bluuebunny/crossref_metadata_2025 huggingface dataset:
On the topological complexity of toral relatively hyperbolic groups
Authors: Li Kevin
Published: July 2021

We prove that the topological complexity

TC
⁡
(
π
)

\operatorname {TC}(\pi )

equals

c
d
(
π
×
π
)

cd(\pi \times \pi )

for certain toral relatively hyperbolic groups

π
\pi

.
D-MANOVA: fast distance-based multivariate analysis of variance for large-scale microbiome association studies
Authors: Chen Jun , Zhang Xianyang
Published: July 2021

PERMANOVA (permutational multivariate analysis of variance based on distances) has been widely used for testing the association between the microbiome and a covariate of interest. Statistical significance is established by permutation, which is computationally intensive for large sample sizes. As large-scale microbiome studies, such as American Gut Project (AGP), become increasingly popular, a computationally efficient version of PERMANOVA is much needed. To achieve this end, we derive the asymptotic distribution of the PERMANOVA pseudo-F statistic and provide analytical P-value calculation based on chi-square approximation. We show that the asymptotic P-value is close to the PERMANOVA P-value even under a moderate sample size. Moreover, it is more accurate and an order-of-magnitude faster than the permutation-free method MDMR. We demonstrated the use of our procedure D-MANOVA on the AGP dataset.

Availability and implementation

D-MANOVA is implemented by the dmanova function in the CRAN package GUniFrac.

Supplementary information

Supplementary data are available at Bioinformatics online.
Openness weighted association studies: leveraging personal genome information to prioritize non-coding variants
Authors: Song Shuang , Shan Nayang , Wang Geng , Yan Xiting , Liu Jun S , Hou Lin
Published: July 2021

Motivation

Identification and interpretation of non-coding variations that affect disease risk remain a paramount challenge in genome-wide association studies (GWAS) of complex diseases. Experimental efforts have provided comprehensive annotations of functional elements in the human genome. On the other hand, advances in computational biology, especially machine learning approaches, have facilitated accurate predictions of cell-type-specific functional annotations. Integrating functional annotations with GWAS signals has advanced the understanding of disease mechanisms. In previous studies, functional annotations were treated as static of a genomic region, ignoring potential functional differences imposed by different genotypes across individuals.

Results

We develop a computational approach, Openness Weighted Association Studies (OWAS), to leverage and aggregate predictions of chromosome accessibility in personal genomes for prioritizing GWAS signals. The approach relies on an analytical expression we derived for identifying disease associated genomic segments whose effects in the etiology of complex diseases are evaluated. In extensive simulations and real data analysis, OWAS identifies genes/segments that explain more heritability than existing methods, and has a better replication rate in independent cohorts than GWAS. Moreover, the identified genes/segments show tissue-specific patterns and are enriched in disease relevant pathways. We use rheumatic arthritis and asthma as examples to demonstrate how OWAS can be exploited to provide novel insights on complex diseases.

Availability and implementation

The R package OWAS that implements our method is available at https://github.com/shuangsong0110/OWAS.

Supplementary information

Supplementary data are available at Bioinformatics online.
Macrophage phagocytosis after spinal cord injury: when friends become foes
Authors: Van Broeckhoven Jana , Sommer Daniela , Dooley Dearbhaile , Hendrix Sven , Franssen Aimée J P M
Published: July 2021

After spinal cord injury, macrophages can exert either beneficial or detrimental effects depending on their phenotype. Aside from their critical role in inflammatory responses, macrophages are also specialized in the recognition, engulfment, and degradation of pathogens, apoptotic cells, and tissue debris. They promote remyelination and axonal regeneration by removing inhibitory myelin components and cellular debris. However, excessive intracellular presence of lipids and dysregulated intracellular lipid homeostasis result in the formation of foamy macrophages. These develop a pro-inflammatory phenotype that may contribute to further neurological decline. Additionally, myelin-activated macrophages play a crucial role in axonal dieback and retraction.

Here, we review the opposing functional consequences of phagocytosis by macrophages in spinal cord injury, including remyelination and regeneration versus demyelination, degeneration, and axonal dieback. Furthermore, we discuss how targeting the phagocytic ability of macrophages may have therapeutic potential for the treatment of spinal cord injury.
X-linked serotonin 2C receptor is associated with a non-canonical pathway for sudden unexpected death in epilepsy
Authors: Massey Cory A , Thompson Samantha J , Ostrom Ryan W , Drabek Janice , Sveinsson Olafur A , Tomson Torbjörn , Haas Elisabeth A , Mena Othon J , Goldman Alica M , Noebels Jeffrey L
Published: July 2021

Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic drive as a critical pathogenic step. Accordingly, the G protein-coupled, membrane serotonin receptor 5-HT2C inhibits forebrain and brainstem networks by exciting GABAergic interneurons, and deletion of this gene lowers the threshold for lethal evoked audiogenic seizures. Here, we characterize epileptogenesis throughout the lifespan of mice lacking X-linked, 5-HT2C receptors (loxTB Htr2c). We find that loss of Htr2c generates a complex, adult-onset spontaneous epileptic phenotype with a novel progressive hyperexcitability pattern of absences, non-convulsive, and convulsive behavioural seizures culminating in late onset sudden mortality predominantly in male mice. RNAscope localized Htr2c mRNA in subsets of Gad2+ GABAergic neurons in forebrain and brainstem regions. To evaluate the contribution of 5-HT2C receptor-mediated inhibitory drive, we selectively spared their deletion in GAD2+ GABAergic neurons of pan-deleted loxTB Htr2c mice, yet unexpectedly found no amelioration of survival or epileptic phenotype, indicating that expression of 5-HT2C receptors in GAD2+ inhibitory neurons was not sufficient to prevent hyperexcitability and lethal seizures. Analysis of human Sudden Unexpected Death in Epilepsy and epilepsy genetic databases identified an enrichment of HTR2C non-synonymous variants in Sudden Unexpected Death in Epilepsy cases. Interestingly, while early lethality is not reflected in the mouse model, we also identified variants mainly among male Sudden Infant Death Syndrome patients. Our findings validate HTR2C as a novel, sex-linked candidate gene modifying Sudden Unexpected Death in Epilepsy risk, and demonstrate that the complex epilepsy phenotype does not arise solely from 5-HT2C-mediated synaptic disinhibition. These results strengthen the evidence for the serotonin hypothesis of Sudden Unexpected Death in Epilepsy risk in humans, and advance current efforts to develop gene-guided interventions to mitigate premature mortality in epilepsy.
Coronavirus Disease 2019 (COVID-19) Outbreak Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) P.1 Lineage in a Long-Term Care Home After Implementation of a Vaccination Program—Ontario, Canada, April–May 2021
Authors: Williams Chantal , Al-Bargash Dana , Macalintal Celeste , Stuart Rebecca , Seth Anu , Latham Julienne , Gitterman Leah , Fedsin Stephanie , Godoy Marion , Kozak Robert , Guthrie Jennifer L , Wood Heidi , McGeer Allison , Hota Susy , Rea Elizabeth
Published: July 2021

In a P.1 coronavirus disease 2019 (COVID-19) outbreak in a long-term care home, vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 52.5% (95% confidence interval: 26.9%–69.1%) in residents and 66.2% (2.3%–88.3%) in staff. Vaccine effectiveness against severe illness was 78.6% (47.9%–91.2%) in residents. Two of 19 vaccinated resident case patients died. Outbreak management required both vaccination and infection control measures.
Adalimumab, Infliximab, and Vedolizumab in Treatment of Ulcerative Colitis: A Long-Term Retrospective Study in a Tertiary Referral Center
Authors: Gagnon Ann-Lorie , Beauchesne William , Tessier Laurence , David Charles , Berbiche Djamal , Lavoie Alexandre , Michaud-Herbst Alban , Tremblay Karine
Published: July 2021

Background

Biological therapies have changed the landscape of pharmacological management of ulcerative colitis (UC). However, a large proportion of patients do not respond to biologics, lose their response over time, or present adverse drug events. This study aims to assess therapeutic response and treatment persistence to adalimumab, infliximab, and vedolizumab, 3 agents widely used in a tertiary referral center of Saguenay–Lac-Saint-Jean (Quebec, Canada).

Methods

We conducted a retrospective population-based study with a thorough review of patients’ medical charts. Adults at UC diagnosis, with current or past use of adalimumab, infliximab, or vedolizumab, were included in the study. Clinical data were collected in order to assess response phenotypes and persistence to treatment. Kaplan–Meier curves were performed to assess treatment persistence, and predictors for discontinuation were assessed using Cox regression analyses.

Results

A total of 134 patients were included in this study. For the cases exposed to adalimumab, infliximab, and vedolizumab, 56.9%, 62.5%, and 47.5% were responders, respectively. Mean persistence rates (95% CI) were 5.5 (4.3–6.6), 10.1 (8.7–11.5), and 3.6 (2.9–4.2) years for adalimumab, infliximab, and vedolizumab, respectively. Increased persistence rates were observed in biologic-naïve patients treated with infliximab in comparison to those with the previous exposition to 2 biologics, but no such effect was observed for adalimumab or vedolizumab. Overall, 61.9% of cases had adverse drug events and of these, 6 led to treatment discontinuation.

Conclusion

This study presents long-term treatment persistence data with adalimumab, infliximab, and vedolizumab, showing that more than half of cases treated with these biologics remained on treatment at least 24 months after initiation.
Focus on the road to modelling cardiomyopathy in muscular dystrophy
Authors: Canonico Francesco , Chirivi Maila , Maiullari Fabio , Milan Marika , Rizzi Roberto , Arcudi Alessandra , Galli Mattia , Pane Marika , Gowran Aoife , Pompilio Giulio , Mercuri Eugenio , Crea Filippo , Bearzi Claudia , D’Amario Domenico
Published: July 2021

Alterations in the DMD gene, which codes for the protein dystrophin, cause forms of dystrophinopathies such as Duchenne muscular dystrophy, an X-linked disease. Cardiomyopathy linked to DMD mutations is becoming the leading cause of death in patients with dystrophinopathy. Since phenotypic pathophysiological mechanisms are not fully understood, the improvement and development of new disease models, considering their relative advantages and disadvantages, is essential. The application of genetic engineering approaches on induced pluripotent stem cells, such as gene-editing technology, enables the development of physiologically relevant human cell models for in vitro dystrophinopathy studies. The combination of induced pluripotent stem cells-derived cardiovascular cell types and 3D bioprinting technologies hold great promise for the study of dystrophin-linked cardiomyopathy. This combined approach enables the assessment of responses to physical or chemical stimuli, and the influence of pharmaceutical approaches. The critical objective of in vitro microphysiological systems is to more accurately reproduce the microenvironment observed in vivo. Ground-breaking methodology involving the connection of multiple microphysiological systems comprised of different tissues would represent a move toward precision body-on-chip disease modelling could lead to a critical expansion in what is known about inter-organ responses to disease and novel therapies that have the potential to replace animal models. In this review, we will focus on the generation, development, and application of current cellular, animal, and potential for bio-printed models, in the study of the pathophysiological mechanisms underlying dystrophin-linked cardiomyopathy in the direction of personalized medicine.
Clinical impact of left atrial appendage filling defects in patients undergoing transcatheter aortic valve implantation
Authors: Okuno Taishi , Lanz Jonas , Stortecky Stefan , Heg Dik , Bernhard Benedikt , Gräni Christoph , Huber Adrian , Praz Fabien , Räber Lorenz , Valgimigli Marco , Siontis George C M , Windecker Stephan , Pilgrim Thomas
Published: July 2021

Aims

Incidental detection of left atrial appendage (LAA) filling defects is a common finding on multi-detector computed tomography in aortic stenosis patients under evaluation for transcatheter aortic valve implantation (TAVI). We aimed to investigate the incidence of LAA filling defects before TAVI and its impact on clinical outcomes.

Methods and results

In a prospective registry, LAA filling defects were retrospectively evaluated and categorized into one of four sub-types: thrombus-like, heterogeneous, horizontal, and Hounsfield Unit (HU)-run-off. The primary endpoint was the composite of cardiovascular death or disabling stroke up to 1-year follow-up. Among 1621 patients undergoing TAVI between August 2007 and June 2018, LAA filling defects were present in 177 patients (11%), and categorized as thrombus-like in 22 (1.4%), heterogeneous in 37 (2.3%), horizontal in 80 (4.9%), and HU-run-off in 38 (2.4%). Compared to patients with normal LAA filling, patients with LAA filling defects had greater prevalence of atrial fibrillation (84.7% vs. 26.4%, P < 0.001) and history of cerebrovascular events (16.4% vs. 10.9%, P = 0.045). The primary endpoint occurred in 131 patients (9.2%) with normal LAA filling and in 36 patients (21.2%) with LAA filling defects (P < 0.001). Subgroup analysis suggested that the risk of disabling stroke was greatest in the thrombus-like pattern (23.0%), followed by the HU-run-off (8.0%), the heterogeneous (6.2%), and the horizontal pattern (1.2%).

Conclusion

LAA filling defects were observed in 11% of aortic stenosis patients undergoing TAVI and associated with an increased risk of cardiovascular death and disabling stroke up to 1 year following TAVI.

Trial Registration

https://www.clinicaltrials.gov. NCT01368250.
Association of ruptured sinus of Valsalva aneurysm and congenital ventricular septal defect: a case series
Authors: Sarhan Hatem Hemdan Taha , Shawky Abdel Haleem , Anilkumar Smitha , Elmaghraby Ahmed , Sivadasan Praveen C , Omar Amr S , Al-Mulla Abdul Wahid
Published: July 2021

Background

Ruptured sinus of Valsalva aneurysm (RSOVA) is rare, and it is more common in Asians. Typically, the patient presents with acute/subacute shortness of breath (SOB) and chest pain. Echocardiography is the gold standard for diagnosis in most of these cases. Surgery has remained the first line of management.

Case summary

We present two cases of RSOVA in which the patients presented to the emergency department with SOB. Their preoperative echocardiography results showed RSOVA into the right ventricle. During surgical repair, ventricular septal defect (VSD) was also found.

Discussion

RSOVA is frequently associated with other congenital anomalies, and most often with VSD. In our cases, we believe that VSDs were missed preoperatively because either the large aneurysmal sacs covered the VSD or there was overlap between the two shunts. Additionally, in the first case, right ventricular pressure was high approaching systemic pressure, which probably reduced the shunt across the VSD. Early intervention is recommended to prevent endocarditis or enlargement of the ruptured aneurysm; long-term results were excellent after surgical repair. Most patients undergo surgery between 20 and 40 years of age, and the reported survival rate is 95% at 20 years. If left untreated, patients typically die of heart failure or endocarditis within 1 year after onset of symptoms.
A case report of cryoballoon-based pulmonary vein isolation in a patient with situs inversus abdominalis and levocardia
Authors: Anwar Omar , Espersen Tobias , Willems Stephan , Eickholt Christian
Published: July 2021

Background

Cryoballoon-based pulmonary vein isolation (cbPVI) is a standardized treatment of atrial fibrillation. In complex anatomies, radiofrequency ablation (rfPVI) is usually preferred. We describe the first cbPVI in a rare patient with SI and levocardia.

Case summary

A 41-year-old male patient with paroxysmal atrial fibrillation was referred to our clinic after a previous, unsuccessful cbPVI procedure. Observation of an atypical lead-wire position due to an abnormal anatomy of the inferior vena cava led to its initial termination. A subsequent thoraco-abdominal computed tomography revealed situs inversus abdominalis and levocardia and the procedure was re-attempted in our clinic. Transseptal puncture (TSP) was guided via transoesophageal echocardiography and fluoroscopy, using a SL0-Sheath and a standard BRK-needle. Advancement of the sheath initially failed but after additional dilatation with an Inoue® dilator, transseptal passage of the sheath was successful. Due to the unusual antero-cranial TSP, the septal pulmonary veins (PV) contrasted poorly. After repeat TSP, a steerable FlexCath Advance® sheath was introduced into the left atrium using an Amplatz Super Stiff® guidewire. Subsequently, all PV were intubated with the Achieve® catheter, over which a 2nd generation cryoballoon was introduced. Despite the practical challenges in this case, all PV were isolated.

Discussion

The main challenges include the achievement of transseptal access and manipulation of the cryoballoon to achieve a patent seal of the pulmonary veins. cbPVI eliminates the need for constant re-positioning of the ablation catheter and might facilitate the creation of durable lesions under such difficult anatomical conditions.
Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study
Authors: Kim Kyoung Jin , Kim Min Sun , Hong Namki , Bae Jae Hyun , Kim Kyeong Jin , Kim Nam Hoon , Rhee Yumie , Lee Juneyoung , Kim Sin Gon
Published: July 2021

Aims

This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort.

Methods and results

From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99–1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17–2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23–2.91; P < 0.01), compared with no calcium supplementation.

Conclusion

Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.
Cardiovascular health in emerging adults with type 1 diabetes
Authors: McCarthy Margaret , Yan Joeyee , Jared Mary Christine , You Erica , Ilkowitz Jeniece , Gallagher Mary Pat , Vaughan Dickson Victoria
Published: July 2021

Aims

Individuals with type 1 diabetes (T1D) face increased risk for cardiovascular disease (CVD). Controlling individual cardiovascular risk factors can prevent or slow the onset of CVD. Ideal cardiovascular health is associated with a lower incidence of CVD. Identifying areas of suboptimal cardiovascular health can help guide CVD prevention interventions. To assess cardiovascular health and explore the barriers and facilitators to achieving ideal cardiovascular health in a sample of young adults with T1D.

Methods and results

We used a sequential mixed-method design to assess the seven factors of cardiovascular health according to American Heart Association. Qualitative interviews, guided by Pender’s Health Promotion Model, were used to discuss participant’s cardiovascular health results and the barriers and facilitators to achieving ideal cardiovascular health. We assessed the frequency of ideal levels of each factor. The qualitative data were analysed using content analysis. Qualitative and quantitative data were integrated in the final analysis phase. The sample (n = 50) was majority female (70%), White (86%), with a mean age of 22 ± 2.4 and diabetes duration of 10.7 ± 5.5 years. Achievement of the seven factors of cardiovascular health were: non-smoking (96%); cholesterol <200 mg/dL (76%); body mass index <25 kg/m2 (54%); blood pressure <120/<80 mmHg (46%); meeting physical activity guidelines (38%); haemoglobin A1c <7% (40%); and healthy diet (14%). Emerging qualitative themes related to the perceived benefits of action, interpersonal influences on their diabetes self-management, and perceived self-efficacy.

Conclusion

We found areas of needed improvement for cardiovascular health. However, these young adults expressed a strong interest in healthy habits which can be supported by their healthcare providers.
Exploring molecular determinants of polysaccharide lyase family 6–1 enzyme activity
Authors: Violot Sébastien , Galisson Frédéric , Carrique Loïc , Jugnarain Vinesh , Conchou Léa , Robert Xavier , Thureau Aurélien , Helbert William , Aghajari Nushin , Ballut Lionel
Published: July 2021

The polysaccharide lyase family 6 (PL6) represents one of the 41 polysaccharide lyase families classified in the CAZy database with the vast majority of its members being alginate lyases grouped into three subfamilies, PL6_1–3. To decipher the mode of recognition and action of the enzymes belonging to subfamily PL6_1, we solved the crystal structures of Pedsa0632, Patl3640, Pedsa3628 and Pedsa3807, which all show different substrate specificities and mode of action (endo-/exolyase). Thorough exploration of the structures of Pedsa0632 and Patl3640 in complex with their substrates as well as docking experiments confirms that the conserved residues in subsites −1 to +3 of the catalytic site form a common platform that can accommodate various types of alginate in a very similar manner but with a series of original adaptations bringing them their specificities of action. From comparative studies with existing structures of PL6_1 alginate lyases, we observe that in the right-handed parallel β-helix fold shared by all these enzymes, the substrate-binding site harbors the same overall conserved structures and organization. Despite this apparent similarity, it appears that members of the PL6_1 subfamily specifically accommodate and catalyze the degradation of different alginates suggesting that this common platform is actually a highly adaptable and specific tool.
Alternatives to in-person exercise classes and training in Germany during the first COVID-19 lockdown
Authors: Füzéki Eszter , Fischer Martin , Würzberger Laura , Groneberg David A , Banzer Winfried
Published: July 2021

COVID-19 containment efforts in most countries included temporary closure of all non-essential services, such as sports and exercise facilities. Also in Germany, sports clubs (SC) had to close for about 2 months starting mid-March 2020. The aim of the present study was to assess what alternatives German SC developed to in-person exercise classes and training. We conducted an anonymous online survey among large German SC. Invitation was sent to 178 SC, 61 data sets could be analyzed. A total of 92% of SC have offered alternatives to in-person exercise classes and training, most of which were digital. Reasons for not offering any alternatives were the lack of financial, personal or technical resources. The large majority (82.1%) of the SC have also allowed non-club members free access to digital alternatives, and 69.6% considered keeping this freely accessible even after the restrictions have been lifted. Almost three quarters (72.3%) of the sport clubs have received no support from their regional umbrella sports organization. In light of the dynamic development of the COVID-19 pandemic, SC must be prepared to offer alternatives to in-person exercise classes and training also on the middle term. These efforts should be supported by sports organizations and communities.
Never-smokers and the fraction of breast cancer attributable to second-hand smoke from parents during childhood: the Norwegian Women and Cancer Study 1991–2018
Authors: Gram Inger T , Wiik Arne Bastian , Lund Eiliv , Licaj Idlir , Braaten Tonje
Published: July 2021

Background

Second-hand smoke (SHS) is not an established risk factor for breast cancer. We examined exposure to SHS from parents during childhood and breast-cancer risk overall and by oestrogen- and progesterone-receptor status in the Norwegian Women and Cancer Study. Furthermore, we utilized our nationally representative prospective cohort study to estimate the fraction of breast cancer attributable to parental SHS during childhood.

Methods

We followed 45 923 never-smoking women, aged 34–70 years, who completed a baseline questionnaire between 1991 and 2007 through linkages to national registries through December 2018. We used Cox proportional-hazards models to estimate age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). We estimated the attributable and the population attributable fraction of breast cancer with 95% CIs.

Results

During a mean follow-up of 19.8 (6.8) years, 2185 women developed invasive breast cancer, confirmed by histology. Women exposed to SHS from parents during childhood had an 11% higher (95% CI: 1.02–1.22) risk of breast cancer compared with those who were not. No difference was found for oestrogen (Pheterogeneity = 0.31) and progesterone (Pheterogeneity = 0.95) receptor status. For women exposed, the attributable fraction was 10.3% (95% CI: 1.8–18.0), whereas the population attributable fraction of breast cancer was 7.0% (95% CI: 1.0–13.0).

Conclusions

Our results suggest that 1 in 14 breast-cancer cases could have been avoided in the absence of SHS exposure from parents during childhood in a population of never-smoking women. The cancer burden attributable to SHS may be underestimated.
Assessment of Vaccine Herd Protection: Lessons Learned From Cholera and Typhoid Vaccine Trials
Authors: Deen Jacqueline , Clemens John D
Published: July 2021

Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors, and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies.
Factors Associated With Self-Reported Medical Errors Among Healthcare Workers: A Cross-Sectional Study From Oman
Authors: Al Balushi Amal Ahmed , Alameddine Mohamad , Fai Chan Moon , Al Sadoon Muna , Bou-Karroum Karen , Al-Adawi Samir
Published: July 2021

Background

Despite efforts to improve patient safety, medical errors remain prevalent among healthcare workers. The aim of this study is to investigate the relationships between self-reported medical errors, occupational outcomes and socio-demographic variables.

Methods

The study employed a cross-sectional design to survey healthcare workers at a large tertiary hospital in Muscat, Oman. The survey questionnaire included socio-demographic variables, a self-assessment of medical errors, work-life balance, occupational burnout, and work-related bullying.

Results

A total of 297 healthcare workers participated in this study. In this sample, the average self-reported medical errors was 5.4±3.3. The prevalence of work-life imbalance, bullying, and moderate/high burnout was 90.2%, 31.3%, and 19.5%, respectively. Multivariate analysis showed that gender, nationality, age, profession, occupational burnout, and bullying were significantly associated with self-reported medical error. Being male was associated with higher self-reported medical errors compared to female workers (ß=1.728, p<.001). Omani workers reported higher medical errors compared to their non-Omani colleagues (ß=2.668, p<.001). Similarly, healthcare workers in a younger age group reported higher medical errors compared with those in the older age group (ß=-1.334, p<.001). Physicians reported higher medical error than nurses (ß=3.126, p<.001). Among occupational outcomes, self-reported medical errors increased with higher burnout rates (ß=1.686, p=0.003) and frequent exposure to bullying (ß=1.609, p<.001).

Conclusion

Improving patient safety has become paramount in the modern age of quality improvement. In this study, medical errors reported by healthcare workers were strongly related to their degree of burnout and exposure to work-related bullying practice. This study makes a unique and tangible contribution to the current knowledge of medical errors among healthcare workers in Oman.
Added value of rapid respiratory syndromic testing at point of care versus central laboratory testing: a controlled clinical trial
Authors: Bouzid Donia , Casalino Enrique , Mullaert Jimmy , Laurent Odile , Duval Xavier , Lescure François Xavier , Peiffer Smadja Nathan , Tubiana Sarah , Armand Lefèvre Laurence , Descamps Diane , Fidouh Nadhira , Choquet Christophe , Lucet Jean-Christophe , Visseaux Benoit
Published: July 2021

Background

Virus-associated respiratory infections are in the spotlight with the emergence of SARS-CoV-2 and the expanding use of multiplex PCR (mPCR). The impact of molecular testing as a point-of-care test (POCT) in the emergency department (ED) is still unclear.

Objectives

To compare the impact of a syndromic test performed in the ED as a POCT and in the central laboratory on length of stay (LOS), antibiotic use and single-room assignment.

Methods

From 19 November 2019 to 9 March 2020, adults with acute respiratory illness seeking care in the ED of a large hospital were enrolled, with mPCR performed with a weekly alternation in the ED as a POCT (week A) or in the central laboratory (week B).

Results

474 patients were analysed: 275 during A weeks and 199 during B weeks. Patient characteristics were similar. The hospital LOS (median 7 days during week A versus 7 days during week B, P = 0.29), the proportion of patients with ED-LOS <1 day (63% versus 60%, P = 0.57) and ED antibiotic prescription (59% versus 58%, P = 0.92) were not significantly different. Patients in the POCT arm were more frequently assigned a single room when having a positive PCR for influenza, respiratory syncytial virus and metapneumovirus [52/70 (74%) versus 19/38 (50%) in the central testing arm, P = 0.012].

Conclusions

Syndromic testing performed in the ED compared with the central laboratory failed to reduce the LOS or antibiotic consumption in patients with acute respiratory illness, but was associated with an increased single-room assignment among patients in whom a significant respiratory pathogen was detected.
PrEP monitoring and HIV incidence after PrEP initiation in France: 2016–18 nationwide cohort study
Authors: Tassi Marc-Florent , Laurent Emeline , Gras Guillaume , Lot Florence , Barin Francis , de Gage Sophie Billioti , Stefic Karl , Grammatico-Guillon Leslie
Published: July 2021

Background

Clinical trials have demonstrated that oral pre-exposure prophylaxis (PrEP) has high efficacy in preventing HIV transmission. In many countries, HIV testing is recommended prior to PrEP initiation, 1 month after and quarterly thereafter. We assessed the uptake of HIV testing and estimated the incidence of HIV infections after oral PrEP initiation, by using the French national health database (SNDS).

Methods

A historic cohort study included every adult person who started oral PrEP between 1 January 2016 and 30 June 2018 in France. HIV infection was tracked in the follow-up, from first PrEP dispensation up to 31 December 2018. Factors associated with adherence to HIV testing in PrEP follow-up were analysed using a generalized linear mixed model.

Results

PrEP users (9893) were followed for a median duration of 551 days (IQR 350–769). The first HIV test, 1 month after PrEP initiation, was performed by 64% of users. For subsequent tests, this rate exceeded 81% and remained stable over time. HIV testing was lower among PrEP users without prescription refill (OR 0.15; 99% CI 0.12–0.20), but higher if the last prescription was made by a hospital practitioner (OR 2.03; 99% CI 1.69–2.45). Twenty-nine HIV infections were identified, leading to an incidence of 0.19 cases per 100 person-years (99% CI 0.12–0.30).

Conclusions

We confirmed good adherence to HIV testing and efficacy of PrEP in users, which should help in decreasing HIV incidence in France. This study also revealed that SNDS could be a powerful automated tool for the epidemiological monitoring of PrEP users.
Regulation of polyphosphate glucokinase gene expression through cotranscriptional processing in Mycobacterium tuberculosis H37Rv
Authors: Bokolia Naveen Prakash , Khan Inshad Ali
Published: July 2021

Transcription is a molecular process that involves the synthesis of RNA chain into the 5ʹ–3ʹ direction, and simultaneously nascent RNA chain tends to form geometric structures, known as cotranscriptional folding. This folding determines the functional properties of RNA molecules and possibly has a critical role during the synthesis. This functioning includes the characterized properties of riboswitches and ribozymes, which are significant when the transcription rate is comparable to the cellular environment. This study reports a novel noncoding region important in the genetic expression of polyphosphate glucokinase (ppgk) in Mycobacterium tuberculosis. This noncoding element of ppgk gene undergoes cleavage activity during the transcriptional process in M.tuberculosis. We revealed that cleavage occurs within the nascent RNA, and the resultant cleaved 3ʹRNA fragment carries the Shine–Dalgarno (SD) sequence and expression platform. We concluded cotranscriptional processing at the noncoding region as the required mechanism for ppgk expression that remains constitutive within the bacterial environment. This study defines the molecular mechanism dependent on the transient but highly active structural features of the nascent RNA.
The Symptoms and Factors Associated With Posttraumatic Stress Disorder for Burns Nurses: A Cross-Sectional Study From Guangdong Province in China
Authors: Zhu Piao-Piao , Chen Li-Ying , Pan Jian-Hua , Kang Chan-Juan , Ye Xue-Mei , Ye Jie-Yu , Li Hai-Yan , Huang Miao , Li Ping , Tan Hui-Yi
Published: July 2021

The symptoms of posttraumatic stress disorder (PTSD) among medical staff have become a significant issue. Environments related to burns are highly stressful for nurses and can lead to PTSD, thus affecting their mental health. It is vital to consider that the quality of burns care, and the outcomes of such treatments, may be threatened if nurses experience PTSD. We evaluated PTSD symptoms in burns nurses and explored the correlations between demographic characteristics, work-related characteristics, professional identity, turnover intention, and PTSD symptoms. This was a cross-sectional study involving 273 nurses working in the burns unit from Guangdong, China, between July and August 2019. Nurses were recruited from 30 hospitals and completed three validated psychological questionnaires: Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Professional Identity Scale (PIS) for nurses, and Turnover Intention Questionnaire (TIQ). We also collated information relating to sociodemographic and work-related characteristics. The cutoff point for the PCL-C was defined as 38 points; 17.22% (n = 47) of participants scored higher than or equal to 38. The PCL-C score was negatively correlated with professional identity level (P < .01) and positively correlated with turnover intention (P < .01). The workplace, mean monthly income, experience of workplace violence, and professional identity level were important factors and all associated with the severity of PTSD. PTSD symptoms were common in burns nurses. Attention should be paid to the mental well-being of these staff. Screening processes need to be initiated to identify individuals suffering from PTSD and take appropriate early interventional action.
Electoral Competition, Voter Bias, and Women in Politics
Authors: Le Barbanchon Thomas , Sauvagnat Julien
Published: July 2021

We quantify the implications of voter bias and electoral competition for politicians’ gender composition. Unfavorable voters’ attitudes toward women and local gender earnings gap correlate negatively with the share of female candidates in Parliamentary elections. Using within-candidate variation across the different polling stations of an electoral district in a given election year, we find that female candidates obtain fewer votes in municipalities with higher gender earnings gaps. We show theoretically that when voters are biased against women, parties facing gender quotas select male candidates in the most contestable districts. We find empirical support for such a strategic party response to voter gender bias. Simulating our calibrated model confirms that competition significantly hinders the effectiveness of gender quotas.
Redshift-space distortions in simulations of the 21-cm signal from the cosmic dawn
Authors: Ross Hannah E , Giri Sambit K , Mellema Garrelt , Dixon Keri L , Ghara Raghunath , Iliev Ilian T
Published: July 2021

The 21-cm signal from the Cosmic Dawn (CD) is likely to contain large fluctuations, with the most extreme astrophysical models on the verge of being ruled out by observations from radio interferometers. It is therefore vital that we understand not only the astrophysical processes governing this signal, but also other inherent processes impacting the signal itself, and in particular line-of-sight effects. Using our suite of fully numerical radiative transfer simulations, we investigate the impact on the redshifted 21-cm from the CD from one of these processes, namely the redshift-space distortions (RSDs). When RSDs are added, the resulting boost to the power spectra makes the signal more or equally detectable for our models for all redshifts, further strengthening hopes that a power spectra measurement of the CD will be possible. RSDs lead to anisotropy in the signal at the beginning and end of the CD, but not while X-ray heating is underway. The inclusion of RSDs, however, decreases detectability of the non-Gaussianity of fluctuations from inhomogeneous X-ray heating as measured by the skewness and kurtosis. On the other hand, mock observations created from all our simulations that include telescope noise corresponding to 1000 h of observation with the Square Kilometre Array telescope show that we may be able to image the CD for all heating models considered and suggest RSDs dramatically boost fluctuations coming from the inhomogeneous Ly α background.
Inferring time-dependent distribution functions from kinematic snapshots
Authors: Darling Keir , Widrow Lawrence M
Published: July 2021

We propose a method for constructing the time-dependent phase space distribution function (DF) of a collisionless system from an isolated kinematic snapshot. In general, the problem of mapping a single snapshot to a time-dependent function is intractable. Here, we assume a finite series representation of the DF, constructed from the spectrum of the system’s Koopman operator. This reduces the original problem to one of mapping a kinematic snapshot to a discrete spectrum rather than to a time-dependent function. We implement this mapping with a convolutional neural network. The method is demonstrated on two example models: the quantum simple harmonic oscillator and a self-gravitating isothermal plane. The latter system exhibits phase space spiral structure similar to that observed in Gaia Data Release 2.
Fluid simulations of cosmic ray-modified shocks
Authors: Tsung Tsun Hin Navin , Oh S Peng , Jiang(姜燕飞) Yan-Fei
Published: July 2021

Cosmic ray (CR)-modified shocks are a demanding test of numerical codes. We use them to test and validate the two-moment method for CR hydrodynamics, as well as characterize the realism of CR shock acceleration in two-fluid simulations which inevitably arises. Previously, numerical codes were unable to incorporate streaming in this demanding regime, and have never been compared against analytic solutions. First, we find a new analytic solution highly discrepant in acceleration efficiency from the standard solution. It arises from bi-directional streaming of CRs away from the subshock, similar to a Zeldovich spike in radiative shocks. Since fewer CRs diffuse back upstream, this favours a much lower acceleration efficiency, typically ${\lesssim}10{{\ \rm per\ cent}}$ (even for Mach number > 10) as opposed to ${\gtrsim}50{{\ \rm per\ cent}}$ found in previous analytic work. At Mach number ≳10, the new solution bifurcates into three branches, with efficient, intermediate, and inefficient CR acceleration. Our two-moment code accurately recovers these solutions across the entire parameter space probed, with no ad hoc closure relations. For generic initial conditions, the inefficient branch is robustly chosen by the code; the intermediate branch is unstable. The preferred branch is very weakly modified by CRs. At high Mach numbers (≳10), the gas jump conditions approach that of a purely hydrodynamic shock, and a sub-grid prescription for thermal injection is required for reasonable acceleration efficiencies ${\sim}10{{\ \rm per\ cent}}$. CR-modified shocks have very long equilibration times (∼1000 diffusion time) required to develop the precursor, which must be resolved by ≳10 cells for convergence. Non-equilibrium effects, poor resolution, and obliquity of the magnetic field all reduce CR acceleration efficiency. Shocks in galaxy-scale simulations will generally contribute little to CR acceleration without sub-grid modification.
Rates and delay times of type Ia supernovae in the Dark Energy Survey
Authors: Wiseman P , Sullivan M , Smith M , Frohmaier C , Vincenzi M , Graur O , Popovic B , Armstrong P , Brout D , Davis T M , Galbany L , Hinton S R , Kelsey L , Kessler R , Lidman C , Möller A , Nichol R C , Rose B , Scolnic D , Toy M , Zontou Z , Asorey J , Carollo D , Glazebrook K , Lewis G F , Tucker B E , Abbott T M C , Aguena M , Allam S , Andrade-Oliveira F , Annis J , Bacon D , Bertin E , Brooks D , Buckley-Geer E , Burke D L , Rosell A Carnero , Kind M Carrasco , Carretero J , Costanzi M , da Costa L N , Pereira M E S , Desai S , Diehl H T , Doel P , Everett S , Ferrero I , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Giannantonio T , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hollowood D L , Honscheid K , Hoyle B , James D J , Krause E , Kuehn K , Kuropatkin N , Maia M A G , Marshall J L , Martini P , Menanteau F , Miquel R , Morgan R , Ogando R L C , Palmese A , Paz-Chinchón F , Petravick D , Pieres A , Malagón A A Plazas , Romer A K , Sanchez E , Scarpine V , Schubnell M , Serrano S , Sevilla-Noarbe I , Soares-Santos M , Suchyta E , Swanson M E C , Tarle G , Thomas D , To C , Varga T N , Walker A R
Published: July 2021

We use a sample of 809 photometrically classified type Ia supernovae (SNe Ia) discovered by the Dark Energy Survey (DES) along with 40415 field galaxies to calculate the rate of SNe Ia per galaxy in the redshift range 0.2 < z < 0.6. We recover the known correlation between SN Ia rate and galaxy stellar mass across a broad range of scales 8.5 ≤ log (M*/M⊙) ≤ 11.25. We find that the SN Ia rate increases with stellar mass as a power-law with index 0.63 ± 0.02, which is consistent with previous work. We use an empirical model of stellar mass assembly to estimate the average star-formation histories (SFHs) of galaxies across the stellar mass range of our measurement. Combining the modelled SFHs with the SN Ia rates to estimate constraints on the SN Ia delay time distribution (DTD), we find the data are fit well by a power-law DTD with slope index β = −1.13 ± 0.05 and normalisation A = 2.11 ± 0.05 × 10−13SNeM⊙−1yr−1,, which corresponds to an overall SN Ia production efficiency $N_{\mathrm{Ia}}/M_* = 0.9 _{-0.7}^{+4.0} \times 10^{-3} \mathrm{SNe} \mathrm{M}_{\odot }^{-1}$,. Upon splitting the SN sample by properties of the light curves, we find a strong dependence on DTD slope with the SN decline rate, with slower-declining SNe exhibiting a steeper DTD slope. We interpret this as a result of a relationship between intrinsic luminosity and progenitor age, and explore the implications of the result in the context of SN Ia progenitors.
Growth of aggregates with liquid-like ice shells in protoplanetary discs
Authors: Musiolik Grzegorz
Published: July 2021

During the first stages of planet formation, the collision growth of dust aggregates in protoplanetary discs (PPDs) is interrupted at the bouncing barrier. Dust aggregates coated by different species of ice turn out to be helpful to shift the bouncing barrier towards larger sizes due to their enhanced sticking properties in some cases. A rarely noticed fact is that H2O ice and H2O–CH3OH–NH3 ice behave liquid-like when UV irradiated within a PPD-similar environment. Dust aggregates coated by these ice species might be damped in collisions due to the liquid-like ice shell, which would effectively result in an increase of the sticking velocity. In this work, collisions of dust aggregates covered by the liquid-like H2O–CH3OH–NH3 ice shell are considered numerically. The coefficient of restitution and the sticking velocity are calculated for different thicknesses of the ice shell. The simulation predicts that an ice-shell thickness of few microns would be sufficient to allow the growth of cm-sized clusters in the PPD.