bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of relative fat mass algorithm for incident hypertension: a 6-year prospective study in Chinese population
Authors: Yu Peng , Huang Teng , Hu Senlin , Yu Xuefeng
Published: October 2020

Objectives

Individuals with obesity especially excessive visceral adiposity have high risk for incident hypertension. Recently, a new algorithm named relative fat mass (RFM) was introduced to define obesity. Our aim was to investigate whether it can predict hypertension in Chinese population and to compare its predictive power with traditional indices including body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR).

Design

A 6-year prospective study.

Setting

Nine provinces (Hei Long Jiang, Liao Ning, Jiang Su, Shan Dong, He Nan, Hu Bei, Hu Nan, Guang Xi and Gui Zhou) in China.

Participants

Those without hypertension in 2009 survey and respond in 2015 survey.

Intervention

Logistic regression were performed to investigate the association between RFM and incident hypertension. Receiver operating characteristic (ROC) analysis was performed to compare the predictive ability of these indices and define their optimal cut-off values.

Main outcome measures

Incident hypertension in 2015.

Results

The prevalence of incident hypertension in 2015 based on RFM quartiles were 14.8%, 21.2%, 26.8% and 35.2%, respectively (p for trend <0.001). In overall population, the OR for the highest quartile compared with the lowest quartile for RFM was 2.032 (1.567–2.634) in the fully adjusted model. In ROC analysis, RFM and WHtR had the highest area under the curve (AUC) value in both sexes but did not show statistical significance when compared with AUC value of BMI and WC in men and AUC value of WC in women. The performance of the prediction model based on RFM was comparable to that of BMI, WC or WHtR.

Conclusions

RFM can be a powerful indictor for predicting incident hypertension in Chinese population, but it does not show superiority over BMI, WC and WHtR in predictive power.
Associations between biological and sociodemographic risks for developmental vulnerability in twins at age 5: a population data linkage study in Western Australia
Authors: Dhamrait Gursimran Kaur , Christensen Daniel , Pereira Gavin , Taylor Catherine Louise
Published: October 2020

Objective

To investigate the prevalence of, and associations between, prenatal and perinatal risk factors and developmental vulnerability in twins at age 5.

Design

Retrospective cohort study using bivariate and multivariable logistic regression.

Setting

Western Australia (WA), 2002–2015.

Participants

828 twin pairs born in WA with an Australian Early Development Census (AEDC) record from 2009, 2012 or 2015.

Main outcome measures

The AEDC is a national measure of child development across five domains. Children with scores <10th percentile were classified as developmentally vulnerable on, one or more domains (DV1), or two or more domains (DV2).

Results

In this population, 26.0% twins were classified as DV1 and 13.5% as DV2. In the multivariable model, risk factors for DV1 were maternal age <25 years (adjusted OR (aOR): 7.06, 95% CI: 2.29 to 21.76), child speaking a language other than English at home (aOR: 6.45, 95% CI: 2.17 to 19.17), male child (aOR: 5.08, 95% CI: 2.89 to 8.92), age younger than the reference category for the study sample (≥5 years 1 month to <5 years 10 months) at time of AEDC completion (aOR: 3.34, 95% CI: 1.55 to 7.22) and having a proportion of optimal birth weight (POBW) <15th percentile of the study sample (aOR: 2.06, 95% CI 1.07 to 3.98). Risk factors for DV2 were male child (aOR: 7.87, 95% CI: 3.45 to 17.97), maternal age <25 (aOR: 5.60, 95% CI: 1.30 to 24.10), age younger than the reference category (aOR: 5.36, 95% CI: 1.94 to 14.82), child speaking a language other than English at home (aOR: 4.65, 95% CI: 1.14 to 19.03), mother’s marital status as not married at the time of twins’ birth (aOR: 4.59, 95% CI: 1.13 to 18.55), maternal occupation status in the lowest quintile (aOR: 3.30, 95% CI: 1.11 to 9.81) and a POBW <15th percentile (aOR: 3.11, 95% CI: 1.26 to 7.64).

Conclusion

Both biological and sociodemographic risk factors are associated with developmental vulnerability in twins at 5 years of age.
Impact of incarceration on cardiovascular disease risk factors: a systematic review and meta-regression on weight and BMI change
Authors: Bondolfi Constantin , Taffe Patrick , Augsburger Aurélie , Jaques Cécile , Malebranche Mary , Clair Carole , Bodenmann Patrick
Published: October 2020

Objective

Cardiovascular disease is an underappreciated issue in prison medicine. Recent studies have revealed a higher prevalence of cardiovascular disease risk factors (CVDRFs) among individuals in prison, but the impact of incarceration on CVDRFs over time is not well understood. This review aimed to assess available literature and quantify the relationship between incarceration and trends in major CVDRFs in high-income countries.

Design

Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-regression on weight change and obesity.

Data sources

Medline, Embase, PubMed, Cochrane Central Wiley and Web of Science.

Eligibility criteria for selecting studies

Longitudinal studies reporting on the incidence of, or trends in any CVDRF among current or former people in prison over time, in high-income countries.

Data extraction and synthesis

Two authors independently screened articles for eligibility, extracted data and assessed quality using an adapted version of the Newcastle-Ottawa Scale. Trends in CVDRFs during and following incarceration were summarised and in those with sufficient data a meta-regression was performed.

Results

Twenty-six articles were identified. CVDRFs assessed included obesity, hypertension, diabetes, dyslipidaemia, tobacco use, physical inactivity and unhealthy diet. A meta-regression on change in weight during incarceration found a mean increase of 5.3 kg (95% CI 0.5 to 10.1) and change in body mass index of 1.8 kg/m2 (95% CI −0.9 to 4.6) at 2 years. Weight gain appeared most pronounced right after entering prison and then plateaued at 2 years. Concerning hypertension, the results were inconclusive, despite a trend towards rising blood pressure or prevalence of hypertension during incarceration, and an increased incidence of hypertension following incarceration. Results are contradictory or inconclusive for the other CVDRFs reviewed.

Conclusion

Possible explanations for the association between incarceration and weight include a sedentary lifestyle, unhealthy diet, forced smoking cessation, psychotropic medication use and high levels of stress. Incarceration may be an independent risk factor for cardiovascular disease.
Cohort profile: gastric cancer in the population-based, Finnish National Esophago-Gastric Cancer Cohort (FINEGO) Study
Authors: Kauppila Joonas H , Ohtonen Pasi , Rantanen Tuomo , Tyrväinen Tuula , Toikkanen Vesa , Pääaho Minna , Valtola Antti , Räsänen Jari , Kallio Raija , Sihvo Eero , Saarnio Juha , Karttunen Tuomo J , Pohjanen Vesa-Matti , Ristimäki Ari , Laine Simo , Kokkola Arto
Published: October 2020

Purpose

The Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established with the aim of identifying factors that could contribute to improved outcomes in oesophago-gastric cancer. The aim of this study is to describe the patients with gastric cancer included in FINEGO.

Participants

A total of 10 457 patients with gastric cancer or tumour diagnosis in the Finnish Cancer Registry or the Finnish Patient Registry during 1987–2016 were included in the cohort, with follow-up from Causes of Death Registry until 31 December 2016. All of the participants were at least 18 years of age, and had undergone either resectional or endoscopic mucosal surgery with curative or palliative intent.

Findings to date

Of the 10 457 patients, 90.1% were identified to have cancer in both cancer and patient registries. In all, the median age was 70 at the time of surgery, 54.5% of the patients were men and 64.4% had no comorbidities. Education data were available for 31.1% of the patients, of whom the majority had had <12 years of formal education. Of the 7798 with cancer staging data available, 41.1% had a local cancer. Adenocarcinoma was the most common (94.2%) histological type. Almost all patients underwent open gastrectomy and 214% in hospitals with annual volume of more than 30 gastrectomies per year. A total of 8561 deaths occurred during the study period, of which 6474 were due to oesophago-gastric cancers. The 5-year survival was 34.6% and 5-year cancer-specific survival was 39.7%.

Future plans

The data in FINEGO can be currently used for registry-based research but is being expanded by data extraction from patient records and scanning of histological samples from the Finnish biobanks. Initially, we are planning on studies on the national trends in treatment and mortality, and studies on the demographic factors and their influence on survival.
Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma
Authors: Heitmann Jonas S , Walz Juliane S , Pflügler Martin , Kauer Joseph , Schlenk Richard F , Jung Gundram , Salih Helmut R
Published: October 2020

Introduction

Prostate cancer is the second most common cancer in men worldwide. When the disease becomes resistant to androgen-deprivation therapy, treatment options are sparse. To address the high medical need in castration-resistant prostate cancer (CRPC), we generated a novel PSMAxCD3 bispecific antibody termed CC-1. CC-1 binds to prostate-specific membrane antigen that is expressed on prostate cancer cells and tumour vessels, thereby allowing a dual anticancer effect.

Methods and analysis

This first in human clinical study is a prospective and multicentre trial which enrols patients with metastatic CRPC after failure of established third-line therapy. CC-1 is applied after prophylactic interleukin-6 receptor blockade with tocilizumab (once 8 mg/kg body weight). Each patient receives at least one cycle of CC-1 over a time course of 7 days in an inpatient setting. If clinical benefit is observed, up to five additional cycles of CC-1 can be applied. The study is divided in two parts: (1) a dose escalation phase with intraindividual dose increase from 28 µg to the target dose of 1156 µg based on a modified fast titration design by Simonet alto determine safety, tolerability and the maximum tolerated dose (MTD) as primary endpoints and (2) a dose expansion phase with additional 14 patients on the MTD level of part (1) to identify first signs of efficacy. Secondary endpoints compromise overall safety, tumour response, survival and a translational research programme with, among others, the analysis of CC-1 half-life, the induced immune response, as well as the molecular profiling in liquid biopsies.

Ethics and dissemination

The PSMAxCD3 study was approved by the Ethics Committee of The University Hospital Tübingen (100/2019AMG1) and the Paul-Ehrlich-Institut (3684/02). Clinical trial results will be published in peer-reviewed journals.

Trial registration numbers

ClinicalTrials.gov Registry (NCT04104607) and ClinicalTrials.eu Registry (EudraCT2019-000238-20).
Triaging of respiratory protective equipment on the assumed risk of SARS-CoV-2 aerosol exposure in patient-facing healthcare workers delivering secondary care: a rapid review
Authors: Ramaraj Prashanth , Super Jonathan , Doyle Ruben , Aylwin Christopher , Hettiaratchy Shehan
Published: October 2020

Objectives

In patient-facing healthcare workers delivering secondary care, what is the evidence behind UK Government personal protective equipment (PPE) guidance on surgical masks versus respirators for SARS-CoV-2 protection?

Design

Two independent reviewers performed a rapid review. Appraisal was performed using Critical Appraisal Skills Programme checklists and Grading of Recommendations, Assessment, Development and Evaluations methodology. Results were synthesised by comparison of findings and appraisals.

Data sources

MEDLINE, Google Scholar, UK Government COVID-19 website and grey literature.

Eligibility criteria

Studies published on any date containing primary data comparing surgical facemasks and respirators specific to SARS-CoV-2, and studies underpinning UK Government PPE guidance, were included.

Results

Of 30 identified, only 3 laboratory studies of 14 different respirators and 12 surgical facemasks were found. In all three, respirators were significantly more effective than facemasks when comparing protection factors, reduction factors, filter penetrations, total inspiratory leakages at differing particle sizes, mean inspiratory flows and breathing rates. Tests included live viruses and inert particles on dummies and humans. In the six clinical studies (6502 participants) included the only statistically significant result found continuous use of respirators more effective in clinical respiratory illness compared with targeted use or surgical facemasks. There was no consistent definition of ‘exposure’ to determine the efficacy of respiratory protective equipment (RPE). It is difficult to define ‘safe’.

Conclusions

There is a paucity of evidence on the comparison of facemasks and respirators specific to SARS-CoV-2, and poor-quality evidence in other contexts. The use of surrogates results in extrapolation of non-SARS-CoV-2 specific data to guide UK Government PPE guidance. The appropriateness of this is unknown given the uncertainty over the transmission of SARS-CoV-2.

This means that the evidence base for UK Government PPE guidelines is not based on SARS-CoV-2 and requires generalisation from low-quality evidence of other pathogens/particles. There is a paucity of high-quality evidence regarding the efficacy of RPE specific to SARS-CoV-2. UK Government PPE guidelines are underpinned by the assumption of droplet transmission of SARS-CoV-2.

These factors suggest that the triaging of filtering face piece class 3 respirators might increase the risk of COVID-19 faced by some.
Cessation of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
Authors: Middeldorp Melissa E , Gupta Aashray , Elliott Adrian , Kadhim Kadhim , Thiyagarajah Anand , Gallagher Celine , Hendriks Jeroen , Linz Dominik , Emami Mehrdad , Mahajan Rajiv , Lau Dennis , Sanders Prashanthan
Published: October 2020

Objective

To characterise the rate, causes and predictors of cessation of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF).

Patients and methods

Consecutive patients with AF with a long-term anticoagulation indication treated with NOACs (dabigatran, apixaban and rivaroxaban) in our centre from September 2010 through December 2016 were included. Prospectively collected data with baseline characteristics, causes of cessation, mean duration-to-cessation and predictors of cessation were analysed.

Results

The study comprised 1415 consecutive patients with AF, of whom 439 had a CHA2DS2-VASc≥1 and were on a NOAC. Mean age was 71.9±8.7 years and 37% were females. Over a median follow-up of 3.6 years (IQR=2.7–5.3), 147 (33.5%) patients ceased their index-NOAC (113 switched to a different form of OAC), at a rate of 8.8 per 100 patient-years. Serious adverse events warranting NOAC cessation occurred in 28 patients (6.4%) at a rate of 1.6 events per 100 patient-years. The mean duration-to-cessation was 4.9 years (95% CI 4.6 to 5.1) and apixaban had the longest duration-to-cessation with (5.1, 95% CI 4.8 to 5.4) years, compared with dabigatran (4.6, 95% CI 4.2 to 4.9) and rivaroxaban (4.5, 95% CI 3.9 to 5.1), pairwise log-rank p=0.002 and 0.025, respectively. In multivariable analyses, age was an independent predictor of index-NOAC cessation (HR 1.03, 95% CI 1.01 to 1.05; p=0.006). Female gender (HR 2.2, 95% CI 1.04 to 4.64; p=0.04) independently predicted serious adverse events.

Conclusion

In this ‘real world’ cohort, NOAC use is safe and well-tolerated when prescribed in an integrated care clinic. Whether apixaban is better tolerated compared with other NOACs warrants further study.
Cardiovascular disease recurrence and long-term mortality in a tri-ethnic British cohort
Authors: Vyas Manav V , Chaturvedi Nish , Hughes Alun D , Marmot Michael , Tillin Therese
Published: October 2020

Objective

Ethnic differences in cardiovascular disease incidence, but not cardiovascular disease recurrence, are reported. We characterised long-term risk of major adverse cardiovascular event (MACE) and mortality following a non-fatal cardiovascular event in a British cohort of South Asians, African Caribbeans and Europeans.

Methods

We identified index and recurrent cardiovascular events and mortality between 1988 and 2017 using hospital records and death registry. Using multivariable hazards models, we separately calculated the adjusted HR of MACE and death following index event, adjusting for demographics, vascular and lifestyle risk factors. Using interaction terms, we evaluated if decade of index event modified the association between ethnicity and outcomes.

Results

South Asians were younger at the index event (median age 66 years, n=396) than Europeans (69 years, n=335) and African Caribbeans (70 years, n=70). During 4228 person-years, of the 801 patients, 537 developed MACE and 338 died, with the highest crude rate of MACE in South Asians. On adjustment of baseline factors, compared with the Europeans, the higher risk of MACE (HR 0.97, 95% CI 0.77 to 1.21) and the lower risk of mortality (HR 0.95, 95% CI 0.72 to 1.26) in South Asians was eliminated. African Caribbeans had similar outcomes to Europeans (HR MACE 1.04, 95% CI 0.74 to 1.47; and HR death 1.07, 95% CI 0.70 to 1.64). Long-term survival following an index event improved in South Asians (ptrend 0.02) and African Caribbeans (ptrend 0.07) compared with Europeans.

Conclusions

Baseline vascular risk factors explained the observed ethnic variation in cardiovascular disease recurrence and long-term mortality, with a relative improvement in survival of minority ethnic groups over time.
Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx)
Authors: Awada Gil , Ben Salama Laila , De Cremer Jennifer , Schwarze Julia Katharina , Fischbuch Lydia , Seynaeve Laura , Du Four Stephanie , Vanbinst Anne-Marie , Michotte Alex , Everaert Hendrik , Rogiers Anne , Theuns Peter , Duerinck Johnny , Neyns Bart
Published: October 2020

Background

No treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.

Methods

Adult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.

Results

Between June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.

Conclusion

The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.
Impact of COVID-19 on patients with rheumatic complications of cancer immunotherapy: results of a registry survey
Authors: Ghosh Nilasha , Tirpack Aidan , Chan Karmela K , Bass Anne R
Published: October 2020

Immune checkpoint inhibitors (ICI) block negative regulatory molecules, such as CTLA-4, PD-1 and PD-L1, in order to mount an antitumor response. T cells are important for antiviral defense, but it is not known whether patients with cancer treated with ICI are more or less vulnerable to viral infections such as COVID-19. Furthermore, immunosuppressive treatment of immune-related adverse events (irAE) may also impact infection risk. Rheumatic irAEs are often persistent, and can require long-term treatment with immunosuppressive agents. The aim of this study was to determine the incidence of COVID-19 infection and assess changes in ICI and immunosuppressive medication use among patients enrolled in a prospective rheumatic irAE registry during the height of the COVID-19 pandemic. On April 16 2020, following the ‘surge’ of COVID-19 infections in the New York Tri-State area, we sent a 23-question survey to 88 living patients enrolled in a single institutional registry of patients with rheumatic irAE. Questions addressed current cancer and rheumatic irAE status, ICI and immunosuppressant medication use, history of COVID-19 symptoms and/or diagnosed infection. A follow-up survey was sent out 6 weeks later. Sixty-five (74%) patients completed the survey. Mean age was 63 years, 59% were female, 70% had received anti-PD-(L)1 monotherapy and 80% had had an irAE affecting their joints. Six patients (10%) had definite or probable COVID-19, but all recovered uneventfully, including two still on ICI and on low-to-moderate dose prednisone. Of the 25 on ICI within the last 6 months, seven (28%) had their ICI held due to the pandemic. In patients on immunosuppression for irAE, none had changes made to those medications as a result of the pandemic. The incidence of COVID-19 was no higher in patients still on ICI. Ten percent of rheumatic irAE patients developed COVID-19 during the NY Tri-state ‘surge’ of March–April 2020. Oncologists held ICI in a quarter of the patients still on them, particularly women, those on anti-PD-(L)1 monotherapy, and those who had had a good cancer response. The incidence of COVID-19 was no higher on patients still on ICI. None of the patients on disease-modifying antirheumatic drugs or biological immunosuppressive medications developed COVID-19.
Drug-coated balloon for vertebral artery origin stenosis: a pilot study
Authors: Wang Yabing , Feng Yiding , Wang Tao , Ma Yan , Gao Peng , Chen Jian , Chen Yanfei , Yang Bin , Jiao Liqun
Published: October 2020

Background

Drug-coated balloon (DCB) is a potential treatment for patients with low restenosis risk in vertebral artery origin stenosis (VAOS). However, the clinical data of long-term outcome are limited.

Objective

To evaluate the safety and efficacy of a DCB in patients with severe VAOS.

Methods

A prospective, non-randomized, single-center pilot study enrolled 30 patients with severe VAOS treated with DCB between 2017 and 2018. The first 20 patients were treated with a balloon-to-vessel ratio of predilation (pBVR)＜0.8 (small-size balloon predilation) and the following 10 patients were treated with a pBVR 0.8–1.0 (large-size balloon predilation). Primary safety endpoints included 30-day death, stroke, and transient ischemic attack (TIA). The main efficacy outcome was restenosis at 6 months, defined as a peak systolic velocity >140 cm/s measured by Doppler ultrasound. Long-term outcomes, including TIAs, stroke, death, and modified Rankin Scale score, were followed up to 2 years.

Results

Technical success (<50% residual stenosis) was achieved in 26 patients (mean age 66.2±7.0; seven women). Four patients received bailout stenting and were excluded. Ultrasound confirmed restenosis at 6 months in 10 (38.5%) of 26, which was significantly less frequent in LSBP (LSBP vs SSBP=10% vs 56.3%, p<0.05). No adverse events occurred within 30 days of treatment. 19 patients were followed up for 2 years, with two deaths due to cancer.

Conclusion

This pilot study suggests that DCB is a safe approach for VAOS. The relatively low restenosis rate indicates the its potential long-term efficacy for VAOS. Future randomized controlled trials to confirm its efficacy are warranted.
Thirteen‐month duration of immunity of an oral canine vaccine against challenge with Bordetella bronchiseptica
Authors: Scott‐Garrard Maya , Wang Xinshuo , Chiang Yu‐Wei , David Frederic
Published: October 2020

Background

Very few studies have evaluated the duration of immunity of Bordetella bronchiseptica vaccines in dogs, and to date, no studies have been published on the duration of immunity of oral canine Bordetella bronchiseptica vaccines. This study was designed to determine the effectiveness of a single dose of an oral B bronchiseptica vaccine in dogs when challenged 13 months after vaccination.

Methods

Two groups of approximately eight‐week‐old beagles were vaccinated once with 1 ml of placebo vaccine (oral, n=17) or 1 ml of Recombitek Oral Bordetella (oral, n=17). Thirteen months after vaccination, both groups were challenged with virulent B bronchiseptica via aerosolisation.

Results

Thirteen of 17 dogs in the placebo group (76.5 per cent) and no dogs in the Recombitek Oral Bordetella vaccine group (0.0 per cent) developed spontaneous cough of two or more consecutive days (disease case definition). Dogs in the Recombitek Oral Bordetella group had a significantly lower prevalence of disease with prevented fraction of 1 (100 per cent prevention). In addition, the number of days coughing, duration of cough and prevalence of tracheal and nasal shedding were significantly lower for dogs vaccinated with Recombitek Oral Bordetella.

Conclusions

The study demonstrated that vaccination with Recombitek Oral Bordetella is effective in preventing disease and reducing shedding 13 months after vaccination when compared with dogs vaccinated with a placebo.
Late Devonian magmatism and clastic deposition in the upper Earn Group (central Yukon, Canada) mark the transition from passive to active margin along western Laurentia
Authors: Cobbett Rose N. , Colpron Maurice , Crowley James L. , Cordey Fabrice , Blodgett Robert B. , Orchard Micheal J.
Published: October 2020

The Earn Group of central Yukon records the transition from a passive to an active margin along western Laurentia in the Late Devonian. Fine-grained clastic rocks and chert of the lower Earn Group contain late Early to Middle Devonian fossils and were deposited in an offshelf environment. The upper Earn Group comprises a mixture of sandstone and conglomerate, fine-grained siliciclastic rocks, and widespread crystal lithic tuff. Zircons from this succession are precisely dated using chemical abrasion isotope dilution thermal ionization mass spectrometry (CA–ID–TIMS) methods on igneous (ca. 363 Ma) and detrital (ca. 378–363 Ma) grains and the ages were confirmed by Frasnian to Famennian fossils. Abrupt, along-strike facies changes within the upper Earn Group of the Glenlyon–Tay River area occur across mapped faults that are inferred to have originated as syndepositional extension faults in the Late Devonian. Occurrences of ca. 363 Ma tuff horizons within all facies of the upper Earn Group provide a temporal correlation across the area. Diorite plutons intrude lower Paleozoic rocks in the area and have U–Pb zircon crystallization dates of ca. 364 Ma. The diorite has calc-alkaline composition consistent with arc magmatism or crustal contamination. The Late Devonian magmatism in the Earn Group is coincident with onset of arc magmatism in the allochthonous Yukon–Tanana terrane, and extension related to rifting and opening of the Slide Mountain ocean in a back-arc setting. Magmatic rocks in the Earn Group of central Yukon thus represent part of a remnant continental arc and back-arc stranded behind the Slide Mountain ocean in the Mississippian.
Evolving the core microbial community in pit mud based on bioturbation of fortified Daqu
Authors: Chen Suqi , Huang Jun , Qin Hui , He Guiqiang , Zhou Rongqing , Yang Yan , Qiu Chuanfeng , Zhang Suyi
Published: October 2020

Directional stress is an effective measure to change the community structure and improve the bioactivity of pit mud (PM). In this study, the addition of fortified Daqu to artificial PM (APM) was intended to disturb the microbial community and further affect metabolites. To evaluate the effect of fortified Daqu on culturing APM, the microbial communities of APM with or without the addition of fortified Daqu were investigated by fluorescence in situ hybridization and Illumina MiSeq. The results indicated that microbes (Clostridium sp., Clostridium kluyveri, hydrogenotrophic methanogens, and acetotrophic methanogens) related to the production of key aroma compounds increased notably when fortified Daqu was added. In particular, the hydrogenotrophic and acetotrophic methanogens increased by 6.19- and 4.63-fold after 30 days of culture. Subsequently, metabolites (organic acids, volatile compounds) were also analyzed by HPLC (high-performance liquid chromatography) and HS-SPME–GC–MS (headspace solid phase microextraction – gas chromatography – mass spectrometry). The results showed that the content of butyric acid and hexanoic acid was significantly higher when fortified Daqu was added to APM. In addition, the proportion of esters and phenols was also higher than in APM without fortified Daqu. A survey of the microbial compositions of APMs with or without added fortified Daqu indicated that the microbial community evolves into a functional community favoring liquor brewing. We have developed a novel process by disturbing the community diversity.
Uncertainty Updating of Finite Element Models Using Interval Analysis
Authors: Shan Deshan , Chai Y. H. , Dong Hao , Li Zhonghui
Published: October 2020

Uncertainties in structural parameters and measurements can be accounted for by incorporating interval analysis into the updating scheme of finite element models using a response-surface function. To facilitate the interval arithmetic operation, two different strategies are proposed in this paper to transform the response-surface function into a corresponding interval response-surface function. These strategies minimize the inherent interval overestimation that can arise from the variable dependency of the surrogate model. In the first strategy, the natural extension and centered-form extension methods are used to mitigate the interval overestimation of the surrogate model, which may or may not contain interaction terms. In the second strategy, the natural extensión method is also adopted to realize the interval transformation of the surrogate model containing interaction terms but an affine arithmetic is further introduced to minimize the interval overestimation. To demonstrate the efficacy of the proposed method, model parameters are determined from an instrumented model of a cable-stayed bridge tested on a shaking table. Results show that the proposed updating method is feasible and effective for applications to finite element models of complex bridge structures.
PHIST
Authors: Thies Jonas , Röhrig-Zöllner Melven , Overmars Nigel , Basermann Achim , Ernst Dominik , Hager Georg , Wellein Gerhard
Published: October 2020

The increasing complexity of hardware and software environments in high-performance computing poses big challenges on the development of sustainable and hardware-efficient numerical software. This article addresses these challenges in the context of sparse solvers. Existing solutions typically target sustainability, flexibility, or performance, but rarely all of them.

Our new library PHIST provides implementations of solvers for sparse linear systems and eigenvalue problems. It is a productivity platform for performance-aware developers of algorithms and application software with abstractions that do not obscure the view on hardware-software interaction.

The PHIST software architecture and the PHIST development process were designed to overcome shortcomings of existing packages. An interface layer for basic sparse linear algebra functionality that can be provided by multiple backends ensures sustainability, and PHIST supports common techniques for improving scalability and performance of algorithms such as blocking and kernel fusion.

We showcase these concepts using the PHIST implementation of a block Jacobi-Davidson solver for non-Hermitian and generalized eigenproblems. We study its performance on a multi-core CPU, a GPU, and a large-scale many-core system. Furthermore, we show how an existing implementation of a block Krylov-Schur method in the Trilinos package Anasazi can benefit from the performance engineering techniques used in PHIST.
RuleHub
Authors: Ahmadi Naser , Truong Thi-Thuy-Duyen , Dao Le-Hong-Mai , Ortona Stefano , Papotti Paolo
Published: October 2020

Entity-centric knowledge graphs (KGs) are now popular to collect facts about entities. KGs have rich schemas with a large number of different types and predicates to describe the entities and their relationships. On these rich schemas, logical rules are used to represent dependencies between the data elements. While rules are useful in query answering, data curation, and other tasks, they usually do not come with the KGs. Such rules have to be manually defined or discovered with the help of rule mining methods. We believe this rule-collection task should be done collectively to better capitalize our understanding of the data and to avoid redundant work conducted on the same KGs. For this reason, we introduce
RuleHub
, our extensible corpus of rules for public KGs. RuleHub provides functionalities for the archival and the retrieval of rules to all users, with an extensible architecture that does not constrain the KG or the type of rules supported. We are populating the corpus with thousands of rules from the most popular KGs and report on our experiments on automatically characterizing the quality of a rule with statistical measures.
A Feature-complete SPIKE Dense Banded Solver
Authors: Spring Braegan S. , Polizzi Eric , Sameh Ahmed H.
Published: October 2020

This article presents a parallel, effective, and feature-complete recursive SPIKE algorithm that achieves near feature-parity with the standard linear algebra package banded linear system solver. First, we present a flexible parallel implementation of the recursive SPIKE scheme that aims at removing its original limitation that the number of cores/processors be restricted to powers of two. A new transpose solve option for SPIKE is then developed to satisfy a standard requirement of most numerical solver libraries. Finally, a pivoting recursive SPIKE strategy is presented as an alternative to the non-pivoting scheme to improve numerical stability. All these new enhancements lead to the release of a new black-box feature-complete SPIKE-OpenMP package that significantly improves upon the performance and scalability obtained with other state-of-the-art banded solvers.
A Comparison of Touchscreen and Mouse for Real-World and Abstract Tasks with Older Adults
Authors: Kim Sung-Hee , Zhang Kailun , McGrenere Joanna , Booth Kellogg S. , Jacova Claudia
Published: October 2020

Computer technology is increasingly being used to facilitate the timely identification of cognitive impairment in older adults. Our
Cognitive Testing on Computer (C-TOC)
project aims to develop a self-administered online test for older adults to take at their home. Due to the freedom of devices they can use, it is important to investigate whether different input devices can impact test performance. We compared touchscreen and mouse input on both abstract and real-world pointing and dragging tasks: classic Fitts’s Law tasks and tasks drawn from C-TOC. The abstract and real-world tasks were designed to require equivalent motor skills. Our research goals were to determine (1) if performance on computerized cognitive tasks are affected by input device, and (2) if performance differences due to input device can be explained by those observed on Fitts’s Law tasks. Sixteen older adults completed both types of tasks using a touchscreen and a mouse. We found that input device affected speed on three out of four cognitive tasks while only affecting accuracy on one task. Secondarily, our results suggest that Fitts’s Law results of differences in mouse and touch cannot be used to predict device differences in the performance on C-TOC tests. As an additional research goal, we looked into the movement patterns of one real-world dragging task—the C-TOC Pattern Construction task—to see if they could provide richer performance measures, beyond speed and accuracy. Such measures could compensate for the lack of a clinician observer who is typically present in comparable paper-based cognitive tests. We found that older adults naturally adopted different movement patterns on the two devices: they tended to make shorter moves and a greater number of moves on a touchscreen than with a mouse. Altogether, our results suggest that careful device-based performance calibration will be needed in computerized tests.
A High Accuracy Preserving Parallel Algorithm for Compact Schemes for DNS
Authors: Sengupta Tapan K. , Sundaram Prasannabalaji , Suman Vajjala K. , Bhaumik Swagata
Published: October 2020

A new accuracy-preserving parallel algorithm employing compact schemes is presented for direct numerical simulation of the Navier-Stokes equations. Here the connotation of accuracy preservation is having the same level of accuracy obtained by the proposed parallel compact scheme, as the sequential code with the same compact scheme. Additional loss of accuracy in parallel compact schemes arises due to necessary boundary closures at sub-domain boundaries. An attempt to circumvent this has been done in the past by the use of Schwarz domain decomposition and compact filters in “A new compact scheme for parallel computing using domain decomposition,” J. Comput. Phys. 220, 2 (2007), 654--677, where a large number of overlap points was necessary to reduce error. A parallel compact scheme with staggered grids has been used to report direct numerical simulation of transition and turbulence by the Schwarz domain decomposition method. In the present research, we propose a new parallel algorithm with two benefits. First, the number of overlap points is reduced to a single common boundary point between any two neighboring sub-domains, thereby saving the number of points used, with resultant speed-up. Second, with a proper design, errors arising due to sub-domain boundary closure schemes are reduced to a user designed error tolerance, bringing the new parallel scheme on par with sequential computing. Error reduction is achieved by using global spectral analysis, introduced in “Analysis of central and upwind compact schemes,” J. Comput. Phys. 192, 2, (2003) 677--694, which analyzes any discrete computing method in the full domain integrally. The design of the parallel compact scheme is explained, followed by a demonstration of the accuracy of the method by solving benchmark flows: (1) periodic two-dimensional Taylor-Green vortex problem; (2) flow inside two-dimensional square lid-driven cavity (LDC) at high Reynolds number; and (3) flow inside a non-periodic three-dimensional cubic LDC with the staggered grid arrangement.
Cardiac Regeneration: New Hope for an Old Dream
Authors: Weinberger Florian , Eschenhagen Thomas
Published: October 2020

The regenerative capacity of the heart has long fascinated scientists. In contrast to other organs such as liver, skin, and skeletal muscle, the heart possesses only a minimal regenerative capacity. It lacks a progenitor cell population, and cardiomyocytes exit the cell cycle shortly after birth and do not re-enter after injury. Thus, any loss of cardiomyocytes is essentially irreversible and can lead to or exaggerate heart failure, which represents a major public health problem. New therapeutic options are urgently needed, but regenerative therapies have remained an unfulfilled promise in cardiovascular medicine until today. Yet, through a clearer comprehension of signaling pathways that regulate the cardiomyocyte cell cycle and advances in stem cell technology, strategies have evolved that demonstrate the potential to generate new myocytes and thereby fulfill an essential central criterion for heart repair.
Space-Time Covariance Structures and Models
Authors: Chen Wanfang , Genton Marc G. , Sun Ying
Published: October 2020

In recent years, interest has grown in modeling spatio-temporal data generated from monitoring networks, satellite imaging, and climate models. Under Gaussianity, the covariance function is core to spatio-temporal modeling, inference, and prediction. In this article, we review the various space-time covariance structures in which simplified assumptions, such as separability and full symmetry, are made to facilitate computation, and associated tests intended to validate these structures. We also review recent developments on constructing space-time covariance models, which can be separable or nonseparable, fully symmetric or asymmetric, stationary or nonstationary, univariate or multivariate, and in Euclidean spaces or on the sphere. We visualize some of the structures and models with visuanimations. Finally, we discuss inference for fitting space-time covariance models and describe a case study based on a new wind-speed data set.
Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes
Authors: Sun Lili , Zou Shengyi , Ding Sisi , Du Xuan , Shen Yu , Liu Cuiping , Shi Bimin , Zhang Xueguang
Published: October 2020

Aims. Obesity is highly associated with type 2 diabetes mellitus (T2DM). The TIM3/galectin-9 pathway plays an important role in immune tolerance. Herein, we aimed to investigate the expression of TIM3 and galectin-9 in peripheral blood and to evaluate their clinical significance in patients with obesity and obesity-related T2DM. Methods. We performed flow cytometry on peripheral blood samples from healthy donors (HC), patients with simple obesity (OB), and patients with obesity comorbid T2DM (OD). The expression of TIM3 on CD3+, CD4+, and CD8+ T cells was determined. The level of galectin-9 in plasma was detected by ELISA. Results. We demonstrated the enhancement of TIM3 on CD3+, CD4+, and CD8+ T cells in the OB group when compared with healthy controls, while it was decreased significantly in the OD group. The TIM3+CD8+ T cells of the OB group were positively correlated with risk factors including BMI, body fat rate, and hipline. The concentration of galectin-9 of the OD group in plasma was significantly higher than that of healthy donors and the OB group. Moreover, the level of galectin-9 of the OD group was positively correlated with fasting insulin and C-peptide, which were two clinical features that represented pancreatic islet function in T2DM. Conclusions. Our results suggested that TIM3 and galectin-9 may be potential biomarkers related to the pathogenesis of obesity-related T2DM.
A Miniature and Low-Power-Consumption Stress Measurement System for Embedded Explosive in Multilayer Target Penetration
Authors: Hang Yu , Shang Fei , Gao Shang , Kong Deren , Zhang Xuehui
Published: October 2020

When a penetrator penetrates a target, security issues such as detonation and deflagration sometimes occur in the embedded explosive under an extreme environment with high overload and severe mechanical shock. Explosives withstand multiple impact stresses with high amplitudes during a multilayer target penetration (MTP) process. Manganin pressure gauges and external dynamic testing systems are common instruments to evaluate explosive safety. However, this method is unsuitable for an MTP experiment where the penetrator flies with a long distance. This article proposes a stress measurement system (SMS) installed in a penetrator for explosive stress detection based on a qualitative analysis for the stress characteristics of the explosive. A high-strength mechanical structure is designed for the SMS to survive in the MTP environment. A low-power management mechanism realized by dual MCUs (STM32 + FPGA) is proposed to reduce the power consumption of the SMS. An experimental investigation is carried out to verify the feasibility of the measurement system designed in this paper. An MTP numerical simulation is carried out to reveal the characteristics of stress occurring and propagating in the explosive. An MTP experiment is conducted and the impact stresses on the explosive surface are measured by the fabricated SMS prototypes. The measurement results are consistent with the simulation results, which indicate that the prototypes have the abilities of high-precision data acquisition and storage in the MTP experiment.
Lupus and NMOSD: The Blending of Humoral Autoimmunity
Authors: Ochi Maria Goretti S. , Shapiro Samantha C. , Melamed Esther
Published: October 2020

Systemic lupus erythematous (SLE) is a chronic autoimmune disease that can target any organ of the body. It may coexist with other autoimmune neurologic conditions such as neuromyelitis optica spectrum disorder (NMOSD). NMOSD, previously known as Devic’s disease, is an autoimmune inflammatory disorder of the central nervous system (CNS) that targets the spinal cord, optic nerves, and certain brain regions. Most current evidence suggests that NMOSD is best described as a CNS astrocytopathy. While these diseases share several immunosuppressive treatment options, timely diagnosis of NMOSD is critical as patients may benefit from treatment tailored specifically to NMOSD as opposed to SLE. Steroids, plasmapheresis, intravenous immunoglobulin, cyclophosphamide, azathioprine, mycophenolate mofetil, and rituximab are used to treat both SLE and NMOSD. However, there are several new therapies (inebilizumab, eculizumab, and satralizumab) recently approved specifically for use in NMOSD. In this case series, we report on three patients with coexisting SLE and NMOSD. We describe a 31-year-old woman who suffered an NMOSD flare after 11 years of clinical remission in the context of receiving an influenza vaccination; her SLE remained quiescent on hydroxychloroquine. Next, we describe a 52-year-old woman with emergence of neurologically devastating seropositive NMOSD in the setting of active treatment for SLE with intravenous cyclophosphamide, oral steroids, and hydroxychloroquine. Last, we describe a 48-year-old woman with emergence of seronegative NMOSD in the setting of SLE that was well-controlled on azathioprine and hydroxychloroquine. These cases illustrate the importance of accurate diagnosis and targeted treatment of NMOSD when coexisting with SLE.
Combined Bile Duct and Pancreatic Duct Injuries during Distal Gastrectomy for Obstructing Peptic Ulcer Disease
Authors: Pandit Narendra , Deo Kunal Bikram
Published: October 2020

A combination of bile and pancreatic duct injuries is very rare. Anomalous ductal anatomy, distorting duodenal fibrosis, and pancreatic atrophy predispose to this untoward complication during performance of distal gastrectomy for benign peptic stricture. The technical challenges posed by this complication and experience gained by managing it are shared.