bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing of venous thromboembolism prophylaxis initiation after injury: Findings from the consensus conference to implement optimal VTE prophylaxis in trauma
Authors: Schellenberg Morgan , Costantini Todd , Joseph Bellal , Price Michelle A. , Bernard Andrew C. , Haut Elliott R.
Published: February 2023

Optimizing prophylaxis against venous thromboembolic events (VTEs) is a critical issue in the care of injured patients. Although these patients are at significant risk of developing VTE, they also present competing concerns related to exacerbation of bleeding from existing injuries. Especially after high-risk trauma, including injuries to the abdominal solid organs, brain, and spine, trauma providers must delineate the time period in which VTE prophylaxis successfully reduces VTE rates without encouraging bleeding. Although existing data are primarily retrospective in nature and further study is required, literature supports early VTE chemoprophylaxis initiation even for severely injured patients. Early initiation is most frequently defined as <48 hours from admission but varies from <24 hours to 72 hours and occasionally refers to time from initial trauma. Prior to chemical VTE prophylaxis initiation in patients at risk for bleeding, an observation period is necessary during which injuries must show themselves to be hemostatic, either clinically or radiographically. In the future, prospective examination of optimal timing of VTE prophylaxis is necessary. Further study of specific subsets of trauma patients will allow for development of effective VTE mitigation strategies based upon collective risks of VTE and hemorrhage progression.
Novel therapeutic medications for venous thromboembolism prevention in trauma patients: Findings from the Consensus Conference to Implement Optimal Venous Thromboembolism Prophylaxis in Trauma
Authors: Dhillon Navpreet K. , Haut Elliott R. , Price Michelle A. , Costantini Todd W. , Teichman Amanda L. , Cotton Bryan A. , Ley Eric J.
Published: February 2023

Trauma patients are at high risk for venous thromboembolism (VTE). Despite evidence-based guidelines and concerted efforts in trauma centers to implement optimal chemoprophylaxis strategies, VTE remains a frequent diagnosis in trauma patients. Current chemoprophylaxis strategies largely focus on the subcutaneous injection of low-molecular-weight heparin, which is administered twice daily. Novel approaches to pharmacologic VTE prophylaxis have the potential to reduce VTE rates by improving patient compliance through oral administration or through their ability to target alternative pathways that mediate thrombosis. While novel pharmacologic VTE prophylaxis strategies have been studied in nontrauma patients, there is a paucity of literature in trauma patients where the risk of thrombosis versus hemorrhage must be carefully considered. As a component of the 2022 Consensus Conference to Implement Optimal VTE Prophylaxis in Trauma, this review provides an update of the novel chemoprophylaxis agents for potential use in trauma patients. Here, we will consider the relative risks and benefits related to the use of these drugs, evaluate the current literature in nontrauma patients, and consider future directions that could potentially improve posttrauma VTE prophylaxis.
Approaches for optimizing venous thromboembolism prevention in injured patients: Findings from the consensus conference to implement optimal venous thromboembolism prophylaxis in trauma
Authors: Teichman Amanda L. , Cotton Bryan A. , Byrne James , Dhillon Navpreet K. , Berndtson Allison E. , Price Michelle A. , Johns Tracy J. , Ley Eric J. , Costantini Todd , Haut Elliott R.
Published: February 2023

Venous thromboembolism (VTE) is a major issue in trauma patients. Without prophylaxis, the rate of deep venous thrombosis approaches 60% and even with chemoprophylaxis may be nearly 30%. Advances in VTE reduction are imperative to reduce the burden of this issue in the trauma population. Novel approaches in VTE prevention may include new medications, dosing regimens, and extending prophylaxis to the postdischarge phase of care. Standard dosing regimens of low-molecular-weight heparin are insufficient in trauma, shifting our focus toward alternative dosing strategies to improve prophylaxis. Mixed data suggest that anti-Xa–guided dosage, weight-based dosing, and thromboelastography are among these potential strategies. The concern for VTE in trauma does not end upon discharge, however. The risk for VTE in this population extends well beyond hospitalization. Variable extended thromboprophylaxis regimens using aspirin, low-molecular-weight heparin, and direct oral anticoagulants have been suggested to mitigate this prolonged VTE risk, but the ideal approach for outpatient VTE prevention is still unclear. As part of the 2022 Consensus Conference to Implement Optimal Venous Thromboembolism Prophylaxis in Trauma, a multidisciplinary array of participants, including physicians from multiple specialties, pharmacists, nurses, advanced practice providers, and patients met to attack these issues. This paper aims to review the current literature on novel approaches for optimizing VTE prevention in injured patients and identify research gaps that should be investigated to improve VTE rates in trauma.
Prehospital shock index predicts outcomes after prolonged transport: A multicenter rural study
Authors: Bardes James M. , Price Bradley S. , Bailey Hannah , Quinn Alexander , Warriner Zachary D. , Bernard Andrew C. , LaRiccia Aimee , Spalding M. Chance , Linskey Dougherty Melissa B. , Armen Scott B. , Wilson Alison
Published: February 2023

BACKGROUND

Shock index (SI) predicts outcomes after trauma. Prior single-center work demonstrated that emergency medical services (EMSs) initial SI was the most accurate predictor of hospital outcomes in a rural environment. This study aimed to evaluate the predictive ability of SI in multiple rural trauma systems with prolonged transport times to a definitive care facility.

METHODS

This retrospective review was performed at four American College of Surgeons–verified level 1 trauma centers with large rural catchment basins. Adult trauma patients who were transferred and arrived >60 minutes from scene during 2018 were included. Patients who sustained blunt chest or abdominal trauma were analyzed. Subjects with missing data or severe head trauma (Abbreviated Injury Scale score, >2) were excluded. Poisson and binomial logistic regression were used to study the effect of SI and delta shock index (∆SI) on outcomes.

RESULTS

After applying the criteria, 789 patients were considered for analysis (502 scene patients and 287 transfers). The mean Injury Severity Score was 8 (interquartile range, 6) for scene and 8.9 (interquartile range, 5) for transfers. Initial EMSs SI was a significant predictor of the need for blood transfusion and intensive care unit care in both scene and transferred patients. An increase in ∆SI was predictive of the need for operative intervention (p < 0.05). There were increased odds for mortality for every 0.1 change in EMSs SI; those changes were not deemed significant among both scene and transfer patients (p < 0.1).

CONCLUSION

Providers must maintain a high level of clinical suspicion for patients who had an initially elevated SI. Emergency medical services SI is a significant predictor for use of blood and intensive care unit care, as well as mortality for scene patients. This highlights the importance of SI and ∆SI in rural trauma care.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Establishing a core outcomes set for massive transfusion: An Eastern Association for the Surgery of Trauma modified Delphi method consensus study
Authors: Gelbard Rondi B. , Nahmias Jeffry , Byerly Saskya , Ziesmann Markus , Stein Deborah , Haut Elliott R. , Smith Jason W. , Boltz Melissa , Zarzaur Ben , Callum Jeannie , Cotton Bryan A. , Cripps Michael , Gunter Oliver L. , Holcomb John B. , Kerby Jeffrey , Kornblith Lucy Z. , Moore Ernest E. , Riojas Christina M. , Schreiber Martin , Sperry Jason L. , Yeh D. Dante
Published: February 2023

BACKGROUND

The management of severe hemorrhage has changed significantly over recent decades, resulting in a heterogeneous description of diagnosis, treatment, and outcomes in the literature, which is not suitable for data pooling. Therefore, we sought to develop a core outcome set (COS) to help guide future massive transfusion (MT) research and overcome the challenge of heterogeneous outcomes reporting.

METHODS

Massive transfusion content experts were invited to participate in a modified Delphi study. For Round 1, participants submitted a list of proposed core outcomes. In subsequent rounds, panelists used a 9-point Likert scale to score proposed outcomes for importance. Core outcomes consensus was defined as >85% of scores receiving 7 to 9 and <15% of scores receiving 1 to 3. Feedback and aggregate data were shared between rounds.

RESULTS

From an initial panel of 16 experts, 12 (75%) completed three rounds of deliberation to reevaluate variables not achieving predefined consensus criteria. A total of 64 items were considered, with 4 items achieving consensus for inclusion as core outcomes: blood products received in the first 6 hours, 6-hour mortality, time to mortality, and 24-hour mortality.

CONCLUSION

Through an iterative survey consensus process, content experts have defined a COS to guide future MT research. This COS will be a valuable tool for researchers seeking to perform new MT research and will allow future trials to generate data that can be used in pooled analyses with enhanced statistical power.

LEVEL OF EVIDENCE

Diagnostic Test or Criteria; Level V.
Vaccine Effectiveness Against the SARS-CoV-2 B.1.1.529 Omicron Variant in Solid Organ and Islet Transplant Recipients in England: A National Retrospective Cohort Study
Authors: Callaghan Chris J. , Curtis Rebecca M.K. , Mumford Lisa , Whitaker Heather , Pettigrew Gavin , Gardiner Dale , Marson Lorna , Thorburn Douglas , White Steven , Parmar Jas , Ushiro-Lumb Ines , Manas Derek , Ravanan Rommel ,   on behalf of the NHS Blood and Transplant Organ and Tissue Donation and Transplantation Clinical Team
Published: February 2023

Background.

The effectiveness of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 Omicron variant in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear.

Methods.

National registries in England were linked to identify SARS-CoV-2 positive tests, noninjury hospitalization within 14 d, and deaths within 28 d between December 7, 2020, and March 31, 2022 in adult SOT recipients. Incidence rate ratios (IRRs) for infection, and hospitalization or death, were adjusted for recipient demographics and calendar month for the Omicron-dominant period (December 20, 2021, to March 31, 2022). Mortality risk following SARS-CoV-2 infection was adjusted for recipient demographics and dominant variant using a Cox proportional-hazards model for the entire time period.

Results.

During the Omicron-dominant period, infection IRRs (95% confidence intervals) were higher in those receiving 2, 3, and 4 vaccine doses than in unvaccinated patients (1.25 [1.08-1.45], 1.46 [1.28-1.67], and 1.79 [1.54-2.06], respectively). However, hospitalization or death IRRs during this period were lower in those receiving 3 or 4 vaccine doses than in unvaccinated patients (0.62 [0.45-0.86] and 0.39 [0.26-0.58], respectively). Risk-adjusted analyses for deaths after SARS-CoV-2 infection between December 7, 2020, and March 31, 2022, found hazard ratios (95% confidence intervals) of 0.67 (0.46-0.98), 0.46 (0.30-0.69), and 0.18 (0.09-0.35) for those with 2, 3, and 4 vaccine doses, respectively, when compared with the unvaccinated group.

Conclusions.

In immunosuppressed SOT recipients, vaccination is associated with incremental, dose-dependent protection against hospitalization or death after SARS-CoV-2 infection, including against the Omicron variant.
Influence of Patient Age and Presence of Optic Disc Drusen on Fluctuations in Retinal Nerve Fiber Layer Thickness
Authors: Tonagel Felix , Wilhelm Helmut , Stock Lydia , Kelbsch Carina
Published: February 2023

Background:

It is generally believed that optic disc drusen (ODD) change only over long periods of time. Because, in our experience, this does not apply to younger patients, we investigated the natural course of changes of the peripapillary retinal nerve fiber layer (RNFL) in patients with ODD.

Methods:

In this retrospective study, 40 eyes with and 40 eyes without ODD were examined, both cohorts were equally subdivided into younger subjects (20 years or younger) and older subjects (21 years or older). Three optical coherence tomography (OCT) scans of the peripapillary RNFL that had an interval of at least 1 month were required for each patient to be included in this study. The largest difference in total RNFL thickness (delta RNFL-t) and in RNFL thickness of the most differing sector (delta RNFL max) measured by OCT was compared.

Results:

The differences in total RNFL thickness and in the most differing RNFL sector in the group of patients with ODD younger than 21 years were significantly larger than in each of the other 3 groups (P = 0.0001). The other 3 groups did not differ significantly.

Conclusions:

Patients with ODD younger than 21 years have distinct variations in peripapillary RNFL thickness without evidence of increased intracranial pressure. In the absence of further pathological findings or neurological symptoms, an observational approach seems adequate in these patients.
Frequency and Etiologies of Visual Disturbance After Cataract Surgery Identified in Neuro-Ophthalmology Clinics
Authors: Lin Shuai-Chun , Giang Angie , Liu Grant T. , Avery Robert A. , Shindler Kenneth S. , Hamedani Ali G. , Ross Ahmara G. , Tamhankar Madhura A.
Published: February 2023

Background:

To identify the frequency and etiologies of visual disturbances after cataract surgery in patients referred to Neuro-ophthalmology.

Methods:

This study is a retrospective chart review. Records of patients 18 years and older referred to neuro-ophthalmology clinics for new-onset visual disturbances within 6 months of cataract surgery were reviewed. Those with pre-existing neuro-ophthalmic disorders, combined intraocular procedures with cataract surgery, or inadequate follow-up were excluded. The main outcome measures were frequency and etiologies of visual disturbances after cataract surgery. Secondary analyses of a cohort of patients who had cataract surgery at our institution were performed to determine the frequency and etiology of visual disturbances after uneventful cataract surgery.

Results:

One hundred seventy-three patients met the inclusion criteria (internal referral: 36/173, from outside surgeons: 137/173). Sixty-one percent (106/173) were newly diagnosed with neuro-ophthalmic etiologies, including 21% (36/173) with afferent and 40% (70/173) with efferent disorders. Thirty-six percent (62/173) of patients had non neuro-ophthalmic causes and 3% (5/173) had systemic conditions responsible for visual disturbances postoperatively. Decompensated strabismus causing diplopia was the most common neuro-ophthalmic diagnosis after cataract surgery (50%, 53/106). Of the 13,715 patients who had cataract surgery performed at our institution over a 9-year period, 20 of 36 patients referred for visual disturbances were identified with neuro-ophthalmic etiologies of which 85% (17/20) had postoperative diplopia.

Conclusions:

In our study, decompensated strabismus causing diplopia was the most common neuro-ophthalmic visual disturbance after cataract surgery. Detailed history and ocular alignment should be assessed before cataract surgery to identify patients with the risk.
Shared Decision-Making in General Surgery: Prospective Comparison of Telemedicine vs In-Person Visits
Authors: Hawkins Alexander T , Ueland Thomas , Aher Chetan , Geiger Timothy M , Spann Matthew D , Horst Sara N , Schafer Isabella V , Ye Fei , Fan Run , Sharp Kenneth W
Published: February 2023

BACKGROUND:

The coronavirus disease 2019 (COVID-19) pandemic has accelerated a shift toward virtual telemedicine appointments with surgeons. While this form of healthcare delivery has potential benefits for both patients and surgeons, the quality of these interactions remains largely unstudied. We hypothesize that telemedicine visits are associated with lower quality of shared decision-making.

STUDY DESIGN:

We performed a mixed-methods, prospective, observational cohort trial. All patients presenting for a first-time visit at general surgery clinics between May 2021 and June 2022 were included. Patients were categorized by type of visit: in-person vs telemedicine. The primary outcome was the level of shared decision-making as captured by top box scores of the CollaboRATE measure. Secondary outcomes included quality of shared decision-making as captured by the 9-item Shared Decision-Making Questionnaire and satisfaction with consultation survey. An adjusted analysis was performed accounting for potential confounders. A qualitative analysis of open-ended questions for both patients and practitioners was performed.

RESULTS:

During a 13-month study period, 387 patients were enrolled, of which 301 (77.8%) underwent in-person visits and 86 (22.2%) underwent telemedicine visits. The groups were similar in age, sex, employment, education, and generic quality-of-life scores. In an adjusted analysis, a visit type of telemedicine was not associated with either the CollaboRATE top box score (odds ratio 1.27; 95% CI 0.74 to 2.20) or 9-item Shared Decision-Making Questionnaire (β −0.60; p = 0.76). Similarly, there was no difference in other outcomes. Themes from qualitative patient and surgeon responses included physical presence, time investment, appropriateness for visit purpose, technical difficulties, and communication quality

CONCLUSIONS:

In this large, prospective study, there does not appear to be a difference in quality of shared decision making in patients undergoing in-person vs telemedicine appointments.
Long-Term Survival Outcomes after Operative Management of Chronic Pancreatitis: Two Decades of Experience
Authors: Wilson Gregory C , Turner Kevin M , Delman Aaron M , Wahab Shaun , Ofosu Andrew , Smith Milton T , Choe Kyuran A , Patel Sameer H , Ahmad Syed A
Published: February 2023

Background:

Chronic pancreatitis is a debilitating, life altering disease; however, the long-term outcomes following operative intervention have not been established.

Study Design:

Patients who underwent operative intervention at a single institution between 2000 to 2020 for chronic pancreatitis were included and survival assessed utilizing the National Death Index.

Results:

493 patients who underwent 555 operative interventions for chronic pancreatitis over two decades were included. 48.5% underwent total pancreatectomy ± islet auto transplantation, 21.7% underwent a duodenal preserving pancreatic head resection and/or drainage procedure, 16.2% underwent a pancreaticoduodenectomy, and 12.8% underwent a distal pancreatectomy. The most common etiology of chronic pancreatitis was idiopathic (41.8%), followed by alcohol (28.0%), and known genetic polymorphisms (9.9%). With a median follow-up of 83.9 months, median overall survival (OS) was 202.7 months, with a 5- and 10-year OS of 81.3% and 63.5%. 165 patients were deceased, and the most common causes of death included: infections (16.4%, n=27), cardiovascular disease (12.7%, n=21), and diabetes related causes (10.9%, n=18). On long-term follow-up, 73.1% (n=331) of patients remained opioid free while 58.7% (n=266) were insulin dependent diabetics. On multivariate cox-proportional hazards modeling, only persistent opioid use (HR:3.91 95%CI:2.45-6.24, p<0.01) was associated worse OS.

Conclusion:

Our results represent the largest series to date evaluating long-term survival outcomes in patients with chronic pancreatitis following operative intervention. Our data give insight into the cause of death and allow for the development of mitigation strategies and long-term monitoring of co-morbid conditions.
Effective interventions to reduce loneliness in big cities
Authors: Fischer Ronald , Hartle Larissa
Published: February 2023

Purpose of review

Loneliness is a state of distress or discomfort between the desired and experienced level of connectedness to others. These feelings may be particular salient in urban environments that seemingly offer more opportunities for social contact, highlighting the discrepancy. The topic of loneliness has received increased attention because of its negative impact on mental and physical health combined with concerns of increased loneliness due to lockdowns and social distancing regulations during the coronavirus disease 2019 pandemic. We provide a bibliometric and random-effects meta-analysis of clinical trials published since 2020 and available via PubMed.

Recent findings

Loneliness interventions have predominantly focused on elderly in the community. Adolescents and young adults as a second group at risk have received much less attention. On average across 44 effect sizes studied in 38 trials, interventions show moderate levels of effectiveness but are characterized by high heterogeneity and trials are often underpowered and use low quality designs. Multidimensional interventions show promise for alleviating loneliness, but the intervention context needs greater attention.

Scalable and effective interventions for the general population and at-risk groups of loneliness are still scarce. Some promising interventions have been trialled and merit further attention.
Age-Dependent Dose Increase During an Acute Electroconvulsive Therapy Series
Authors: Plemper Jana , Sartorius Alexander , Karl Sebastian
Published: February 2023

Introduction

Electroconvulsive therapy (ECT) dose is highly relevant for ECT efficacy as well as adverse effects. It is often based on seizure threshold (ST). Studies have shown that ST increases over the course of an ECT series. Clinical observation suggests that this rise might be more pronounced in geriatric patients.

Methods

Retrospectively, we analyzed ECT dose during the first 20 ECT treatments in 472 patients undergoing ECT. Dose adjustments were assessed in relation to patients' age using generalized least squares regression analysis. Response was defined as Clinical Global Impression Improvement Scale < 4.

Results

Dose increased in all patients during the course of the ECT series (mean initial dose, 64.97 ± 68.04 mC; at 10th ECT, 385.46 ± 211.28 mC). Dose was significantly correlated with ECT treatment number, electrode placement, and the interaction between age and ECT treatment number. In other words, dose increase was significantly positively correlated with increasing age, that is dose increased more in older compared with younger patients during the course of an ECT series (z = 9.47, P < 0.001). Response was not correlated with age-dependent dose increase; however, the length of the ECT series in responders was negatively associated with the dose increase from the first to the seventh ECT session (F = 5.28, P = 0.0228).

Conclusions

Our results indicate that ST increases more rapidly during the course of an ECT series in older compared with younger patients. To ensure high efficacy throughout the course of treatment, attention should be paid to decreasing seizure quality, especially in older patients, and dose should be adjusted accordingly.
Distribution and origins of Mycobacterium tuberculosis L4 in Southeast Asia
Authors: Ashton Philip M. , Cha Jaeyoon , Anscombe Catherine , Thuong Nguyen T. T. , Thwaites Guy E. , Walker Timothy M.
Published: February 2023

Molecular and genomic studies have revealed that

Mycobacterium tuberculosis

Lineage 4 (L4, Euro-American lineage) emerged in Europe before becoming distributed around the globe by trade routes, colonial migration and other historical connections. Although L4 accounts for tens or hundreds of thousands of tuberculosis (TB) cases in multiple Southeast Asian countries, phylogeographical studies have either focused on a single country or just included Southeast Asia as part of a global analysis. Therefore, we interrogated public genomic data to investigate the historical patterns underlying the distribution of L4 in Southeast Asia and surrounding countries. We downloaded 6037 genomes associated with 29 published studies, focusing on global analyses of L4 and Asian studies of

M. tuberculosis

. We identified 2256 L4 genomes including 968 from Asia. We show that 81 % of L4 in Thailand, 51 % of L4 in Vietnam and 9 % of L4 in Indonesia belong to sub-lineages of L4 that are rarely seen outside East and Southeast Asia (L4.2.2, L4.4.2 and L4.5). These sub-lineages have spread between East and Southeast Asian countries, with no recent European ancestor. Although there is considerable uncertainty about the exact direction and order of intra-Asian

M. tuberculosis

dispersal, due to differing sampling frames between countries, our analysis suggests that China may be the intermediate location between Europe and Southeast Asia for two of the three predominantly East and Southeast Asian L4 sub-lineages (L4.2.2 and L4.5). This new perspective on L4 in Southeast Asia raises the possibility of investigating host population-specific evolution and highlights the need for more structured sampling from Southeast Asian countries to provide more certainty of the historical and current routes of dispersal.
In vivo Tracing of the Ascending Vagal Projections to the Brain with Manganese Enhanced Magnetic Resonance Imaging
Authors: Oleson Steven , Cao Jiayue , Wang Xiaokai , Liu Zhongming
Published: February 2023

The vagus nerve, the primary neural pathway mediating brain-body interactions, plays an essential role in transmitting bodily signals to the brain. Despite its significance, our understanding of the detailed organization and functionality of vagal afferent projections remains incomplete. In this study, we utilized manganese-enhanced magnetic resonance imaging (MEMRI) as a non-invasive method for tracing vagal nerve projections to the brainstem in vivo and assessing their functional dependence on cervical vagus nerve stimulation (VNS). Manganese chloride solution was injected into the nodose ganglion of rats, and T1-weighted MRI scans were performed 12 and 24 hours post-injection. Our findings reveal that vagal afferent neurons can uptake and transport manganese ions, serving as a surrogate for calcium ions, to the nucleus tractus solitarius (NTS) in the brainstem. In the absence of VNS, we observed significant contrast enhancements of around 19 to 24% in the NTS ipsilateral to the injection side. Application of VNS for four hours further promoted nerve activity, leading to greater contrast enhancements of 40 to 43% in the NTS. These results underline the potential of MEMRI for high-resolution, activity-dependent tracing of vagal afferents, providing a valuable tool for the structural and functional assessment of the vagus nerve and its influence on brain activity.
A panel-agnostic strategy ‘HiPPo’ improves diagnostic efficiency in the UK Genome Medicine Service
Authors: Seaby Eleanor G. , Thomas N. Simon , Hunt David , Baralle Diana , Rehm Heidi L. , O’Donnell-Luria Anne , Ennis Sarah
Published: February 2023

Genome sequencing is now available as a clinical test on the National Health Service (NHS) through the Genome Medicine Service (GMS). The GMS have set out an analytical strategy that predominantly filters genome data on a pre-selected gene panel(s). Whilst this approach reduces the number of variants requiring assessment by reporting laboratories, pathogenic variants outside of the gene panel applied may be missed, and candidate variants in novel genes are largely ignored.

This study sought to compare a research exome analysis to an independent clinical genome analysis performed through the NHS for the same group of patients. When analysing the exome data, we applied a panel agnostic approach filtering for variants withHighPathogenicPotential (HiPPo) using ClinVar, allele frequency, andin silicoprediction tools. We then compared this gene agnostic analysis to the panel-based approach as applied by the GMS to genome data. Later we restricted HiPPo variants to a panel of the Gene Curation Coalition (GenCC) morbid genes and compared the diagnostic yield with the variants filtered using the GMS strategy.

24 patients from 8 families underwent parallel research exome sequencing and GMS genome sequencing. HiPPo analysis applied to research exome data identified a similar number of variants as the gene panel-based approach applied by the GMS. GMS clinical genome analysis identified and returned 2 pathogenic variants and 3 variants of uncertain significance. HiPPo research exome analysis identified the same variants plus an additional pathogenic variant and a further 3de novovariants of uncertain significance in novel genes, where case series and functional studies are underway. When HiPPo was restricted to GenCC disease genes (strong or definitive), the same pathogenic variants were identified yet statistically fewer variants required assessment to identify more diagnostic variants than reported by the GMS genome strategy. This gave a diagnostic rate per variant assessed of 20% for HiPPo restricted to GenCC versus 3% for the GMS panel-based approach. With plans to sequence 5 million more NHS patients, strategies are needed to optimise the full potential of genome data beyond gene panels whilst minimising the burden of variants that require clinical assessment.
Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study
Authors: Liu Minghua , Khasiyev Farid , Sariya Sanjeev , Spagnolo-Allende Antonio , Sanchez Danurys L , Andrews Howard , Yang Qiong , Beiser Alexa , Qiao Ye , Thomas Emy A , Romero Jose Rafael , Rundek Tatjana , Brickman Adam M , Manly Jennifer J , Elkind Mitchell SV , Seshadri Sudha , Chen Christopher , Sacco Ralph L , Hilal Saima , Wasserman Bruce A , Tosto Giuseppe , Fornage Myriam , Gutierrez Jose
Published: February 2023

Background

Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.

Results

We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10−8) (top SNP, rs7921574; β =0.06, P=1.54×10−8). This locus mapped to an intron ofCNNM2. A trans-ancestry GWAS meta-analysis identified two more loci atNT5C2(rs10748839; P=2.54×10−8) and atAS3MT(rs10786721; P=4.97×10−8), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression ofCNNM2(rs7897654, β=0.12, P=6.17×10−7) andAL356608.1(rs10786719, β =-0.17, P=6.60×10−6) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron ofTCF25were identified (top SNP, rs35994878; β =0.11, P=2.94×10−8). For the anterior brain arterial diameter, one locus atADAP1was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10−8).

Conclusion

Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.
Taxonomic difference in marine bloom-forming phytoplanktonic species affects dynamics of both bloom-responding prokaryotes and prokaryotic viruses
Authors: Takebe Hiroaki , Tominaga Kento , Isozaki Tatsuhiro , Watanabe Tetsuhiro , Yamamoto Keigo , Kamikawa Ryoma , Yoshida Takashi
Published: February 2023

The production of dissolved organic matter during phytoplankton blooms and consumption by heterotrophic prokaryotes promotes marine carbon biogeochemical cycling. Although prokaryotic viruses are crucial biological entities, their dynamics during such blooms are not fully understood. Here, we investigated the dynamics of coastal prokaryotic communities and viruses during blooms in a microcosm experiment using dissolved intracellular fractions of taxonomically distinct phytoplankton, the diatomChaetocerossp. (CIF) and the raphidophycean algaHeterosigma akashiwo(HIF). Ribosomal RNA gene amplicon and viral metagenomic analyses revealed that particular prokaryotes and prokaryotic viruses specifically increased in either CIF and HIF, indicating that different phytoplankton intracellular fractions promote distinct dynamics of not only prokaryotic community but also prokaryotic viruses. Our microcosm experiments and environmental data mining identified both known and novel possible host-virus pairs. In particular, a growth of phytoplanktonic organic matter-associated prokaryotes, such as BacteroidetesPolaribacterand NS9 marine group,Vibriospp., and RhodobacterialesNereidaandPlanktomarina, was accompanied by an increase in viruses predicted to infect Bacteroidetes,Vibrio, and Rhodobacteriales, respectively. Collectively, our findings suggest that elucidating tripartite relationships among phytoplankton, prokaryotes, and prokaryotic viruses would further our understanding of coastal microbial ecosystems.

We state that

-All the data underlying the study are available at the DNA Data Bank of Japan (DDBJ) under project number PRJDB14359 and accession number DRA014887.

-This study was supported by Grants-in-Aid for Scientific Research (No. 16H06429, No. 17H03850, No. 21H05057, and No. 21J14854) from the Japan Society for the Promotion of Science (JSPS).

-We have no potential conflicts of interest to declare.

-We have read and understood your journal’s policies, and we believe that neither the manuscript nor the study violates any of these.

-We do not use any clinical data, human subjects, or laboratory animals.

-None of the materials have been published or are under consideration for publication elsewhere.

CRediT

Hiroaki Takebe: Funding acquisition, conceptualization, investigation, formal analysis, visualization, and writing (original draft). Kento Tominaga: Conceptualization, investigation, and writing (review and editing). Tatsuhiro Isozaki: investigation. Tetsuhiro Watanabe: Resources. Keigo Yamamoto: Resources. Ryoma Kamikawa: Conceptualization, supervision, and writing (review and editing). Takashi Yoshida: Funding acquisition, project administration, conceptualization, supervision, and writing (review and editing).
Aurora kinase A/AURKA interacts with the mitochondrial ATP synthase to regulate energy metabolism and cell death
Authors: Sharma Rakesh Kumar , Chafik Abderrahman , Bertolin Giulia
Published: February 2023

Cancer cells often hijack metabolic pathways to obtain the energy required to sustain their proliferation. Understanding the molecular mechanisms underlying cancer cell metabolism is key to fine-tune the metabolic preference of specific tumors, and potentially offer new therapeutic strategies. Here, we show that the pharmacological inhibition of mitochondrial Complex V delays the cell cycle by arresting breast cancer cell models in the G0/G1 phase. Under these conditions, the abundance of the multifunctional protein Aurora kinase A/AURKA is specifically lowered. We then demonstrate that AURKA directly interacts with the mitochondrial Complex V core subunits ATP5F1A and ATP5F1B. Altering the AURKA/ATPF1A/ATPF1B nexus is sufficient to trigger G0/G1 arrest, and this is accompanied by decreased glycolysis and mitochondrial respiration rates. Last, we discover that the roles of the AURKA/ATPF1A/ATPF1B nexus depend on the specific metabolic propensity of triple-negative breast cancer cell lines, where they correlate with cell fate. On one hand, the nexus induces G0/G1 arrest in cells relying on oxidative phosphorylation as the main source of energy. On the other hand, it allows to bypass cell cycle arrest and it triggers cell death in cells with a glycolytic metabolism. Altogether, we provide evidence that AURKA and mitochondrial Complex V subunits cooperate to maintain cell metabolism in breast cancer cells. Our work paves the way to novel anti-cancer therapies targeting the AURKA/ATPF1A/ATPF1B nexus to lower cancer cell metabolism and proliferation.
The hidden barriers to social value delivery in megaprojects: investigating the decision-making environment
Authors: Siva Jessica , Gajendran Thayaparan
Published: February 2023

Purpose

Megaprojects are seen as vehicles for delivering significant social value. However, megaproject decision-making, which is deeply embedded in networks comprising formal and informal practices involving the exercise of power, can facilitate or hinder social value delivery. Moreover, these decision-making practices are often intentionally designed and executed to remain hidden and so are not easily identifiable but have implications for maximising social value. This paper aims to identify the hidden barriers to social value delivery on megaprojects resulting from the decision-making environment.

Design/methodology/approach

Governmentality theory was used to deconstruct the megaproject decision-making environment. The critical realism philosophy was merged with a narrative inquiry approach to analyse the everyday, taken-for-granted practices that resulted in the decision-making outcomes. Data were collected through 22 in-depth semi-structured interviews to uncover stories highlighting the nature of power relations underpinning the decision-making environment of one megaproject in the Asia Pacific region.

Findings

Governmentality theory as a lens showed that emergent, informal governing practices blend with formal governance mechanisms, creating a complex mix of overt and covert power dynamics. The findings suggest that the exercise of covert power by project team members through deviant tactics hinders social value delivery. Therefore, understanding the power dynamics that influence the decision-making of project team members is key for maximising social value delivery.

Originality/value

Originality stems from the use of governmentality theory and critical realism to deconstruct and explain the megaproject decision-making environment, enabling observation of otherwise challenging-to-understand, complex and hidden barriers to the delivery of social value. This paper offers a novel way of explaining social value delivery through megaproject decision-making.
Transnational sensemaking narratives of highly skilled Canadian immigrants' career change
Authors: Palic Dunja , Nardon Luciara , Hari Amrita
Published: February 2023

Purpose

The authors answer calls for research on the experiences of international professionals' career transitions by investigating how highly skilled immigrants make sense of their career changes in the host country's labor market.

Design/methodology/approach

The authors report on a qualitative, inductive and elaborative study, drawing on sensemaking theories and career transitions literature and nine semi-structured reflective interviews with highly skilled Canadian immigrants.

Findings

The authors identified four career change narratives: mourning the past, accepting the present, recreating the past and starting fresh. These narratives are made sense of in a transnational context: participants contended with tensions between past, present and future careers and between relevant home and host country factors affecting their career decisions. Participants who were mourning the past or recreating the past identified more strongly with their home country professions and struggled to find resources in Canada. In accepting the present and starting fresh, participants leveraged host country networks to find career opportunities and establish themselves and their families in the new environment.

Originality/value

A transnational ontology emphasizes that immigrants' lives are multifaceted and span multiple national contexts. The authors highlight how the tensions between the home and host country career contexts shape immigrants' sensemaking narratives of their international career change. The authors encourage scholars and practitioners to take a transnational contextual approach (spatial and temporal) to guide immigrants' career transitions and integration into the new social environment.
A novel approach for measuring the accuracy of front end engineering design
Authors: Gibson G. Edward , El Asmar Mounir , Yussef Abdulrahman , Ramsey David
Published: February 2023

Purpose

Assessing front end engineering design (FEED) accuracy is significant for project owners because it can support informed decision-making, including confidence in cost and schedule predictions. A framework to measure FEED accuracy does not exist in the literature or in practice, not does systematic data directly linking FEED accuracy to project performance. This paper aims to focus first on gauging and quantifying FEED accuracy, and second on measuring its impact on project performance in terms of cost change, schedule change, change performance, financial performance and customer satisfaction.

Design/methodology/approach

A novel measurement scheme was developed for FEED accuracy as a comprehensive assessment of factors related to the project leadership and execution teams, management processes and resources; to assess the environment surrounding FEED. The development of this framework built on a literature review and focus groups, and used the research charrettes methodology, guided by a research team of 20 industry professionals and input from 48 practitioners representing 31 organizations. Data were collected from 33 large industrial projects representing over $8.8 billion of installed cost, allowing for a statistical analysis of the framework's impact on performance.

Findings

This paper describes: (1) twenty-seven critical FEED accuracy factors; (2) an objective and scalable method to measure FEED accuracy; and (3) data showing that projects with high FEED accuracy outperformed projects with low FEED accuracy by 20 percent in terms of cost growth in relation to their approved budgets.

Practical implications

FEED accuracy is defined as the degree of confidence in the measured level of maturity of the FEED deliverables to serve as a basis of decision at the end of detailed scope, prior to detailed design. Assessing FEED accuracy is significant for project owners because it can support informed decision-making, including confidence in cost and schedule predictions.

Originality/value

FEED accuracy has not been assessed before, and it turned out to have considerable project performance implications. The new framework presented in this paper is the first of its kind, it has been tested rigorously, and it contributes to both the literature body of knowledge as well as to practice. As one industry leader recently stated, “it not only helped to assess the quality and adequacy of the technical documentation required, but also provided an opportunity to check the organization's readiness before making a capital investment decision.”
Are work–life policies fair for a woman’s career? An Italian qualitative study of the backlash phenomenon
Authors: Bertola Lara , Colombo Lara , Fedi Angela , Martini Mara
Published: February 2023

Purpose

Work–family balance practices available in several work organizations to help employees with children to manage the demands of work and family life can have a negative impact on employees with family commitments, on childless employees and on the organization itself, as Perrigino et al. show in their theoretical review. This is the work–family backlash phenomenon expressed by the four mechanisms of stigma, spillover, inequity and strategic. Even if the stigma mechanism towards working women with children was widely explored, no study until now considered the four backlash mechanisms jointly, in the Italian context. The purpose of this paper is offering a first empirical exploration of these mechanisms in Italian work organizations.

Design/methodology/approach

For this study, 15 Italian career women with different care burdens were interviewed, and the four mechanisms were analysed from the perspective of women with and without children, and of organizations.

Findings

Analysis has shown that the backlash phenomenon can trigger a vicious cycle of perceived inequity that leads to job dissatisfaction and low work motivation. Management responsiveness and fairness in dealing with employees’ needs are central to promoting well-being by effectively balancing career paths with personal needs, especially in a cultural context where most responsibility for family needs is still left to women and few public supports are available.

Originality/value

This study, in spite of some limitations, offers a first contribution to the analysis of the different facets of the work–family backlash in the Italian context and suggests several possible research and practical developments.
Natural hazards affecting cultural heritage: assessment of flood and landslide risk for the 28 existing Norwegian stave churches
Authors: Bertolin Chiara , Sesana Elena
Published: February 2023

Purpose

The overall objective of this study is envisaged to provide decision makers with actionable insights and access to multi-risk maps for the most in-danger stave churches (SCs) among the existing 28 churches at high spatial resolution to better understand, reduce and mitigate single- and multi-risk. In addition, the present contribution aims to provide decision makers with some information to face the exacerbation of the risk caused by the expected climate change.

Design/methodology/approach

Material and data collection started with the consultation of the available literature related to: (1) SCs' conservation status, (2) available methodologies suitable in multi-hazard approach and (3) vulnerability leading indicators to consider when dealing with the impact of natural hazards specifically on immovable cultural heritage.

Findings

The paper contributes to a better understanding of place-based vulnerability with local mapping dimension also considering future threats posed by climate change. The results highlight the danger at which the SCs of Røldal, in case of floods, and of Ringebu, Torpo and Øye, in case of landslide, may face and stress the urgency of increasing awareness and preparedness on these potential hazards.

Originality/value

The contribution for the first time aims to homogeneously collect and report all together existing spread information on architectural features, conservation status and geographical attributes for the whole group of SCs by accompanying this information with as much as possible complete 2D sections collection from existing drawings and novel 3D drawn sketches created for this contribution. Then the paper contributes to a better understanding of place-based vulnerability with local mapping dimension also considering future threats posed by climate change. Then it highlights the danger of floods and landslides at which the 28 SCs are subjected. Finally it reports how these risks will change under the ongoing impact of climate change.