We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
This groundbreaking volume assembles an unparalleled roster of media experts and First Amendment luminaries to chart the future of press freedom in America's changing media landscape. Current and former deans of top US law schools, a Pulitzer Prize-winning journalist, former Supreme Court clerks, and renowned scholars of law and communications offer their collective wisdom on safeguarding journalism amidst unprecedented challenges. Their contributions provide an incisive analysis of emerging threats to press freedom, from technological and economic disruptions to eroding public trust, while proposing innovative legal and policy solutions. The volume tackles cutting-edge issues like artificial intelligence in news production and the evolving definition of 'the press' in the digital age. Blending rigorous scholarship with practical insights, this essential resource equips journalists, press advocates, policymakers, and engaged citizens with expert knowledge to defend press freedom. This title is also available as Open Access on Cambridge Core.
The American press is facing a perilous moment. A confluence of economic, cultural, technological, and political shifts has abruptly upended our longstanding sense of how the news media operates. Suddenly, it seems, these sweeping changes have realigned the traditional relationships between and among democracy, newsgathering, and press freedom, prompting new questions about what it means to value and support a free press in the United States.
Background: Our prior six-year review (n=2165) revealed 24% of patients undergoing posterior decompression surgeries (laminectomy or discectomy) sought emergency department (ED) care within three months post-surgery. We established an integrated Spine Assessment Clinic (SAC) to enhance patient outcomes and minimize unnecessary ED visits through pre-operative education, targeted QI interventions, and early post-operative follow-up. Methods: We reviewed 13 months of posterior decompression data (n=205) following SAC implementation. These patients received individualized, comprehensive pre-operative education and follow-up phone calls within 7 days post-surgery. ED visits within 90 days post-surgery were tracked using provincial databases and compared to our pre-SAC implementation data. Results: Out of 205 patients, 24 (11.6%) accounted for 34 ED visits within 90 days post-op, showing a significant reduction in ED visits from 24% to 11.6%, and decreased overall ED utilization from 42.1% to 16.6% (when accounting for multiple visits by the same patient). Early interventions including wound monitoring, outpatient bloodwork, and prescription adjustments for pain management, helped mitigate ED visits. Patient satisfaction surveys (n=62) indicated 92% were “highly satisfied” and 100% would recommend the SAC. Conclusions: The SAC reduced ED visits after posterior decompression surgery by over 50%, with pre-operative education, focused QI initiatives, and its individualized, proactive approach.
Background: Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) are associated with pathogenic variants in SCN1A. While most such cases are heterozygous, there have been 16 reported homozygous cases. We report two new biallelic cases associated with divergent phenotypes.Methods: We performed a chart review for two patients with different homozygous SCN1A variants and reviewed all previously published biallelic SCN1A pathogenic variants. Results: Our first patient exhibited early afebrile seizures and severe developmental delay, without febrile seizures or status epilepticus. A homozygous c. 1676T>A, (p. Ile559Asn) variant of uncertain significance was identified, carried by asymptomatic parents. The second patient exhibited early, recurrent, and prolonged febrile seizures, moderate developmental delay, and motor dysfunction; a homozygous pathogenic c. 4970G>A, (p. Arg1657His) variant carried by asymptomatic parents was identified.
Of 18 known cases of biallelic SCN1A pathogenic variants, 15/18 (83%) have diagnoses of Dravet or GEFS+. The remaining 3/18 (17%) had pharmacoresponsive epilepsy with prominent GDD. Cognitive phenotypes ranged from intact neurodevelopment to profound developmental delay. Eleven out of 18 cases (61%) had motor concerns. Conclusions: These cases expand the phenotypic spectrum of biallelic SCN1A variants. While some patients present typically for Dravet/GEFS+, others present with developmental delay and controllable epilepsy.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Diet is a key modifiable factor for improving suboptimal lipoprotein profiles and reducing cardiovascular disease (CVD) risk(1). Dietary patterns like the Dietary Approaches to Stop Hypertension (DASH) or the Mediterranean Diet, with varying macronutrient components, have shown positive effects on total cholesterol and low-density lipoproteins (LDL)(2). However, limited research exists on the impact of different healthy diets on lipoprotein subclass profiles, which are increasingly known to influence CVD risk. This study aims to compare the nuclear magnetic resonance (NMR)-measured 112 lipoprotein profiles across three healthy dietary patterns: a carbohydrate-rich diet (CARB), similar to the DASH diet; a protein-rich diet (PROT); and an unsaturated fat-rich diet (USFA), similar to the Mediterranean diet. Lipoprotein parameters were generated using the Bruker IVDr Lipoprotein Subclass Analysis (B.I.LISA) method(3). The lipoprotein subclasses included different molecular components of very low-density lipoprotein (VLDL, 0.950–1.006 kg/L), low-density lipoprotein (LDL, density 1.09–1.63 kg/L), intermediate-density lipoprotein (IDL, density 1.006–1.019 kg/L), and high-density lipoprotein (HDL, density 1.063–1.210 kg/L). The LDL subfraction was further divided into six density classes, and the HDL subfractions were divided into four different density classes. Plasma samples from a randomised cross-over intervention study involving 156 individuals who completed more than two dietary patterns were included for the NMR analysis (registered at www.clinicaltrials.gov as NCT00051350 and NCT03369535). The Friedman’s test with post-hoc analysis, corrected for multiple testing, showed that all healthy dietary patterns led to a reduction in overall lipoprotein subclasses known to be associated with atherogenic risk. This reduction included large and medium-sized LDL subclasses, all intermediate-density IDL subclasses, as well as total plasma cholesterol, triglycerides, apolipoprotein-B100, apo-B100/apo-A1 ratio, and LDL-cholesterol (p < 0.05). Additional variations in lipoprotein subclasses specific to each diet were also observed. The PROT diet showed a decrease in small-sized and dense LDL, large to medium VLDL subclasses, and large-sized HDL subclasses. Conversely, the CARB diet exhibited an increase in smaller-sized and denser LDL, along with a decrease in large-sized HDL and an increase in smaller-sized HDL subclasses. The USFA diet led to decreases in LDL and overall VLDL subclasses, while increasing LDL and HDL subclasses (p < 0.05). The impact of different healthy diets with differential effects on lipoproteins suggests the possibility of targeting the cholesterol status of individuals to optimise lipoprotein profiles and thereby reduce CVD risk. Preliminary exploratory analyses based on linear mixed-effect models coupled with a latent profile analysis, adjusted for cholesterol status, showed that individual lipoprotein responses to specific diets varied. Inter-individual variations in lipoprotein responses to healthy diets were evident. A small proportion of individuals only responded to specific diets, suggesting potential of personalised nutrition based on individual lipoprotein profiles. These observed variations highlight the complexity of individual responses to dietary interventions.
Bronze Age–Early Iron Age tin ingots recovered from four Mediterranean shipwrecks off the coasts of Israel and southern France can now be provenanced to tin ores in south-west Britain. These exceptionally rich and accessible ores played a fundamental role in the transition from copper to full tin-bronze metallurgy across Europe and the Mediterranean during the second millennium BC. The authors’ application of a novel combination of three independent analyses (trace element, lead and tin isotopes) to tin ores and artefacts from Western and Central Europe also provides the foundation for future analyses of the pan-continental tin trade in later periods.
The Hippoboscidae are ectoparasites of birds and mammals, which, as a group, are known to vector multiple diseases. Avipoxvirus (APV) is mechanically vectored by various arthropods and causes seasonal disease in wild birds in the United Kingdom (UK). Signs of APV and the presence of louse flies (Hippoboscidae) on Dunnocks Prunella modularis were recorded over a 16·5-year period in a rural garden in Somerset, UK. Louse flies collected from this site and other sites in England were tested for the presence of APV DNA and RNA sequences. Louse flies on Dunnocks were seen to peak seasonally three weeks prior to the peak of APV lesions, an interval consistent with the previously estimated incubation period of APV in Dunnocks. APV DNA was detected on 13/25 louse flies, Ornithomya avicularia and Ornithomya fringillina, taken from Dunnocks, both with and without lesions consistent with APV, at multiple sites in England. Collectively these data support the premise that louse flies may vector APV. The detection of APV in louse flies, from apparently healthy birds, and from sites where disease has not been observed in any host species, suggests that the Hippoboscidae could provide a non-invasive and relatively cheap method of monitoring avian diseases. This could provide advanced warnings of disease, including zoonoses, before they become clinically apparent.