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The UK's relationship with the European Union (EU) is now embodied in two principal legal instruments: the EU–UK Trade and Cooperation Agreement, which formally entered into force on 1 May 2021; and the Withdrawal Agreement, with its Protocol on Ireland/Northern Ireland, which continues to apply. Using a ‘building blocks’ framework for analysis of national health systems derived from the World Health Organisation, this article examines the likely impacts in the UK of this legal settlement on the National Health Service (NHS), health and social care. Specifically, we determine the extent to which the trade, cooperation and regulatory aspects of those legal measures support positive impacts for the NHS and social care. We show that, as there is clear support for positive health and care outcomes in only one of the 17 NHS ‘building blocks’, unless mitigating action is taken, the likely outcomes will be detrimental. However, as the legal settlement gives the UK a great deal of regulatory freedom, especially in Great Britain, we argue that it is crucial to track the effects of proposed new health and social care-related policy choices in the months and years ahead.
The rift setting of eastern Africa preserves exceptional records of mammalian (including hominin) fossils and archeology. The Afar region is host to multiple deposits with sediments ranging in age from>9 Ma to the present (Chorowicz, 2005; Katoh et al., 2016) and plays a major role in our understanding of human origins. The Gona project area contains fossiliferous deposits that span ca. 6.3 to <0.15 Ma (Quade et al., 2008); the duration of this record means that it can make a distinct contribution to understanding the environmental context for human evolution within the Afar and in eastern Africa (Figures 17.1 and 17.2). The primary units at Gona include the late Miocene Adu-Asa Formation, which contains fossils of Ardipithecus kaddaba; the early Pliocene Sagantole Formation with fossils of Ardipithecus ramidus; the mid- to late-Pliocene Hadar Formation; and the Busidima Formation (ca. 2.7 Ma to <0.15 Ma), which contains a record of the earliest Oldowan stone tools, fossils of Homo erectus, and Acheulean artifacts (Figure 17.2).
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
To achieve the elimination of the hepatitis C virus (HCV), sustained and sufficient levels of HCV testing is critical. The purpose of this study was to assess trends in testing and evaluate the effectiveness of strategies to diagnose people living with HCV. Data were from 12 primary care clinics in Victoria, Australia, that provide targeted services to people who inject drugs (PWID), alongside general health care. This ecological study spanned 2009–2019 and included analyses of trends in annual numbers of HCV antibody tests among individuals with no previous positive HCV antibody test recorded and annual test yield (positive HCV antibody tests/all HCV antibody tests). Generalised linear models estimated the association between count outcomes (HCV antibody tests and positive HCV antibody tests) and time, and χ2 test assessed the trend in test yield. A total of 44 889 HCV antibody tests were conducted 2009–2019; test numbers increased 6% annually on average [95% confidence interval (CI) 4–9]. Test yield declined from 2009 (21%) to 2019 (9%) (χ2P = <0.01). In more recent years (2013–2019) annual test yield remained relatively stable. Modest increases in HCV antibody testing and stable but high test yield within clinics delivering services to PWID highlights testing strategies are resulting in people are being diagnosed however further increases in the testing of people at risk of HCV or living with HCV may be needed to reach Australia's HCV elimination goals.
Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality.
This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.
A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013.
Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance.
This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
This chapter presents an overview of the nature, assessment, and treatment of obsessive-compulsive and related disorders (OCRD), including obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder (HD), hair-pulling disorder (HPD), and skin-picking disorder (SPD). Specifically, we review the DSM-V diagnostic criteria, epidemiology and impact, clinical features and course, and etiological insights for each of these disorders in turn. Next, we discuss key points to consider when making a differential diagnosis with disorders outside the OCRD category. From there, we turn to a discussion of the assessment and treatment of these disorders using pharmacological, cognitive-behavioral, and neuromodulation interventions. Future directions in the research on OCRDs then follows.
The classical model for studying one-phase Hele-Shaw flows is based on a highly nonlinear moving boundary problem with the fluid velocity related to pressure gradients via a Darcy-type law. In a standard configuration with the Hele-Shaw cell made up of two flat stationary plates, the pressure is harmonic. Therefore, conformal mapping techniques and boundary integral methods can be readily applied to study the key interfacial dynamics, including the Saffman–Taylor instability and viscous fingering patterns. As well as providing a brief review of these key issues, we present a flexible numerical scheme for studying both the standard and nonstandard Hele-Shaw flows. Our method consists of using a modified finite-difference stencil in conjunction with the level-set method to solve the governing equation for pressure on complicated domains and track the location of the moving boundary. Simulations show that our method is capable of reproducing the distinctive morphological features of the Saffman–Taylor instability on a uniform computational grid. By making straightforward adjustments, we show how our scheme can easily be adapted to solve for a wide variety of nonstandard configurations, including cases where the gap between the plates is linearly tapered, the plates are separated in time, and the entire Hele-Shaw cell is rotated at a given angular velocity.
Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.
To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.
A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.
An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.
While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
Nearly three times as many people detained in a jail have a serious mental illness (SMI) when compared to community samples. Once an individual with SMI gets involved in the criminal justice system, they are more likely than the general population to stay in the system, face repeated incarcerations, and return to prison more quickly when compared to their nonmentally ill counterparts.
Health disparities between Appalachia and the rest of the country are widening. To address this, the Appalachian Translational Research Network (ATRN) organizes an annual ATRN Health Summit. The most recent Summit was held online September 22–23, 2020, and hosted by Wake Forest Clinical and Translational Science Institute in partnership with the Northwest Area Health Education Center. The Summit, titled “Community-Engaged Research in Translational Science: Innovations to Improve Health in Appalachia,” brought together a diverse group of 141 stakeholders from communities, academic institutions, and the National Center for Advancing Translational Science (NCATS) to highlight current research, identify innovative approaches to translational science and community-engaged research, develop cross-regional research partnerships, and establish and disseminate priorities for future Appalachian-focused research. The Summit included three plenary presentations and 39 presentations within 12 concurrent breakout sessions. Here, we describe the Summit planning process and implementation, highlight some of the research presented, and outline nine emergent themes to guide future Appalachian-focused research.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Prestigious journals are widely admired for publishing quality scholarship, yet the primary indicators of journal prestige (i.e., impact factors) do not directly assess audience admiration. Moreover, the publication landscape has changed substantially in the last 20 years, with electronic publishing changing the way we consume scientific research. Given that it has been 18 years since the publication of the last journal prestige survey of SIOP members, the authors conducted a new survey and used these results to reflect on changing practices within industrial and organizational (I-O) psychology. SIOP members (n = 557) rated the prestige and relevance of I-O and management journals. Responses were analyzed according to job setting, and were compared to a survey conducted by Zickar and Highhouse (2001) in 2000. There was considerable consistency in prestige ratings across settings (i.e., management department vs. psychology department; academic vs. applied), especially among the top journals. There was considerable variance, however, in the perceived usefulness of different journals. Results also suggested considerable consistency across the two time periods, but with some increases in prestige among OB-oriented journals. Changes in the journal landscape are discussed, including the rise of OHP as a topic of concentration in I-O. We suggest that I-O programs will continue to attract the top researchers in talent management and OHP, which should result in the use of a broader set of journals for judging I-O program impact.
Competition in the US Congress has been characterised along a single, left-right ideological dimension. We challenge this characterisation by showing that the content of legislation has far more predictive power than alternative measures, most notably legislators’ ideological positions derived from scaling roll call votes. Using a machine learning approach, we identify a topic model for final passage votes in the 111th through the 113th House of Representatives and conduct out-of-sample tests to evaluate the predictive power of bill topics relative to other measures. We find that bill topics and congressional committees are important for predicting roll call votes but that other variables, including member ideology, lack predictive power. These findings raise serious doubts about the claim that congressional politics can be boiled down to competition along a single left-right continuum and shed new light on the debate about levels of polarisation in Congress.
Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.
To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.
Multicenter prospective surveillance study.
Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.
From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.
We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.
Successful conservation depends on human attitudes, values, and support. Increasingly scientists and managers analyse not only species status and needs, but also the long-term cost, risk, and effectiveness of activities. Socioeconomic costs and benefits are integral to these analyses. Gorongosa National Park in Mozambique provides a case study of conservation integrated with local community needs. Endangered Delta smelt in California exemplify conflicts around water apportionment. Case studies demonstrating the importance of socioeconomic considerations are provided by management of gray wolves and grizzly bears in the United States. The story of sage grouse illustrates how a regional agreement that resulted from many years of collaboration among stakeholders can be nullified by political changes at the national level. The cultural and socioeconomic values and rights of indigenous people play a prominent role in salmon management that can run counter to the interests of hydroelectric companies and other water users. Case studies illustrate how habitat management can be facilitated by participation by non-governmental organizations. Socioeconomic and political consideration also underlie the question of who can take responsibility for managing conservation-reliant species.