Search

Indigenous Peoples in Canada face healthcare inequities impacting access to solid organ transplantation. The experiences of Indigenous patients during the liver transplant process, and how transplant professionals perceive challenges faced by Indigenous Peoples, has not been studied. Thirteen semi-structured qualitative interviews were conducted via telehealth with Indigenous liver transplant patients ( n  = 7) and transplant care providers ( n  = 6) across British Columbia, Canada between April 2021-May 2022. Themes were identified to inform clinical approaches and transplant care planning and validated by Indigenous health experts. Among patient participants: transplants occurred between 1992-2020; all were women; and the mean age at the time of interview was 60 years. Among transplant care provider participants: roles included nursing, social work, and surgery; 83% were women; and the median number of years in transplant care was ten. Three broad themes were identified: Indigenous strengths and resources, systemic and structural barriers, and inconsistent care and cultural safety across health professions impact Indigenous patient care during liver transplantation. This study contributes insights into systemic barriers and Indigenous resilience in the liver transplant journey. Dismantling structural barriers to early linkage to care is needed, and training for transplant clinicians on Indigenous histories, cultural protocols, and cultural safety is strongly recommended.

Phenomenon: Marginalized individuals in medicine face many structural inequities which can have enduring consequences on their progress. Therefore, inequity must be addressed by dismantling underlying unjust policies, environments, and curricula. However, once these injustices have been taken apart, how do we build more just systems from the rubble? Many current strategies to address this question have foundational values of urgency, solutionism, and top-down leadership., Approach: This paper explores a counternarrative: Design Justice. As a set of guiding principles, Design Justice centers the experiences and perspectives of marginalized individuals and communities. These principles include mutual accountability and transparency, co-ownership, and community-led outcomes, and honoring local, traditional, Indigenous knowledge., Findings: Rooted in critical scholarship and critical design, Design Justice recognizes the interconnectedness of various forms of marginalization and works to critically examine power dynamics that exist in every design process. These co-created principles act as practical guardrails, directing progress toward justice., Insights: This paper begins with an overview of Design Justice's history in critical scholarship and critical design, providing foundational background knowledge for medical educators, scholars, and leaders in key concepts of justice and design. We explore how the Design Justice principles were developed and have been applied across sectors, highlighting its applications, including education applications. Finally, we raise critical questions about medical education prompted by Design Justice.

In this preliminary study, we explored the relationship between auditory imagery ability and the maintenance of tonal and temporal accuracy when singing and audiating with altered auditory feedback (AAF). Actively performing participants sang and audiated (sang mentally but not aloud) a self-selected piece in AAF conditions, including upward pitch-shifts and delayed auditory feedback (DAF), and with speech distraction. Participants with higher self-reported scores on the Bucknell Auditory Imagery Scale (BAIS) produced a tonal reference that was less disrupted by pitch shifts and speech distraction than musicians with lower scores. However, there was no observed effect of BAIS score on temporal deviation when singing with DAF. Auditory imagery ability was not related to the experience of having studied music theory formally, but was significantly related to the experience of performing. The significant effect of auditory imagery ability on tonal reference deviation remained even after partialling out the effect of experience of performing. The results indicate that auditory imagery ability plays a key role in maintaining an internal tonal center during singing but has at most a weak effect on temporal consistency. In this article, we outline future directions in understanding the multifaceted role of auditory imagery ability in singers' accuracy and expression., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches., Methods: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity., Findings: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I 2 =61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I 2 =59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I 2 =68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes., Interpretation: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines., Funding: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre., Competing Interests: Declaration of interests J-PD-C received research grants and consulting fees from the Dairy Farmers of Canada, research grants from The Weston Family Foundation, and travel support from the International Dairy Federation in the past 5 years, unrelated to the submitted work. SS-M received research funding (2019 and 2023 unrestricted grants) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation, and funds from Nutrimedes (Affligem, Belgium)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aesthetic preference is intricately linked to learning and creativity. Previous studies have largely examined the perception of novelty in terms of pleasantness and the generation of novelty via creativity separately. The current study examines the connection between perception and generation of novelty in music; specifically, we investigated how pleasantness judgements and brain responses to musical notes of varying probability (estimated by a computational model of auditory expectation) are linked to learning and creativity. To facilitate learning de novo, 40 non-musicians were trained on an unfamiliar artificial music grammar. After learning, participants evaluated the pleasantness of the final notes of melodies, which varied in probability, while their EEG was recorded. They also composed their own musical pieces using the learned grammar which were subsequently assessed by experts. As expected, there was an inverted U-shaped relationship between liking and probability: participants were more likely to rate the notes with intermediate probabilities as pleasant. Further, intermediate probability notes elicited larger N100 and P200 at posterior and frontal sites, respectively, associated with prediction error processing. Crucially, individuals who produced less creative compositions preferred higher probability notes, whereas individuals who composed more creative pieces preferred notes with intermediate probability. Finally, evoked brain responses to note probability were relatively independent of learning and creativity, suggesting that these higher-level processes are not mediated by brain responses related to performance monitoring. Overall, our findings shed light on the relationship between perception and generation of novelty, offering new insights into aesthetic preference and its neural correlates., (© 2024. The Author(s).)

This article describes a national sample of 989 current mental health clients' views regarding whether and how their mental health care providers integrated the client's religion/spirituality (RS) into treatment. Within the online Qualtrics survey, two open-ended items asked respondents what (if anything) the client perceived their therapist having done regarding the client's RS that was (1) helpful/supportive or (2) hurtful/harmful. Participants also reported various ways therapists included the topic of RS in practice, if any. Nearly half freely described helpful ways their providers integrated the client's RS, and half indicated it was not discussed or applicable. Although 9.6% described hurtful experiences, most indicated their provider had not done anything harmful related to integrating RS. Implications for practice and training across mental health disciplines are discussed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Music is a non-verbal human language, built on logical, hierarchical structures, that offers excellent opportunities to explore how the brain processes complex spatiotemporal auditory sequences. Using the high temporal resolution of magnetoencephalography, we investigated the unfolding brain dynamics of 70 participants during the recognition of previously memorized musical sequences compared to novel sequences matched in terms of entropy and information content. Measures of both whole-brain activity and functional connectivity revealed a widespread brain network underlying the recognition of the memorized auditory sequences, which comprised primary auditory cortex, superior temporal gyrus, insula, frontal operculum, cingulate gyrus, orbitofrontal cortex, basal ganglia, thalamus, and hippocampus. Furthermore, while the auditory cortex responded mainly to the first tones of the sequences, the activity of higher-order brain areas such as the cingulate gyrus, frontal operculum, hippocampus, and orbitofrontal cortex largely increased over time during the recognition of the memorized versus novel musical sequences. In conclusion, using a wide range of analytical techniques spanning from decoding to functional connectivity and building on previous works, our study provided new insights into the spatiotemporal whole-brain mechanisms for conscious recognition of auditory sequences., (© The Author(s) 2024. Published by Oxford University Press.)

In the past century, the history of popular music has been analyzed from many different perspectives, with sociologists, musicologists and philosophers all offering distinct narratives characterizing the evolution of popular music. However, quantitative studies on this subject began only in the last decade and focused on features extracted from raw audio, which limits the scope to low-level components of music. The present study investigates the evolution of a more abstract dimension of popular music, specifically melody, using a new dataset of popular melodies spanning from 1950 to 2023. To identify "melodic revolutions", changepoint detection was applied to a multivariate time series comprising features related to the pitch and rhythmic structure of the melodies. Two major revolutions in 1975 and 2000 and one smaller revolution in 1996, characterized by significant decreases in complexity, were located. The revolutions divided the time series into three eras, which were modeled separately with autoregression, linear regression and vector autoregression. Linear regression of autoregression residuals underscored inter-feature relationships, which become stronger in post-2000 melodies. The overriding pattern emerging from these analyses shows decreasing complexity and increasing note density in popular melodies over time, especially since 2000., (© 2024. The Author(s).)

Aims: This review aims to identify the evidence base for the consequences of over and undertreatment of type 2 diabetes mellitus in a frail population., Method: In this systematic review, we searched MEDLINE, Embase, PubMed, CINAHL and the Cochrane Library for studies from January 2001 to 15th August 2022. We included a variety of study types that assessed and reported frailty including patients ≥18 years old. Studies included those that reported the prevalence of over or undertreatment of diabetes mellitus in a frail population and those examining outcomes related to glucose control in frail older people living with diabetes. Data were extracted using a bespoke extraction table using a narrative synthesis approach., Results: A total of 4114 articles were identified with 112 meeting inclusion criteria. These included 15,130 participants across the 11 studies with sample sizes ranging from 101 to 11,140. Several areas were identified in the included studies where under or overtreatment of diabetes impacted outcomes for patients. These included hospital admissions, readmissions, length of stay, falls, mortality, cognitive impairment and cardiovascular disease outcomes., Conclusion: The results showed that there was a high heterogeneity of outcomes between the studies and that many examined small numbers of participants. In this review, both over and undertreatment were shown to increase adverse outcomes in frail older people. Further research around optimal glycaemic control for frail older people living with diabetes is required with the aim to identify ideal target ranges and produce practical clinical guidelines to promote attainment of these., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Home parenteral nutrition (HPN) refers to the intravenous administration of macronutrients, micronutrients and fluid. The aims of treatment are to increase survival and improve quality of life (QoL). However, patients struggle with physiological symptoms, time-consuming invasive therapy and an increased occurrence of depression and social isolation. Our aim is to understand how HPN impacts the QoL of patients, and the contribution played by the complications of treatment, for example, liver disease., Methods and Analysis: A multicentre, longitudinal, observational study will be conducted using routinely collected clinical data. Participants will also be asked to complete three QoL questionnaires (EuroQol-5 Dimensions, Short Form 36 and HPN-QoL) at baseline and 12 months. The primary outcome is mean change in QoL scores over 12 months. Secondary outcomes include how factors including liver function, gut microbiota, number of infusions of PN per week, nutritional composition of PN and nutritional status impact on QoL scores., Ethics and Dissemination: Ethical approval was obtained from HRA and Health and Care Research Wales Research Ethics Committee (21/SC/0316). The study was eligible for portfolio adoption, Central Portfolio Management System ID 50506. Results will be disseminated through peer-reviewed scientific journals and presented at national and international meetings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

G-protein-coupled receptors (GPCRs) are the largest and most versatile cell surface receptor family with a broad repertoire of ligands and functions. We've learned an enormous amount about discovering drugs of this receptor class since the first GPCR was cloned and expressed in 1986, such that it's now well-recognized that GPCRs are the most successful target class for approved drugs. Here we take the reader through a GPCR drug discovery journey from target to the clinic, highlighting the key learnings, best practices, challenges, trends and insights on discovering drugs that ultimately modulate GPCR function therapeutically in patients. The future of GPCR drug discovery is inspiring, with more desirable drug mechanisms and new technologies enabling the delivery of better and more successful drugs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John Unitt reports a relationship with Sygnature Discovery Ltd that includes: employment and equity or stocks. All authors are employees of Sygnature Discovery Ltd., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A large body of evidence indicates that spiritual and religious backgrounds, beliefs, and practices (SRBBPs) are related to better psychological health. Spirituality and religion (R/S) are also important aspects of multicultural diversity. There is evidence that clients would like to talk about their spirituality, and that including it in assessment and treatment planning can be beneficial. However, the extent to which practicing mental health professionals view SRBBPs as relevant to mental health and clinical practice is unclear., Methods: A survey examining several aspects of addressing SRBBPs in clinical practice was distributed to 894 professionals across mental health disciplines, including psychiatry, psychology, social work, marriage family therapy, licensed professional counselors, certified chemical dependency counselors, and psychiatric mental health nurses., Results: 89% of mental health professionals agreed that clinicians should receive training in R/S competencies. There were no differences between mental health disciplines in ratings of importance of such training. Younger individuals and those who identify as more spiritual were more likely to consider R/S training as important. Although 47.1% of professionals had not received much R/S training, many perceived themselves to be highly competent in R/S clinical integration practices (57.8% considered themselves able to display them very much or completely). In addition, respondents with more R/S training evaluated themselves as more proficient in R/S clinical integration. Nearly two-thirds (65.2%) of respondents reported encountering few to no barriers to engaging in R/S competent mental health care., Conclusions: There is a growing consensus among mental health care professionals that mental health professionals should be trained in R/S competencies. Strong agreement exists that basic R/S competencies include respect, empathy, examination of bias, and routine assessment of R/S in mental health care. Four in five of those surveyed agree that more active competencies, such as identifying and addressing religious and spiritual struggles and problems and helping clients explore and access R/S strengths and resources should be included, whereas one in five report less comfort with these competencies., (© 2023. The Author(s).)

Objectives: Given the predicted rise in dementia prevalence around the world, targeting modifiable risk factors (often lifestyle related) is a priority. This work sought to understand the role of physical inactivity (PI) as a modifiable risk factor for dementia., Study Design: Ecological study using globally available ecological data (both 2010 and 2016) from 192 countries., Methods: Age-standardised PI prevalence and dementia prevalence data were accessed from the World Health Organisation (WHO) and the Global Burden of Disease Study. Linear regression was used to assess the relationship between PI and dementia, with stratified analyses used to further explore the impact of sex, WHO region, and World Bank income group on the relationship., Results: Linear regression showed a positive association between inactivity and dementia prevalence in 2010 (b = 1.38 [95% confidence interval {CI}: 0.04, 2.71] P = 0.044) and 2016 (coefficient = 2.52 [95% CI: 1.07, 3.96] P = 0.0007). Sub-group analyses of sex-specific data showed the strength of the relationship was stronger in men than in women. Rates of both dementia and inactivity rose with increasing world income group., Conclusions: This analysis of global data indicates the presence of a positive relationship between prevalence of PI and dementia prevalence, which has increased in strength with time, and is stronger in men than in women. This highlights the importance of public health interventions on a global scale to reduce the percentage of the population failing to reach or exceed the recommended physical activity guidelines., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Australian producers have long used macrocyclic lactones (MLs) to successfully control cattle gastrointestinal nematodes (GINs) and consequently improve production parameters. However, the trajectory of ML resistance development in cattle GINs is following that of small ruminant nematode populations, highlighting a need for novel treatment options to provide efficacy in the current environment and interrupt the long-term establishment of ML-resistant GIN populations in Australian cattle. Here, we describe three field studies conducted in Australia to evaluate the efficacy of a single administration of a novel fixed-dose combination injectable (FDCI) endectocide against naturally acquired infections of cattle GINs. The FDCI is administered subcutaneously to deliver 0.2 mg/kg doramectin and 6 mg/kg levamisole hydrochloride (HCl). Study sites consisted of three farms in New South Wales (n = 2) and Victoria (n = 1). At each site, cattle were randomly allocated into one of three treatment groups: (1) untreated control (saline), (2) FDCI (0.2 mg/kg doramectin, 6 mg/kg levamisole HCl) or (3) positive control (0.2 mg/kg ivermectin). All treatments were administered on Day 0. Fecal samples were collected prior to treatment on Days -1 (Study 3) or 0 (Studies 1 and 2) and again on Day 14 (post-treatment) to evaluate efficacy via fecal egg count (FEC) and for coproculture. Adequacy of infection was confirmed at all three study sites, with Day 14 geometric mean (GM) FECs for saline-treated cattle ranging from 32.5 eggs per gram (EPG) to 623.7 EPG. FECs for FDCI-treated cattle were significantly reduced compared to saline-treated cattle (p ≤ 0.0001) on Day 14, with GM-based efficacy ≥ 99.7% at all three study sites. In contrast, ivermectin was 97.4% effective against cattle GINs in Study 1 but was only 47.2% and 39.8% effective at study site 2 and 3, respectively. Genus-specific efficacies suggest the presence of ivermectin-resistant Cooperia spp. (Study 1), Haemonchus spp. (Study 2) and Ostertagia spp. (Study 3) populations in the naturally infected cattle used in these studies. The post-treatment FEC and genus-specific efficacy estimations indicate the doramectin + levamisole HCl FDCI was highly efficacious against cattle GINs even in the face of ivermectin LOE at study sites 2 and 3. The efficacy of the new FDCI against both ML-susceptible and ML-resistant economically important cattle GINs in Australia affirms it is a valuable treatment option for producers operating in an environment of ML loss of efficacy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew A. DeRosa reports a relationship with Zoetis Inc that includes: employment. Raj Packianathan reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Hodge reports a relationship with Zoetis Australia Pty Limited that includes: employment. Jacqueline Wright reports a relationship with Zoetis Australia Pty Limited that includes: employment. Michael Pearce reports a relationship with Zoetis Australia Pty Limited that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

We describe a new fixed-dose combination injectable (FDCI) formulated with doramectin and levamisole hydrochloride (HCl) to target broad and overlapping spectra of gastrointestinal nematodes (GINs) through two distinct modes of action. Here, we demonstrate the superior efficacy of the FDCI against mixed populations of cattle GINs in two dose confirmation studies conducted in Australia using artificially induced adult (Study 1) and immature (Study 2) GIN infections. Artificial infections consisted of Cooperia spp., Haemonchus placei, Ostertagia ostertagi, and Trichostrongylus axei. In both studies, cattle were inoculated with third-stage larvae and infections were confirmed by fecal egg count (FEC). Treatment groups in both studies were as follows: (1) negative control (saline, 0.9% sodium chloride), (2) positive control injectable endectocide (Study 1-0.2 mg/kg ivermectin; Study 2-0.2 mg/kg doramectin), (3) positive control injectable anthelmintic (7.5 mg/kg levamisole HCl), and (4) FDCI (0.2 mg/kg doramectin + 6.0 mg/kg levamisole HCl). Cattle were treated either 28 days (Study 1) or 6 days (Study 2) post-infection. On Days 14-16 (Study 1) or Days 20-21 (Study 2) post-treatment, cattle were euthanized and necropsied for the recovery, identification, and enumeration of worms. Treatment efficacy was calculated as reduction in worm burdens of treated cattle compared to saline-treated cattle, and treatments were considered effective if the geometric mean worm burden in the treatment group was reduced by ≥ 95% compared to the negative control group. In both studies, saline-treated cattle remained positive for GIN infections for the study duration. Ivermectin was less than 95% effective against Cooperia spp. (80.2%) and H. placei (24.8%) in Study 1, and levamisole HCl was less than 95% effective against Ostertagia spp. (47.1%) in Study 2. In contrast, the novel FDCI was 100% effective in treating adult and immature life stages of all cattle GINs included in the artificial infections, with no worms recovered at necropsy from doramectin + levamisole HCl-treated cattle. These data show a single administration of the FDCI provides broad-spectrum treatment of economically important cattle GINs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew A. DeRosa reports a relationship with Zoetis Inc that includes: employment. Raj Packianathan reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Hodge reports a relationship with Zoetis Australia Pty Limited that includes: employment. Jacqueline Wright reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Pearce reports a relationship with Zoetis Australia Pty Limited that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Stable and radiogenic isotope analysis - particularly using lead isotope analysis (LIA) - has previously been shown to be a useful tool for the provenancing of ancient metal artefacts of silver and copper and its alloys, but less progress has been made in the provenancing of iron artefacts, despite their importance and frequency in the archaeological record. In this pilot study we investigate for the first time the possibilities of iron isotope analysis in combination with trace strontium isotope analysis and LIA for the provenancing of iron objects believed to be from the Viking Age in the British Isles. Previous studies have shown that analysis of each of these isotopes can contribute to provenancing iron artefacts, but they are not individually resolutory. In this proof-of-concept study, we examine the Fe, Sr and Pb isotopes of 7 artefacts believed to derive from the Viking Age: 3 from Meols - a former Viking seaport on Wirral and 4 samples from the probable location of the AD 1066 Battle of Fulford in North Yorkshire. We also examine an additional artefact of unknown antiquity from Bebington Heath - a possible location of the AD 937 Battle of Brunanburh. Although the pilot data set is too small to make definitive conclusions, it has paved the way for a fuller study involving 100 samples (including 30 from the former Viking camp of Torksey, Lincolnshire) funded by the NEIF fund of the UK National Environmental Research Council. The high range of 87 Sr/ 86 Sr values in the present data set of 8 is beyond what would be expected for bog iron (with a cut-off ∼ 0.709) and suggests that mined ore was being used, a preliminary conclusion supported by the narrow range of Fe isotope data., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: To identify, synthesise and appraise evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and pregnancy., Design: Mixed-methods systematic review, using convergent segregated design., Data Sources: MEDLINE, EMBASE, Scopus, PsycINFO, CINAHL, MedRxiv, PROSPERO and grey literature sources through 6 August 2023., Eligibility Criteria: We included original research studies, expert opinion and grey literature reporting on ME/CFS and pregnancy/post partum (up to 2 years), risk of pregnancy outcomes with ME/CFS or experiences during pregnancy for mother, partner or health and social care professionals following ME/CFS during pregnancy, all where the evidence was relevant to a confirmed ME/CFS diagnosis prior to pregnancy., Data Extraction and Synthesis: Three independent reviewers completed all screening, data extraction and quality assessment. Risk of bias was assessed using the mixed-methods appraisal tool V.2018. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses. Findings were integrated through configuration., Results: Searches identified 3675 articles, 16 met the inclusion criteria: 4 quantitative (1 grey), 11 qualitative (9 grey) and 1 grey mixed-methods study. Of the four quantitative studies that reported on ME/CFS severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one found most women had no change in ME/CFS symptoms and one found ME/CFS improved; this difference in symptom severity across studies was supported by the qualitative evidence. The qualitative literature also highlighted the importance of individualised care throughout pregnancy and birth, and the need for additional support during family planning, pregnancy and with childcare. Only one quantitative study reported on pregnancy outcomes, finding decreased vaginal births and higher rates of spontaneous abortions and developmental and learning delays associated with pregnancies in those with ME/CFS., Conclusions: Current evidence on ME/CFS in pregnancy is limited and findings inconclusive. More high-quality research is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Music performances are rich in systematic temporal irregularities called "microtiming", too fine-grained to be notated in a musical score but important for musical expression and communication. Several studies have examined listeners' preference for rhythms varying in microtiming, but few have addressed precisely how microtiming is perceived, especially in terms of cognitive mechanisms, making the empirical evidence difficult to interpret. Here we provide evidence that microtiming perception can be simulated as a process of probabilistic prediction. Participants performed an XAB discrimination test, in which an archetypal popular drum rhythm was presented with different microtiming. The results indicate that listeners could implicitly discriminate the mean and variance of stimulus microtiming. Furthermore, their responses were effectively simulated by a Bayesian model of entrainment, using a distance function derived from its dynamic posterior estimate over phase. Wide individual differences in participant sensitivity to microtiming were predicted by a model parameter likened to noisy timekeeping processes in the brain. Overall, this suggests that the cognitive mechanisms underlying perception of microtiming reflect a continuous inferential process, potentially driving qualitative judgements of rhythmic feel., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population., Design: Systematic review and cohort-level dose-response meta-analysis., Data Sources: PubMed, Scopus, Web of Science and reference lists of published studies., Eligibility Criteria: Prospective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney)., Results: 196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted., Conclusions: Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. PROSPERO registration number CRD42018095481., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: In many grant review settings, proposals are selected for funding on the basis of summary statistics of review ratings. Challenges of this approach (including the presence of ties and unclear ordering of funding preference for proposals) could be mitigated if rankings such as top-k preferences or paired comparisons, which are local evaluations that enforce ordering across proposals, were also collected and incorporated in the analysis of review ratings. However, analyzing ratings and rankings simultaneously has not been done until recently. This paper describes a practical method for integrating rankings and scores and demonstrates its usefulness for making funding decisions in real-world applications., Methods: We first present the application of our existing joint model for rankings and ratings, the Mallows-Binomial, in obtaining an integrated score for each proposal and generating the induced preference ordering. We then apply this methodology to several theoretical "toy" examples of rating and ranking data, designed to demonstrate specific properties of the model. We then describe an innovative protocol for collecting rankings of the top-six proposals as an add-on to the typical peer review scoring procedures and provide a case study using actual peer review data to exemplify the output and how the model can appropriately resolve judges' evaluations., Results: For the theoretical examples, we show how the model can provide a preference order to equally rated proposals by incorporating rankings, to proposals using ratings and only partial rankings (and how they differ from a ratings-only approach) and to proposals where judges provide internally inconsistent ratings/rankings and outlier scoring. Finally, we discuss how, using real world panel data, this method can provide information about funding priority with a level of accuracy in a well-suited format for research funding decisions., Conclusions: A methodology is provided to collect and employ both rating and ranking data in peer review assessments of proposal submission quality, highlighting several advantages over methods relying on ratings alone. This method leverages information to most accurately distill reviewer opinion into a useful output to make an informed funding decision and is general enough to be applied to settings such as in the NIH panel review process., (© 2023. The Author(s).)

Understanding urban travel behaviour is crucial for planning healthy and sustainable cities. Africa is urbanising at one of the fastest rates in the world and urgently needs this knowledge. However, the data and literature on urban travel behaviour, their correlates, and their variation across African cities are limited. We aimed to describe and compare travel behaviour characteristics and correlates of two Kenyan cities (Nairobi and Kisumu). We analysed data from 16,793 participants (10,000 households) in a 2013 Japan International Cooperation Agency (JICA) household travel survey in Nairobi and 5790 participants (2760 households) in a 2016 Institute for Transportation and Development Policy (ITDP) household travel survey in Kisumu. We used the Heckman selection model to explore correlations of travel duration by trip mode. The proportion of individuals reporting no trips was far higher in Kisumu (47% vs 5%). For participants with trips, the mean number [lower - upper quartiles] of daily trips was similar (Kisumu (2.2 [2-2] versus 2.4 [2-2] trips), but total daily travel durations were lower in Kisumu (65 [30-80] versus 116 [60-150] minutes). Walking was the most common trip mode in both cities (61% in Kisumu and 42% in Nairobi), followed by motorcycles (17%), matatus (minibuses) (11%), and cars (5%) in Kisumu; and matatus (28%), cars (12%) and buses (12%) in Nairobi. In both cities, females were less likely to make trips, and when they did, they travelled for shorter durations; people living in households with higher incomes were more likely to travel and did so for longer durations. Gender, income, occupation, and household vehicle ownership were associated differently with trip making, use of transport modes and daily travel times in cities. These findings illustrate marked differences in reported travel behaviour characteristics and correlates within the same country, indicating setting-dependent influences on travel behaviour. More sub-national data collection and harmonisation are needed to build a more nuanced understanding of patterns and drivers of travel behaviour in African cities., (© 2023 The Authors. Published by Elsevier Ltd.)

According to the cultural distance hypothesis (CDH), individuals learn culture-specific statistical structures in music as internal stylistic models and use these models in predictive processing of music, with musical structures closer to their home culture being easier to predict. This cultural distance effect may be affected by domain-specific (musical ability) and domain-general individual characteristics (openness, implicit cultural bias). To test the CDH and its modulation by individual characteristics, we recruited Chinese and Western adults to categorize stylistically ambiguous and unambiguous Chinese and Western melodies by cultural origin. Categorization performance was better for unambiguous (low CD) than ambiguous melodies (high CD), and for in-culture melodies regardless of ambiguity for both groups, providing evidence for CDH. Musical ability, but not other traits, correlated positively with melody categorization, suggesting that musical ability refines internal stylistic models. Therefore, both cultures show musical enculturation in their home culture with a modulatory effect of individual musical ability., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Advancement of Spiritual and religious competencies aligns with increasing attention to the pivotal role of multiculturalism and intersectionality, as well as shifts in organizational values and strategies, that shape the delivery of psychological services (e.g., evidence-based practice). A growing evidence base also attests to ethical integration of peoples' religious faith and/or spirituality (R/S) in their mental care as enhancing the utilization and efficacy of psychological services. When considering the essential attitudes, knowledge, and skills for addressing religious and spiritual aspects of clients' lives, lack of R/S competencies among psychologists and other mental health professionals impedes ethical and effective practice. The purpose of this article is to discuss the following: (a) skills for negotiating ethical challenges with spiritually integrated care; and (b) strategies for assessing a client's R/S. We also describe systemic barriers to ethical integration of R/S in mental health professions and briefly introduce our Spiritual and Religious Competencies project. Looking ahead, a strategic, interdisciplinary, and comprehensive approach is needed to transform the practice of mental health care in a manner that more fully aligns with the values, principles, and expectations across our disciplines' professional ethical codes and accreditation standards. We propose that explicit training across mental health professions is necessary to more fully honor R/S diversity and the importance of this layer of identity and intersectionality in many peoples' lives. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Patients with persistent orofacial pain (POFP) can go through complex care pathways to receive a diagnosis and management, which can negatively affect their pain. This study aimed to describe 44-y trends in attendances at Welsh medical practices for POFP and establish the number of attendances per patient and referrals associated with orofacial pain and factors that may predict whether a patient is referred. A retrospective observational study was completed using the nationwide Secure Anonymised Information Linkage Databank of visits to general medical practices in Wales (UK). Data were extracted using diagnostic codes ("Read codes"). Orofacial and migraine Read codes were extracted between 1974 and 2017. Data were analyzed using descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 468,827 POFP and migraine diagnostic codes, accounting for 468,137 patient attendances, or 301,832 patients. The overall attendance rate was 4.22 attendances per 1,000 patient-years (95% confidence interval [CI], 4.21-4.23). The attendance rate increased over the study period. Almost one-third of patients ( n = 92,192, 30.54%) attended more than once over the study period, and 15.83% attended more than once within a 12-mo period. There were 20,103 referral codes that were associated with 8,183 patients, with over half these patients being referred more than once. Odds of receiving a referral were highest in females (odds ratio [OR], 1.23; 95% CI, 1.17-1.29), in those living in rural locations (OR, 1.17; 95% CI, 1.12-1.22), and in the least deprived quintile (OR, 1.39; 95% CI, 1.29-1.48). Odds also increased with increasing age (OR, 1.03; 95% CI, 1.03-1.03). The increasing attendance may be explained by the increasing incidence of POFP within the population. These patients can attend on a repeated basis, and very few are referred, but when they are, this may occur multiple times; therefore, current care pathways could be improved.

Introduction: Socioeconomic inequalities contribute to poor health. Inequitable access to diverse and healthy foods can be a risk factor for non-communicable diseases, especially in individuals of low socioeconomic status. We examined the extent of socioeconomic inequalities in food purchasing practices, expenditure, and consumption in a resource-poor setting in Kenya., Methods: We conducted a secondary analysis of baseline cross-sectional data from a natural experimental study with a sample size of 512 individuals from 376 households in western Kenya. Data were collected on household food sources, expenditure and food consumption. Household socioeconomic status (SES) was assessed using the multiple correspondence analysis (MCA) model. Concentration indices (Ci) and multivariable linear regression models were used to establish socioeconomic inequalities., Results: About half (47.9%) of individuals achieved a minimum level of dietary diversity with the majority coming from wealthier households. The two most consumed food groups were grains and roots (97.5%, n = 499) and dark green leafy vegetables (73.8%, n = 378), but these did not vary by SES. The consumption of dark green leafy vegetables was similar across wealth quantiles (Ci = 0.014, p = 0.314). Overall, the wealthier households spent significantly more money on food purchases with a median of USD 50 (IQR = 60) in a month compared to the poorest who spent a median of USD 40 (IQR = 40). Of all the sources of food, the highest amount was spent at open-air markets median of USD 20 (IQR = 30) and the expenditure did not vary significantly by SES (Ci = 0.4, p = 0.684). The higher the socioeconomic status the higher the total amount spent on food purchases. In multivariable regression analysis, household SES was a significant determinant of food expenditure [Adjusted coefficient = 6.09 (95%confidence interval CI = 2.19, 9.99)]., Conclusion: Wealthier households spent more money on food compared to the poorest households, especially on buying food at supermarkets. Individuals from the poorest households were dominant in eating grains and roots and less likely to consume a variety of food groups, including pulses, dairy, eggs and fruits, and vegetables. Individuals from the poorest households were also less likely to achieve adequate dietary diversity. Deliberate policies on diet and nutrition are required to address socioeconomic inequalities in food purchasing practices., 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 Were, Foley, Musuva, Pearce, Wadende, Lwanga, Mogo, Turner-Moss and Obonyo.)

Little is known about expertise-related plasticity of neural mechanisms for auditory feature integration. Here, we contrast two diverging hypotheses that musical expertise is associated with more independent or more integrated predictive processing of acoustic features relevant to melody perception. Mismatch negativity (MMNm) was recorded with magnetoencephalography (MEG) from 25 musicians and 25 non-musicians, exposed to interleaved blocks of a complex, melody-like multi-feature paradigm and a simple, oddball control paradigm. In addition to single deviants differing in frequency (F), intensity (I), or perceived location (L), double and triple deviants were included reflecting all possible feature combinations (FI, IL, LF, FIL). Following previous work, early neural processing overlap was approximated in terms of MMNm additivity by comparing empirical MMNms obtained with double and triple deviants to modeled MMNms corresponding to summed constituent single-deviant MMNms. Significantly greater subadditivity was found in musicians compared to non-musicians, specifically for frequency-related deviants in complex, melody-like stimuli. Despite using identical sounds, expertise effects were absent from the simple oddball paradigm. This novel finding supports the integrated processing hypothesis whereby musicians recruit overlapping neural resources facilitating more integrative representations of contextually relevant stimuli such as frequency (perceived as pitch) during melody perception. More generally, these specialized refinements in predictive processing may enable experts to optimally capitalize upon complex, domain-relevant, acoustic cues., 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 © 2022 Hansen, Højlund, Møller, Pearce and Vuust.)

Objectives: To investigate which five activity interference categories out of pain, fatigue, mood, dryness and brain fog/mental fatigue scored highest in patients with primary Sjögren's syndrome (pSS) and to investigate the association between activity interference and mood and physical functioning in these patients., Methods: The Comprehensive Pain Evaluation Questionnaire (CPEQ) assessed activity interference (actions performed in daily life that are hindered) in 149 UK pSS patients. This was modified to include four additional symptoms (fatigue, mood, dryness and brainfog/mental fatigue). Functional impairment was measured using the Hospital Anxiety and Depression Scale (HADS) and the Improved Health Assessment Questionnaire (Improved HAQ). Univariable linear regression models were estimated to investigate the association between CPEQ results and the outcome scores obtained from the HADS and Improved HAQ. Multivariable linear regression models were estimated adjusting for patient age and length of disease., Results: Fatigue had the biggest impact on seven activity domains: physical exercise (mean score of 3.49 out of 5 [s.d. 1.26]), performing household chores (mean 3.14 [s.d. 1.18]), gardening or shopping (mean 3.18 [s.d. 1.20]), socializing with others (mean 2.62 [s.d. 1.24]), recreation/hobbies (mean 2.88 [s.d. 1.20]), sexual relations (mean 3.00 [s.d. 1.52]), and mental efficacy (mean 2.69 [s.d. 1.17]). Regression analysis showed a positive correlation in which every point increase in an activity interference category saw the overall mood and physical functioning scores increase., Conclusion: Fatigue has the largest impact on pSS patients' daily activities in this cohort. Length of disease reduced the impact of activity interference on patients' overall health score., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The COVID-19 pandemic brought about the placement of severe social restrictions in the United Kingdom, limiting activity and impacting public behavior. Limited studies have been published on the relationship of the coronavirus pandemic with the presentation and management of upper limb fractures. The aims of this study were first to assess the change in the incidence of upper limb fractures at key points during the COVID-19 pandemic such as the enactment and lifting of lockdowns, and second to evaluate the relationship between local COVID-19 burden and measures of service efficiency across our trust., Methods: We undertook a retrospective analysis of all upper limb fracture referrals, admissions, and surgical procedures from the 1 st of March 2020 to the 28 th of February 2021. Changes in upper limb fracture incidence were mapped to significant changes in social restrictions. Measurements of service efficiency including time from admission to theatre and length of stay for admitted upper limb fracture patients were mapped to local COVID-19 burden. Subgroup analysis was undertaken to compare across age groups, including the pediatric population, all adults, and the elderly., Results: The study involved 1251, 659, and 641 patients with upper limb fracture referrals, admissions, and procedures across the trust, respectively. Referrals (n=128) and procedures (n=72) both peaked in August 2020. Admissions peaked in both May and December 2020 (63 for both). Admissions and procedures both demonstrated a decrease in March and April 2020 compared to the rest of the study period (40 and 38 admissions, as well as 48 and 29 procedures respectively). Across the cohort, referrals and admissions did not demonstrate a statistically significant relationship with the relaxing of social restrictions ( P=0.504 ). There were statistically significant differences among referrals, admissions, and procedures when stratifying patients by age ( p =<0.001 ). Length of stay demonstrated an inverse relationship with COVID-19 burden throughout the study period, with the shortest average length of stay recorded in months with the highest number of local COVID-19 cases. The average time from injury occurrence to theatre increased during the winter months ( P=0.001 )., Conclusion: There is a relationship between changes in social restrictions and the incidence of upper limb fractures. These changes also had differing impacts on upper limb fracture rates when stratifying by patient age groups. The orthopedic service demonstrated adaptability in response to the local COVID-19 burden, and further research is needed to determine what effect this had on clinical outcomes.

Purpose: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world., Methods: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis., Results: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRR pooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I 2  = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRR pooled per 1 SD = 1.057, 95% CI 1.027-1.088)., Conclusion: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed., (© 2022. The Author(s).)

Long-term and culture-specific experience of music shapes rhythm perception, leading to enculturated expectations that make certain rhythms easier to track and more conducive to synchronized movement. However, the influence of enculturated bias on the moment-to-moment dynamics of rhythm tracking is not well understood. Recent modeling work has formulated entrainment to rhythms as a formal inference problem, where phase is continuously estimated based on precise event times and their correspondence to timing expectations: PIPPET (Phase Inference from Point Process Event Timing). Here we propose that the problem of optimally tracking a rhythm also requires an ongoing process of inferring which pattern of event timing expectations is most suitable to predict a stimulus rhythm. We formalize this insight as an extension of PIPPET called pPIPPET (PIPPET with pattern inference). The variational solution to this problem introduces terms representing the likelihood that a stimulus is based on a particular member of a set of event timing patterns, which we initialize according to culturally-learned prior expectations of a listener. We evaluate pPIPPET in three experiments. First, we demonstrate that pPIPPET can qualitatively reproduce enculturated bias observed in human tapping data for simple two-interval rhythms. Second, we simulate categorization of a continuous three-interval rhythm space by Western-trained musicians through derivation of a comprehensive set of priors for pPIPPET from metrical patterns in a sample of Western rhythms. Third, we simulate iterated reproduction of three-interval rhythms, and show that models configured with notated rhythms from different cultures exhibit both universal and enculturated biases as observed experimentally in listeners from those cultures. These results suggest the influence of enculturated timing expectations on human perceptual and motor entrainment can be understood as approximating optimal inference about the rhythmic stimulus, with respect to prototypical patterns in an empirical sample of rhythms that represent the music-cultural environment of the listener., Competing Interests: The authors have declared that no competing interests exist.

The EMBL-EBI search and sequence analysis tools frameworks provide integrated access to EMBL-EBI's data resources and core bioinformatics analytical tools. EBI Search (https://www.ebi.ac.uk/ebisearch) provides a full-text search engine across nearly 5 billion entries, while the Job Dispatcher tools framework (https://www.ebi.ac.uk/services) enables the scientific community to perform a diverse range of sequence analysis using popular bioinformatics applications. Both allow users to interact through user-friendly web applications, as well as via RESTful and SOAP-based APIs. Here, we describe recent improvements to these services and updates made to accommodate the increasing data requirements during the COVID-19 pandemic., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Thousands of phacoemulsification surgeries are performed on eyes with age-related macular degeneration (AMD) complicated by choroidal neovascular membrane (CNV) in the United Kingdom each year. As populations age this number is expected to rise. Controversy over phacoemulsification's influence on CNV activity limits the information which clinicians and these patients use to decide on surgery. This observational study aims to resolve this controversy by reporting on intravitreal injection (IVI) frequency as a pragmatic marker of CNV activity in a large cohort., Methods: A cohort of eyes with AMD complicated by CNV (n = 327) that underwent cataract surgery at a single tertiary centre from 2014 to 2019 were identified. These cases were matched by interval since CNV diagnosis at a specified 'time zero' within the follow-up of pseudophakic eyes with AMD (n = 327). Data concerning demographics, visual acuity (VA) and intravitreal injection frequency before and after 'time zero'/phacoemulsification were collected., Results: Following 'time zero'/phacoemulsification' the mean reduction in annual IVI frequency was 0.6 injections/year (95% CI 0.4,0.9) and 0.4 injections/year (95% CI 0.1,0.7) in the comparison and phacoemulsification cohorts respectively. The mean VA gain 12 months after phacoemulsification in the intervention cohort was 11.3 (95% CI 9.2,13.4) early treatment of diabetic retinopathy study (ETDRS) letters, with 214 eyes (65.4%) having gained ≥5 ETDRS letters after surgery., Conclusions: Phacoemulsification has no clinically significant impact on the activity of pre-existent CNV secondary to AMD. Phacoemulsification should be offered to patients with AMD and cataract that limits vision, regardless of CNV activity., (© 2021. Crown.)

There is a lack of data on physical activity (PA), active travel, and the comparison of measurement instruments in low-resource settings. The objective of this paper is to describe PA behaviour and the agreement of walking estimates from the Global Physical Activity Questionnaire (GPAQ) and the travel diary in a low-resource setting. We used a cross-sectional survey design to capture data from the residents of Accra (Ghana) between May 2020 and March 2021. Of the 863 participants aged 15+ years, 65% were females, and 86% reported PA. The median weekly PA was 18 (interquartile range: 5-75) metabolic equivalent of task hours, with 50% of females and 37% of males achieving low PA levels. In the GPAQ, 80% of participants reported weekly walking; the mean number of days walked was 3.8 (standard deviation (SD): 2.5); hence, 54% of participants reported walking on any day, and the mean daily walking duration was 51 (SD: 82) minutes. In the diary, 56% of participants reported walking for over 24 h, with a mean walking duration of 31 (SD: 65) minutes. The correlation of walking duration between instruments was weak (rho: 0.31; 95% Confidence Interval: 0.25-0.37); the mean bias was 20 min, with GPAQ estimates being 0.1 to 9 times higher than diary estimates. We concluded that low PA is prevalent in Accra, and while the travel diary and GPAQ estimate similar walking prevalence, their walking duration agreement is poor. We recommend accompanying PA questionnaires with objective measures for calibration.

The relatively large molecular size, diastereoisomeric nature, and complex impurity profiles of therapeutic phosphorothioate oligonucleotides create significant analytical challenges for the quality control laboratory. To overcome the lack of selectivity inherent to traditional chromatographic approaches, an ion pair liquid chromatography-mass spectrometry (LCMS) method combining ultraviolet and mass spectrometry quantification was developed and validated for >35 different oligonucleotide drug substances and products, including several commercialized drugs. The selection of chromatographic and spectrometric conditions, data acquisition and processing, critical aspects of sample and buffer preparation and instrument maintenance, and results from method validation experiments are discussed.

Importance: Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and depression is uncertain., Objective: To systematically review and meta-analyze the dose-response association between physical activity and incident depression from published prospective studies of adults., Data Sources: PubMed, SCOPUS, Web of Science, PsycINFO, and the reference lists of systematic reviews retrieved by a systematic search up to December 11, 2020, with no language limits. The date of the search was November 12, 2020., Study Selection: We included prospective cohort studies reporting physical activity at 3 or more exposure levels and risk estimates for depression with 3000 or more adults and 3 years or longer of follow-up., Data Extraction and Synthesis: Data extraction was completed independently by 2 extractors and cross-checked for errors. A 2-stage random-effects dose-response meta-analysis was used to synthesize data. Study-specific associations were estimated using generalized least-squares regression and the pooled association was estimated by combining the study-specific coefficients using restricted maximum likelihood., Main Outcomes and Measures: The outcome of interest was depression, including (1) presence of major depressive disorder indicated by self-report of physician diagnosis, registry data, or diagnostic interviews and (2) elevated depressive symptoms established using validated cutoffs for a depressive screening instrument., Results: Fifteen studies comprising 191 130 participants and 2 110 588 person-years were included. An inverse curvilinear dose-response association between physical activity and depression was observed, with steeper association gradients at lower activity volumes; heterogeneity was large and significant (I2 = 74%; P < .001). Relative to adults not reporting any activity, those accumulating half the recommended volume of physical activity (4.4 marginal metabolic equivalent task hours per week [mMET-h/wk]) had 18% (95% CI, 13%-23%) lower risk of depression. Adults accumulating the recommended volume of 8.8 mMET hours per week had 25% (95% CI, 18%-32%) lower risk with diminishing potential benefits and higher uncertainty observed beyond that exposure level. There were diminishing additional potential benefits and greater uncertainty at higher volumes of physical activity. Based on an estimate of exposure prevalences among included cohorts, if less active adults had achieved the current physical activity recommendations, 11.5% (95% CI, 7.7%-15.4%) of depression cases could have been prevented., Conclusions and Relevance: This systematic review and meta-analysis of associations between physical activity and depression suggests significant mental health benefits from being physically active, even at levels below the public health recommendations. Health practitioners should therefore encourage any increase in physical activity to improve mental health.

In long-haul fiber-optic networks, precise modeling of physical-layer impairments (PLIs) is crucial to optimizing network resource usage while ensuring adequate transmission quality. In order to accurately estimate PLIs, many mathematical models have been proposed. Among them, the so-called Gaussian noise (GN) model is one of the most accurate and simple enough to use on complex continental-size networks. However, the closed-form GN model assumes that the signals can be represented as having rectangular spectra, leading to a significant estimation error in typical cases when this assumption is violated. We propose the component-wise Gaussian noise (CWGN) PLI model that can account for arbitrary spectral-shaped demands. The CWGN model is computationally simple and suitable for most network management approaches. Results indicate that the CWGN model can prevent as much as a 136% overestimation of the PLIs resulting from the closed-form GN model applied to network lightpaths containing cascaded filters.

One-third of the UK population is composed of problem-oriented dental attenders, seeking dental care only when they have acute dental pain or problems. Patients seek urgent dental care from a range of health care professionals, including general medical practitioners. This study aimed to identify trends in dental attendance at Welsh medical practices over a 44-y period, specifically in relation to dental policy change and factors associated with repeat attendance. A retrospective observational study was completed via the nationwide Secure Anonymised Information Linkage (SAIL) Databank of visits to general medical practice in Wales. Read codes associated with dental diagnoses were extracted for patients attending their general medical practitioner between 1974 and 2017. Data were analyzed with descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 439,361 dental Read codes, accounting for 288,147 patient attendances. The overall attendance rate was 2.60 attendances per 1,000 patient-years (95% CI, 2.59 to 2.61). The attendance rate was negligible through 1987 but increased sharply to 5.0 per 1,000 patient-years in 2006 (95% CI, 4.94 to 5.09) before almost halving to 2.6 per 1,000 in 2017 (95% CI, 2.53 to 2.63) to a pattern that coincided with changes to National Health Service policies. Overall 26,312 patients were repeat attenders and were associated with living in an area classified as urban and deprived (odds ratio [OR], 1.22; 95% CI, 1.19 to 1.25; P  < 0.0001) or rural (OR, 0.84; 95% CI, 0.83 to 0.85; P  < 0.0001). Repeat attendance was associated with greater odds of having received an antibiotic prescription (OR, 2.53; 95% CI, 2.50 to 2.56; P  < 0.0001) but lower odds of having been referred to another service (OR, 0.75; 95% CI, 0.70 to 0.81; P  < 0.0001). Welsh patients' reliance on medical care for dental problems was influenced by social deprivation and health policy. This indicates that future interventions to discourage dental attendance at medical practitioners should be targeted at those in the most deprived urban areas or rural areas. In addition, health policy may influence attendance rates positively and negatively and should be considered in the future when decisions related to policy change are made.

Background: Porcine reproductive and respiratory syndrome (PRRS) is a major endemic pig disease worldwide and is associated with considerable economic costs., Methods: In Scotland, three abattoir surveys were conducted in 2006 (158 farms), 2012-2013 (94 farms) and 2017-2018 (97 farms) to estimate seroprevalence to PRRS virus (PRRSV) in commercial finishing pigs. These surveys covered around 79%, 59% and 66% of the Quality Meat Scotland assured farms slaughtering pigs in Scotland in 2006, 2012-13 and, 2017-18 respectively. In the 2006 survey, six pigs per farm were sampled and tested using the CIVTEST SUIS PRRS E/S test. In the 2012-2013 and 2017-2018 surveys, 10 pigs per farm were sampled and tested using the IDEXX PRRS X3 Ab test. A farm was considered positive if it had one or more seropositive samples., Results: The prevalence of positive farms was 45.6% (95% CI: 38.0-53.4), 47.8% (95% CI: 38.1-57.9) and 45.4% (95% CI: 35.8-55.3) in the 2006, 2012-2013 and 2017-2018 surveys, respectively, and 70%-75.5% farms did not change their status between sampling periods., Conclusion: The prevalence of PRRSV exposure in Scottish pig herds was high and changed little from 2006 to 2018. These surveys have informed planning for a prospective PRRS control programme in Scotland., (© 2021 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset., Methods: The British Columbia Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in British Columbia, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT., Results: In total, 13 803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2704/5770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT had started HCV treatment. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95% confidence interval {CI}, 1.50, 2.26])., Conclusions: Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction Around one-third of the UK population are 'problem-orientated dental attenders', only seeking care when suffering with dental pain and often on a repeated basis to secondary care. Little is known about attendance in primary care. The aim here was to examine the period prevalence of repeat urgent care attenders and establish predictors of repeat attendance in primary care.Methods Data on urgent and emergency dental care attendances in primary dental care in the North East and Cumbria were analysed from 2013-2019. Variables included: patient sex; ten-year age band; lower super output area; and Index of Multiple Deprivation. Period prevalence was calculated and data were considered year by year to identify trends in attendances. Analysis was with descriptive statistics and predictors of repeat attendance were identified using logistic regression modelling.Results Over the six-year period, there were 601,432 attendances for urgent primary dental care, equating to a period prevalence of 2.76% for the geographic population studied. In total, 16.15% of attendances were repeat attendances (period prevalence 0.45%) and predictors included being a woman and residence in deprived and rural areas. All urgent care attendances decreased over the six-year period, with one-off attendances beginning to increase again in 2019, while repeat attendances stabilised.Conclusion Interventions to encourage regular dental attendances should be targeted at patients from the most deprived and rural areas of the North East and Cumbria; however, a decrease in repeat attendance was noted in these areas., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Magnetically frustrated systems provide fertile ground for complex behaviour, including unconventional ground states with emergent symmetries, topological properties, and exotic excitations. A canonical example is the emergence of magnetic-charge-carrying quasiparticles in spin-ice compounds. Despite extensive work, a reliable experimental indicator of the density of these magnetic monopoles is yet to be found. Using measurements on single crystals of Ho 2 Ir 2 O 7 combined with dipolar Monte Carlo simulations, we show that the isothermal magnetoresistance is highly sensitive to the monopole density. Moreover, we uncover an unexpected and strong coupling between the monopoles on the holmium sublattice and the antiferromagnetically ordered iridium ions. These results pave the way towards a quantitative experimental measure of monopole density and demonstrate the ability to control antiferromagnetic domain walls using a uniform external magnetic field, a key goal in the design of next-generation spintronic devices., (© 2022. The Author(s).)

The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena), maintained at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) provides freely accessible services, both for deposition of, and access to, open nucleotide sequencing data. Open scientific data are of paramount importance to the scientific community and contribute daily to the acceleration of scientific advance. Here, we outline the major updates to ENA's services and infrastructure that have been delivered over the past year., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure in a community setting. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes. Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood. The aim of this study is to systematically review and evaluate the evidence for the differential effects of HPN solutions and to understand what features are associated with differences in clinical endpoints., Methods: A systematic literature search was conducted between September and December 2020, and updated in July 2021 using the MEDLINE (Ovid), EMBASE, Scopus, and Web of Science databases. Studies were selected according to the following criteria (a) adult participants (>18 years old) dependent on HPN; (b) randomised controlled trials, prospective cohort and cross-sectional study designs; (c) primary research comparing two or more HPN solutions and (d) published in English language. Data were extracted and study quality assessed using Cochrane Collaboration's tools: Risk of Bias for Randomised Controlled Trials (RCTs); Risk of Bias in Non-Randomised Studies of Interventions; and the Newcastle Ottawa Scale for cross-sectional studies., Results: Of the 5148 articles identified, seven RCTs, two prospective cohort and one cross-sectional study were included with a total of 295 participants. Studies varied in terms of duration (one to 60 months) and sample size (n = 5 to 88). Ten studies compared lipid emulsions (LE) and one study also compared LE with lipid-free HPN. No studies were found that compared the amino acid, vitamin, trace element or electrolyte components of HPN. In general, LE were well tolerated with no significant adverse effects. LE containing olive +/or fish oil were associated with a lower ω-6:ω-3 fatty acid ratio, positive reductions in markers of liver function, and changes in blood and cell fatty acid profiles., Conclusions: Despite the increasing use of HPN, there is surprisingly little evidence available to guide the provision of macro and micronutrients in the adult population requiring this therapy. Although LE containing olive +/or fish oil show promise with regards to liver function and blood and cell fatty acid profiles, further studies are needed before drawing definitive conclusions on the clinical value of these emulsions. It is likely that one type of HPN solution alone cannot be uniformly applied to patient care, and each patient should be assessed on an individual basis., Competing Interests: Conflict of Interest The authors disclose no conflict of interests., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

The triple burden of malnutrition in many low- and middle-income countries (LMICs) is partly a result of changing food environments and a shift from traditional diets to high-calorie Western-style diets. Exploring the relationship between food sources and food- and nutrition-related outcomes is important to understanding how changes in food environments may affect nutrition in LMICs. This study examined associations of household food source with household food insecurity, individual dietary diversity and individual body mass index in Western Kenya. Interview-administered questionnaire and anthropometric data from 493 adults living in 376 randomly-selected households were collected in 2019. Adjusted regression analyses were used to assess the association of food source with measures of food insecurity, dietary diversity and body mass index. Notably, participants that reported rearing domesticated animals for consumption ('own livestock') had lower odds of moderate or severe household food insecurity (odds ratio (OR) = 0.29 (95% CI: 0.09, 0.96)) and those that reported buying food from supermarkets had lower odds of moderate or severe household food insecurity (borderline significant, OR = 0.37 (95% CI: 0.14, 1.00)), increased dietary diversity scores (Poisson coefficient = 0.17 (95% CI: 0.10, 0.24)) and higher odds of achieving minimum dietary diversity (OR = 2.84 (95% CI: 1.79, 4.49)). Our findings provide insight into the relationship between food environments, dietary patterns and nutrition in Kenya, and suggest that interventions that influence household food source may impact the malnutrition burden in this context.

When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in connectivity underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)-and its modulation by context predictability and musical expertise-are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)-typically related to gain control-or extrinsic connections between A1 and STG-typically related to propagation of prediction and error signals-better explained magnetoencephalography responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Gram-negative bloodstream infections (GNBSI) are confirmed by the presence of gram-negative bacteria in the bloodstream and pose a significant healthcare issue as they increase the risk of sepsis and mortality. In England, the aim is to reduce GNBSI cases and further deterioration through enhanced population surveillance of patients with a laboratory-confirmed GNBSI to inform on healthcare policies. The objective of this study was to evaluate the factors associated with in-hospital mortality in patients with a laboratory-confirmed Escherichia coli, Klebsiella or Pseudomonas aeruginosa GNBSIs, with data obtained from the enhanced data capture for the surveillance of GNBSIs. All patients with a laboratory-confirmed GNBSI at a single centre, admitted between April 2017 and March 2019, were included in this retrospective observational study. Demographic and recent exposure to healthcare risk factors were collected and assessed for the association with in-hospital mortality. In 1113 patients with laboratory-confirmed GNBSIs, the in-hospital mortality rate was 13%. Multivariable analysis confirmed that patients with respiratory (OR = 3.73, 95%CI = 2.05-6.76), gastrointestinal (2.61; 1.22-5.58) or skin (3.61; 1.24-10.54) infection primary focus had a greater risk of in-hospital mortality, compared to upper urinary tract infections. Increased risk of in-hospital mortality was also observed in patients with hospital-onset GNBSIs (OR = 1.87; 1.17-2.97) compared with community-onset healthcare acquired GNBSIs, or who were on dialysis at the time of the GNBSI (3.28; 1.01-10.14), as well as in patients who had recently been discharged from hospital (1.55; 1.01-2.38), or had a vascular device recently manipulated (2.41; 1.01-5.74). Results confirm that the data obtained from the enhanced data capture for GNBSIs in England can predict in-hospital mortality in patients with a GNBSI. Several factors associated with an increased risk of in-hospital mortality have been identified. Results should be reported back to clinicians in order to identify patients at a greater risk of dying in-hospital who may benefit from further monitoring., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada., Methods: We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality., Results: Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality., Conclusions: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs., Lay Summary: We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection., Competing Interests: Conflict of interest MK has received grant funding via his institution from Roche Molecular Systems, Boehringer Ingelheim, Merck, Siemens Healthcare Diagnostics and Hologic Inc. SB has advised and spoken for Gilead Sciences (all personal payments given as unrestricted donations to BC Centre for Disease Control Foundation for Public Health). Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Health surveillance initiatives targeted at populations evacuated from, and residing in, areas affected by radiation contamination were implemented by international institutions as well as national and local governments after the nuclear accidents of Chernobyl and Fukushima Dai-ichi nuclear power plants. Most of these initiatives included a component of childhood thyroid cancer monitoring, with the more comprehensive schemes corresponding to national programmes of health monitoring for adults and children around general health and wellbeing. This article provides a short overview of available data on the costs and resources associated with surveillance responses to two recent nuclear accidents: Chernobyl and the Fukushima Dai-Ichi nuclear plant accidents. Moreover, because the balance of costs and benefits of health surveillance after a nuclear accident can influence decisions on implementation, we also present a brief overview of the principles of economic evaluation for collecting and presenting data on costs and outcomes of a surveillance programme after a nuclear accident. We apply these principles in a balance sheet analysis of a post-accident ultrasound thyroid screening programme for children., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)