Publications by authors named "Elizabeth George"

210 Publications

Gastroenteritis Rehydration Of children with Severe Acute Malnutrition (GASTROSAM): A Phase II Randomised Controlled trial: Trial Protocol.

Wellcome Open Res 2021 23;6:160. Epub 2021 Jun 23.

Clinical Trials Facility, KEMRI-Wellcome Trust Research Programme, Kilifi, PO Box 230, Kenya.

Children hospitalised with severe acute malnutrition (SAM) are frequently complicated (>50%) by diarrhoea ( 3 watery stools/day) which is accompanied by poor outcomes. Rehydration guidelines for SAM are exceptionally conservative and controversial, based upon expert opinion. The guidelines only permit use of intravenous fluids for cases with advanced shock and exclusive use of low sodium intravenous and oral rehydration solutions (ORS) for fear of fluid and/or sodium overload. Children managed in accordance to these guidelines have a very high mortality. The proposed GASTROSAM trial is the first step in reappraising current recommendations. We hypothesize that liberal rehydration strategies for both intravenous and oral rehydration in SAM children with diarrhoea may reduce adverse outcomes. An open Phase II trial, with a partial factorial design, enrolling Ugandan and Kenyan children aged 6 months to 12 years with SAM hospitalised with gastroenteritis (>3 loose stools/day) and signs of moderate and severe dehydration.  In Stratum A (severe dehydration) children will be randomised (1:1:2) to WHO plan C (100mls/kg Ringers Lactate (RL) with intravenous rehydration given over 3-6 hours according to age including boluses for shock), slow rehydration (100 mls/kg RL over 8 hours (no boluses)) or  WHO SAM rehydration regime (ORS only (boluses for shock (standard of care)).  Stratum B incorporates all children with moderate dehydration and severe dehydration post-intravenous rehydration and compares (1:1 ratio) standard WHO ORS given for non-SAM (experimental) versus WHO SAM-recommended low-sodium ReSoMal. The primary outcome for intravenous rehydration is urine output (mls/kg/hour at 8 hours post-randomisation), and for oral rehydration a change in sodium levels at 24 hours post-randomisation. This trial will also generate feasibility, safety and preliminary data on survival to 28 days. . If current rehydration strategies for non-malnourished children are safe in SAM this could prompt future evaluation in Phase III trials.
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http://dx.doi.org/10.12688/wellcomeopenres.16885.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276193PMC
June 2021

Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.

Elife 2021 Jul 6;10. Epub 2021 Jul 6.

Malaria, Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis, is imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model we re-analysed clinical and genetic data from 2,220 Kenyan children with clinically defined severe malaria and 3,940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.
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http://dx.doi.org/10.7554/eLife.69698DOI Listing
July 2021

Association of Frailty and the Expanded Operative Stress Score with Preoperative Acute Serious Conditions, Complications and Mortality in Males Compared to Females: A Retrospective Observational Study.

Ann Surg 2021 Jun 25. Epub 2021 Jun 25.

Department of Surgery, University of Texas Health San Antonio, San Antonio, Texas South Texas Veterans Health Care System, San Antonio, Texas University Health, San Antonio, Texas Center for Health Equity Research and Promotion, and Geriatric Research Education and Clinical Care Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania Wolff Center, UPMC, Pittsburgh, Pennsylvania Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee Department of Surgery, University of North Carolina, Chapel Hill, North Carolina Department of Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas Department of Surgery, Stanford University School of Medicine, Stanford, California. Division of Health Services Research and Development, VA Palo Alto Healthcare System, Palo Alto, California Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania School of Biomedical Informatics, The University of Texas Health Science Center at Houston, TX, United States Division of General Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX, United States.

Objective: Expand Operative Stress Score (OSS) increasing procedural coverage and assessing OSS and frailty association with Preoperative Acute Serious Conditions (PASC), complications and mortality in females versus males.

Summary Background Data: Veterans Affairs male-dominated study showed high mortality in frail veterans even after very low stress surgeries (OSS1).

Methods: Retrospective cohort using NSQIP data (2013-2019) merged with 180-day postoperative mortality from multiple hospitals to evaluate PASC, 30-day complications and 30-, 90- and 180-day mortality.

Results: OSS expansion resulted in 98.2% case coverage versus 87.0% using the original. Of 82,269 patients (43.8% male), 7.9% were frail/very frail. Males had higher odds of PASC (aOR = 1.31, 95%CI = 1.21-1.41, P < .001) and severe/life-threatening Clavien-Dindo IV (CDIV) complications (aOR = 1.18, 95%CI = 1.09-1.28, P < .001). While mortality rates were higher (all time points, P < .001) in males versus females, mortality was similar after adjusting for frailty, OSS, and case status primarily due to increased male frailty scores. Additional adjustments for PASC and CDIV resulted in a lower odds of mortality in males (30-day, aOR = 0.81, CI = 0.71-0.92, P = .002) that was most pronounced for males with PASC compared to females with PASC (30-day, aOR = 0.75, CI = 0.56-0.99, P = .04).

Conclusions: Similar to the male-dominated Veteran population, private sector, frail patients have high likelihood of postoperative mortality, even after low stress surgeries. Preoperative frailty screening should be performed regardless of magnitude of the procedure. Despite males experiencing higher adjusted odds of PASC and CDIV complications, females with PASC had higher odds of mortality compared to males, suggesting differences in the aggressiveness of care provided to men and women.
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http://dx.doi.org/10.1097/SLA.0000000000005027DOI Listing
June 2021

Cost-effectiveness analysis of ankle-brachial index screening in patients with coronary artery disease to optimize medical management.

J Vasc Surg 2021 Jun 25. Epub 2021 Jun 25.

Division of Vascular Surgery, Department of Surgery, Stanford University, Stanford, Calif.

Introduction: Screening for peripheral artery disease (PAD) with the ankle-brachial index (ABI) test is currently not recommended in the general population; however, previous studies advocate screening in high-risk populations. Although providers may be hesitant to prescribe low-dose rivaroxaban to patients with coronary artery disease (CAD) alone, given the reduction in cardiovascular events and death associated with rivaroxaban, screening for PAD with the ABI test and accordingly prescribing rivaroxaban may provide additional benefits. We sought to describe the cost-effectiveness of screening for PAD in patients with CAD to optimize this high-risk populations' medical management.

Methods: We used a Markov model to evaluate the ABI test in patients with CAD. We assumed that all patients screened would be candidates for low-dose rivaroxaban. We assessed the cost of ABI screening at $100 per patient and added additional charges for physician visits ($100) and rivaroxaban cost ($470 per month). We used a 30-day cycle and performed analysis over 35 years. We evaluated quality-adjusted life years (QALYs) from previous studies and determined the incremental cost-effectiveness ratio (ICER) according to our model. We performed a deterministic and probabilistic sensitivity analyses of variables with uncertainty and reported them in a Tornado diagram showing the variables with the greatest effect on the ICER.

Results: Our model estimates decision costs to screen or not screen at $94,953 and $82,553, respectively. The QALYs gained from screening was 0.060, generating an ICER of $207,491 per QALY. Factors most influential on the ICER were the reduction in all-cause mortality associated with rivaroxaban and the prohibitively high cost of rivaroxaban. If rivaroxaban cost less than $95 per month, this would make screening cost-effective based on a willingness to pay threshold of $50,000 per QALY.

Conclusions: According to our model, screening patients with CAD for PAD to start low-dose rivaroxaban is not currently cost-effective due to insufficient reduction in all-cause mortality and high medication costs. Nevertheless, vascular surgeons have a unique opportunity to prescribe or advocate for low-dose rivaroxaban in patients with PAD to improve cardiovascular outcomes.
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http://dx.doi.org/10.1016/j.jvs.2021.05.049DOI Listing
June 2021

ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation.

Cell Stem Cell 2021 Jun 11. Epub 2021 Jun 11.

Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland. Electronic address:

AXIN2 and LGR5 mark intestinal stem cells (ISCs) that require WNT/β-Catenin signaling for constant homeostatic proliferation. In contrast, AXIN2/LGR5+ pericentral hepatocytes show low proliferation rates despite a WNT/β-Catenin activity gradient required for metabolic liver zonation. The mechanisms restricting proliferation in AXIN2+ hepatocytes and metabolic gene expression in AXIN2+ ISCs remained elusive. We now show that restricted chromatin accessibility in ISCs prevents the expression of β-Catenin-regulated metabolic enzymes, whereas fine-tuning of WNT/β-Catenin activity by ZNRF3 and RNF43 restricts proliferation in chromatin-permissive AXIN2+ hepatocytes, while preserving metabolic function. ZNRF3 deletion promotes hepatocyte proliferation, which in turn becomes limited by RNF43 upregulation. Concomitant deletion of RNF43 in ZNRF3 mutant mice results in metabolic reprogramming of periportal hepatocytes and induces clonal expansion in a subset of hepatocytes, ultimately promoting liver tumors. Together, ZNRF3 and RNF43 cooperate to safeguard liver homeostasis by spatially and temporally restricting WNT/β-Catenin activity, balancing metabolic function and hepatocyte proliferation.
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http://dx.doi.org/10.1016/j.stem.2021.05.013DOI Listing
June 2021

Digital and Physical Social Exclusion of Older People in Rural Nigeria in the Time of COVID-19.

J Gerontol Soc Work 2021 Sep 27;64(6):629-642. Epub 2021 May 27.

Department of Social Work, University of Nigeria, Nsukka, Nigeria.

As the use of digital technology becomes more widespread across the globe, older people remain among the group with the lowest access and usage. The digital divide may lead to double exclusion as the COVID-19 pandemic has led to limited physical social contact as experts' recommendation of continuous social distancing and lack of access and usage of internet communication will leave older people socially isolated. The aim of this study is to explore how older people in rural Nigeria may be digitally excluded and its impact during the COVID-19 pandemic. Qualitative data was obtained from 11 older people using interviews. The collected data was then transcribed and analyzed thematically. Findings show that older people in rural Nigeria were digitally excluded. However, the older people argued that the digital exclusion is not the reason for their social isolation and loneliness. The study concluded by suggesting how caregivers and social workers can assist rural older people through activity schedule and radio programs designed for older people.
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http://dx.doi.org/10.1080/01634372.2021.1907496DOI Listing
September 2021

To Perform or Not to Perform Surgery for Frail Patients?-Reply.

JAMA Surg 2021 May 19. Epub 2021 May 19.

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1001/jamasurg.2021.1531DOI Listing
May 2021

Life Happens, Even to Surgical Trainees.

JAMA Surg 2021 Jul;156(7):653

Division of General Surgery, Department of Surgery, Stanford University, Stanford, California.

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http://dx.doi.org/10.1001/jamasurg.2021.1811DOI Listing
July 2021

Point-of-care haemoglobin testing in African hospitals: a neglected essential diagnostic test.

Br J Haematol 2021 Jun 15;193(5):894-901. Epub 2021 May 15.

Kenya Medical Research Institute (KEMRI), Wellcome Trust Research Programme, Kilifi, Kenya.

Owing to the rapid turnaround time in the assessment of haemoglobin level by point-of-care tests (POC Hb), these have grown in popularity and scope in large parts of the world. However, whilst POC testing for malaria and HIV remains has been integrated into patient management in Africa, the use of POC haemoglobin testing remains neglected by health services. The main users of transfusions (paediatric, maternity and trauma services) present largely as emergencies. Ward-based POC Hb could result in more rapid and accurate diagnosis of anaemia, contributing to saving of lives and at the same time reduce unnecessary transfusions which deplete the limited supplies of donated blood in Africa. Severe anaemia requiring transfusion is a major cause of paediatric admission in Africa. At a dissemination meeting to discuss the results of a large phase III paediatric transfusion trial and steps to implementation of the findings participants strongly recommended that one of the most pressing actions required was to prioritise the use of POC haemoglobin testing. This would facilitate implementation of the new transfusion algorithm, developed at the meeting, which refines patient management including blood transfusions. We present the rationale for the strongly recommended prioritisation of POC Hb, using paediatric transfusion as an exemplar.
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http://dx.doi.org/10.1111/bjh.17431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611318PMC
June 2021

Gender Disparity in Surgical Society Leadership and Annual Meeting Programs.

J Surg Res 2021 May 10;266:69-76. Epub 2021 May 10.

Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California; Stanford-Surgery Policy Improvement Research & Education Center, Department of Surgery, Stanford University School of Medicine, Stanford, California; Vascular Surgery Section, Department of Surgery, Palo Alto Veterans Affairs Medical Center, Palo Alto, California. Electronic address:

Introduction: Prior work suggests women surgical role models attract more female medical students into surgical training. We investigate recent trends of women in surgical society leadership and national conference moderator and plenary speaker roles.

Methods: Gender distribution was surveyed at 15 major surgical societies and 14 conferences from 2014 to 2018 using publicly reported data. Roles were categorized as leadership (executive council), moderator, or plenary speaker. Data were cross-checked from online profiles and by contacting societies. Logistic regression with Huber-White clustering by society was utilized to evaluate proportions of women in each role over time and determine associations between the proportion of women in executive leadership, and scientific session moderators and plenary speakers.

Results: The proportion of leadership positions held by women increased slightly from 2014 to 2018 (20.6%-26.6%, P = 0.23), as did the proportion of moderators (26.2%-30.6%, P = 0.027) and plenary speakers (26.2%-30.9%, P = 0.058). The proportion of women in each role varied significantly across societies (all P < 0.001): leaders (range 0.0%-52.0%), moderators (12.5%-58.8%), and plenary speakers (11.3%-60.0%). Three patterns of change were observed: eight societies (53.3%) demonstrated increases in representation of women over time, four societies (26.6%) showed stable moderate-to-good gender balance, and three societies (20.0%) had consistent underrepresentation of women.

Conclusion: There is significant variability in the representation of women at the leadership level of national surgical societies and participating at national surgical conferences as moderators and plenary speakers. Over the past 5 years some societies have achieved advances in gender equity, but many societies still have substantial room for improvement.
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http://dx.doi.org/10.1016/j.jss.2021.02.023DOI Listing
May 2021

The Reply.

Am J Med 2021 05;134(5):e359

Department of Radiology and Biomedical Imaging, University of California San Francisco.

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http://dx.doi.org/10.1016/j.amjmed.2021.01.008DOI Listing
May 2021

Transfusion management of severe anaemia in African children: a consensus algorithm.

Br J Haematol 2021 Jun 6;193(6):1247-1259. Epub 2021 May 6.

Medical Research Council Clinical Trials Unit (MRC CTU), University College London, London, UK.

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice.
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http://dx.doi.org/10.1111/bjh.17429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611319PMC
June 2021

Preparing Radiologists to Lead in the Era of Artificial Intelligence: Designing and Implementing a Focused Data Science Pathway for Senior Radiology Residents.

Radiol Artif Intell 2020 Nov 4;2(6):e200057. Epub 2020 Nov 4.

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (W.F.W., M.T.C., K.M., S.A.G., E.G., M.H.R., G.C.G., K.P.A.); and MGH & BWH Center for Clinical Data Science, Boston, Mass (W.F.W., M.T.C., K.M., K.P.A.).

Artificial intelligence and machine learning (AI-ML) have taken center stage in medical imaging. To develop as leaders in AI-ML, radiology residents may seek a formative data science experience. The authors piloted an elective Data Science Pathway (DSP) for 4th-year residents at the authors' institution in collaboration with the MGH & BWH Center for Clinical Data Science (CCDS). The goal of the DSP was to provide an introduction to AI-ML through a flexible schedule of educational, experiential, and research activities. The study describes the initial experience with the DSP tailored to the AI-ML interests of three senior radiology residents. The authors also discuss logistics and curricular design with common core elements and shared mentorship. Residents were provided dedicated, full-time immersion into the CCDS work environment. In the initial DSP pilot, residents were successfully integrated into AI-ML projects at CCDS. Residents were exposed to all aspects of AI-ML application development, including data curation, model design, quality control, and clinical testing. Core concepts in AI-ML were taught through didactic sessions and daily collaboration with data scientists and other staff. Work during the pilot period led to 12 accepted abstracts for presentation at national meetings. The DSP is a feasible, well-rounded introductory experience in AI-ML for senior radiology residents. Residents contributed to model and tool development at multiple stages and were academically productive. Feedback from the pilot resulted in establishment of a formal AI-ML curriculum for future residents. The described logistical, planning, and curricular considerations provide a framework for DSP implementation at other institutions. © RSNA, 2020.
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http://dx.doi.org/10.1148/ryai.2020200057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082300PMC
November 2020

Seasonal Distribution of Cyanobacteria in Three Urban Eutrophic Lakes Results from an Epidemic-like Response to Environmental Conditions.

Curr Microbiol 2021 Jun 27;78(6):2298-2316. Epub 2021 Apr 27.

Groundwater Characterization & Remediation Division, US EPA Center for Environmental Solutions and Emergency Response, Robert S. Kerr Environmental Research Center, Ada, OK, 74820, USA.

Cyanobacterial communities of three co-located eutrophic sandpit lakes were surveyed during 2016 and 2017 over season and depth using high-throughput DNA sequencing of the 16S rRNA gene. All three lakes were stratified except during April 2017 when the lakes were recovering from a strong mixing event. 16S rRNA gene V4 sequences were parsed into operational taxonomic units (OTUs) at 99% sequence identity. After rarefaction of 139 samples to 25,000 sequences per sample, a combined total of 921,529 partial 16S rRNA gene sequences were identified as cyanobacteria. They were binned into 19,588 unique cyanobacterial OTUs. Of these OTUs, 11,303 were Cyanobium. Filamentous Planktothrix contributed 1537 and colonial Microcystis contributed 265. The remaining 6482 OTUs were considered unclassified. For Planktothrix and Microcystis one OTU accounted for greater than 95% of the total sequences for each genus. However, in both cases the non-dominant OTUs clustered with the dominant OTUs by date, lake, and depth. All Planktothrix OTUs and a single Cyanobium OTU were detected below the oxycline. All other Cyanobium and Microcystis OTUs were detected above the oxycline. The distribution of Cyanobium OTUs between lakes and seasons can be explained by an epidemic-like response where individual OTUs clonally rise from a diverse hypolimnion population when conditions are appropriate. The importance of using 99% identity over the more commonly used 97% is discussed with respect to cyanobacterial community structure. The approach described here can provide another valuable tool for assessing cyanobacterial populations and provide greater insight into the controls of cyanobacterial blooms.
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http://dx.doi.org/10.1007/s00284-021-02498-6DOI Listing
June 2021

Exploring the Impact of COVID-19 Pandemic on Economic Activities and Well-being of Older Adults in South-eastern Nigeria: Lessons for Gerontological Social Workers.

J Gerontol Soc Work 2021 Sep 22;64(6):613-628. Epub 2021 Apr 22.

Department of Social Work, University of Nigeria, Nsukka, Nigeria.

The novel COVID-19 pandemic and its containment measures such as lockdown and physical distancing are remarkedly affecting older adults' economic activities and well-being in ways deserving of urgent attention. To strengthen caregiving and promote targeted care for older adults during and after the pandemic, this paper investigates the impact of the coronavirus on the economic activities and well-being of older adults in Enugu and Anambra states, Nigeria. Hermeneutic phenomenology was adopted and 16 older adults aged between 60 and 81 years, with a majority of them still working as farmers and traders were phone-interviewed. Findings highlighted four key lessons for gerontological social workers including 1) the fear that impact of the containment measures could kill the older adults faster than the virus; 2) the measures generate a feeling of neglect and marginalization of healthcare needs among older adults; 3) altered positive health-seeking behavior among the older adults; 4) and concern about the absence of functional policy and plan to address the welfare of older adults. Therefore, the central focus of the gerontological social workers and Nigerian polity should not be on how to reduce the spread of the disease alone, but on an application of caution in instituting and implementing the measures.
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http://dx.doi.org/10.1080/01634372.2021.1907497DOI Listing
September 2021

Experimental competition induces immediate and lasting effects on the neurogenome in free-living female birds.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Department of Biology, Indiana University, Bloomington, IN 47405.

Periods of social instability can elicit adaptive phenotypic plasticity to promote success in future competition. However, the underlying molecular mechanisms have primarily been studied in captive and laboratory-reared animals, leaving uncertainty as to how natural competition among free-living animals affects gene activity. Here, we experimentally generated social competition among wild, cavity-nesting female birds (tree swallows, ). After territorial settlement, we reduced the availability of key breeding resources (i.e., nest boxes), generating heightened competition; within 24 h we reversed the manipulation, causing aggressive interactions to subside. We sampled females during the peak of competition and 48 h after it ended, along with date-matched controls. We measured transcriptomic and epigenomic responses to competition in two socially relevant brain regions (hypothalamus and ventromedial telencephalon). Gene network analyses suggest that processes related to energy mobilization and aggression (e.g., dopamine synthesis) were up-regulated during competition, the latter of which persisted 2 d after competition had ended. Cellular maintenance processes were also down-regulated after competition. Competition additionally altered methylation patterns, particularly in pathways related to hormonal signaling, suggesting those genes were transcriptionally poised to respond to future competition. Thus, experimental competition among free-living animals shifts gene expression in ways that may facilitate the demands of competition at the expense of self-maintenance. Further, some of these effects persisted after competition ended, demonstrating the potential for epigenetic biological embedding of the social environment in ways that may prime individuals for success in future social instability.
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http://dx.doi.org/10.1073/pnas.2016154118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020798PMC
March 2021

A single GnRH challenge promotes paternal care, changing nestling growth for one day.

Horm Behav 2021 Apr 11;130:104964. Epub 2021 Mar 11.

Indiana University, Department of Biology, United States of America; Indiana University, Center for the Integrated Study of Animal Behavior, United States of America.

Decades of comparative and experimental work suggest that testosterone (T) promotes mating effort at the expense of parental effort in many vertebrates. There is abundant evidence that T-mediated trade-offs span both evolutionary and seasonal timescales, as T is often higher in species or breeding stages with greater mating competition and lower in association with parental effort. However, it is less clear whether transient elevations in T within a male's own reactive scope can affect parental effort in the same way, with effects that are visible to natural selection. Here, we injected free-living male tree swallows (Tachycineta bicolor) with gonadotropin-releasing hormone (GnRH), thus temporarily maximizing T production within an individual's own limit. Passive loggers at each nest showed that GnRH-injected males provisioned more frequently than saline males for the subsequent day, and their offspring gained more mass during that time. The degree of offspring growth was positively correlated with the father's degree of T elevation, but provisioning was not proportional to changes in T, and GnRH- and saline-injected males did not differ in corticosterone secretion. These results suggest that prior knowledge of T-mediated trade-offs garnered from seasonal, evolutionary, and experimental research cannot necessarily be generalized to the timescale of transient fluctuations in T secretion within an individual. Instead, we propose that GnRH-induced T fluctuations may not result in visible trade-offs if selection has already sculpted an individual male's reactive scope based on his ability to handle the competing demands of mating and parental care.
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http://dx.doi.org/10.1016/j.yhbeh.2021.104964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025405PMC
April 2021

The Role of Digital Technology in the EndSars Protest in Nigeria During COVID-19 Pandemic.

J Hum Rights Soc Work 2021 Feb 12:1-2. Epub 2021 Feb 12.

Department of Social Work, University of Nigeria, Nsukka, Nigeria.

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http://dx.doi.org/10.1007/s41134-021-00161-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879136PMC
February 2021

COVID-19 in Rural Nigeria: Diminishing Social Support for Older People in Nigeria.

Gerontol Geriatr Med 2020 Jan-Dec;6:2333721420986301. Epub 2020 Dec 28.

University of Nigeria, Nsukka, Choose, Nigeria.

Social support provided by family, friends and neighbors has been essential for the survival and wellbeing of older people in Nigeria. However, the reduced social contact between older people and their social network because of the social distancing recommendations and other non-pharmaceutical approaches to protect them from COVID-19 may threaten their social support. Our study investigated the impact of the COVID-19 pandemic on rural older people in Nigeria using qualitative data collected from 11 older adults residing in rural Nigeria through in-depth interviews. The collected data was translated and transcribed, coded using Nvivo12 and analyzed thematically. Findings show that the COVID-19 pandemic has led to a reduction in both material support in the forms of food and money, and intangible support in the forms of assistance, communication and care, due to limited social contact. Furthermore, the economic consequence of the pandemic may have severe implications for the health and wellbeing of older people. Social workers should therefore advocate the distribution of food and care supplies to rural older people to cushion the economic impact of diminishing social support, and also creatively help them maintain social connectedness.
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http://dx.doi.org/10.1177/2333721420986301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783879PMC
December 2020

Intraoperative heparin use is associated with reduced mortality without increasing hemorrhagic complications after thoracic endovascular aortic repair for blunt aortic injury.

J Vasc Surg 2021 Jul 18;74(1):71-78. Epub 2020 Dec 18.

Division of Vascular Surgery, Department of Surgery, Stanford Health Care, Stanford, Calif.

Objective: Thoracic endovascular aortic repair (TEVAR) is an effective treatment of blunt thoracic aortic injury (BTAI). However, the risks and benefits of administering intraoperative heparin in trauma patients are not well-defined, especially with regard to bleeding complications.

Methods: The Vascular Quality Initiative registry was queried from 2013 to 2019 to identify patients who had undergone TEVAR for BTAI with or without the administration of intraoperative heparin. Univariate analyses were performed with the Student t test, Fisher exact test, or χ test, as appropriate. Multivariable logistic regression was then performed to assess the association of heparin with inpatient mortality.

Results: A total of 655 patients were included, of whom most had presented with grade III (53.3%) or IV (20%) BTAI. Patients receiving heparin were less likely to have an injury severity score (ISS) of ≥15 (70.2% vs 90.5%; P < .0001) or major head or neck injury (39.6% vs 62.9%; P < .0001). Patients receiving heparin also had a lower incidence of inpatient death (5.1% vs 12.9%; P < .01). Across all injury grades, heparin use was not associated with the need for intraoperative transfusion or postoperative transfusion or the development of hematoma. In patients with grade III BTAI, the nonuse of heparin was associated with an increased risk of lower extremity embolization events (7.4% vs 1.8%; P < .05). On multivariable logistic regression analysis for inpatient mortality, intraoperative heparin use (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.86; P < .05) and female gender (OR, 0.11; 95% CI, 0.11-0.86; P < .05) were associated with better survival, even after controlling for head and neck trauma and injury grade. In contrast, increased age (OR, 1.06; 95% CI, 1.03-1.1; P < .001), postoperative transfusion (OR, 1.06; 95% CI, 1.02-1.11; P < .01), higher ISS (OR, 1.04; 95% CI, 1.01-1.07; P < .05), postoperative dysrhythmia (OR, 4.48; 95% CI, 1.10-18.18; P < .05), and postoperative stroke or transient ischemic attack (OR, 5.54; 95% CI, 1.11-27.67; P < .05) were associated with increased odds of inpatient mortality.

Conclusions: Intraoperative heparin use was associated with reduced inpatient mortality for patients undergoing TEVAR for BTAI, including those with major head or neck trauma and high ISSs. Heparin use did not increase the risk of hemorrhagic complications across all injury grades. Also, in patients with grade III BTAI, heparin use was associated with a reduced risk of lower extremity embolic events. Heparin appears to be safe during TEVAR for BTAI and should be administered when no specific contraindication exists.
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http://dx.doi.org/10.1016/j.jvs.2020.12.068DOI Listing
July 2021

Contemporary Practices and Complications of Surgery for Thoracic Outlet Syndrome in the United States.

Ann Vasc Surg 2021 Apr 3;72:147-158. Epub 2021 Feb 3.

Division of Vascular & Endovascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA. Electronic address:

Background: Thoracic outlet syndrome (TOS) surgery is relatively rare and controversial, given the challenges in diagnosis as well as wide variation in symptomatic and functional recovery. Our aims were to measure trends in utilization of TOS surgery, complications, and mortality rates in a nationally representative cohort and compare higher versus lower volume centers.

Methods: The National Inpatient Sample was queried using International Classification of Diseases, Ninth Revision, codes for rib resection and scalenectomy paired with axillo-subclavian aneurysm (arterial [aTOS]), subclavian deep vein thrombosis (venous [vTOS]), or brachial plexus lesions (neurogenic [nTOS]). Basic descriptive statistics, nonparametric tests for trend, and multivariable hierarchical regression models with random intercept for center were used to compare outcomes for TOS types, trends over time, and higher and lower volume hospitals, respectively.

Results: There were 3,547 TOS operations (for an estimated 18,210 TOS operations nationally) performed between 2010 and 2015 (89.2% nTOS, 9.9% vTOS, and 0.9% aTOS) with annual case volume increasing significantly over time (P = 0.03). Higher volume centers (≥10 cases per year) represented 5.2% of hospitals and 37.0% of cases, and these centers achieved significantly lower overall major complication (defined as neurologic injury, arterial or venous injury, vascular graft complication, pneumothorax, hemorrhage/hematoma, or lymphatic leak) rates (adjusted odds ratio [OR] 0.71 [95% confidence interval 0.52-0.98]; P = 0.04], but no difference in neurologic complications such as brachial plexus injury (aOR 0.69 [0.20-2.43]; P = 0.56) or vascular injuries/graft complications (aOR 0.71 [0.0.33-1.54]; P = 0.39). Overall mortality was 0.6%, neurologic injury was rare (0.3%), and the proportion of patients experiencing complications decreased over time (P = 0.03). However, vTOS and aTOS had >2.5 times the odds of major complication compared with nTOS (OR 2.68 [1.88-3.82] and aOR 4.26 [1.78-10.17]; P < 0.001), and ∼10 times the odds of a vascular complication (aOR 10.37 [5.33-20.19] and aOR 12.93 [3.54-47.37]; P < 0.001], respectively. As the number of complications decreased, average hospital charges also significantly decreased over time (P < 0.001). Total hospital charges were on average higher when surgery was performed in lower volume centers (<10 cases per year) compared with higher volume centers (mean $65,634 [standard deviation 98,796] vs. $45,850 [59,285]; P < 0.001).

Conclusions: The annual number of TOS operations has increased in the United States from 2010 to 2015, whereas complications and average hospital charges have decreased. Mortality and neurologic injury remain rare. Higher volume centers delivered higher value care: less or similar operative morbidity with lower total hospital charges.
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http://dx.doi.org/10.1016/j.avsg.2020.10.046DOI Listing
April 2021

Association Between Patient Frailty and Postoperative Mortality Across Multiple Noncardiac Surgical Specialties.

JAMA Surg 2021 Jan 13;156(1):e205152. Epub 2021 Jan 13.

Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California.

Importance: Frailty is an important risk factor for postoperative mortality. Whether the association between frailty and mortality is consistent across all surgical specialties, especially those predominantly performing lower stress procedures, remains unknown.

Objective: To examine the association between frailty and postoperative mortality across surgical specialties.

Design, Setting, And Participants: A cohort study was conducted across 9 noncardiac specialties in hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and Veterans Affairs Surgical Quality Improvement Program (VASQIP) from January 1, 2010, through December 31, 2014, using multivariable logistic regression to evaluate the association between frailty and postoperative mortality. Data analysis was conducted from September 15, 2019, to April 30, 2020. Patients 18 years or older undergoing noncardiac procedures were included.

Exposures: Risk Analysis Index measuring preoperative frailty categorized patients as robust (Risk Analysis Index ≤20), normal (21-29), frail (30-39), or very frail (≥40). Operative Stress Score (OSS) categorized procedures as low (1-2), moderate (3), and high (4-5) stress. Specialties were categorized by case-mix as predominantly low intensity (>75% OSS 1-2), moderate intensity (50%-75%), or high intensity (<50%).

Main Outcomes And Measures: Thirty-day (both measures) and 180-day (VASQIP only) postoperative mortality.

Results: Of the patients evaluated in NSQIP (n = 2 339 031), 1 309 795 were women (56.0%) and mean (SD) age was 56.49 (16.4) years. Of the patients evaluated in VASQIP (n = 426 578), 395 761 (92.78%) were men and mean (SD) age was 61.1 (12.9) years. Overall, 30-day mortality was 1.2% in NSQIP and 1.0% in VASQIP, and 180-day mortality in VASQIP was 3.4%. Frailty and OSS distributions differed substantially across the 9 specialties. Patterns of 30-day mortality for frail and very frail patients were similar in NSQIP and VASQIP for low-, moderate-, and high-intensity specialties. Frailty was a consistent, independent risk factor for 30- and 180-day mortality across all specialties. For example, in NSQIP, for plastic surgery, a low-intensity specialty, the odds of 30-day mortality in very frail (adjusted odds ratio [aOR], 27.99; 95% CI, 14.67-53.39) and frail (aOR, 5.1; 95% CI, 3.03-8.58) patients were statistically significantly higher than for normal patients. This was also true in neurosurgery, a moderate-intensity specialty, for very frail (aOR, 9.8; 95% CI, 7.68-12.50) and frail (aOR, 4.18; 95% CI, 3.58-4.89) patients and in vascular surgery, a high-intensity specialty, for very frail (aOR, 10.85; 95% CI, 9.83-11.96) and frail (aOR, 3.42; 95% CI, 3.19-3.67) patients.

Conclusions And Relevance: In this study, frailty was associated with postoperative mortality across all noncardiac surgical specialties regardless of case-mix. Preoperative frailty assessment could be implemented across all specialties to facilitate risk stratification and shared decision-making.
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http://dx.doi.org/10.1001/jamasurg.2020.5152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675216PMC
January 2021

ACR Appropriateness Criteria® Postpartum Hemorrhage.

J Am Coll Radiol 2020 Nov;17(11S):S459-S471

Specialty Chair, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Postpartum hemorrhage (PPH) can be categorized as primary or early if occurring in the first 24 hours after delivery, whereas late or delayed PPH occurs between 24 hours and 6 weeks. Most of the causes of PPH can be diagnosed clinically, but imaging plays an important role in the diagnosis of many causes of PPH. Pelvic ultrasound (transabdominal and transvaginal with Doppler) is the imaging modality of choice for the initial evaluation of PPH. Contrast-enhanced CT of the abdomen and pelvis and CT angiogram of the abdomen and pelvis may be appropriate to determine if active ongoing hemorrhage is present, to localize the bleeding, and to identify the source of bleeding. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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http://dx.doi.org/10.1016/j.jacr.2020.09.011DOI Listing
November 2020

Hierarchical assembly of smectic liquid crystal defects at undulated interfaces.

Soft Matter 2020 Sep;16(36):8352-8358

Department of Physics, University of Massachusetts Boston, Boston, MA 02125, USA.

The assembly of topological defects in liquid crystals has drawn significant interest in the last decade due to their ability to trap colloidal objects and direct their arrangements. They have also brought about a high impact in modern technologies, in particular in optics, e.g., microlens arrays, soft lithography templates, and optically selective masks. Here we study the formation of defects in smectic A liquid crystal with hybrid texture at undulated surfaces. We investigate the role of surface topography on the organization of focal conic domains (FCDs) in smectic films. We demonstrate new methods for assembling FCDs and disclinations into hierarchical structures. When the liquid crystal is heated to the nematic phase, we observe stable defect lines forming at specific locations. These defects are created to satisfy anchoring conditions and the geometry of confinement imposed by the boundaries. Once the liquid crystal is cooled to the smectic A phase, the disclinations maintain their positions, but periodic structures of reversible FCDs facing opposite directions arise between them. We report the correlation between the size of these FCDs and their eccentricities with the morphology of the interface. This work paves the way for creating new procedures to control the assembly of functional nanomaterials into tunable assemblies that may find relevance in the field of energy technology including in optoelectronic and photonic applications.
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http://dx.doi.org/10.1039/d0sm01112fDOI Listing
September 2020

The Consequences of Delaying Elective Surgery: Surgical Perspective.

Ann Surg 2020 08;272(2):e79-e80

Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA.

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http://dx.doi.org/10.1097/SLA.0000000000003998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224620PMC
August 2020

Association of Preoperative Frailty and Operative Stress With Mortality After Elective vs Emergency Surgery.

JAMA Netw Open 2020 07 1;3(7):e2010358. Epub 2020 Jul 1.

Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.10358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358909PMC
July 2020

Lumbar Diagnosis and Pressure Difference Variance.

J Am Osteopath Assoc 2020 Jun;120(6):e86-e91

Context: There is no consensus on the correlation between clinical experience and accuracy in diagnosing somatic dysfunctions, which makes it difficult to justify the use of more subjective measures to evaluate this important association. To better understand this relationship, palpatory forces can be observed while diagnosing a somatic dysfunction.

Objective: To quantify the pressure applied in diagnosing lumbar somatic dysfunction, find a correlation between accuracy of diagnosis and palpation pressure, set the standards for palpation, and develop precise palpatory skills for osteopathic medical students.

Methods: The palpatory forces were evaluated between participants with varying experience levels (osteopathic medical students and attending physicians from the New York Institute of Technology College of Osteopathic Medicine). Two osteopathic physicians confirmed an L5 somatic dysfunction diagnosis in a volunteer standardized patient (SP), who served as the control. Participants then palpated the lumbar segment of the SP in a prone position with F-Scan System (TekScan) sensors, which recorded the amount of pressure and time used to reach a full diagnosis.

Results: Participants (11 osteopathic medical students and 10 attending physicians) who diagnosed an L5 somatic dysfunction consistent with the SP's diagnosis had less of a difference in peak force (mean [SD] difference, 62.50 [325.7] g/cm2) between the contact points (right hand vs left hand). In contrast, participants with a dissimilar L5 diagnosis from the SP's had a mean (SD) difference in peak force of 319.38 (703.1) g/cm2. Similarly, the difference in the mean (SD) force of palpation between the contact points was lower in participants who made the correct diagnosis (16.81 [117.4] g/cm2) vs those who made an incorrect diagnosis (123.92 [210.3] g/cm2). No statistical significance was found between the diagnostic accuracy of the students and physicians (P=.387) or the time taken to reach a diagnosis (P=.199).

Conclusion: We observed that using equal pressures in both hands while palpating a lumbar segment correlates to more accurate somatic dysfunction diagnoses.
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http://dx.doi.org/10.7556/jaoa.2020.066DOI Listing
June 2020

Facial Nerve Palsy: Clinical Practice and Cognitive Errors.

Am J Med 2020 09 20;133(9):1039-1044. Epub 2020 May 20.

Department of Radiology and Biomedical Imaging, University of California San Francisco.

Facial paralysis is the most common cranial nerve paralysis and the majority of these are idiopathic. Idiopathic facial nerve paralysis, or Bell palsy, typically presents acutely, affects the entire face, may be associated with hyperacusis, a decrease in lacrimation, salivation, or dysgeusia, and typically resolves spontaneously. The diagnosis of idiopathic facial paralysis is made after a thorough history and physical examination to exclude alternative etiologies and follow-up to ensure recovery of facial function. Atypical presentation, recurrent paralysis, additional neurologic deficits, lack of facial recovery in 2-3 months, or a history of head and neck or cutaneous malignancy are concerning for alternative causes of facial paralysis requiring workup. The erroneous use of the eponym Bell palsy to refer to all causes of facial paralysis, regardless of the history and presentation, may result in cognitive errors, including premature closure, anchoring bias, and diagnosis momentum. Hence, we recommend replacing the eponym Bell palsy with idiopathic facial nerve paralysis.
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http://dx.doi.org/10.1016/j.amjmed.2020.04.023DOI Listing
September 2020

An instrument for assessing the quality of informed consent documents for elective procedures: development and testing.

BMJ Open 2020 05 19;10(5):e033297. Epub 2020 May 19.

Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA.

Objective: To develop a nationally applicable tool for assessing the quality of informed consent documents for elective procedures.

Design: Mixed qualitative-quantitative approach.

Setting: Convened seven meetings with stakeholders to obtain input and feedback on the tool.

Participants: Team of physician investigators, measure development experts, and a working group of nine patients and patient advocates (caregivers, advocates for vulnerable populations and patient safety experts) from different regions of the country.

Interventions: With stakeholder input, we identified elements of high-quality informed consent documents, aggregated into three domains: content, presentation and timing. Based on this comprehensive taxonomy of key elements, we convened the working group to offer input on the development of an abstraction tool to assess the quality of informed consent documents in three phases: (1) selecting the highest-priority elements to be operationalised as items in the tool; (2) iteratively refining and testing the tool using a sample of qualifying informed consent documents from eight hospitals; and (3) developing a scoring approach for the tool. Finally, we tested the reliability of the tool in a subsample of 250 informed consent documents from 25 additional hospitals.

Outcomes: Abstraction tool to evaluate the quality of informed consent documents.

Results: We identified 53 elements of informed consent quality; of these, 15 were selected as highest priority for inclusion in the abstraction tool and 8 were feasible to measure. After seven cycles of iterative development and testing of survey items, and development and refinement of a training manual, two trained raters achieved high item-level agreement, ranging from 92% to 100%.

Conclusions: We identified key quality elements of an informed consent document and operationalised the highest-priority elements to define a minimum standard for informed consent documents. This tool is a starting point that can enable hospitals and other providers to evaluate and improve the quality of informed consent.
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http://dx.doi.org/10.1136/bmjopen-2019-033297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247404PMC
May 2020

Improving Outcomes After Surgery-An Old Medication With Unexpected Benefits.

JAMA Surg 2020 06 17;155(6):e200417. Epub 2020 Jun 17.

Department of Surgery, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1001/jamasurg.2020.0417DOI Listing
June 2020