Search

Detailed detector simulation is the major consumer of CPU resources at LHCb, having used more than 90% of the total computing budget during Run 2 of the Large Hadron Collider at CERN. As data is collected by the upgraded LHCb detector during Run 3 of the LHC, larger requests for simulated data samples are necessary, and will far exceed the pledged resources of the experiment, even with existing fast simulation options. The evolution of technologies and techniques for simulation production is then mandatory to meet the upcoming needs for the analysis of most of the data collected by the LHCb experiment. In this context, we propose Lamarr, a Gaudi-based framework designed to offer the fastest solution for the simulation of the LHCb detector. Lamarr consists of a pipeline of modules parameterizing both the detector response and the reconstruction algorithms of the LHCb experiment. Most of the parameterizations are made of Deep Generative Models and Gradient Boosted Decision Trees trained on simulated samples or alternatively, where possible, on real data. Embedding Lamarr in the general LHCb Gauss Simulation framework allows combining its execution with any of the available generators in a seamless way. Lamarr has been validated by comparing key reconstructed quantities with Detailed Simulation. Good agreement of the simulated distributions is obtained with two order of magnitude speed-up of the simulation phase.

ABSTRACT: For many, digital transformation is the new normal. However, in particular, pipeline businesses in traditional industries, such as standard-setting organizations (SSOs), are reluctant to radically rethink their business models, as they have often successfully prevailed for decades. The literature shows that there is a great deal of theory to be found on digital transformation, but a practical and, at the same time, scientific approach is yet missing. Following the design science framework, this paper introduces a two-step approach to transform a pipeline business model into a digital standardization platform. This is achieved by mapping the incumbent pipeline business mode146l and its ecosystem with the Platform Business Model Canvas introduced by Eisape. The representation of the current ecosystem is then digitally transformed according to the three key transformation points introduced by Alstyne et al., shifting the current ecosystem into the digital realm. The illustrative case study on DIN e.V. (the German SSOs) demonstrates the new methodology and its suitability for real applications. The result is a platform business model for a digital standardization platform, which, compared via an index to the traditional business model, has the potential to disrupt the entire standardization industry.

Background: Controversy remains regarding the results of all arthroscopic rotator cuff repairs compared with the mini-open approach. The purpose of this study was to perform a comprehensive literature search and meta-analysis of clinical trials comparing the results of arthroscopic rotator cuff repairs and mini-open rotator cuff repairs.Hypothesis: There is no difference between the clinical results obtained from all arthroscopic rotator cuff repairs compared with mini-open repairs.Study Design: Meta-analysis.Methods: A computerized search of articles published between 1966 and July 2006 was performed using MEDLINE and PubMed. Additionally, a search of abstracts from 4 major annual meetings each held between 2000 and 2005 was performed to identify Level I to III studies comparing the results of arthroscopic rotator cuff repair and mini-open repair. Studies that included follow-up of an average of over 2 years and a minimum of 1 year and included the use of 1 of 4 validated functional outcome scores used to study shoulder injuries were included in the present meta-analysis. All outcome scores were converted to a 100-point scale to allow for outcome comparison.Results: Five studies that met the inclusion criteria were identified. There was no difference in functional outcome scores or complications between the arthroscopic and mini-open repair groups.Conclusion: Based on current literature, there was no difference in outcomes between the arthroscopic and mini-open rotator cuff repair techniques. [ABSTRACT FROM AUTHOR]

Abstract Background Ghana is bedeviled with the lack of 24-h supply of electricity. This holds back economic growth and sustainable development prospects. Several studies have investigated varied factors that account for household’s willingness-to-pay (WTP) for improved electricity services. However, not much is known about the role of trust as a proxy for social capital and household’s WTP for improved electricity services. We hypothesize that trust (social capital) is a key factor in determining households WTP for a 24-h supply of electricity in Ghana, a service which is largely controlled by the government. Methods This study uses primary data collected in a survey of households and applies the well-known and widely used Contingent Valuation Method (CVM) to estimate how much households who trust and those who do not trust in the government are willing to pay for a 24-h supply of electricity. Results We have evidence that trust in the government is statistically significant and varies negatively with WTP for improved electricity supply. In line with our hypothesis and the few existing studies on trust-WTP relationship, we conclude that trust plays a key role in determining WTP for improved electricity services in Ghana. Our estimates which are downward biased constitute 15–17% of household’s income. Conclusions To advance the course of generating funds to sustain the supply of a 24-h supply of electricity, this study argues based on the evidence from the trust-WTP relationship that most households do not trust the government in the provision of efficient electricity services. Those who trust the government are currently not willing to pay more for an improved electricity service because they believed the promises made to them by politicians that they would be provided with an improved service without them having to pay more. We recommend that government (politicians) should not trivialize anything that bothers on trust as it is not without its associated consequences on consumer’s WTP behaviour. Secondly, for efficient provision of improved electricity supply, policymakers should commence educating citizens on the unsustainability of government’s provision given its limited budget and explore private sector options.

Sexually transmitted diseases (STDs) are commonly encountered in the emergency department setting. Following is a review of selected STD syndromes and their etiologies, and the CDC recommendations for treatment. [ABSTRACT FROM AUTHOR]

Abstract Background HIV-1 reverse transcriptase (RT) is a heterodimer composed of p66 and p51 subunits and is responsible for reverse transcription of the viral RNA genome into DNA. RT can be post-translationally modified in vitro which may be an important mechanism for regulating RT activity. Here we report detection of different p66 and p51 RT isoforms by 2D gel electrophoresis in virions and infected cells. Results Major isoforms of the p66 and p51 RT subunits were observed, with pI's of 8.44 and 8.31 respectively (p668.44 and p518.31). The same major isoforms were present in virions, virus-infected cell lysates and intracellular reverse transcription complexes (RTCs), and their presence in RTCs suggested that these are likely to be the forms that function in reverse transcription. Several minor RT isoforms were also observed. The observed pIs of the RT isoforms differed from the pI of theoretical unmodified RT (p668.53 and p518.60), suggesting that most of the RT protein in virions and cells is post-translationally modified. The modifications of p668.44 and p518.31 differed from each other indicating selective modification of the different RT subunits. The susceptibility of RT isoforms to phosphatase treatment suggested that some of these modifications were due to phosphorylation. Dephosphorylation, however, had no effect on in vitro RT activity associated with virions, infected cells or RTCs suggesting that the phospho-isoforms do not make a major contribution to RT activity in an in vitro assay. Conclusion The same major isoform of p66 and p51 RT is found in virions, infected cells and RTC's and both of these subunits are post-translationally modified. This post-translational modification of RT may be important for the function of RT inside the cell.

Abstract Background Autoimmune diseases are more prevalent in females than in males, whereas males have higher mortality associated with infectious diseases. To increase our understanding of this sexual dimorphism in the immune system, we sought to identify and characterize inherent differences in immune response programs in the spleens of male and female mice before, during and after puberty. Results After the onset of puberty, female mice showed a higher expression of adaptive immune response genes, while males had a higher expression of innate immune genes. This result suggested a requirement for sex hormones. Using in vivo and in vitro assays in normal and mutant mouse strains, we found that reverse signaling through FasL was directly influenced by estrogen, with downstream consequences of increased CD8+ T cell-derived B cell help (via cytokines) and enhanced immunoglobulin production. Conclusion These results demonstrate that sexual dimorphism in innate and adaptive immune genes is dependent on puberty. This study also revealed that estrogen influences immunoglobulin levels in post-pubertal female mice via the Fas-FasL pathway.

We performed treadmill exercise magnetic resonance imaging in 27 patients with exertional chest pain who were referred for contrast coronary angiography to determine the feasibility of this method to identify severe coronary artery stenoses. The sensitivity and specificity for detecting >70% coronary artery luminal diameter narrowings on contrast coronary angiography were 79% and 85%, respectively. [ABSTRACT FROM AUTHOR]

Background: Little is known about the rates of cardiovascular disease (CVD), atherosclerosis, and their risk factors among Canada's Aboriginal people. To establish the relative prevalence of risk factors, atherosclerosis, and CVD, we undertook a population-based study among people of Aboriginal and European ancestry in Canada.Methods: We randomly recruited 301 Aboriginal people from the Six Nations Reservation, and 326 people of European origin from Hamilton, Toronto, and Edmonton, Canada. Clinical CVD was defined by history or electrocardiographic findings, atherosclerosis was measured by B-mode carotid ultrasonography, and conventional and new CVD risk factors were measured using standardised methods.Findings: Aboriginal people had significantly more carotid atherosclerosis (mean of the maximum intimal-medial thickness 0.82 (SD 0.20) mm vs 0.78 (0.20) mm, p=0.027), and had a higher frequency of CVD (18.5% vs 7.6%, p=0.00002) compared with Europeans. Aboriginal people had significantly higher rates of smoking, glucose intolerance, obesity, abdominal obesity, and substantially higher concentrations of fibrinogen, and plasminogen activator inhibitor-1. Aboriginal people had significantly higher rates of unemployment and a lower annual household income. For any given income level, Aboriginal people had higher rates of risk factors and CVD compared with the Europeans.Interpretation: A significant proportion of Aboriginal people live in poverty which is associated with high rates of CVD and CVD risk factors. Improvement of the socioeconomic status of Aboriginal people might be a key to reduce CVD in this group. [ABSTRACT FROM AUTHOR]

Background: Optimal care for seriously ill and older patients often involves advance care planning (ACP), goals-of-care (GOC) conversations, and specialty palliative care consultation, three sometimes overlapping, yet distinct practices. Insufficient staffing and investment in these areas have limited their availability., Objectives: We explored the facilitators and barriers to successful implementation of the VIDEO-PCE trial. The intervention aimed to increase patient engagement in ACP, GOC, and by establishing Palliative Care Educators, a new clinical role integrated into existing hospital wards., Design: This qualitative interview study employed a semi-structured interview guide tailored to the interviewee's clinical role. The interviews elicited perceptions of the facilitators and barriers to integration of palliative care educators (PCEs) into existing workflows. We developed deductive codes a priori and inductive codes as we coded interview transcripts., Setting/subjects: Medical/surgical floor clinical colleagues, palliative care team members, and PCEs from both participating sites were interviewed., Results: Twenty-four individuals were interviewed (12 clinical staff of medical and surgical wards, seven palliative care team members, and five PCEs). Four themes were identified: (1) The work completed by the PCEs provided a foundation for future palliative care involvement; (2) Constituting the new role in practice required revision and creativity; (3) Communication was important to providing continuity of care; and (4) Establishing trust catalyzed the acceptance of the role., Conclusion: The creation and implementation of a new role within existing clinical workflows posed some challenges but were felt to relieve staff from some work burden and allow more patients to engage in ACP and GOC conversations., Trial Registration: ClinicalTrials.gov Identifier: NCT04857060., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Angelo Volandes has a financial interest in ACP Decisions, a non-profit organization developing advance care planning video decision support tools. Dr Volandes’ interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflicts of interest policies. Dr Aretha Delight Davis is the CEO of ACP Decisions, a nonprofit organization focused on strengthening shared decisions making through video decision aids, from which she receives a salary. None of the other authors have any conflicts of interest to disclose.

Migraine is a chronic headache disorder. A prototype mobile app-based system was implemented to test data collection and improve data coverage for the Empatica E4 biometric sensor device. Results from the prototype testing are reported. Future iteration of the app will be tested with patients with migraine to predict events and potentially reduce event duration and therefore disease burden.

Epilepsy is a prevalent neurological disorder characterized by unpredictable seizures despite some known risk factors. Using an mHealth system and Empatica EmbracePlus, we aim to examine if biometric sensor data can detect and predict epileptic seizures. Five participants with epilepsy will be followed for a minimum of 15 seizures. Expected results and possible implications are presented. This study may provide new insights into biological indicators for seizure forecasting.

Clinical studies of major depression (MD) generally focus on group effects, yet interindividual differences in brain function are increasingly recognized as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2, and 8 weeks during which patients received pharmacotherapy (escitalopram, N  = 68) and controls ( N  = 39) received no intervention. The unique contributions of different sources of variation were examined by calculating how much variance in functional connectivity was shared across all participants and sessions, within/across groups (patients vs controls, responders vs nonresponders, female vs male participants), recording sessions, and individuals. Individual differences and common connectivity across groups, sessions, and participants contributed most to the explained variance (>95% across analyses). Group differences related to MD diagnosis, treatment response, and biological sex made significant but small contributions (0.3-1.2%). High individual variation was present in cognitive control and attention areas, while low individual variation characterized primary sensorimotor regions. Group differences were much smaller than individual differences in the context of MD and its treatment. These results could be linked to the variable findings and difficulty translating research on MD to clinical practice. Future research should examine brain features with low and high individual variation in relation to psychiatric symptoms and treatment trajectories to explore the clinical relevance of the individual differences identified here., Competing Interests: B.N.F. has received grant/research support from Alternative Funding Plan Innovations Award, Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Hamilton Health Sciences Foundation, J. P. Bickell Foundation, Ontario Brain Institute, Ontario Mental Health Foundation, Society for Women's Health Research, Teresa Cascioli Charitable Foundation, Eli Lilly, and Pfizer and has received consultant and/or speaker fees from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, CANMAT, Daiichi Sankyo, Lundbeck, Pfizer, Servier, and Sunovion. R.M. has received consulting and speaking honoraria from AbbVie, Allergan, Janssen, KYE, Lundbeck, Otsuka, and Sunovion and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI, and OMHF. S.P. has been a consultant to Takeda, Bristol Myers Squibb, Lundbeck; has had a research contract with Assurex; and has equity in Mensante. R.W.L. has received speaker and consultant honoraria or research funds from AstraZeneca, Brain Canada, Bristol-Myers Squibb, the Canadian Institutes of Health Research (CIHR), the Canadian Network for Mood and Anxiety Treatments, the Canadian Psychiatric Association, Eli Lilly, Janssen, Lundbeck, Lundbeck Institute, Medscape, Otsuka, Pfizer, Servier, St. Jude Medical, Takeda, the University Health Network Foundation, Vancouver Coastal Health Research Institute, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Healthy Minds Canada, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Unity Health, Viatris, and VGH-UBCH Foundation. S.H.K. has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, CIHR, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, and Sun Pharmaceutical and holds stock in Field Trip Health. D.J.M. has received consulting and speaking honoraria from Lundbeck and Genomind. C.S. has received consulting and speaking honoraria from Pfizer, Otsuka, Bayer, Eisai, and research grants from CAN-BIND, CIHR, OBI, and SEAMO. S.C.S. is a senior Scientific Advisor and shareholder in ADMdx, which receives NIH funding, and during the period of this research, he had research grants from Brain Canada, Canada Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), and the Ontario Brain Institute in Canada. Other authors declare no competing financial interests., (Copyright © 2024 van der Wijk et al.)

Variation in gene expression is a feature of all living systems and has recently been characterized extensively among wild strains of the model organism Caenorhabditis elegans. To enable researchers to query gene expression and gene expression variation at any gene of interest, we have created a user-friendly web application that shares RNA-seq transcription data for 208 wild C. elegans strains generated by the Caenorhabditis Natural Diversity Resource (CaeNDR). Here, we describe the features of the web application and the details of the data and data processing underlying it. We hope that this website, wildworm.biosci.gatech.edu/cendrexp/ , will help C. elegans researchers better understand their favorite genes and strains., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Evidence-based home visiting services (EBHV) are available in states and localities nationwide through the federally-funded Maternal, Infant, and Early Childhood Home Visiting (MIECHV) program. Nevertheless, the anticipated benefits of EBHV, such as improved child developmental outcomes and increased positive parenting practices, may be undermined by the fact that most families withdraw from services earlier than the model developers planned. Prior studies have linked family attrition with staff turnover. The current study used a mixed methods design to investigate the conditions under which families remained active in the home visiting program after their assigned home visitor resigned. Coincidence Analysis revealed that giving families advance notice (at least 1 month) prior to the home visitors' upcoming resignation or developing a strong positive working alliance with the inheriting home visitor appears to independently make a difference for ongoing family engagement at 3 and 6 months following a staff transition. These findings suggest that emphasizing how staff turnover is managed may mitigate the risk of family withdrawal during these transitions., (© 2024. The Author(s).)

The impact of preserved museum specimens is transforming and increasing by three-dimensional (3D) imaging that creates high-fidelity online digital specimens. Through examples from the openVertebrate (oVert) Thematic Collections Network, we describe how we created a digitization community dedicated to the shared vision of making 3D data of specimens available and the impact of these data on a broad audience of scientists, students, teachers, artists, and more. High-fidelity digital 3D models allow people from multiple communities to simultaneously access and use scientific specimens. Based on our multiyear, multi-institution project, we identify significant technological and social hurdles that remain for fully realizing the potential impact of digital 3D specimens., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Institute of Biological Sciences.)

The rabies indirect fluorescent antibody (IFA) test was developed to detect various rabies-specific antibody isotypes in sera or cerebral spinal fluid. This test provides rapid results and can be used to detect rabies antibodies in several different scenarios. The rabies IFA test is especially useful for the quick and early detection of antibodies to evaluate the immune response in a patient who has developed rabies. Although other methods for antemortem rabies diagnosis take precedence, this test may be utilized to demonstrate recent rabies virus exposure through antibody detection. The IFA test does not provide a virus-neutralizing antibody (VNA) titer, but the pre-exposure prophylaxis (PrEP) response can be evaluated through positive or negative antibody presence. This test can be utilized in various situations and can provide results for a number of different targets. In this study, we used several paired serum samples from individuals who received PrEP and demonstrated their rabies antibody presence over time using the IFA test.

Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity ( awFC )). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC ) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the 'full picture' of connectivity changes for REMs and NREMs while making for an easy intuitive approach., (© 2024 The Authors.)

The discovery that experimental delivery of dsRNA can induce gene silencing at target genes revolutionized genetics research, by both uncovering essential biological processes and creating new tools for developmental geneticists. However, the efficacy of exogenous RNA interference (RNAi) varies dramatically within the Caenorhabditis elegans natural population, raising questions about our understanding of RNAi in the lab relative to its activity and significance in nature. Here, we investigate why some wild strains fail to mount a robust RNAi response to germline targets. We observe diversity in mechanism: in some strains, the response is stochastic, either on or off among individuals, while in others, the response is consistent but delayed. Increased activity of the Argonaute PPW-1, which is required for germline RNAi in the laboratory strain N2, rescues the response in some strains but dampens it further in others. Among wild strains, genes known to mediate RNAi exhibited very high expression variation relative to other genes in the genome as well as allelic divergence and strain-specific instances of pseudogenization at the sequence level. Our results demonstrate functional diversification in the small RNA pathways in C. elegans and suggest that RNAi processes are evolving rapidly and dynamically in nature., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: Despite similar outcomes for surgery and physical therapy (PT), the number of surgeries to treat rotator cuff related shoulder pain (RCRSP) is increasing. Interventions designed to enhance treatment expectations for PT have been shown to improve patient expectations, but no studies have explored whether such interventions influence patient reports of having had surgery, or being scheduled for surgery. The purpose of this randomized clinical trial was to examine the effect of a cognitive behavioral intervention aimed at changing expectations for PT on patient-report of having had or being scheduled for surgery and on the outcomes of PT., Methods: The Patient Engagement, Education, and Restructuring of Cognitions (PEERC) intervention, was designed to change expectations regarding PT. PEERC was evaluated in a randomized, pragmatic "add-on" trial in by randomizing patients with RCRSP to receive either PT intervention alone (PT) or PT + PEERC. Fifty-four (54) individuals, recruited from an outpatient hospital-based orthopedic clinic, were enrolled in the trial (25 randomized to PT, 29 randomized to PT + PEERC). Outcomes assessed at enrollment, 6 weeks, discharge, and six months after discharge included the patient report of having had surgery, or being scheduled for surgery (primary) and satisfaction with PT outcome, pain, and function (secondary outcomes)., Results: The average age of the 54 participants was 51.81; SD = 12.54, and 63% were female. Chronicity of shoulder pain averaged 174.61 days; SD = 179.58. Study results showed that at the time of six months follow up, three (12%) of the participants in the PT alone group and one (3.4%) in the PT + PEERC group reported have had surgery or being scheduled for surgery (p = .32). There were no significant differences between groups on measures of satisfaction with the outcome of PT (p = .08), pain (p = .58) or function (p = .82)., Conclusions: In patients with RCRSP, PT plus the cognitive behavioral intervention aimed at changing expectations for PT provided no additional benefit compared to PT alone with regard to patient report of having had surgery, or being scheduled to have surgery, patient reported treatment satisfaction with the outcome of PT, or improvements in pain, or function., Trial Registration: The trial is registered on ClinicalTrials.gov: NCT03353272 (27/11/2017)., (© 2023. The Author(s).)

Advance Care Planning (ACP) is a communication process about serious illness decision making designed to inform patients of possible medical options. Native Hawaiians consistently have low rates of ACP and low use of palliative and hospice care services. Our multidisciplinary community and research group partnered to create I kua na'u "Let Me Carry Out Your Last Wishes," an ACP intervention featuring culturally tailored videos and are now testing its efficacy. Focus groups and informant interviews were conducted with Native Hawaiian community members to ensure the curriculum honored the history, opinions, and culture of Native Hawaiians. Native Hawaiian culture has traditionally been an oral culture; the spoken word transmitted the mo'olelo, stories, traditions, histories and genealogies, which merges seamlessly with video media. The I kua na'u intervention included multiple educational sessions enhanced with videos (informational and personal). The specific aims are to compare ACP knowledge (primary outcome) and readiness for ACP engagement, ACP preferences, decisional conflict, and ACP completion rates via electronic medical record review (secondary outcomes) in 220 Native Hawaiians over age 55 in: (a) a randomized controlled trial of 110 people recruited from ambulatory clinics, and (b) a pre-post study design among 110 people living on Hawaiian Homestead communities located on lands set aside for Native Hawaiians or assisted living. Our protocol aims to evaluate the efficacy of our video-based educational intervention for Native Hawaiians to support decision making in this community and decrease disparities in serious illness care. Clinical Trial Registration Number: NCT04771208., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Angelo Volandes has a financial interest in ACP Decisions, a non-profit organization developing advance care planning video decision support tools. Dr. Volandes' interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict-of-interest policies. No other disclosures to report. Dr. Davis (who is married to Dr. Volandes) is a Co-Founder, CEO and Board Member of ACP Decisions, a nonprofit organization that supports shared decision making through video decision aids, from which she receives a salary., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Advance Care Planning (ACP) comprises an iterative communication process aimed at understanding patients' goals, values, and preferences in the context of considering and preparing for future medical treatments and decision making in serious illness. The COVID pandemic heightened patients' and clinicians' awareness of the need for ACP., Objective: Our goal was to explore the experiences of clinicians and administrators in the context of an intervention to improve ACP during the COVID pandemic., Design: Qualitative interview study., Participants: Clinicians and administrators across five sites that participated in the ACP-COVID trial., Approach: We conducted semi-structured, qualitative interviews examining the context and approach to ACP. Interviews were analyzed using template analysis to systematically organize the data and facilitate review across the categories and participants. Templates were developed with iterative input and line-by-line review by the analytic team, to reach consensus. Findings were then organized into emergent themes., Key Results: Across 20 interviews (4 administrators, 16 clinicians) we identified three themes related to how participants thought about ACP: (1) clinicians have varying views of what constitutes ACP; (2) the health system critically shapes ACP culture and norms; and (3) the centrality of clinicians' affective experience and own needs related to ACP. Varying approaches to ACP include a forms-focused approach; a discussion-based approach; and a parental approach. System features that shape ACP norms are (1) the primacy of clinician productivity measures; (2) the role of the EHR; and (3) the culture of quality improvement., Conclusions: Despite high organizational commitment to ACP, we found that the health system channeled clinicians' ACP efforts narrowly on completion of forms, in tension with the ideal of well-grounded ACP. This resulted in a state of moral distress that risks undermining confidence in the process of ACP and may increase risk of harm for patients, family/caregivers, and providers., Trial Registration: ClinicalTrials.gov Identifier: NCT04660422., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Aβ) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance in the brain. Newer drugs modify the progression of the disease by acting against aggregated Aβ plaques. However, not all drugs used in therapy of AD have been granted approval by the United States Food and Drug Administration (FDA). This review categorizes and summarizes the FDA-approved drugs in the treatment of AD in a manner that would make it a convenient reference for researchers and practicing physicians alike. Drugs that mitigate symptoms of dementia may be categorized into mitigators of Behavioral and Psychological Symptoms of Dementia (BPSD), and mitigators of cognitive decline. BPSD mitigators include brexpiprazole, an atypical antipsychotic with a once-daily dosage suited to treat agitation in dementia patients, and suvorexant, an orexin receptor antagonist used to treat sleep disturbances. Cognitive decline mitigators include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine and glutamate inhibitors such as memantine. Donepezil is the most commonly prescribed drug. It is cheap, well-tolerated, and may be prescribed orally once daily, or as a transdermal patch once weekly. It increases ACh levels, enhances oligodendrocyte differentiation and also protects against Aβ toxicity. However, regular cardiac monitoring is required due to reports of cardiac conduction side effects. Rivastigmine requires a twice-daily oral dosage or once-daily replacement of transdermal patch. It has fewer cardiac side effects than donepezil, but local application-site reactions have been noted. Galantamine, in addition to improving cognitive symptoms in a short span of time, also delays the development of BPSDs and has minimal drug-drug interactions by virtue of having multiple metabolic pathways. However, cardiac conduction disturbances must be closely monitored for. Memantine, a glutamate regulator, acts as an anti-Parkinsonian agent and an antidepressant, in addition to improving cognition and neuroprotection, and requires a once-daily dosage in the form of immediate-release or sustained-release oral tablets. Disease-modifying drugs such as aducanumab and lecanemab reduce the Aβ burden. Both act by binding with fibrillary conformations of Aβ plaques in the brain. These drugs have a risk of causing amyloid-related imaging abnormalities, especially in persons with ApoE4 gene. Aducanumab is administered once every 4 weeks and lecanemab once every 2 weeks. The decision on the choice of the drug must be made after considering the availability of drug, compliance of patient (once-daily vs. multiple doses daily), cost, specific comorbidities, and the risk-benefit ratio for the particular patient. Other non-pharmacological treatment modalities must also be adopted to have a holistic approach toward the treatment of AD., Competing Interests: There are no conflicts of interest., (© 2023 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice.)

Importance: Despite the benefits of goals-of-care (GOC) communication, many hospitalized individuals never communicate their goals or preferences to clinicians., Objective: To assess whether a GOC video intervention delivered by palliative care educators (PCEs) increased the rate of GOC documentation., Design, Setting, and Participants: This pragmatic, stepped-wedge cluster randomized clinical trial included patients aged 65 years or older admitted to 1 of 14 units at 2 urban hospitals in New York and Boston from July 1, 2021, to October 31, 2022., Intervention: The intervention involved PCEs (social workers and nurses trained in GOC communication) facilitating GOC conversations with patients and/or their decision-makers using a library of brief, certified video decision aids available in 29 languages. Patients in the control period received usual care., Main Outcome and Measures: The primary outcome was GOC documentation, which included any documentation of a goals conversation, limitation of life-sustaining treatment, palliative care, hospice, or time-limited trials and was obtained by natural language processing., Results: A total of 10 802 patients (mean [SD] age, 78 [8] years; 51.6% male) were admitted to 1 of 14 hospital units. Goals-of-care documentation during the intervention phase occurred among 3744 of 6023 patients (62.2%) compared with 2396 of 4779 patients (50.1%) in the usual care phase (P < .001). Proportions of documented GOC discussions for Black or African American individuals (865 of 1376 [62.9%] vs 596 of 1125 [53.0%]), Hispanic or Latino individuals (311 of 548 [56.8%] vs 218 of 451 [48.3%]), non-English speakers (586 of 1059 [55.3%] vs 405 of 863 [46.9%]), and people living with Alzheimer disease and related dementias (520 of 681 [76.4%] vs 355 of 570 [62.3%]) were greater during the intervention phase compared with the usual care phase., Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of older adults, a GOC video intervention delivered by PCEs resulted in higher rates of GOC documentation compared with usual care, including among Black or African American individuals, Hispanic or Latino individuals, non-English speakers, and people living with Alzheimer disease and related dementias. The findings suggest that this form of patient-centered care delivery may be a beneficial decision support tool., Trial Registration: ClinicalTrials.gov Identifier: NCT04857060.

Though natural systems harbor genetic and phenotypic variation, research in model organisms is often restricted to a reference strain. Focusing on a reference strain yields a great depth of knowledge but potentially at the cost of breadth of understanding. Furthermore, tools developed in the reference context may introduce bias when applied to other strains, posing challenges to defining the scope of variation within model systems. Here, we evaluate how genetic differences among 5 wild Caenorhabditis elegans strains affect gene expression and its quantification, in general and after induction of the RNA interference (RNAi) response. Across strains, 34% of genes were differentially expressed in the control condition, including 411 genes that were not expressed at all in at least 1 strain; 49 of these were unexpressed in reference strain N2. Reference genome mapping bias caused limited concern: despite hyperdiverse hotspots throughout the genome, 92% of variably expressed genes were robust to mapping issues. The transcriptional response to RNAi was highly strain- and target-gene-specific and did not correlate with RNAi efficiency, as the 2 RNAi-insensitive strains showed more differentially expressed genes following RNAi treatment than the RNAi-sensitive reference strain. We conclude that gene expression, generally and in response to RNAi, differs across C. elegans strains such that the choice of strain may meaningfully influence scientific inferences. Finally, we introduce a resource for querying gene expression variation in this dataset at https://wildworm.biosci.gatech.edu/rnai/., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Objective: To develop and evaluate the psychometric properties of a family caregiver-reported survey that assesses family-centeredness of care in the context of pediatric emergency department (ED) encounters., Methods: We created a caregiver-reported scale, incorporated content expert feedback, and iteratively revised it based on cognitive interviews with caregivers. We then field tested the scale in a survey with caregivers. We dichotomized items using top-box scoring and obtained a summary score per respondent. Using a sample of 191 caregivers recruited from 9 EDs, we analyzed internal consistency reliability, dimensionality via item response theory modeling, and convergent validity with the ED Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey., Results: Feedback from the 9 experts led us to remove 4 items. We conducted 16 cognitive interviews and revised the survey in 4 rounds. An 11-item survey was field tested. Mean (standard deviation) respondent 11-item summary score was 77.2 (26.6). We removed 2 items given inconsistent response patterns, poor variability, and poor internal consistency, which increased coefficient alpha from 0.85 to 0.88 for the final scale. A multidimensional model fit the data best, but factor scores correlated strongly with summary scores, suggesting the latter are sufficient for quality improvement and future research. Regarding convergent validity, adjusted partial correlation between our scale's 9-item summary score and the ED CAHPS summary score was 0.75 (95% confidence interval 0.67-0.81)., Conclusions: Psychometric analyses demonstrated strong item performance, reliability, and convergent validity for the 9-item scale. This survey can be used to assess family-centered care in the ED for research and quality improvement purposes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective(s): Deaf American Sign Language (ASL) users are subject to health care disparities resulting from communication and language barriers. Currently, few resources on advance care planning and end-of-life care exist in ASL. This study explores Deaf ASL users' perceptions and experiences with end-of-life care and advance care planning. Methods: Semi-structured 1:1 interviews with Deaf signers were translated, and transcribed into English by a bilingual researcher. Investigators inductively coded transcripts and identified themes of barriers, facilitators, knowledge, and sources of information regarding end-of-life care. Participants' knowledge of advance care planning and completion of advance care planning documents were evaluated using a brief assessment. Results: Eleven Deaf ASL users participated in the study with two deaf interviewers. Participants reported barriers to end-of-life care including poor provider communication, inaccessible sources, and inadequate provision of accommodations, leading to patient distrust. Participants' understanding of advance care planning was facilitated by accessible forms of communication and their social networks, such as family, friends, and Deaf peers. Participants primarily gained information on end-of-life care from first-hand familial experience, peers, and media. Participants' mean advance care planning knowledge was 4.6 out of 15 (SD  =  2.6). Conclusions: Deaf ASL users face scarce accessible resources around end-of-life care, lowering their ability to understand and proceed with advance care planning. Implementation of ASL accessible advance care planning educational tools in health care settings is needed.

In utero, the developing brain is highly susceptible to the environment. For example, adverse maternal experiences during the prenatal period are associated with outcomes such as altered neurodevelopment and emotion dysregulation. Yet, the underlying biological mechanisms remain unclear. Here, we investigate whether the function of a network of genes co-expressed with the serotonin transporter in the amygdala moderates the impact of prenatal maternal adversity on the structure of the orbitofrontal cortex (OFC) in middle childhood and/or the degree of temperamental inhibition exhibited in toddlerhood. T1-weighted structural MRI scans were acquired from children aged 6-12 years. A cumulative maternal adversity score was used to conceptualize prenatal adversity and a co-expression based polygenic risk score (ePRS) was generated. Behavioural inhibition at 18 months was assessed using the Early Childhood Behaviour Questionnaire (ECBQ). Our results indicate that in the presence of a low functioning serotonin transporter gene network in the amygdala, higher levels of prenatal adversity are associated with greater right OFC thickness at 6-12 years old. The interaction also predicts temperamental inhibition at 18 months. Ultimately, we identified important biological processes and structural modifications that may underlie the link between early adversity and future deviations in cognitive, behavioural, and emotional development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sunderji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Concerns about disease and an increase in health anxiety levels are expected consequences of the COVID-19 pandemic. However, there have been few longitudinal studies of health anxiety in the general population during this time period. The aim of this study was to examine health anxiety levels before and during the COVID-19 pandemic in an adult, working population in Norway., Material and Methods: This study included 1012 participants aged 18-70 years with one or more measurements of health anxiety (1402 measurements total) from the pre-pandemic period (2015 to March 11, 2020) and/or during the COVID-19 pandemic (March 12, 2020 to March 31, 2022). Health anxiety was measured with the revised version of the Whiteley Index-6 scale (WI-6-R). We estimated the effect of the COVID-19 pandemic on health anxiety scores with a general estimation equation analysis, and age, gender, education, and friendship were included in subgroup analyses., Results: We found no significant change in health anxiety scores during the COVID-19 pandemic compared to the pre-pandemic period in our adult, working population. A sensitivity analysis restricted to participants with two or more measurements showed similar results. Moreover, the effect of the COVID-19 pandemic on health anxiety scores was not significant in any subgroup analysis., Conclusion: Health anxiety remained stable, with no significant change observed between the pre-pandemic period and the first 2 years of the COVID-19 pandemic in an adult, working population in Norway., Competing Interests: The authors have declared that no competing interests exists., (Copyright: © 2023 Norbye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Environmental perturbations during critical periods can have pervasive, organizational effects on neurodevelopment. To date, the literature examining the long-term impact of early life adversity has largely investigated structural and functional imaging data outcomes independently. However, emerging research points to a relationship between functional connectivity and the brain's underlying structural architecture. For instance, functional connectivity can be mediated by the presence of direct or indirect anatomical pathways. Such evidence warrants the use of structural and functional imaging in tandem to study network maturation. Accordingly, this study examines the impact of poor maternal mental health and socioeconomic context during the perinatal period on network connectivity in middle childhood using an anatomically weighted functional connectivity (awFC) approach. awFC is a statistical model that identifies neural networks by incorporating information from both structural and functional imaging data., Methods: Resting-state fMRI and DTI scans were acquired from children aged 7-9 years old., Results: Our results indicate that maternal adversity during the perinatal period can affect offspring's resting-state network connectivity during middle childhood. Specifically, in comparison to controls, children of mothers who had poor perinatal maternal mental health and/or low socioeconomic status exhibited greater awFC in the ventral attention network., Discussion: These group differences were discussed in terms of the role this network plays in attention processing and maturational changes that may accompany the consolidation of a more adult-like functional cortical organization. Furthermore, our results suggest that there is value in using an awFC approach as it may be more sensitive in highlighting connectivity differences in developmental networks associated with higher-order cognitive and emotional processing, as compared to stand-alone FC or SC analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ayyash, Sunderji, Gallant, Hall, Davis, Pokhvisneva, Meaney, Silveira, Sassi and Hall.)

AbstractCounterillumination is a camouflage strategy employed primarily by mesopelagic fishes, sharks, crustaceans, and squid, which use ventral bioluminescence to obscure their silhouettes when viewed from below. Although certain counterilluminating species have been shown to control the intensity of their ventral emissions to match the background downwelling light, the feedback mechanism mediating this ability is poorly understood. One proposed mechanism involves the presence and use of eye-facing photophores that would allow simultaneous detection and comparison of photophore emissions and downwelling solar light. Eye-facing photophores have been found in at least 34 species of counterilluminating stomiiform fishes and the myctophid Tarletonbeania crenularis . Here, we examined nine phylogenetically spaced myctophid species for eye-facing photophores to assess whether this mechanism is as prevalent in this group as it is in the Stomiiformes. First, microcomputed tomography imaging data were collected for each species, and three-dimensional reconstructions of the fishes were developed to identify potential eye-facing photophores. The fishes were then dissected under a stereomicroscope to confirm the presence of all identified photophores, probe for any photophores missed in the reconstruction analysis, and determine the orientation of the photophores' emissions. Although photophores were identified near the orbits of all species examined, none of the fishes' photophores directed light into their orbits, suggesting that myctophids may regulate bioluminescence through an alternative mechanism.

Background: Providing patients with access to health information that can be obtained outside of an office visit is an important part of education, yet little is known about the effectiveness of outreach modalities to connect older adults to online educational tools. The objective was to identify the effectiveness and cost of outreach modalities providing online information about advance care planning (ACP) for older adults., Methods: Six different outreach modalities were utilized to connect patients to online educational tools (ACP video decision aids). Participants were 13,582 patients aged 65 and older of 185 primary care providers with appointments over a 30-month period within a large health system in the greater New York City area. Main outcome measures were number of online video views and costs per outreach for each modality., Key Results: There were 1150 video views for 21,407 remote outreach events. Text messages, sent to the largest volume of patients (8869), had the highest outcome rate (9.6%) and were the most economical ($0.09). Characterization of phone calls demonstrated 21.7% engagement in the topic of ACP but resulted in minimal video views (<1%) and incurred the highest cost per outreach ($2.88). In-office handouts had negligible results (<1%)., Conclusions: Text was the most cost-effective modality to connect older adults to an online educational tool in this pragmatic trial, though overall efficacy of all modalities was low., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Recently published single-cell sequencing data from individual human sperm ( n =41,189; 969-3377 cells from each of 25 donors) offer an opportunity to investigate questions of inheritance with improved statistical power, but require new methods tailored to these extremely low-coverage data (∼0.01× per cell). To this end, we developed a method, named rhapsodi, that leverages sparse gamete genotype data to phase the diploid genomes of the donor individuals, impute missing gamete genotypes, and discover meiotic recombination breakpoints, benchmarking its performance across a wide range of study designs. We then applied rhapsodi to the sperm sequencing data to investigate adherence to Mendel's Law of Segregation, which states that the offspring of a diploid, heterozygous parent will inherit either allele with equal probability. While the vast majority of loci adhere to this rule, research in model and non-model organisms has uncovered numerous exceptions whereby 'selfish' alleles are disproportionately transmitted to the next generation. Evidence of such 'transmission distortion' (TD) in humans remains equivocal in part because scans of human pedigrees have been under-powered to detect small effects. After applying rhapsodi to the sperm data and scanning for evidence of TD, our results exhibited close concordance with binomial expectations under balanced transmission. Together, our work demonstrates that rhapsodi can facilitate novel uses of inferred genotype data and meiotic recombination events, while offering a powerful quantitative framework for testing for TD in other cohorts and study systems., Competing Interests: SC, KW, AB, HP, DA, RM No competing interests declared, AB is an inventor on a US Patent Application (US20210230667A1, applicant: President and Fellows of Harvard College) relating to the Sperm-seq single-cell sequencing method. Was an occasional consultant for Ohana Biosciences between October 2019 and March 2020, (© 2022, Carioscia, Weaver et al.)

Background: Health anxiety (HA) is associated with increased risk of disability, increased health care utilization and reduced quality of life. However, there is no consensus on which factors are important for the level of HA. The aim of this study was to explore the distribution of HA in a general adult population and to investigate whether demographic and social factors were associated with HA., Methods: This study used cross-sectional data from the seventh Tromsø study. A total of 18 064 participants aged 40 years or older were included in the analysis. The six-item Whiteley Index (WI-6) with a 5-point Likert scale was used to measure HA. Sociodemographic factors included age, sex, education, household income, quality of friendship and participation in an organized activity., Results: HA showed an exponential distribution among the participants with a median score of 2 points out of 24 points. In total, 75% had a total score of 5 points or less, whereas 1% had a score >14 points. Education, household income, quality of friendship and participation in organized activity were significantly associated with HA. The variable quality of friendship demonstrated the strongest association with HA., Conclusion: Our study showed an exponential distribution of HA in a general adult population. There was no evident cut-off point to distinguish participants with severe HA based on their WI-6 score, indicating the importance of analysing HA as a complex, continuous construct. HA demonstrated strong associations with quality of friendship and participation in an organized activity.

Host association-the selective adaptation of pathogens to specific host species-evolves through constant interactions between host and pathogens, leaving a lot yet to be discovered on immunological mechanisms and genomic determinants. The causative agents of Lyme disease (LD) are spirochete bacteria composed of multiple species of the Borrelia burgdorferi sensu lato complex, including B. burgdorferi ( Bb ), the main LD pathogen in North America-a useful model for the study of mechanisms underlying host-pathogen association. Host adaptation requires pathogens' ability to evade host immune responses, such as complement, the first-line innate immune defense mechanism. We tested the hypothesis that different host-adapted phenotypes among Bb strains are linked to polymorphic loci that confer complement evasion traits in a host-specific manner. We first examined the survivability of 20 Bb strains in sera in vitro and/or bloodstream and tissues in vivo from rodent and avian LD models. Three groups of complement-dependent host-association phenotypes emerged. We analyzed complement-evasion genes, identified a priori among all strains and sequenced and compared genomes for individual strains representing each phenotype. The evolutionary history of ospC loci is correlated with host-specific complement-evasion phenotypes, while comparative genomics suggests that several gene families and loci are potentially involved in host association. This multidisciplinary work provides novel insights into the functional evolution of host-adapted phenotypes, building a foundation for further investigation of the immunological and genomic determinants of host association. IMPORTANCE Host association is the phenotype that is commonly found in many pathogens that preferential survive in particular hosts. The Lyme disease (LD)-causing agent, B. burgdorferi ( Bb ), is an ideal model to study host association, as Bb is mainly maintained in nature through rodent and avian hosts. A widespread yet untested concept posits that host association in Bb strains is linked to Bb functional genetic variation conferring evasion to complement, an innate defense mechanism in vertebrate sera. Here, we tested this concept by grouping 20 Bb strains into three complement-dependent host-association phenotypes based on their survivability in sera and/or bloodstream and distal tissues in rodent and avian LD models. Phylogenomic analysis of these strains further correlated several gene families and loci, including ospC , with host-specific complement-evasion phenotypes. Such multifaceted studies thus pave the road to further identify the determinants of host association, providing mechanistic insights into host-pathogen interaction.

Introduction: Despite the known benefit to patients and families, discussions about goals, values and preferences for medical care in advancing serious illness often do not occur. Many system and clinician factors, such as patient and clinician reticence and shortage of specialty palliative care teams, contribute to this lack of communication. To address this gap, we designed an intervention to promote goals-of-care conversations and palliative care referrals in the hospital setting by using trained palliative care educators and video decision aids. This paper presents the rationale, design and methods for a trial aimed at addressing barriers to goals-of-care conversations for hospitalised adults aged 65 and older and those with Alzheimer's disease and related Dementias, regardless of age., Methods and Analysis: The Video Image about Decisions to Improve Ethical Outcomes with Palliative Care Educators is a pragmatic stepped wedge, cluster randomised controlled trial, which aims to improve and extend goals-of-care conversations in the hospital setting with palliative care educators trained in serious illness communication and video decision aids. The primary outcome is the proportion of patients with goals-of-care documentation in the electronic health record. We estimate that over 9000 patients will be included., Ethics and Dissemination: The Institutional Review Board (IRB) at Boston Medical Center will serve as the single IRB of record for all regulatory and ethical aspects of this trial. BMC Protocol Number: H-41482. Findings will be presented at national meetings and in publications. This trial is registered at ClinicalTrials.gov., Trial Registration Number: NCT04857060; ClinicalTrials.gov., Competing Interests: Competing interests: Dr. Angelo Volandes has a financial interest in ACP Decisions, a non-profit organisation developing advance care planning video decision support tools. Dr. Volandes’ interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict-of-interest policies. Aretha Delight Davis is an employee of ACPD and the spouse of Angelo Volandes. No other disclosures to report., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health anxiety (HA) is defined as a worry of disease. An association between HA and mental illness has been reported, but few have looked at the association between HA and physical disease., Objective: To examine the association between HA and number of diseases, different disease categories and cardiovascular risk factors in a large sample of the general population., Methods: This study used cross-sectional data from 18,432 participants aged 40 years or older in the seventh survey of the Tromsø study. HA was measured using a revised version of the Whiteley Index-6 (WI-6-R). Participants reported previous and current status regarding a variety of different diseases. We performed exponential regression analyses looking at the independent variables 1) number of diseases, 2) disease category (cancer, cardiovascular disease, diabetes or kidney disease, respiratory disease, rheumatism, and migraine), and 3) cardiovascular risk factors (high blood pressure or use of cholesterol- or blood pressure lowering medication)., Results: Compared to the healthy reference group, number of diseases, different disease categories, and cardiovascular risk factors were consistently associated with higher HA scores. Most previous diseases were also significantly associated with increased HA score. People with current cancer, cardiovascular disease, and diabetes or kidney disease had the highest HA scores, being 109, 50, and 60% higher than the reference group, respectively., Conclusion: In our general adult population, we found consistent associations between HA, as a continuous measure, and physical disease, all disease categories measured and cardiovascular risk factors., (© 2022. The Author(s).)

Background: Understanding the impact of maternal health behaviours and social conditions on childhood nutrition is important to inform strategies to promote health during childhood. Objective: To describe how maternal health sociodemographic factors (e.g., socioeconomic status, education), health behaviours (e.g., diet), and traditional health care use during pregnancy impact infant diet at age 1-year. Methods: Data were collected from the Indigenous Birth Cohort (ABC) study, a prospective birth cohort formed in partnership with an Indigenous community-based Birthing Centre in southwestern Ontario, Canada. 110 mother-infant dyads are included in the study and were enrolled between 2012 and 2017. Multiple linear regression analyses were performed to understand factors associated with infant diet scores at age 1-year, with a higher score indicating a diet with more healthy foods. Results: The mean age of women enrolled during pregnancy was 27.3 (5.9) years. Eighty percent of mothers had low or moderate social disadvantage, 47.3% completed more than high school education, and 70% were cared for by a midwife during their pregnancy. The pre-pregnancy body mass index (BMI) was <25 in 34.5% of women, 15.5% of mothers smoked during pregnancy, and 14.5% of mothers had gestational diabetes. Being cared for by an Indigenous midwife was associated with a 0.9-point higher infant diet score (p = 0.001) at age 1-year, and lower maternal social disadvantage was associated with a 0.17-point higher infant diet quality score (p = 0.04). Conclusion: This study highlights the positive impact of health care provision by Indigenous midwives and confirms that higher maternal social advantage has a positive impact on child nutrition.

Introduction: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes., Methods and Analysis: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites., Ethics and Dissemination: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results., Trial Registration Number: NCT04347629., Competing Interests: Competing interests: NE is a scientific advisor for Somatus and Davita. MKT has received honoraria from the American Federation of Aging Research and serves as Associate Editor at CJASN. Views expressed are those of the authors and not necessarily those of the Department of Veterans Affairs. AV has a financial interest in ACP decisions, a non-profit organisation developing advance care planning video decision support tools. AV’s interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict-of-interest policies. No other disclosures to report., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. So far, findings are variable and large sample replications scarce. We aimed to replicate and extend altered functional connectivity associated with MDD and pharmacotherapy outcomes in a large, multisite sample. Resting-state fMRI data were collected from 129 patients and 99 controls through the Canadian Biomarker Integration Network in Depression. Symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Connectivity was measured as correlations between four seeds (anterior and posterior cingulate cortex, insula and dorsolateral prefrontal cortex) and all other brain voxels. Partial least squares was used to compare connectivity prior to treatment between patients and controls, and between patients reaching remission (MADRS ≤ 10) early (within 8 weeks), late (within 16 weeks), or not at all. We replicated previous findings of altered connectivity in patients. In addition, baseline connectivity of the anterior/posterior cingulate and insula seeds differentiated patients with different treatment outcomes. The stability of these differences was established in the largest single-site subsample. Our replication and extension of altered connectivity highlighted previously reported and new differences between patients and controls, and revealed features that might predict remission prior to pharmacotherapy. Trial registration:ClinicalTrials.gov: NCT01655706., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clinically oriented studies commonly acquire diffusion MRI (dMRI) data with a single non-zero b -value (i.e. single-shell) and diffusion weighting of b = 1000 s mm -2 . To produce microstructural parameter maps, the tensor model is usually used, despite known limitations. Although compartment models have demonstrated improved fits in multi-shell dMRI data, they are rarely used for single-shell parameter maps, where their effectiveness is unclear from the literature. Here, various compartment models combining isotropic balls and symmetric tensors were fitted to single-shell dMRI data to investigate model fitting optimization and extract the most information possible. Full testing was performed in 5 subjects, and 3 subjects with multi-shell data were included for comparison. The results were tested and confirmed in a further 50 subjects. The Markov chain Monte Carlo (MCMC) model fitting technique outperformed non-linear least squares. Using MCMC, the 2-fibre-orientation mono-exponential ball and stick model (BSME2) provided artifact-free, stable results, in little processing time. The analogous ball and zeppelin model (BZ2) also produced stable, low-noise parameter maps, though it required much greater computing resources (50 000 burn-in steps). In single-shell data, the gamma-distributed diffusivity ball and stick model (BSGD2) underperformed relative to other models, despite being an often-used software default. It produced artifacts in the diffusivity maps even with extremely long processing times. Neither increased diffusion weighting nor a greater number of gradient orientations improvedBSGD2fits. In white matter (WM), the tensor produced the best fit as measured by Bayesian information criterion. This result contrasts with studies using multi-shell data. However, in crossing fibre regions the tensor confounded geometric effects with fractional anisotropy (FA): the planar/linear WM FA ratio was 49%, whileBZ2andBSME2retained 76% and 83% of restricted fraction, respectively. As a result, theBZ2andBSME2models are strong candidates to optimize information extraction from single-shell dMRI studies., (© 2022 Institute of Physics and Engineering in Medicine.)

Predicting pathogen emergence and spillover risk requires understanding the determinants of a pathogens' host range and the traits involved in host competence. While host competence is often considered a fixed species-specific trait, it may be variable if pathogens diversify across hosts. Balancing selection can lead to maintenance of pathogen polymorphisms (multiple-niche-polymorphism; MNP). The causative agent of Lyme disease, Borrelia burgdorferi ( Bb ), provides a model to study the evolution of host adaptation, as some Bb strains defined by their outer surface protein C ( ospC ) genotype, are widespread in white-footed mice and others are associated with non-rodent vertebrates (e.g. birds). To identify the mechanisms underlying potential strain × host adaptation, we infected American robins and white-footed mice, with three Bb strains of different ospC genotypes. Bb burdens varied by strain in a host-dependent fashion, and strain persistence in hosts largely corresponded to Bb survival at early infection stages and with transmission to larvae (i.e. fitness). Early survival phenotypes are associated with cell adhesion, complement evasion and/or inflammatory and antibody-mediated removal of Bb, suggesting directional selective pressure for host adaptation and the potential role of MNP in maintaining OspC diversity. Our findings will guide future investigations to inform eco-evolutionary models of host adaptation for microparasites.

Background: Healthcare use is increasing, and health anxiety (HA) is recognized as an important associated factor. Previous research on the association between HA and healthcare use has mostly explored HA as a dichotomous construct, which contrasts the understanding of HA as a continuous construct, and compared healthcare use to non-use. There is a need for studies that examine the association between healthcare use and the continuum of HA in a general population., Aim: To explore the association between HA and primary, somatic specialist and mental specialist healthcare use and any differences in the association by level of healthcare use., Methods: This study used cross-sectional data from the seventh Tromsø study. Eighteen thousand nine hundred sixty-seven participants aged 40 years or older self-reported their primary, somatic specialist and mental specialist healthcare use over the past 12 months. Each health service was categorized into 5 groups according to the level of use. The Whiteley Index-6 (WI-6) was used to measure HA on a 5-point Likert scale, with a total score range of 0-24. Analyses were conducted using unconstrained continuation-ratio logistic regression, in which each level of healthcare use was compared with all lower levels. Morbidity, demographics and social variables were included as confounders., Results: HA was positively associated with increased utilization of primary, somatic specialist and mental specialist healthcare. Adjusting for confounders, including physical and mental morbidity, did not alter the significant association. For primary and somatic specialist healthcare, each one-point increase in WI-6 score yielded a progressively increased odds ratio (OR) of a higher level of use compared to all lower levels. The ORs ranged from 1.06 to 1.15 and 1.05 to 1.14 for primary and somatic specialist healthcare, respectively. For mental specialist healthcare use, the OR was more constant across levels of use, ranging between 1.06 and 1.08., Conclusions: In an adult general population, HA, as a continuous construct, was significantly and positively associated with primary, somatic specialist and mental healthcare use. A small increase in HA was associated with progressively increased healthcare use across the three health services, indicating that the impact of HA is more prominent with higher healthcare use., (© 2022. The Author(s).)

Importance: COVID-19 has disproportionately killed older adults and racial and ethnic minority individuals, raising questions about the relevance of advance care planning (ACP) in this population. Video decision aids and communication skills training offer scalable delivery models., Objective: To assess whether ACP video decision aids and a clinician communication intervention improved the rate of ACP documentation during an evolving pandemic, with a focus on African American and Hispanic patients., Design, Setting, and Participants: The Advance Care Planning: Communicating With Outpatients for Vital Informed Decisions trial was a pre-post, open-cohort nonrandomized controlled trial that compared ACP documentation across the baseline pre-COVID-19 period (September 15, 2019, to March 14, 2020), the COVID-19 wave 1 period (March 15, 2020, to September 14, 2020), and an intervention period (December 15, 2020, to June 14, 2021) at a New York metropolitan area ambulatory network of 22 clinics. All patients 65 years or older who had at least 1 clinic or telehealth visit during any of the 3 study periods were included., Main Outcomes and Measures: The primary outcome was ACP documentation., Results: A total of 14 107 patients (mean [SD] age, 81.0 [8.4] years; 8856 [62.8%] female; and 2248 [15.9%] African American or Hispanic) interacted with clinicians during the pre-COVID-19 period; 12 806 (mean [SD] age, 81.2 [8.5] years; 8047 [62.8%] female; and 1992 [15.6%] African American or Hispanic), during wave 1; and 15 106 (mean [SD] 80.9 [8.3] years; 9543 [63.2%] female; and 2535 [16.8%] African American or Hispanic), during the intervention period. Clinicians documented ACP in 3587 patients (23.8%) during the intervention period compared with 2525 (17.9%) during the pre-COVID-19 period (rate difference [RD], 5.8%; 95% CI, 0.9%-7.9%; P = .01) and 1598 (12.5%) during wave 1 (RD, 11.3%; 95% CI, 6.3%-12.1%; P < .001). Advance care planning was documented in 447 African American patients (30.0%) during the intervention period compared with 233 (18.1%) during the pre-COVID-19 period (RD, 11.9%; 95% CI, 4.1%-15.9%; P < .001) and 130 (11.0%) during wave 1 (RD, 19.1%; 95% CI, 11.7%-21.2%; P < .001). Advance care planning was documented for 222 Hispanic patients (21.2%) during the intervention period compared with 127 (13.2%) during the pre-COVID-19 period (RD, 8.0%; 95% CI, 2.1%-10.9%; P = .004) and 82 (10.2%) during wave 1 (RD, 11.1%; 95% CI, 5.5%-14.5%; P < .001)., Conclusions and Relevance: This intervention, implemented during the evolving COVID-19 pandemic, was associated with higher rates of ACP documentation, especially for African American and Hispanic patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04660422.

Many previous intervention studies have used functional magnetic resonance imaging (fMRI) data to predict the antidepressant response of patients with major depressive disorder (MDD); however, practical constraints have limited many of those attempts to small, single centre studies which may not adequately reflect how these models will generalize when used in clinical practice. Not only does the act of collecting data at multiple sites generally increase sample sizes (a critical point in machine learning development) it also generates a more heterogeneous dataset due to systematic differences in scanners at different sites, and geographical differences in patient populations. As part of the Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study, 144 MDD patients from six sites underwent resting state fMRI prior to starting escitalopram treatment, and again two weeks after the start. Here, we consider ways to use machine learning techniques to produce models that can predict response (measured at eight weeks after initiation), based on various parcellations, functional connectivity (FC) metrics, dimensionality reduction algorithms, and base learners, and also whether to use scans from one or both time points. Models that use only baseline (pre-treatment) or only week 2 (early-response) whole-brain FC features consistently failed to perform significantly better than default models. Utilizing the change in FC between these two time points, however, yielded significant results, with the best performing analytical pipeline achieving 69.6% (SD 10.8) accuracy. These results appear contrary to findings from many smaller single-site studies, which report substantially higher predictive accuracies from models trained on only baseline resting state FC features, suggesting these models may not generalize well beyond data used for development. Further, these results indicate the potential value of collecting data both before and shortly after treatment initiation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)