bluuebunny/crossref_metadata_2025 huggingface dataset:
The AGCVIII kinase Dw2 modulates cell proliferation, endomembrane trafficking, and MLG/xylan cell wall localization in elongating stem internodes of Sorghum bicolor
Authors: Oliver Joel , Fan Mingzhu , McKinley Brian , Zemelis‐Durfee Starla , Brandizzi Federica , Wilkerson Curtis , Mullet John E.
Published: November 2020

Stems of bioenergy sorghum (Sorghum bicolor L. Moench.), a drought‐tolerant C4 grass, contain up to 50 nodes and internodes of varying length that span 4–5 m and account for approximately 84% of harvested biomass. Stem internode growth impacts plant height and biomass accumulation and is regulated by brassinosteroid signaling, auxin transport, and gibberellin biosynthesis. In addition, an AGCVIII kinase (Dw2) regulates sorghum stem internode growth, but the underlying mechanism and signaling network are unknown. Here we provide evidence that mutation of Dw2 reduces cell proliferation in internode intercalary meristems, inhibits endocytosis, and alters the distribution of heteroxylan and mixed linkage glucan in cell walls. Phosphoproteomic analysis showed that Dw2 signaling influences the phosphorylation of proteins involved in lipid signaling (PLDδ), endomembrane trafficking, hormone, light, and receptor signaling, and photosynthesis. Together, our results show that Dw2 modulates endomembrane function and cell division during sorghum internode growth, providing insight into the regulation of monocot stem development.
Prevalence and potentially prognostic value of C‐circles associated with alternative lengthening of telomeres in canine appendicular osteosarcoma
Authors: Bicanova Ludmila , Kreilmeier‐Berger Theresa , Reifinger Martin , Holzmann Klaus , Kleiter Miriam
Published: November 2020

Alternative lengthening of telomeres (ALT) is a telomerase‐independent telomere maintenance mechanism (TMM) with high prevalence in human osteosarcomas but remains unknown in canine osteosarcomas. The aim of this study was to evaluate the prevalence of ALT by detection of extra‐chromosomal circles of telomeric DNA and to assess clinical outcome in canine patients with spontaneous occurring appendicular osteosarcoma. Fifty dogs with histopathological confirmed osteosarcomas were included into this study. Medical records were retrospectively analysed for patient characteristics, oncologic therapy and survival. DNA was isolated from archived FFPE tumour tissue specimens and applied for C‐ and G‐circle assay (CCA and GCA) and for telomeric content (TC) measurement with radiolabeled probes. ALT activity was detected for 10 of 50 (20%) cases by CCA. Four CCA positive cases were detected even with input DNA below 1 ng and demonstrated the high sensitivity of CCA for canine tumours. G‐circles and TC were not suitable to distinguish CCA positive and negative cases. CCA‐status showed an association with male gender and Rottweiler breed. Dogs with CCA positive osteosarcomas had shorter overall survival times than patients with CCA‐tumours and CCA‐status was a significant prognostic factor besides treatment in the Cox proportional hazard model. These findings make canine osteosarcomas an interesting model for comparative TMM research, but future studies are warranted to investigate if CCA‐status can serve as novel prognostic marker.
The Gender Wage Gap in Developing Countries
Authors: Si Chengyu , Nadolnyak Denis , Hartarska Valentina
Published: November 2020

The labor literature documents a gender wage gap between the earnings of men and women in the developed countries but research on the gap in developing countries is less common and usually focuses on individual countries. Research typically identifies a part of the wage gap that is due to observable characteristics, or endowments, and an unexplained part attributable to differences in gender wage equation coefficients sometimes interpreted as gender bias. The focus of recent gender wage gap research has been on understanding how the gender gap varies along the earnings distribution. In this paper, we investigate the determinants of the gender wage gap across 12 developing countries using data from the World Bank’s STEP (Skills Toward Employment and Productivity) Measurement survey that provides information on household demographic characteristics, education and training, employment, and job skills. We apply the classical Blinder-Oaxaca decomposition and combined with quantile regression and also use decomposition methods based on the recentered influence function to obtain distributional decomposition of the wage gap by covariates and by quantiles. Our results show that there are significant gender pay differences that generally decrease with earnings and are mostly due to differences in the intercepts and a slightly offsetting difference in returns to education that are higher for women. The explained part of the gender wage gap, although much smaller, is attributed almost entirely to lower educational level of women and the motherhood penalty. The main conclusion is that improvements in women’s education and training, as well as child friendly labor policies, remain the most important factors that can help to narrow the gender gap in developing countries, which is consistent with previous work.
How does oxygen diffuse from capillaries to tissue mitochondria? Barriers and pathways
Authors: Pias Sally C.
Published: November 2020

Timely delivery of oxygen (O2) to tissue mitochondria is so essential that elaborate circulatory systems have evolved to minimize diffusion distances within tissue. Yet, knowledge is surprisingly limited regarding the diffusion pathway between blood capillaries and tissue mitochondria. An established and growing body of work examines the influence cellular and extracellular structures may have on subcellular oxygen availability. This brief review discusses the physiological and pathophysiological significance of oxygen availability, highlights recent computer modelling studies of transport at the cell‐membrane level, and considers alternative diffusion pathways within tissue. Experimental and computer modelling studies suggest that oxygen diffusion may be accelerated by cellular lipids, relative to cytosolic and interstitial fluids. Such acceleration, or ‘channelling’, would occur due to greatly enhanced oxygen solubility in lipids, especially near the midplane of lipid bilayers. Rapid long‐range movement would be promoted by anisotropically enhanced lateral diffusion of oxygen along the midplane and by junctions holding lipid structures in close proximity to one another throughout the tissue. Clarifying the biophysical mechanism of oxygen transport within tissue will shed light on limitations and opportunities in tumour radiotherapy and tissue engineering.

image
Cyclic approach for silicon nitride spacer etching in fin field-effect transistors and stacked nanowire devices
Authors: Pollet Olivier , Ah-Leung Vincent , Barnola Sebastien , Posseme Nicolas
Published: November 2020

Spacer etching in 3D CMOS technologies has become a very challenging step to be able to complete the etching while preserving channel and shallow trench insulation materials. The formation of parasitic spacers along fin sidewalls requires a lengthy overetch compared to conventional planar integrations to remove these undesired features, thereby drastically increasing the needed etching selectivities between silicon nitride, silicon (or SiGe), and silicon oxide. Based on an alternative etching chemistry, a new approach is assessed in this work, whose principle relies on selective passivation with an oxidelike material replacing the fluorine-containing organic layer encountered in dielectric etching with common fluorocarbons. Surface composition analyses demonstrate the preferential deposition on silicon with respect to silicon nitride yielding a high selectivity measured through etch rate tests on blanket films. The selectivity achieved is compatible with 3D CMOS spacer etching requirements. Despite the benefits shown by this alternative chemistry, some limitations prevent reaching the thorough elimination of parasitic spacer. A cyclic approach alternating selective passivation and nonselective etching is developed to overcome these limitations, which still provides effective silicon protection from etching. This cyclic sequence is evaluated on nanowire-type patterned structures and shows the complete removal of the parasitic spacer while providing a silicon loss of less than 2 nm. Work in development currently carries on to further improve this process and to fulfill all specifications for 3D CMOS spacer etching.
Rotavirus induces intercellular calcium waves through ADP signaling
Authors: Chang-Graham Alexandra L. , Perry Jacob L. , Engevik Melinda A. , Engevik Kristen A. , Scribano Francesca J. , Gebert J. Thomas , Danhof Heather A. , Nelson Joel C. , Kellen Joseph S. , Strtak Alicia C. , Sastri Narayan P. , Estes Mary K. , Britton Robert A. , Versalovic James , Hyser Joseph M.
Published: November 2020

Riding the calcium waves

Rotavirus causes severe diarrhea and vomiting in children worldwide, yet how infection causes these diseases remains poorly understood. A leading theory is that virus-infected cells secrete paracrine signaling molecules that dysregulate epithelial cells. Chang-Graham
et al.
found that rotavirus-infected cells trigger cell-to-cell signaling that manifests as intercellular calcium waves (see the Perspective by Stanifer and Boulant). This signal results from the repeated release of adenosine 5′-diphosphate by rotavirus-infected cells. This release activates receptors on nearby uninfected cells, resulting in a calcium signal. The intercellular calcium waves activate chloride and serotonin secretion, which contributes to diarrhea and vomiting. Blocking this paracrine signal could represent a target for antidiarrheal pharmacotherapy.

Science
, this issue p.
eabc3621
; see also p.
909
Coordination between microbiota and root endodermis supports plant mineral nutrient homeostasis
Authors: Salas-González Isai , Reyt Guilhem , Flis Paulina , Custódio Valéria , Gopaulchan David , Bakhoum Niokhor , Dew Tristan P. , Suresh Kiran , Franke Rochus Benni , Dangl Jeffery L. , Salt David E. , Castrillo Gabriel
Published: November 2020

Microbes modify plant root permeability

The root provides mineral nutrients and water to the plant. Diffusion barriers seal the root, preventing the loss of internal water and nutrients. Salas-González
et al.
found that microbes living on and in roots of the model plant
Arabidopsis thaliana
influence diffusion barrier formation, which affects the balance of mineral nutrients in the plant (see the Perspective by Busch and Chory). Plants with modified root diffusion barriers show altered bacterial community composition. Microbes tap into the plant's abscisic acid hormone signals to stabilize the root diffusion barrier against perturbations in environmental nutrient availability, thus enhancing plant stress tolerance.

Science
, this issue p.
eabd0695
; see also p.
125
Tailored quinones support high-turnover Pd catalysts for oxidative C–H arylation with O
2
Authors: Salazar Chase A. , Flesch Kaylin N. , Haines Brandon E. , Zhou Philip S. , Musaev Djamaladdin G. , Stahl Shannon S.
Published: November 2020

A subtle balancing act for quinones

Palladium catalysis is widely used in drug synthesis to form carbon-carbon bonds, but typically both carbon centers need to be activated ahead of time. Although introducing oxygen as an oxidant diminishes the need for preactivation, the catalysis then tends to be less efficient, especially in the case of arene coupling. Salazar
et al.
pinpointed the role of quinone co-catalysts in these processes and determined that after accelerating carbon-carbon bond formation, the quinone slows down catalyst reoxidation by oxygen. Appending bulky substituents to the quinone struck a better balance and substantially enhanced catalytic efficiency.

Science
, this issue p.
1454
The more and less of electronic-skin sensors
Authors: Liu Xinyu
Published: November 2020

Sensors can measure both strain and temperature or measure force without affecting touch
The origin of diarrhea in rotavirus infection
Authors: Stanifer Megan , Boulant Steeve
Published: November 2020

Messengers from rotavirus-infected cells induce pathogenic signaling in neighboring cells
Do Students Learn Better with Pecha Kucha, an Alternative Presentation Format?
Authors: Liao Min-Ken , Lewis Greg , Winiski Mike
Published: November 2020

Oral presentation assignments help students develop and engage multiple learning skills. In the process of preparing a presentation, students search and evaluate information (evidence-based engagement), decide whether to include it (content relevancy), organize information in an engaging manner (audience engagement), adhere to the presentation instructions (logistics), and attempt to appear credible (credibility). The final product is often a 15-minute PowerPoint presentation. In this study, we introduced students to the Pecha Kucha presentation format: 20 slides shown for 20 seconds each. While previous studies claimed that Pecha Kucha is pedagogically superior to traditional formats, particularly in the presentation and communication competence, its impacts on learning have not been examined. This study, which involved students in three classes, was designed to do so. All the students presented twice in a semester, but in one class, the first presentation was in Pecha Kucha and second in the traditional format and in the other two classes, the first was in the traditional format and second in Pecha Kucha. Five decision-making categories were assessed: evidence-based engagement, content relevancy, audience engagement, logistics, and credibility. Also assessed were the students’ confidence levels in presentation. The statistically significant differences between these two formats mostly reflected the intentional selection of presentation material to meet the time constraint of the Pecha Kucha format. However, all were slightly more confident in presentation after the second one. Students also reported that they preferred listening to Pecha Kucha than to traditional PowerPoint presentations.
Detection of Envelope Glycoprotein Assembly from Old World Hantaviruses in the Golgi Apparatus of Living Cells
Authors: Petazzi R. A. , Koikkarah A. A. , Tischler N. D. , Chiantia S.
Published: November 2020

In this work, we investigate protein-protein interactions that drive the assembly of the hantavirus envelope. These emerging pathogens have the potential to cause deadly outbreaks in the human population.
Supplemental Material: Definition of tectonic elements in Tehuantepec, southeast Mexico: An integrated geophysical, geochronological, and stratigraphic perspective
Authors: Molina Garza Roberto S. , al. et
Published: November 2020

U-Pb LA-ICPMS geochronology data
Fifteen-minute consultation: Neonatal hypertension
Authors: Singh Yogen , McGeoch Luke , Job Sajeev
Published: November 2020

Neonatal hypertension is a rare but well recognised condition, especially in newborns needing invasive monitoring in the intensive care unit. Recognition of newborns with hypertension remains challenging because of natural variability in blood pressure with postconceptional age and the lack of reference data for different gestational ages. Investigation of neonates with hypertension can be challenging in light of the myriad differing aetiologies. This may be simplified by a systematic approach to investigation. There remains a relative paucity of data to guide the use of pharmacological therapies for hypertension in neonates. Clinicians rely on empirical management protocols based on experience and expert opinion. Much of the information on dosing regimens and protocols has simply been derived from the use of antihypertensive agents in older children and in adults, despite fundamental pathophysiological differences.
Effectiveness of progressive tendon-loading exercise therapy in patients with patellar tendinopathy: a randomised clinical trial
Authors: Breda Stephan J , Oei Edwin H G , Zwerver Johannes , Visser Edwin , Waarsing Erwin , Krestin Gabriel P , de Vos Robert-Jan
Published: November 2020

Objective

To compare the effectiveness of progressive tendon-loading exercises (PTLE) with eccentric exercise therapy (EET) in patients with patellar tendinopathy (PT).

Methods

In a stratified, investigator-blinded, block-randomised trial, 76 patients with clinically diagnosed and ultrasound-confirmed PT were randomly assigned in a 1:1 ratio to receive either PTLE or EET. The primary end point was clinical outcome after 24 weeks following an intention-to-treat analysis, as assessed with the validated Victorian Institute of Sports Assessment for patellar tendons (VISA-P) questionnaire measuring pain, function and ability to play sports. Secondary outcomes included the return to sports rate, subjective patient satisfaction and exercise adherence.

Results

Patients were randomised between January 2017 and July 2019. The intention-to-treat population (mean age, 24 years, SD 4); 58 (76%) male) consisted of patients with mostly chronic PT (median symptom duration 2 years). Most patients (82%) underwent prior treatment for PT but failed to recover fully. 38 patients were randomised to the PTLE group and 38 patients to the EET group. The improvement in VISA-P score was significantly better for PTLE than for EET after 24 weeks (28 vs 18 points, adjusted mean between-group difference, 9 (95% CI 1 to 16); p=0.023). There was a trend towards a higher return to sports rate in the PTLE group (43% vs 27%, p=0.13). No significant between-group difference was found for subjective patient satisfaction (81% vs 83%, p=0.54) and exercise adherence between the PTLE group and EET group after 24 weeks (40% vs 49%, p=0.33).

Conclusions

In patients with PT, PTLE resulted in a significantly better clinical outcome after 24 weeks than EET. PTLE are superior to EET and are therefore recommended as initial conservative treatment for PT.
Role of ceramide-to-dihydroceramide ratios for insulin resistance and non-alcoholic fatty liver disease in humans
Authors: Apostolopoulou Maria , Gordillo Ruth , Gancheva Sofiya , Strassburger Klaus , Herder Christian , Esposito Irene , Schlensak Matthias , Scherer Philipp E , Roden Michael
Published: November 2020

Introduction

Sphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans.

Research design and methods

Thus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery.

Results

Surprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitis (NASH) and related inversely to liver fat content. Specifically, hepatic ceramide/dihydroceramide (species 16:0) related negatively to hepatic mitochondrial capacity and lipid peroxidation. In visceral adipose tissue, ceramide/dihydroceramide (species 16:0) associated positively with markers of inflammation.

Conclusion

These results failed to confirm the relationships of ceramide/dihydroceramide in humans with different degree of insulin resistance. However, the low hepatic ceramide/dihydroceramide favor a role for dihydroceramide accumulation in NASH, while a specific ceramide/dihydroceramide ratio in visceral adipose tissue suggests a role of ceramides in obesity-associated low-grade inflammation.
Semiautomated Glasgow-Blatchford Bleeding Score helps direct bed placement for patients with upper gastrointestinal bleeding
Authors: Schembre Drew B , Ely Robson E , Connolly Janice M , Padhya Kunjali T , Sharda Rohit , Brandabur John J
Published: November 2020

Objective

The Glasgow-Blatchford Bleeding Score (GBS) was designed to identify patients with upper gastrointestinal bleeding (UGIB) who do not require hospitalisation. It may also help stratify patients unlikely to benefit from intensive care.

Design

We reviewed patients assigned a GBS in the emergency room (ER) via a semiautomated calculator. Patients with a score ≤7 (low risk) were directed to an unmonitored bed (UMB), while those with a score of ≥8 (high risk) were considered for MB placement. Conformity with guidelines and subsequent transfers to MB were reviewed, along with transfusion requirement, rebleeding, length of stay, need for intervention and death.

Results

Over 34 months, 1037 patients received a GBS in the ER. 745 had an UGIB. 235 (32%) of these patients had a GBS ≤7. 29 (12%) low-risk patients were admitted to MBs. Four low-risk patients admitted to UMB required transfer to MB within the first 48 hours. Low-risk patients admitted to UMBs were no more likely to die, rebleed, need transfusion or require more endoscopic, radiographic or surgical procedures than those admitted to MBs. No low-risk patient died from GIB. Patients with GBS ≥8 were more likely to rebleed, require transfusion and interventions to control bleeding but not to die.

Conclusion

A semiautomated GBS calculator can be incorporated into an ER workflow. Patients with a GBS ≤7 are unlikely to need MB care for UGIB. Further studies are warranted to determine an ideal scoring system for MB admission.
Studying Accompaniment model Feasibility and Effectiveness (SAFE) Study: study protocol for a prospective observational cohort study of the effectiveness of self-managed medication abortion
Authors: Moseson Heidi , Keefe-Oates Brianna , Jayaweera Ruvani T , Filippa Sofia , Motana Relebohile , Bercu Chiara , Egwuatu Ijeoma , Grosso Belen , Kristianingrum Ika Ayu , Nmezi Sybil , Zurbriggen Ruth , Friedman Emmeline , Gerdts Caitlin
Published: November 2020

Introduction

A range of barriers deter or prevent people from accessing facility-based abortion care. As a result, people are obtaining and using abortifacient medications to end their pregnancies outside of the formal healthcare system, without clinical supervision. One model of self-managed abortion has come to be known as the ‘accompaniment’ model, in which grassroots organisations provide pregnant people with evidence-based counselling and support through the medication abortion process. Data are needed to understand the safety and effectiveness of this increasingly common model of abortion care.

Methods and analysis

This is a large, prospective, observational study in Argentina and Nigeria. All people who contact one of two accompaniment groups seeking information for their own self-managed medication abortion, are ages 13 years and older, have no contraindications for medication abortion, are within the gestational range supported by the group (up to 12 weeks’ gestation for the primary outcome) and are willing to be contacted for follow-up will be recruited. Participants will respond to an interviewer-administered baseline survey at enrolment, and 1–4 additional surveys over 6 weeks to ascertain whether they obtain medications for abortion, dosing and route of administration of medications, physical and emotional experience of medication abortion self-management, and effectiveness and safety outcomes. Analyses will include estimates of the primary outcome: the proportion of participants that report a complete abortion without surgical intervention at last recorded follow-up; as well as secondary outcomes including a pseudo-experimental test of non-inferiority of the effectiveness of self-managed medication abortion as compared with clinical medication abortion.

Ethics and dissemination

We describe the ethical considerations and protections for this study, as well the creation of a study-specific Data Monitoring and Oversight Committee. We describe dissemination plans to ensure that study results are shared widely with all relevant audiences, particularly researchers, advocates, policymakers and clinicians.

Trial registration number

ISRCTN95769543.
Does geographical variation confound the relationship between host factors and the human gut microbiota: a population-based study in China
Authors: Sun Shan , Wang Huijun , Tsilimigras Matthew CB , Howard Annie Green , Sha Wei , Zhang Jiguo , Su Chang , Wang Zhihong , Du Shufa , Sioda Michael , Fouladi Farnaz , Fodor Anthony , Gordon-Larsen Penny , Zhang Bing
Published: November 2020

Objective

The human gut microbiota plays important roles in human health but is also known to be highly diverse between populations from different regions. Yet most studies inadequately account for this regional diversity in their analyses. This study examines the extent to which geographical variation can act as a confounding variable for studies that associate the microbiota with human phenotypic variation.

Design

Population-based study.

Setting

China.

Participants

2164 participants from 15 province-level divisions in China.

Primary and secondary outcome measures

We analysed the impact of geographic location on associations between the human gut microbiota and 72 host factors representing a wide variety of environmental-level, household-level and individual-level factors.

Results

While the gut microbiota varied across a wide range of host factors including urbanisation, occupation and dietary variables, the geographic region (province/megacity) of the participants explained the largest proportion of the variance (17.9%). The estimated effect sizes for other host factors varied substantially by region with little evidence of a reproducible signal across different areas as measured by permutational multivariate analysis of variance and random forest models.

Conclusions

Our results suggest that geographic variation is an essential factor that should be explicitly considered when generalising microbiota-based models to host phenotype across different populations.
Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
Authors: Baumgartner Christine , Klok Frederikus A , Carrier Marc , Limacher Andreas , Moor Jeanne , Righini Marc , Beer Jürg-Hans , Peluso Martina , Rakovic Damiana , Huisman Menno V , Aujesky Drahomir
Published: November 2020

Introduction

The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE.

Methods and analysis

SAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation.

Ethics and dissemination

The local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal.

Trial registration number

NCT04263038.
Modifiable and non-modifiable risk factors for COVID-19, and comparison to risk factors for influenza and pneumonia: results from a UK Biobank prospective cohort study
Authors: Ho Frederick K , Celis-Morales Carlos A , Gray Stuart R , Katikireddi S Vittal , Niedzwiedz Claire L , Hastie Claire , Ferguson Lyn D , Berry Colin , Mackay Daniel F , Gill Jason MR , Pell Jill P , Sattar Naveed , Welsh Paul
Published: November 2020

Objectives

We aimed to investigate demographic, lifestyle, socioeconomic and clinical risk factors for COVID-19, and compared them to risk factors for pneumonia and influenza in UK Biobank.

Design

Cohort study.

Setting

UK Biobank.

Participants

49–83 year olds (in 2020) from a general population study.

Main outcome measures

Confirmed COVID-19 infection (positive SARS-CoV-2 test). Incident influenza and pneumonia were obtained from primary care data. Poisson regression was used to study the association of exposure variables with outcomes.

Results

Among 235 928 participants, 397 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index and higher glycated haemoglobin (HbA1C) (RR 1.28 and RR 1.14 per SD increase, respectively), smoking (RR 1.39), slow walking pace as a proxy for physical fitness (RR 1.53), and use of blood pressure medications as a proxy for hypertension (RR 1.33). Higher forced expiratory volume in 1 s (FEV1) and high-density lipoprotein (HDL) cholesterol were both associated with lower risk (RR 0.84 and RR 0.83 per SD increase, respectively). Non-modifiable risk factors included male sex (RR 1.72), black ethnicity (RR 2.00), socioeconomic deprivation (RR 1.17 per SD increase in Townsend Index), and high cystatin C (RR 1.13 per SD increase). The risk factors overlapped with pneumonia somewhat, less so for influenza. The associations with modifiable risk factors were generally stronger for COVID-19, than pneumonia or influenza.

Conclusion

These findings suggest that modification of lifestyle may help to reduce the risk of COVID-19 and could be a useful adjunct to other interventions, such as social distancing and shielding of high risk.
An Exploration of the help-seeking experiences of patients in an allied professions-led rapid access chest pain pathway: a qualitative study
Authors: Stain Nolan , Cheshire Anna , Ross Catherine , Ridge Damien
Published: November 2020

Objective

A number of studies have explored delayed help-seeking practices for acute coronary syndrome (ACS) and have indentified multiple intersecting factors which may play a role, for example, attributing symptoms, age, gender, ethnicity and contextual influences. However, the pathway to diagnosis for suspected coronary heart disease (CHD) symptoms in a rapid access chest pain clinic (RACPC) context is underexplored. The objective of this study was to examine patients’ help-seeking experiences of accessing RACPC services, from the point at which they notice and interpret symptoms, to their decision to seek help from their general practitioner.

Design

Qualitative study.

Setting

Interviews were conducted in the RACPC at Queen Mary’s Roehampton Hospital, London, UK.

Participants

Maximum variation sampling was used to recruit 30 participants (15 men and 15 women) referred to a RACPC, using sampling dimensions of age, ethnicity and occupation.

Methods

Semi-structured interviews focussed on the patient experience of their pathway to the RACPC. Thematic analysis was used to analyse the interview data.

Results

Participant interpretation of symptoms was shaped by multiple influences; reluctance to seek help contributed to delay; various factors acted as drivers as well as barriers to help-seeking; and GP referrals to RACPC were based on symptoms as well as patients’ need for reassurance.

Conclusion

We found complex issues shaped the patient’s decision-making when accessing the RACPC, including making sense of symptoms and help-seeking practices. These findings can be used to develop health promotion literature to encourage early help-seeking and improve RACPC services.
Temporal trends of physician geographical distribution and high and intermediate physician density areas and factors related to physicians’ movement to low physician density areas in Japan: a longitudinal study (1996–2016)
Authors: Ishikawa Masatoshi
Published: November 2020

Objectives

A major issue in Japan’s health policy is the geographical maldistribution of physicians. This study aimed to analyse temporal trends in the geographical distribution of physicians and analyse physicians in high and intermediate physician density areas and factors related to their movement to low physician density areas in Japan.

Design

A longitudinal study.

Setting

All physicians in 344 secondary medical districts.

Participants

I analysed data from the biennial national census, conducted by the Ministry of Health, Labour and Welfare between 1996 and 2016 and and divided it into two cohorts of 10 years each: 1996–2006 and 2006–2016.

Primary and secondary outcome measures

I estimated the temporal trends in the number and percentages of physicians, and used logistic regression to analyse physicians in high and intermediate physician density areas and the factors related to their movement to low physician density areas.

Results

The overall number of Japanese doctors increased by 31% between 1996 and 2016. The number of physicians per population in the physician high-density areas increased by 29%, while those in low-density areas increased by 32%, suggesting that the gap between areas marginally decreased. The multivariable logistic regression analyses revealed that academic hospital experience had the highest OR for predicting physician movement to low physician density areas after 10 years, both in the 1996 and 2006 cohorts. Other factors that positively correlated with physician movement were being male, being younger than 40 years, being qualified after the age of 30, urban area, intermediate physician density area and practice in a non-academic hospital.

Conclusions

As less-experienced physicians demonstrate high mobility among geographic categories, and retention rates are low in low physician density areas, especially for less-experienced physicians, a new system that considers these factors would create opportunities for younger physicians to work in low-density areas.
Load progression criteria in exercise programmes in lower limb tendinopathy: a systematic review
Authors: Escriche-Escuder Adrian , Casaña Jose , Cuesta-Vargas Antonio I
Published: November 2020

Objective

The objective of this study is to summarise and analyse the current literature about what progression criteria are applied in loading exercise programmes in lower limb tendinopathies and their evidence and effectiveness.

Design

Systematic review.

Methods

PubMed, Embase, Scopus and PEDrowere searched from inception to 24 September 2020. The inclusion criteria were randomised controlled trials that included patients with midportion Achilles, patellar or gluteal tendinopathy; assessed function, pain or performance; included at least one group where progressive physical exercise was administered as monotherapy; included at least a control group. We excluded studies that included subjects with previous tendon surgical treatment; studies with control group that conducted a supplemented modality of the exercise performed in the intervention group. A narrative synthesis was conducted. Cohen’s d and the percentage of change of main clinical and performance outcomes were obtained. Methodological quality was assessed using the PEDro scale.

Results

Thirty studies that described progression criteria were included. Six types of criteria grouped in two categories were identified and included in a new classification proposal: pain as a primary criterion (evoking and avoid-pain based), and pain and symptom control as a secondary criterion (conditioning stages, fatigue-based, subjective perception and temporary linear increase). Most of the studies applied a pain-based criterion. Criteria based on conditioning stages were also commonly applied. Other criteria such as fatigue, a temporary linear increase, or the subjective perception of the patient’s abilities were occasionally applied.

Conclusions

There is a predominant use of pain-based criteria, but the utilisation of these criteria is not supported by strong evidence. This review evidences the need for studies that compare the same exercise programme using different progression criteria. A new classification of the existing progression criteria is proposed based on the use of pain as the primary or secondary criterion.

PROSPERO registration number

CRD42018110997.
Alcohol-related mortality by ethnic origin of natives: a prospective cohort study based on multigenerational population register data from Finland and Sweden
Authors: Saarela Jan , Kolk Martin
Published: November 2020

Objectives

The aim was to assess alcohol-related mortality of persons with mixed and uniform ethnic origins in two national contexts.

Setting

Data were from the multigenerational population registers of the total population of Finland and Sweden observed from 1971 to 2017. Study persons were men and women of ethnic Finnish and Swedish background, born in their country of residence.

Participants

Persons were born between 1953 and 1999. In Finland, ethnic origin was assessed through own, mother’s and father’s Finnish or Swedish ethnolinguistic affiliation. Data on Sweden included persons born in Sweden, with mother and father born in Sweden or Finland. A total of 2 997 867 and 4 148 794 persons were included in the Finnish and Swedish data, respectively. The total number of alcohol-related deaths by main cause was 13 204 and 3336. Cox regressions were used to examine associations.

Outcome measures

For the period 1971–2017, we studied alcohol as the main cause of death. For the period 1996–2017, we observed if alcohol was the main or contributing cause of death. Parallel analyses were performed for all-cause mortality.

Results

For men in Finland, the hazard rate of alcohol-related mortality of Swedish speakers with uniform Swedish background was 0.44 (95% CI: 0.38 to 0.52) that of Finnish speakers with uniform Finnish background. The corresponding hazard rate for women was 0.40 (95% CI: 0.28 to 0.55). In Sweden, the hazard rate of men with both parents born in Sweden was 0.40 (95% CI: 0.32 to 0.49) that of men with both parents born in Finland. The corresponding hazard rate for women was 0.50 (95% CI: 0.31 to 0.79). In both countries, persons with mixed background had an alcohol-related mortality rate between that of persons with uniform Finnish and Swedish background.

Conclusion

The consistent pattern across countries necessitates increased policy attention towards offspring disadvantaged via parental ethnicity to minimise harmful consequences of alcohol consumption across and within ethnic groups.
Predicting dementia diagnosis from cognitive footprints in electronic health records: a case–control study protocol
Authors: Luo Hao , Lau Kui Kai , Wong Gloria H Y , Chan Wai-Chi , Mak Henry K F , Zhang Qingpeng , Knapp Martin , Wong Ian C K
Published: November 2020

Introduction

Dementia is a group of disabling disorders that can be devastating for persons living with it and for their families. Data-informed decision-making strategies to identify individuals at high risk of dementia are essential to facilitate large-scale prevention and early intervention. This population-based case–control study aims to develop and validate a clinical algorithm for predicting dementia diagnosis, based on the cognitive footprint in personal and medical history.

Methods and analysis

We will use territory-wide electronic health records from the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong between 1 January 2001 and 31 December 2018. All individuals who were at least 65 years old by the end of 2018 will be identified from CDARS. A random sample of control individuals who did not receive any diagnosis of dementia will be matched with those who did receive such a diagnosis by age, gender and index date with 1:1 ratio. Exposure to potential protective/risk factors will be included in both conventional logistic regression and machine-learning models. Established risk factors of interest will include diabetes mellitus, midlife hypertension, midlife obesity, depression, head injuries and low education. Exploratory risk factors will include vascular disease, infectious disease and medication. The prediction accuracy of several state-of-the-art machine-learning algorithms will be compared.

Ethics and dissemination

This study was approved by Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 18-225). Patients’ records are anonymised to protect privacy. Study results will be disseminated through peer-reviewed publications. Codes of the resulted dementia risk prediction algorithm will be made publicly available at the website of the Tools to Inform Policy: Chinese Communities’ Action in Response to Dementia project (https://www.tip-card.hku.hk/).
COVID-19 aerosol box as protection from droplet and aerosol contaminations in healthcare workers performing airway intubation: a randomised cross-over simulation study
Authors: Noor Azhar Muhaimin , Bustam Aida , Poh Khadijah , Ahmad Zahedi Ahmad Zulkarnain , Mohd Nazri Mohd Zahir Amin , Azizah Ariffin Mohammad Aizuddin , Md Yusuf Mohd Hafyzuddin , Zambri Aliyah , Chong Johnathan Y O , Kamarudin Anhar , Ang Bin Ting , Iskandar Affan , Chew Keng Sheng
Published: November 2020

Background

Concerns over high transmission risk of SARS-CoV-2 have led to innovation and usage of an aerosol box to protect healthcare workers during airway intubation in patients with COVID-19. Its efficacy as a barrier protection in addition to the use of a standard personal protective equipment (PPE) is not fully known. We performed a simulated study to investigate the relationship between aerosol box usage during intubation and contaminations on healthcare workers pre-doffing and post-doffing of PPE.

Methods

This was a randomised cross-over study conducted between 9 April to 5 May 2020 in the ED of University Malaya Medical Centre. Postgraduate Emergency Medicine trainees performed video laryngoscope-assisted intubation on an airway manikin with and without an aerosol box in a random order. Contamination was simulated by nebulised Glo Germ. Primary outcome was number of contaminated front and back body regions pre-doffing and post-doffing of PPE of the intubator and assistant. Secondary outcomes were intubation time, Cormack-Lehane score, number of intubation attempts and participants’ feedback.

Results

Thirty-six trainees completed the study interventions. The number of contaminated front and back body regions pre-doffing of PPE was significantly higher without the aerosol box (all p values<0.001). However, there was no significant difference in the number of contaminations post-doffing of PPE between using and not using the aerosol box, with a median contamination of zero. Intubation time was longer with the aerosol box (42.5 s vs 35.5 s, p<0.001). Cormack-Lehane scores were similar with and without the aerosol box. First-pass intubation success rate was 94.4% and 100% with and without the aerosol box, respectively. More participants reported reduced mobility and visibility when intubating with the aerosol box.

Conclusions

An aerosol box may significantly reduce exposure to contaminations but with increased intubation time and reduced operator’s mobility and visibility. Furthermore, the difference in degree of contamination between using and not using an aerosol box could be offset by proper doffing of PPE.
Efficacy and immune-related adverse event associations in avelumab-treated patients
Authors: Kelly Karen , Manitz Juliane , Patel Manish R , D’Angelo Sandra P , Apolo Andrea B , Rajan Arun , Kasturi Vijay , Speit Isabell , Bajars Marcis , Warth John , Gulley James L
Published: November 2020

Background

Adverse events (AEs) of special interest that arise during treatment with immune checkpoint inhibitors, including immune-related AEs (irAEs), have been reported to be associated with improved clinical outcomes. We analyzed patients treated with avelumab from the JAVELIN Solid Tumor and Merkel 200 trials, examining the association between AEs and efficacy while adjusting for confounding factors such as treatment duration and event order.

Methods

We analyzed efficacy and safety data from 1783 patients treated with the programmed death ligand 1 inhibitor avelumab who were enrolled in expansion cohorts of the JAVELIN Solid Tumor and Merkel 200 trials. To analyze the association between irAEs and efficacy with regard to survival, we used a time-dependent Cox model with time-varying indicators for irAEs, as well as multistate models that accounted for competing risks and time inhomogeneity.

Results

295 patients (16.5%) experienced irAEs and 454 patients (25.5%) experienced infusion-related reactions. There was a reduced risk of death in patients who experienced irAEs compared with those who did not (HR 0.71, 95% CI 0.59 to 0.85) using the time-dependent Cox model. The multistate model did not suggest that the occurrence of irAEs could predict response; however, it predicted a higher chance of irAEs occurring after a response. No association was observed between response and infusion-related reactions.

Conclusions

Patients who experience irAEs showed improved survival. Although irAEs are not predictors for response to immune checkpoint inhibitors, increased vigilance for irAEs is needed after treatment with avelumab.

Trial registration numbers

NCT01772004 and NCT02155647.
Towards a practical management of fatigue in systemic lupus erythematosus
Authors: Mertz Philippe , Schlencker Aurélien , Schneider Matthias , Gavand Pierre-Edouard , Martin Thierry , Arnaud Laurent
Published: November 2020

Significant fatigue is reported by two-thirds of patients with SLE and severe fatigue by one-third. The assessment and treatment of fatigue remains a major challenge in SLE, especially in patients with no disease activity. Here, we suggest a practical algorithm for the management of fatigue in SLE. First, common but non–SLE-related causes of fatigue should be ruled out based on medical history, clinical and laboratory examinations. Then, presence of SLE-related disease activity or organ damage should be assessed. In patients with active disease, remission is the most appropriate therapeutic target while symptomatic support is needed in case of damage. Both anxiety and depression are major independent predictors of fatigue in SLE and require dedicated assessment and care with psychological counselling and pharmacological intervention if needed. This practical algorithm will help in improving the management of one the most common and complex patient complaints in SLE.