bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysphagia due to necrotizing otitis externa
Authors: Dwivedi Rajesh , Rasquinha Melroy , Harwood Rowan
Published: February 2021

An 88-year-old man presented with delirium, and subsequently developed hoarseness and oropharyngeal dysphagia. This was due to skull-based osteomyelitis from necrotizing otitis externa (NOE), causing lower cranial nerve (X, XII) palsies and venous sinus thrombosis. Diagnosis was delayed as the patient reported no otalgia, had an almost normal looking external auditory canal and was not diabetic. He deteriorated and died despite intravenous antibiotics. We need a high index of suspicion for NOE and its complications in patients presenting with otolaryngeal symptoms.
The Effects of Placebo and Moderate Dose Alcohol on Attentional Bias, Inhibitory Control and Subjective Craving
Authors: McNeill Adam M , Monk Rebecca L , Qureshi Adam W , Litchfield Damien , Heim Derek
Published: February 2021

Aims

Previous research indicates that acute alcohol intoxication and placebo can inhibit people’s control over consumption behaviour and heighten attentional bias (AB) towards alcohol-related stimuli and craving. We designed a study to disentangle anticipated from pharmacological effects of alcohol in order to gain a clearer view of their relative contributions to alcohol consumption.

Methods

In a within-participants design (moderate alcohol dose, placebo and control), and over a minimum 2-week period, participants completed a battery of questionnaires and cognitive tasks, followed by a bogus taste task to measure ad libitum consumption.

Results

Both alcohol preload and placebo resulted in cognitive and psychological changes, including impaired inhibitory control, heightened AB and craving. However, ad libitum consumption only increased following alcohol and not placebo. Furthermore, inhibitory control impairments did not mediate the relationship between initial intoxication and ad libitum consumption, and findings indicate that increases in craving may mediate this association.

Conclusion

Psychological processes such as craving may be more important in driving consummatory behaviour relative to transient changes in cognitive processes, such as inhibitory control.
Long-Term Effects of Platelet-Rich Fibrin on Fat Graft Survival and Their Optimal Mixing Ratio
Authors: Yu Panxi , Yang Xiaonan , Zhai Zhen , Gao Qiuni , Yang Zhenyu , Qi Zuoliang
Published: February 2021

Background

Platelet-rich fibrin (PRF) can promote fat graft survival, but the reported mixing ratio of PRF to fat ranges from 1:25 to 1:2, lacking a clear standard for clinical application.

Objectives

The authors sought to explore the long-term effects of PRF on grafted fat and their optimal mixing ratio.

Methods

Nude mice were randomly divided into a control group (receiving subcutaneous injection of fat granules) and 4 PRF groups (receiving subcutaneous injection of PRF and fat granules at volume ratios of 1:5, 1:10, 1:15, and 1:20, respectively). The graft samples (n = 12) were obtained in weeks 4, 8, and 12 to (1) calculate retention rates; (2) evaluate gene and protein expression of vascular endothelial growth factor A (VEGF-A), peroxisome proliferator-activated receptor-γ (PPAR-γ), type I collagen A1 (COL1-A1), and B-cell lymphoma-2 associated X protein (BAX); (3) perform hematoxylin and eosin, Masson’s trichrome, α-smooth muscle action, and periplipin-1 stainings; and (4) count the microvessels and viable adipocytes.

Results

Compared with the control group, PRF groups had higher retention rates, a higher gene/protein expression of VEGF-A, a lower gene/protein expression of COL1-A1 and BAX, less fibrosis, and more microvessels and viable adipocytes. Group 1:10 was superior to other groups in terms of retention rates and other evaluation indexes. The expression of PPAR-γ did not significantly differ among groups.

Conclusions

PRF may not play a long-term effect on adipogenesis, but it can still promote fat graft survival through facilitating vascularization, regulating collagen production, and inhibiting apoptosis. PRF can achieve the best promoting effect when the mixing ratio of PRF to fat is 1:10, which is recommended as the optimal ratio for clinical application.
Regulation of gene expression in the bovine blastocyst by colony-stimulating factor 2 is disrupted by CRISPR/Cas9-mediated deletion ofCSF2RA
Authors: Xiao Yao , Uh Kyungjun , Negrón-Pérez Veronica M , Haines Hannah , Lee Kiho , Hansen Peter J
Published: February 2021

Colony-stimulating factor 2 (CSF2) functions in the reproductive tract to modulate the function of the preimplantation embryo. The β subunit of the CSF2 receptor (CSF2RB) is not expressed in the embryo, and signal transduction is therefore different than for myeloid cells where the receptor is composed of α (CSF2RA) and β subunits. Here, we produced embryos in which exons 5 and 6 of CSF2RA were disrupted using the CRISPR/Cas 9 system to test whether CSF2RA signaling was essential for actions of CSF2 in the bovine embryo. Wild-type and CSF2RA knockout embryos were treated with 10 ng/mL CSF2 or vehicle at day 5 of development. Blastocysts were harvested at day 8 to determine transcript abundance of 90 genes by real-time polymerase chain reaction (PCR). Responses in female blastocysts were examined separately from male blastocysts because actions of CSF2 are sex-dependent. For wild-type embryos, CSF2 altered expression of 10 genes in females and 20 in males. Only three genes were affected by CSF2 in a similar manner for both sexes. Disruption of CSF2RA prevented the effect of CSF2 on expression for 9 of 10 CSF2-regulated genes in females and 19 of 20 genes in males. The results confirm the importance of CSF2RA for regulation of gene expression by CSF2 in the blastocyst.
Rbm46, a novel germ cell-specific factor, modulates meiotic progression and spermatogenesis
Authors: Dai Xiangyan , Cheng Xinkai , Huang Jianfei , Gao Yanping , Wang Deshou , Feng Zhi , Zhai Gang , Lou Qiyong , He Jiangyan , Wang Zhijian , Yin Zhan
Published: February 2021

It has been suggested that many novel RNA-binding proteins (RBPs) are required for gametogenesis, but the necessity of few of these proteins has been functionally verified. Here, we identified one RBP, Rbm46, and investigated its expression pattern and role in zebrafish reproduction. We found that rbm46 is maternally provided and specifically expressed in the germ cells of gonadal tissues using in situ hybridization, reverse transcription-PCR, and quantitative real-time polymerase chain reaction (qRT-PCR). Two independent rbm46 mutant zebrafish lines were generated via the transcription activator-like effector nuclease technique. Specific disruption of rbm46 resulted in masculinization and infertility in the mutants. Although the spermatogonia appeared grossly normal in the mutants, spermatogenesis was impaired, and meiosis events were not observed. The introduction of a tp53M214K mutation could not rescue the female-to-male sex-reversal phenotype, indicating that rbm46 acts independently of the p53-dependent apoptotic pathway. RNA sequencing and qRT-PCR subsequently indicated that Rbm46 might be involved in the posttranscriptional regulation of functional genes essential for germ cell development, such as nanos3, dazl, and sycp3, during gametogenesis. Together, our results reveal for the first time the crucial role of rbm46 in regulating germ cell development in vivo through promotion of germ cell progression through meiosis prophase I.
Connecting Top-Down and Bottom-Up Approaches in Environmental Observing
Authors: Eicken Hajo , Danielsen Finn , Sam Josephine-Mary , Fidel Maryann , Johnson Noor , Poulsen Michael K , Lee Olivia A , Spellman Katie V , Iversen Lisbeth , Pulsifer Peter , Enghoff Martin
Published: February 2021

Effective responses to rapid environmental change rely on observations to inform planning and decision-making. Reviewing literature from 124 programs across the globe and analyzing survey data for 30 Arctic community-based monitoring programs, we compare top-down, large-scale program driven approaches with bottom-up approaches initiated and steered at the community level. Connecting these two approaches and linking to Indigenous and local knowledge yields benefits including improved information products and enhanced observing program efficiency and sustainability. We identify core principles central to such improved links: matching observing program aims, scales, and ability to act on information; matching observing program and community priorities; fostering compatibility in observing methodology and data management; respect of Indigenous intellectual property rights and the implementation of free, prior, and informed consent; creating sufficient organizational support structures; and ensuring sustained community members’ commitment. Interventions to overcome challenges in adhering to these principles are discussed.
Towards a Critical Pedagogy of Atmosphere in Social Work Education: Using Counter-Mapping to Examine the Emplaced Power Relations of Practice
Authors: Gutiérrez-Ujaque Daniel , Jeyasingham Dharman
Published: February 2021

In recent years, neoliberal government policies relating to higher education have diminished universities as spaces of learning and encounter with difference. This article discusses a teaching project that occurred on social work qualifying programmes in two universities in Britain and Spain. The project aimed to produce new opportunities for students to encounter and critically reflect on how power relations are produced and maintained in social work practice, by engaging students in mapping the atmospheres of stigmatised urban spaces. Students used counter-mapping techniques, which aim to make visible power relations and inequalities, in order to critically reflect on their experiences of and practices in such spaces. The article evaluates data in the form of students’ cartographies and narratives, and educators’ photographs and reflections on teaching, arguing for the benefits of moving teaching outside of the classroom and engaging with the material, sensed realities of places where social workers work. The article builds on recent conceptualisations of atmosphere and space in social work literature, contributes to discussions of critical reflection and critical pedagogy in social work and provides examples of the use of counter-mapping as a pedagogical tool in higher education contexts.
Prolotherapy for chronic low back pain: a review of literature
Authors: Giordano Lorenzo , Murrell William D , Maffulli Nicola
Published: February 2021

Introduction

Low back pain is common and imposes major societal burdens for patient suffering and costs. Prolotherapy injections are used for musculoskeletal conditions including tendinopathies, osteoarthritis and low back pain to enhance soft-tissue healing. This review aims to clarify the place of prolotherapy in chronic low back pain (CLBP).

Sources of data

Using multiple databases, a systematic search was performed to identify studies detailing the use of prolotherapy to manage CLBP. A total of 12 articles was included in the present work.

Areas of agreement

Considering the level of evidence and the quality of the studies assessed using the modified Coleman Score, prolotherapy is an effective management modality for CLBP patients in whom conservative therapies failed.

Areas of controversy

The presence of co-interventions and the clinical heterogeneity of the work contributes to confound the overall conclusions.

Growing points and areas for research

The analysis of the studies included in the review, using appropriate tools, showed how their quality has decreased over the years, reflecting the need for appropriately powered well planned and performed randomized control trials.
Prevalence and severity of neurovascular compression in hemifacial spasm patients
Authors: Traylor Katie S , Sekula Raymond F , Eubanks Komal , Muthiah Nallammai , Chang Yue-Fang , Hughes Marion A
Published: February 2021

Hemifacial spasm is typically caused by vascular compression of the proximal intracranial facial nerve. Although the prevalence of neurovascular compression has been investigated in a cohort of patients with classical trigeminal neuralgia, the prevalence and severity of neurovascular compression has not been well characterized in patients with hemifacial spasm. We aimed to investigate whether presence and severity of neurovascular compression are correlated to the symptomatic side in patients with hemifacial spasm. All patients in our study were evaluated by a physician who specializes in the management of cranial nerve disorders. Once hemifacial spasm was diagnosed on physical exam, the patient underwent a dedicated cranial nerve protocol magnetic resonance imaging study on a 3 T scanner. Exams were retrospectively reviewed by a neuroradiologist blinded to the symptomatic side. The presence, severity, vessel type, and location of neurovascular compression along the facial nerve was recorded. Neurovascular compression was graded as contact alone (vessel touching the facial nerve) versus deformity (indentation or deviation of the nerve by the culprit vessel). A total of 330 patients with hemifacial spasm were included. The majority (232) were female while the minority (98) were male. The average age was 55.7 years. Neurovascular compression (arterial) was identified on both the symptomatic (97.88%) and asymptomatic sides (38.79%) frequently. Neurovascular compression from an artery along the susceptible/proximal portion of the nerve was much more common on the symptomatic side (96.36%) than on the asymptomatic side (12.73%), odds ratio = 93.00, P < 0.0001. When we assessed severity of arterial compression, the more severe form of neurovascular compression, deformity, was noted on the symptomatic side (70.3%) much more frequently than on the asymptomatic side (1.82%) (odds ratio = 114.00 P < 0.0001). We conclude that neurovascular compression that results in deformity of the susceptible portion of the facial nerve is highly associated with the symptomatic side in hemifacial spasm.
Understanding Drivers of Coronavirus Disease 2019 Vaccine Hesitancy Among Blacks
Authors: Momplaisir Florence , Haynes Norrisa , Nkwihoreze Hervette , Nelson Maria , Werner Rachel M , Jemmott John
Published: February 2021

Background

Coronavirus disease 2019 (COVID-19) has disproportionately affected communities of color, with black persons experiencing the highest rates of disease severity and mortality. A vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to reduce the race mortality gap from COVID-19; however, hesitancy toward the vaccine in the black community threatens vaccine uptake.

Methods

We conducted focus groups with black barbershop and salon owners living in zip codes of elevated COVID-19 prevalence to assess their attitudes, beliefs, and norms around a COVID-19 vaccine. We used a modified grounded theory approach to analyze the transcripts.

Results

We completed 4 focus groups (N = 24 participants) in July and August 2020. Participants were an average age of 46 years, and 89% were black non-Hispanic. Hesitancy against the COVID-19 vaccine was high due to mistrust in the medical establishment, concerns with the accelerated timeline for vaccine development, limited data on short- and long-term side effects, and the political environment promoting racial injustice. Some participants were willing to consider the vaccine once the safety profile is robust and reassuring. Receiving a recommendation to take the vaccine from a trusted healthcare provider served as a facilitator. Health beliefs identified were similar to concerns around other vaccines and included the fear of getting the infection with vaccination and preferring to improve one’s baseline physical health through alternative therapies.

Conclusions

We found that hesitancy of receiving the COVID-19 vaccine was high; however, provider recommendation and transparency around the safety profile might help reduce this hesitancy.
Impact of nutritional vitamin D supplementation on parathyroid hormone and 25-hydroxyvitamin D levels in non-dialysis chronic kidney disease: a meta-analysis
Authors: Bover Jordi , Gunnarsson Joel , Csomor Philipp , Kaiser Edelgard , Cianciolo Giuseppe , Lauppe Rosa
Published: February 2021

Background

Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced vitamin D signalling and hypocalcaemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers.

Methods

A systematic literature search was performed in PubMed to identify relevant randomized control trials to be included in the meta-analysis. Fixed- and random-effects models were used to pool study-level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels.

Results

Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/mL) and larger when compared with placebo/no treatment (pooled reduction: 49.7 pg/mL). NVD supplementation increased levels of 25-hydroxyvitamin D [25(OH)D] in both analyses (increase within NVD study arm: 20.6 ng/mL, increase versus placebo/no treatment: 26.9 ng/mL). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 were observed, NVD supplementation caused calcium levels to increase when compared with placebo/no treatment (increase: 0.23 mg/dL).

Conclusions

Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in non-dialysis-CKD patients with SHPT is limited.
TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn’s Disease Patients
Authors: Caër Charles , Gorreja Frida , Forsskåhl Sophia K , Brynjolfsson Siggeir F , Szeponik Louis , Magnusson Maria K , Börjesson Lars G , Block Mattias , Bexe-Lindskog Elinor , Wick Mary Jo
Published: February 2021

Background and Aims

Uncontrolled activation of intestinal mononuclear phagocytes [MNPs] drives chronic inflammation in inflammatory bowel disease [IBD]. Triggering receptor expressed on myeloid cells 1 [TREM-1] has been implicated in the pathogenesis of IBD. However, the role of TREM-1+ cell subsets in driving IBD pathology and the link with clinical parameters are not understood. We investigated TREM-1 expression in human intestinal MNP subsets and examined blocking TREM-1 as a potential IBD therapy.

Methods

TREM-1 gene expression was analysed in intestinal mucosa, enriched epithelial and lamina propria [LP] layers, and purified cells from controls and IBD patients. TREM-1 protein on immune cells was assessed by flow cytometry and immunofluorescence microscopy. Blood monocyte activation was examined by large-scale gene expression using a TREM-1 agonist or LP conditioned media [LP-CM] from patients in the presence or absence of TREM-1 and tumour necrosis factor [TNF] antagonist antibodies.

Results

TREM-1 gene expression increases in intestinal mucosa from IBD patients and correlates with disease score. TREM-1+ cells, which are mainly immature macrophages and CD11b+ granulocytes, increase among LP cells from Crohn’s disease patients and their frequency correlates with inflammatory molecules in LP-CM. LP-CM from Crohn’s disease patients induces an inflammatory transcriptome in blood monocytes, including increased IL-6 expression, which is reduced by simultaneous blocking of TREM-1 and TNF.

Conclusions

High intestinal TREM-1 expression, reflecting a high frequency of TREM-1+ immature macrophages and TREM-1+CD11b+ granulocytes, is linked to the deleterious inflammatory microenvironment in IBD patients. Therefore, blocking the TREM-1 pathway, especially simultaneously with anti-TNF therapy, has potential as a new IBD therapy.
Prevalence and extent of mitral annular disjunction in structurally normal hearts: comprehensive 3D analysis using cardiac computed tomography
Authors: Toh Hiroyuki , Mori Shumpei , Izawa Yu , Fujita Hiroshi , Miwa Keisuke , Suzuki Masataka , Takahashi Yu , Toba Takayoshi , Watanabe Yoshiaki , Kono Atsushi K , Tretter Justin T , Hirata Ken-Ichi
Published: February 2021

Aims

Mitral annular disjunction is fibrous separation between the attachment of the posterior mitral leaflet and the basal left ventricular myocardium initially described in dissected hearts. Currently, it is commonly evaluated by echocardiography, and potential relationships with mitral valve prolapse and ventricular arrhythmia have been suggested. However, controversy remains as its prevalence and extent have not been fully elucidated in normal living subjects.

Methods and results

Systolic datasets of cardiac computed tomography obtained from 98 patients (mean age, 69.1 ± 12.6 years; 81% men) with structurally normal hearts were assessed retrospectively. Circumferential extent of both mitral leaflets and disjunction was determined by rotating orthogonal multiplanar reconstruction images around the central axis of the mitral valvar orifice. Distribution angle within the circumference of the mitral valvar attachment and maximal height of disjunction were quantified. In total, 96.0% of patients demonstrated disjunction. Average distribution angles of the anterior and posterior mitral leaflets were 91.3 ± 9.4° and 269.8 ± 9.7°, respectively. Average distribution angle of the disjunction was 105.1 ± 49.2°, corresponding to 39.0 ± 18.2% of the entire posterior mitral valvar attachment. Median value of the maximal height of disjunction was 3.0 (1.5–7.0) mm. Distribution prevalence map of the disjunction revealed characteristic double peaks, with frequent sites of the disjunction located at the anterior to antero-lateral and inferior to infero-septal regions.

Conclusion

Mitral annular disjunction is a rather common finding in the normal adult heart with bimodal distribution predominantly observed involving the P1 and P3 scallops of the posterior mitral leaflet.
Soft tissue evaluation of functional therapy in growing patients with Class II malocclusion: a long-term study
Authors: Gazzani Francesca , Franchi Lorenzo , Lione Roberta , Cozza Paola , Pavoni Chiara
Published: February 2021

Objective

The objective of this study was to analyse the soft tissue changes produced by the functional treatment of mandibular advancement in growing Class II patients.

Materials

The treated group consisted of 25 Caucasian patients (12 females and 13 males) with dento-skeletal Class II malocclusion treated with functional therapy (Activator). All patients were evaluated before treatment (T1; mean age, 9.9 years), at the end of functional treatment phase (T2; mean age, 11.9 years), and at a post-pubertal follow-up observation (T3; mean age, 18.5 years). The treated group was compared with a matched control group of 25 untreated subjects (13 females, 12 males) with untreated Class II division 1 malocclusion. Statistical comparisons between the two groups were performed with independent samples t-tests (P < 0.05).

Results

Significant improvements were found during the long-term interval for mandibular sulcus (9.9°) and the profile facial angle (9.8°) in the treated group. No significant effects were found in terms of lower face percentage between the two groups.

Conclusion

Removable functional appliances induced positive effects on the soft tissue profile in Class II growing subjects with good stability in the long-term.
Global, regional, and national burden of aortic aneurysm, 1990–2017: a systematic analysis of the Global Burden of Disease Study 2017
Authors: Tyrovolas Stefanos , Tyrovola Dimitra , Giné-Vázquez Iago , Koyanagi Ai , Bernabe-Ortiz Antonio , Rodriguez-Artalejo Fernando , Haro Josep Maria , Pan William K , Miranda J Jaime , Panagiotakos Demosthenes
Published: February 2021

Aims

This study aimed at evaluating the age, sex, and country-income patterns in aortic aneurysm disease burden, analysing trends in mortality and years of life lost (YLLs), as well as their causal drivers and risk factors, using the 2017 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2017).

Methods and results

We described the temporal, global, and regional (195 countries) patterns of aortic aneurysm (thoracic and abdominal) mortality, YLLs, their drivers [sociodemographic index (SDI), healthcare access and quality index (HAQ index)] and risk factors using the GBD 1990–2017. Correlation and mixed multilevel modelling between aortic aneurysm mortality, YLLs, HAQ index and other variables were applied. From 1990 to 2017, a global declining trend in age-standardized aortic aneurysm mortality was found [2.88 deaths/100 000 (95% uncertainty intervals, UI 2.79 to 3.03) in 1990 and 2.19 deaths/100 000 (95% UI 2.09 to 2.28) in 2017]. Among high-income countries (HICs) a consistent declining Spearman’s correlation between age-standardised aortic aneurysm mortality, SDI (HICs; 1990 rho: 0.57, P ≤ 0.001; 2017 rho: 0.41, P = 0.001) and HAQ index was observed (HICs; 1990 rho: 0.50, P <0.001; 2016 rho: 0.35, P = 0.006); in comparison with low- and middle-income countries where correlation trends were weak and mixed. At a global level, higher HAQ index was related with lower aortic aneurysm mortality and YLLs [mortality, coef: −0.05, 95% confidence interval (CI): −0.06, −0.04; YLLs, coef: −0.94, 95% CI: −1.17, −0.71].

Conclusions

Age-standardized aortic aneurysm mortality declined globally between 1990 and 2017. Globally, age-standardized aortic aneurysm mortality and YLLs were related to changes in SDI and HAQ index levels, while country-level income-related variations were also observed.
Women’s Health Initiative Strong and Healthy Pragmatic Physical Activity Intervention Trial for Cardiovascular Disease Prevention: Design and Baseline Characteristics
Authors: Stefanick Marcia L , King Abby C , Mackey Sally , Tinker Lesley F , Hlatky Mark A , LaMonte Michael J , Bellettiere John , Larson Joseph C , Anderson Garnet , Kooperberg Charles L , LaCroix Andrea Z
Published: February 2021

Background

National guidelines promote physical activity to prevent cardiovascular disease (CVD), yet no randomized controlled trial has tested whether physical activity reduces CVD.

Methods

The Women’s Health Initiative (WHI) Strong and Healthy (WHISH) pragmatic trial used a randomized consent design to assign women for whom cardiovascular outcomes were available through WHI data collection (N = 18 985) or linkage to the Centers for Medicare and Medicaid Services (N30 346), to a physical activity intervention or “usual activity” comparison, stratified by ages 68–99 years (in tertiles), U.S. geographic region, and outcomes data source. Women assigned to the intervention could “opt out” after receiving initial physical activity materials. Intervention materials applied evidence-based behavioral science principles to promote current national recommendations for older Americans. The intervention was adapted to participant input regarding preferences, resources, barriers, and motivational drivers and was targeted for 3 categories of women at lower, middle, or higher levels of self-reported physical functioning and physical activity. Physical activity was assessed in both arms through annual questionnaires. The primary outcome is major cardiovascular events, specifically myocardial infarction, stroke, or CVD death; primary safety outcomes are hip fracture and non-CVD death. The trial is monitored annually by an independent Data Safety and Monitoring Board. Final analyses will be based on intention to treat in all randomized participants, regardless of intervention engagement.

Results

The 49 331 randomized participants had a mean baseline age of 79.7 years; 84.3% were White, 9.2% Black, 3.3% Hispanic, 1.9% Asian/Pacific Islander, 0.3% Native American, and 1% were of unknown race/ethnicity. The mean baseline RAND-36 physical function score was 71.6 (± 25.2 SD). There were no differences between Intervention (N = 24 657) and Control (N = 24 674) at baseline for age, race/ethnicity, current smoking (2.5%), use of blood pressure or lipid-lowering medications, body mass index, physical function, physical activity, or prior CVD (10.1%).

Conclusion

The WHISH trial is rigorously testing whether a physical activity intervention reduces major CV events in a large, diverse cohort of older women.

Clinical Trials Registration Number: NCT02425345
The COVID-19 Pandemic, Biogerontology, and the Ageing of Humanity
Authors: Farrelly Colin
Published: February 2021

The World Health Organization designated the decade 2020–2030 as the “decade of healthy ageing.” It is a tragic irony that the year 2020 should begin with a pandemic that is so lethal for older persons. Not only are older persons the most vulnerable to COVID-19 mortality, but many of the mitigation efforts to slow the spread of the virus have imposed yet further emotional and mental health burdens on the most vulnerable among those older than 70 years. To help prevent future infectious disease mortality and suffering, as well as the profound health burdens from the chronic diseases associated with ageing, insights from biogerontology must become an integral part of global public health priorities. The timing is ripe for making the public health aspiration of developing an applied gerontological intervention a reality.
National Institute on Aging Workshop: Repurposing Drugs or Dietary Supplements for Their Senolytic or Senomorphic Effects: Considerations for Clinical Trials
Authors: Romashkan Sergei , Chang Henry , Hadley Evan C
Published: February 2021

Background

Cell senescence is implicated in numerous age-related conditions. Drugs and nutritional supplements developed for a variety of purposes kill senescent cells (senolytics) or suppress their secretions (senomorphics). There is interest in repurposing such drugs to treat or prevent age-related diseases. To date, only small-scale preliminary trials have been conducted.

Method

At a workshop convened by the National Institute on Aging in August 2019, academic, industry, and government scientists reviewed issues for phase II trials of potentially repurposable drugs, or dietary supplements, to assess benefits and risks of their senolytic (killing senescent cells) or senomorphic (altering senescent cells’ phenotypes) effects in treating or preventing age-related conditions.

Results

Participants reviewed mechanisms and effects of cellular senescence, senolytics, and senomorphics of several classes and their potential role in treating or preventing disease, modulators of the senescence-associated secretory phenotype, needs for senescence markers, data and specimen resources, infrastructure for planning trials, and potential effects on outcomes in older patients with multimorbidity and polypharmacy.

Conclusions

Participants noted the importance of considering potential effects of candidate drugs on multiple aging outcomes. It is important to assess drugs’ specificity for killing senescent cells and the balance between senolytic and cytotoxic effects. Markers of specific senescent cell types are needed to assess intervention responses. There are potential interactions with coexisting diseases and their treatments in older persons. Standardized measures could enhance comparisons and pooling of data. Additional characterization of human cell senescent phenotypes is needed for developing better and more specific senolytics and senomorphics.
Enhancing Older Adults’ Well-Being and Quality of Life Through Purposeful Activity: A Systematic Review of Intervention Studies
Authors: Owen Rebecca , Berry Katherine , Brown Laura J E
Published: February 2021

Background and Objectives

Population aging represents a significant challenge for health and social care services. Older adults who engage in activities that offer a sense of purpose have significantly better physical and psychological health outcomes. However, age-related functional limitations and losses of social roles can present barriers to engaging in purposeful activity, especially for those older adults within the “oldest-old” age range (i.e., 80 years and older). This review aimed to determine the nature and effectiveness of purposeful activity interventions in older adults, aged 80 years and older, with respect to well-being and quality-of-life outcomes.

Research Design and Methods

Three databases were searched from their inception to April 2020. The search yielded 8,916 records, which resulted in eight eligible studies.

Results

The interventions were divided into two groups: (a) interventions that gave participants a specific functional role, such as volunteer or mentor (n = 5), and (b) interventions that supported participants to develop a new skill (n = 3). The quality of the evidence was variable. The strongest evidence was for interventions that assigned a functional role, which appeared to be somewhat effective in improving well-being outcomes.

Discussion and Implications

There is preliminary evidence that purposeful activity interventions, particularly those that involved taking on a functional role, can improve well-being and quality-of-life outcomes in older adults aged 80 years and older. These findings have implications for professionals and carers to support older adults to access more purposeful social roles and create opportunities for helping and reciprocation.
On the adaptive spectral approximation of functions using redundant sets and frames
Authors: Coppé Vincent , Huybrechs Daan
Published: February 2021

The approximation of smooth functions with a spectral basis typically leads to rapidly decaying coefficients, where the rate of decay depends on the smoothness of the function and vice versa. The optimal number of degrees of freedom in the approximation can be determined with relative ease by truncating the coefficients once a threshold is reached. Recent approximation schemes based on redundant sets and frames extend the applicability of spectral approximations to functions defined on irregular geometries and to certain nonsmooth functions. However, due to their inherent redundancy, the expansion coefficients in frame approximations do not necessarily decay even for very smooth functions. In this paper, we highlight this lack of equivalence between smoothness and coefficient decay, and we explore approaches to determine an optimal number of degrees of freedom for such redundant approximations.
Strictly positive definite kernels on the 2-sphere: from radial symmetry to eigenvalue block structure
Authors: Buhmann Martin , Jäger Janin
Published: February 2021

The paper introduces a new characterization of strict positive definiteness for kernels on the 2-sphere without assuming the kernel to be radially (isotropic) or axially symmetric. The results use the series expansion of the kernel in spherical harmonics. Then additional sufficient conditions are proven for kernels with a block structure of expansion coefficients. These generalize the result derived by Chen et al. (2003, A necessary and sufficient condition for strictly positive definite functions on spheres. Proc. Amer. Math. Soc., 131, 2733–2740) for radial kernels to nonradial kernels.
Time and predictors of time to treatment for aneurysmal subarachnoid haemorrhage (aSAH): a systematic review
Authors: Phuong nguyen Thuy , Rehman Sabah , Stirling Christine , Chandra Ronil , Gall Seana
Published: February 2021

Background

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious form of stroke, for which rapid access to specialist neurocritical care is associated with better outcomes. Delays in the treatment of aSAH appear to be common and may contribute to poor outcomes. We have a limited understanding of the extent and causes of these delays, which hinders the development of interventions to reduce delays and improve outcomes. The aim of this systematic review was to quantify and identify factors associated with time to treatment in aSAH.

Methods

This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines and was registered in PROSPERO (Reg. No. CRD42019132748). We searched four electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) for manuscripts published from January 1998 using pre-designated search terms and search strategy. Main outcomes were duration of delays of time intervals from onset of aSAH to definitive treatment and/or factors related to time to treatment.

Results

A total of 64 studies with 16 different time intervals in the pathway of aSAH patients were identified. Measures of time to treatment varied between studies (e.g. cut-off timepoints or absolute mean/median duration). Factors associated with time to treatment fell into two categories—individual (n = 9 factors, e.g. age, sex and clinical characteristics) and health system (n = 8 factors, e.g. pre-hospital delay or presentation out-of-hours). Demographic factors were not associated with time to treatment. More severe aSAH reduced treatment delay in most studies. Pre-hospital delays (patients delay, late referral, late arrival of ambulance, being transferred between hospitals or arriving at the hospital outside of office hours) were associated with treatment delay. In-hospital factors (patients with complications, procedure before definitive treatment, slow work-up and type of treatment) were less associated with treatment delay.

Conclusions

The pathway from onset to definitive treatment of patients with aSAH consists of multiple stages with multiple influencing factors. This review provides the first comprehensive understanding of extent and factors associated with time to treatment of aSAH. There is an opportunity to target modifiable factors to reduce time to treatment, but further research considering more factors are needed.
Bringing Researchers Back In: Debating the Role of Interpretive Epistemology in Global IR
Authors: Vandamme Dorothée
Published: February 2021

The article discusses interpretive epistemology in international relations (IR) and its advantages to address the field's sociological composition, its scholars’ identity, and knowledge structuration. The research proposes to engage in sociological reflexivity on IR methods and the way in which knowledge accumulation and structuration are driven by canonical assumptions of what are considered “normal”/“good” scientific procedures. The central argument focuses on interpretive epistemological approaches as possible venues for research to participate in the collective effort to address, and redress, the imbalance between the sociology of the field and its knowledge production and structuration processes. By allowing dialogue around meanings and interpretation among increasingly diverse members, an interpretive stance on IR opens the floor to criticism and rival interpretations. More specifically, the paper presents the methodology of interpretive phenomenological analysis as a method which both emphasizes context and actor specificity with regard to the subject of study and fully acknowledges the researcher's identity and voice in scientific inquiry.
Practice and market factors associated with provider volume of health information exchange
Authors: Apathy Nate C , Vest Joshua R , Adler-Milstein Julia , Blackburn Justin , Dixon Brian E , Harle Christopher A
Published: February 2021

Objective

To assess the practice- and market-level factors associated with the amount of provider health information exchange (HIE) use.

Materials and Methods

Provider and practice-level data was drawn from the Meaningful Use Stage 2 Public Use Files from the Centers for Medicare and Medicaid Services, the Physician Compare National Downloadable File, and the Compendium of US Health Systems, among other sources. We analyzed the relationship between provider HIE use and practice and market factors using multivariable linear regression and compared primary care providers (PCPs) to non-PCPs. Provider volume of HIE use is measured as the percentage of referrals sent with electronic summaries of care (eSCR) reported by eligible providers attesting to the Meaningful Use electronic health record (EHR) incentive program in 2016.

Results

Providers used HIE in 49% of referrals; PCPs used HIE in fewer referrals (43%) than non-PCPs (57%). Provider use of products from EHR vendors was negatively related to HIE use, while use of Athenahealth and Greenway Health products were positively related to HIE use. Providers treating, on average, older patients and greater proportions of patients with diabetes used HIE for more referrals. Health system membership, market concentration, and state HIE consent policy were unrelated to provider HIE use.

Discussion

HIE use during referrals is low among office-based providers with the capability for exchange, especially PCPs. Practice-level factors were more commonly associated with greater levels of HIE use than market-level factors.

Conclusion

This furthers the understanding that market forces, like competition, may be related to HIE adoption decisions but are less important for use once adoption has occurred.
A dynamic mammary gland model describing colostrum immunoglobulin transfer and milk production in lactating sows
Authors: Krogh Uffe , Quesnel Hélène , Le Floch Nathalie , Simongiovanni Aude , van Milgen Jaap
Published: February 2021

The physiology of the sow mammary gland is qualitatively well described and understood. However, the quantitative effect of various biological mechanisms contributing to the synthesis of colostrum and milk is lacking and more complicated to obtain. The objective of this study was to integrate physiological and empirical knowledge of the production of colostrum and milk in a dynamic model of a single sow mammary gland to understand and quantify parameters controlling mammary gland output. In 1983, Heather Neal and John Thornley published a model of the mammary gland in cattle, which was used as a starting point for the development of this model. The original cattle model was reparameterized, modified, and extended to describe the production of milk by the sow mammary gland during lactation and the prepartum production of colostrum as the combined output of immunoglobulins (Ig) and milk. Initially, the model was reparameterized to simulate milk synthesis potential of a single gland by considering biological characteristics and empirical estimations of sows and piglets. Secondly, the model was modified to simulate more accurately the responses to changes in milk removal rates. This was done by linking the ejectable milk storage capacity to the number of secretory cells rather than being constant throughout lactation. Finally, the model was extended to include the prepartum synthesis of milk and the kinetics of Ig into and out of the mammary gland. A progressive capacity of secretory cells to synthesize milk was used to differentiate the time between the onset of milk synthesis and Ig transfer. Changes in maximum milk removal rate, duration of milk ejection, and nursing interval exerted a great impact on the modeled milk output. Changes by ±60% in one of these parameters were capable of increasing milk output by 28% to 39% during the first 4 wk in lactation compared with the reference parameterization. This suggests that the ability of the piglet to remove milk from the gland exerts a key control on milk synthesis during lactation. Modeling colostrum as the combined output of Ig and milk allowed to represent the rapid decline in Ig concentration observed during the first hours after farrowing. In conclusion, biological and empirical knowledge was integrated into a model of the sow mammary gland and constitutes a simple approach to explore in which conditions and to what extent individual parameters influence Ig kinetics and milk production.
A quasi-3D model of the whole lung: airway extension to the tracheobronchial limit using the constrained constructive optimization and alveolar modeling, using a sac–trumpet model
Authors: Kannan Ravishekar (Ravi) , Singh Narender , Przekwas Andrzej , Zhou Xianlian Alex , Walenga Ross , Babiskin Andrew
Published: February 2021

Existing computational models used for simulating the flow and species transport in the human airways are zero-dimensional (0D) compartmental, three-dimensional (3D) computational fluid dynamics (CFD), or the recently developed quasi-3D (Q3D) models. Unlike compartmental models, the full CFD and Q3D models are physiologically and anatomically consistent in the mouth and the upper airways, since the starting point of these models is the mouth–lung surface geometry, typically created from computed tomography (CT) scans. However, the current resolution of CT scans limits the airway detection between the 3rd–4th and 7th–9th generations. Consequently, CFD and the Q3D models developed using these scans are generally limited to these generations. In this study, we developed a method to extend the conducting airways from the end of the truncated Q3D lung to the tracheobronchial (TB) limit. We grew the lung generations within the closed lung lobes using the modified constrained constructive optimization, creating an aerodynamically optimized network aiming to produce equal pressure at the distal ends of the terminal segments. This resulted in a TB volume and lateral area of ∼165 cc and ∼2000 cm2, respectively. We created a “sac–trumpet” model at each of the TB outlets to represent the alveoli. The volumes of the airways and the individual alveolar generations match the anatomical values by design: with the functional residual capacity at 2611 cc. Lateral surface areas were scaled to match the physiological values. These generated Q3D whole lung models can be efficiently used for conducting multiple breathing cycles of drug transport and deposition simulations.
Semi-exact local absorbing boundary condition for seismic wave simulation
Authors: Izadian Saeed , Aghazade Kamal , Amini Navid , Wang Yanghua
Published: February 2021

An absorbing boundary condition is necessary in seismic wave simulation for eliminating the unwanted artificial reflections from model boundaries. Existing boundary condition methods often have a trade-off between numerical accuracy and computational efficiency. We proposed a local absorbing boundary condition for frequency-domain finite-difference modelling. The proposed method benefits from exact local plane-wave solution of the acoustic wave equation along predefined directions that effectively reduces the dispersion in other directions. This method has three features: simplicity, accuracy and efficiency. Numerical simulation demonstrated that the proposed method has higher efficiency than the conventional methods such as the second-order absorbing boundary condition and the perfectly matched layer (PML) method. Meanwhile, the proposed method shared the same low-cost feature as the first-order absorbing boundary condition method.