newtonian regime. The nonrelativistic theory of the leading order potentials contains the full non-linear dynamics of the stationary sector of GR.
Doubling coverings via resolution of singularities and preparation
Authors: Cluckers Raf , Friedland Omer , Yomdin Yosef
Published: June 2020

In this paper, we provide asymptotic upper bounds on the complexity in two (closely related) situations. We confirm for the total doubling coverings and not only for the chains the expected bounds of the form [Formula: see text] This is done in a rather general setting, i.e. for the [Formula: see text]-complement of a polynomial zero-level hypersurface [Formula: see text] and for the regular level hypersurfaces [Formula: see text] themselves with no assumptions on the singularities of [Formula: see text]. The coefficient [Formula: see text] is the ambient dimension [Formula: see text] in the first case and [Formula: see text] in the second case. However, the question of a uniform behavior of the coefficient [Formula: see text] remains open. As a second theme, we confirm in arbitrary dimension the upper bound for the number of a-charts covering a real semi-algebraic set [Formula: see text] of dimension [Formula: see text] away from the [Formula: see text]-neighborhood of a lower dimensional set [Formula: see text], with bound of the form [Formula: see text] holding uniformly in the complexity of [Formula: see text]. We also show an analogue for level sets with parameter away from the [Formula: see text]-neighborhood of a low dimensional set. More generally, the bounds are obtained also for real subanalytic and real power-subanalytic sets.
Minimization of eigenvalues for the Camassa–Holm equation
Authors: Feng Hao , Meng Gang
Published: June 2020

A key basis for seeking solutions of the Camassa–Holm equation is to understand the associated spectral problem [Formula: see text] We will study in this paper the optimal lower bound of the smallest eigenvalue for the Camassa–Holm equation with the Neumann boundary condition when the [Formula: see text] norm of potentials is given. First, we will study the optimal lower bound for the smallest eigenvalue in the measure differential equations to make our results more applicable. Second, Based on the relationship between the minimization problem of the smallest eigenvalue for the ODE and the one for the MDE, we find the explicit optimal lower bound of the smallest eigenvalue for the Camassa–Holm equation.
A NOVEL GAIT TRAINING DEVICE FOR BEDRIDDEN PATIENTS’ REHABILITATION
Authors: JIANG CHANG , XIANG ZHONGXIA
Published: June 2020

To assist bedridden patients to do rehabilitation exercise in bed, a kind of adjustable rehabilitation training device was designed and kinematic analysis was performed on the model of this device. It is shown that this device can generate trajectory similar to the ankle trajectory of normal gait. Based on the analysis, the human–machine integrated model was then built and biomechanical analysis was applied on it by AnyBody Modeling System. Regarding the forces of some mainly used muscles as study object, the mapping relationships between patient’s posture and tendon forces under the same conditions were analyzed, all these results suggested that this novel device has the capacity to train different muscles with the most appropriate postures and thus it has the potential application in future.
ENTREPRENEURIAL SPAWNING IN THE INFORMAL ECONOMY
Authors: ALNAHEDH MISHARI , ALSANOUSI SALEM
Published: June 2020

What is the career background of formal and informal entrepreneurs and does this influence their formalization decision? We employ the theory of planned behavior, social identity theory and embedded career capital framework to develop hypotheses on how the new venture formalization decision is dependent on the entrepreneur’s career history. We find that employment in a family business and in the private sector is related positively to founding a formal new venture. Furthermore, our results show that a career in the same industry as the new venture increases the likelihood of formalizing the venture. These findings emphasize the role of the career background in the entrepreneur’s formalization decision through building embedded-career capital, influencing the social identity and determining the attitude toward starting a formal versus informal new venture.
Preparation of Nitrogen-Deficient Graphitic Carbon Nitride with a Large Specific Surface Area by Melt Pretreatment and Its Photocatalytic Performance
Authors: Li Xuelei , Bai Jinfeng , Li Jiaqi , Li Chao , Zhang Junru , Deng Shuping
Published: June 2020

In this study, nitrogen-deficient graphitic carbon nitride (M-LS-g-C3N4) with a mesoporous structure and a large specific surface area was obtained by calcination after melt pretreatment using urea as a precursor. X-ray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption, X-ray photoelectron spectroscopy (XPS), UV-Vis, ESR and photoluminescence (PL) were used to characterize the structure, morphology and optical performance of the samples. The TEM results showed the formation of a mesoporous structure on the 0.1[Formula: see text]M-LS-g-C3N4 surface. The porous structure led to an increase in the specific surface area from 41.5[Formula: see text]m2/g to 124.3[Formula: see text]m2/g. The UV-Vis results showed that nitrogen vacancies generated during the modification process reduced the band gap of g-C3N4 and improved the visible light absorption. The PL spectra showed that the nitrogen defects promoted the separation of photogenerated electron–hole pairs. In the visible light degradation of methyl orange (MO), the reaction rate constant of 0.1[Formula: see text]M-LS-g-C3N4 reached 0.0086[Formula: see text][Formula: see text], which was 5.05 times that of pure g-C3N4. Superoxide radicals and photogenerated holes were found to be the main active species in the reaction system. This study provides an efficient, green and convenient means of preparing graphitic carbon nitride with a large specific surface area.
RESPONSE OF CALCAREOUS NANNOPLANKTON TO PALEOCENE–EOCENE THERMAL MAXIMUM IN NORTHERN IRAQ
Authors: AL-HYALY RAGHDA SAAD , AL-BADRANI OMAR AHMED
Published: June 2020

The Paleocene–Eocene Thermal Maximum (PETM) was an abrupt global warming event in the geological record. Based on calcareous nannofossils from thirteen samples of Aaliji Formation from K-116 well, Northern Iraq, sixty species are identified and can be used to divide the studied section into five biozones. Especially, the transition in the Discoaster multiraditus Biozone (CP8) occurred which is marked by higher speciation for calcareous nannofossils and the occurrences of Discoaster Tan. Such atransition is closely related to global warming during the transition from Paleocene to Eocene.
Rapakivi granite in the architecture of St Petersburg: a potential Global Heritage Stone from Finland and Russia
Authors: Bulakh Andrey , Härmä Paavo , Panova Elena , Selonen Olavi
Published: June 2020

Rapakivi granites were in use during the Middle Ages in Finland. Their most spectacular use, however, was for structures built in St Petersburg between 1760 and 1917. Remarkable examples are the majestic and slender Alexander Column and the 112 columns of St Isaac's Cathedral. All Rapakivi granite was extracted from the Wiborg Rapakivi granite batholith in several quarries around the municipality of Virolahti in SE Finland (old Russia). Today, the 1640 Ma-old Wiborg batholith is the most important area for natural stone production in Finland and in the Leningrad region, Russian Federation. The main quarried stone varieties of Rapakivi granite (Baltic Brown, Baltic Green, Carmen Red, Karelia Red, Eagle Red and Balmoral Red) are regularly produced in large quantities in Finland for the global stone market due to the stone's unique qualities. Examples of applications in Rapakivi granite from Finland can be found in the USA, China, South Africa, the UK, Italy, Austria, Ireland, Spain and Germany as well as in Scandinavia and Russia. There are also quarries near Vyborg, the Russian Federation: Vozrozhdenie and Ala-Noskua.