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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.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
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.
This paper explores some of the problems associated with traditional canonical correlation. A response surface methodology is developed to examine the stability of the derived linear functions, where one wishes to investigate how much the coefficients can change and still be in an ɛ-neighborhood of the globally optimum canonical correlation value. In addition, a discrete (or constrained) canonical correlation method is formulated where the derived coefficients of these linear functions are constrained to be in some small set, e.g., {1, 0, −1}, to aid in the interpretation of the results. An example concerning the psychographic responses of Wharton MBA students of the University of Pennsylvania regarding driving preferences and life-style considerations is provided.
The Students Participating as Ambassadors for Research in Kentucky (SPARK) program provides novel health equity research training and targeted mentorship for undergraduates, particularly those from groups underrepresented in the biomedical and behavioral research and workforce. SPARK aims to address inadequate diversity in the medical and scientific research fields by providing comprehensive research mentorship and skill-building. Unlike most existing research training programs that are brief, focus on laboratory research, or are limited to graduate students and junior faculty, SPARK delivers a 16-month intensive behavioral and population health science training, equipping students with needed tools to conceptualize, plan, execute, and analyze their own health equity research study. Trainees complete didactic coursework on health equity, study design and proposal development, data analysis, and ethics. Students receive a stipend and research expenses, and multiple mentors guide them in creating original research projects for which they serve as Principal Investigator. Students disseminate their findings annually at an academic research conference as a capstone. Evaluation data from the first three cohorts suggest SPARK has been pivotal in preparing students for graduate studies and research careers in health equity and behavioral and population health sciences, providing strong support for further investments in similar undergraduate research training models.
Large datasets, combined with modeling techniques, provide a quantitative way to estimate when known archaeological sites will be impacted by climatological changes. With over 4,000 archaeological sites recorded on the coast of Georgia, USA, the state provides an ideal opportunity to compare methods. Here, we compare the popular passive “bathtub” modeling with the dynamic Sea Level Affecting Marshes Model (SLAMM) combined with the Marshes Equilibrium Model (MEM). The goal of this effort is to evaluate prior modeling and test the benefits of more detailed ecological modeling in assessing site loss. Our findings indicate that although rough counts of archaeological sites destroyed by sea-level rise (SLR) are similar in all approaches, using the latter two methods provides critical information needed in prioritizing site studies and documentation before irrevocable damages occur. Our results indicate that within the next 80 years, approximately 40% of Georgia's coastal sites will undergo a loss of archaeological context due to wetlands shifting from dry ecological zones to transitional marshlands or submerged estuaries and swamps.
Plastics used in agriculture, commonly known as agriplastics (AP), offer numerous advantages in terrestrial agriculture, forestry, fisheries and aquaculture, but the diffusion of AP-intensive practices has led to extensive pollution. This review aims to synthesise scientific and policy discussions surrounding AP, examining evidence of their benefits and detrimental environmental and agricultural impacts. Following the proposal of a preliminary general taxonomy of AP, this paper presents the findings from a survey conducted among international experts from the plastic industry, farmer organisations, NGOs and environmental research institutes. This analysis highlights knowledge gaps, demands and perspectives for the sustainable future use of AP. Stakeholder positions vary on the options of ‘rejection’ or ‘reduction’ of AP, as well as the role of alternative materials such as (bio)degradable and compostable plastics. However, there is consensus on critical issues such as redesign, labelling, traceability, environmental safety standards, deployment and retrieval standards, as well as innovative waste management approaches. All stakeholders express concern for the environment. A ‘best practice’-based circular model was elaborated capturing these perspectives. In the context of global food systems increasingly reliant on AP, scientists emphasise the need to simultaneously preserve nature-based and traditional knowledge-based sustainable agricultural practices to enhance food system resilience.
SCN2A encodes a voltage-gated sodium channel (designated NaV1.2) vital for generating neuronal action potentials. Pathogenic SCN2A variants are associated with a diverse array of neurodevelopmental disorders featuring neonatal or infantile onset epilepsy, developmental delay, autism, intellectual disability and movement disorders. SCN2A is a high confidence risk gene for autism spectrum disorder and a commonly discovered cause of neonatal onset epilepsy. This remarkable clinical heterogeneity is mirrored by extensive allelic heterogeneity and complex genotype-phenotype relationships partially explained by divergent functional consequences of pathogenic variants. Emerging therapeutic strategies targeted to specific patterns of NaV1.2 dysfunction offer hope to improving the lives of individuals affected by SCN2A-related disorders. This Element provides a review of the clinical features, genetic basis, pathophysiology, pharmacology and treatment of these genetic conditions authored by leading experts in the field and accompanied by perspectives shared by affected families. This title is also available as Open Access on Cambridge Core.
When archaeologists discuss ‘ancestor cults’ or ‘ancestor veneration’, what this might entail in practice usually remains vague, leading to charges that the concept of ‘ancestors’ is often applied generically. In this article, the authors combine bioarchaeological, taphonomic, radiocarbon, and isotopic studies to explore the ritual practice of the selective retention, curation, and deposition of a group of human crania and mandibles. Between 5500–5400 bc, Neolithic people at Masseria Candelaro (Puglia, Italy) deposited broken crania and mandibles from about fifteen individuals in a heap in the centre of the village. These individuals were mostly probable males, collected over the course of two centuries and actively used, with their deposition marking the final disposal of a ritual collection. The motivations for the curation of cranial bone are investigated through comparison with archaeological and ethnographic examples, advancing an interpretation of ritual practice directed towards ancestors.
For thousands of years, humans have been entertained by board games. The earliest documented game boards date to at least 6000 BC in the Near East (Sebbane 2001), and we know the name, Senet, and rules of a board game from Egypt dating to 3500–3100 BC. Aspects of inequality are omnipresent in the dynamics of the competition and cooperation inherent in games. In this review, I assess the digital version of the board game Catan, which is also called Catan Universe, discussing how anthropological theories such as human behavioral ecology are recognizable in the digital game. Playing this game provides a unique way to test models of inequality.
Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) when compared to glucose-based carbohydrates(1). Galactose has recently been shown to increase postprandial lipaemia compared to glucose(2), but mechanisms remain uncharacterised. The aim of this study was to assess the effect and mechanisms of lactose-induced lipaemia.
Twenty-four non-obese adults (12 male and 12 female) completed three trials in a randomised, crossover design (28 ± 7-day washout). During trials, participants consumed test drinks containing 50 g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Data were converted into incremental under the curve (iAUC) and were checked for normality by visual inspection of residuals. Differences between trials were assessed by one-way ANOVA. Where a main effect of trial was detected, post- hoc t-tests were performed to determine which trials differed from lactose according to the principle of closed-loop testing.
The plasma triacylglycerol iAUC (mean ± SD) in response to maltodextrin was 51 ± 68 mmol/L*360 min. Following lactose ingestion, plasma triacylglycerol iAUC increased to 98 ± 88 mmol/L*360 min (p<0.001 vs maltodextrin), which was comparable to sucrose [90 ± 95 mmol/L*360 min (p=0.41 vs lactose)]. Hepatic DNL in response to maltodextrin was 6.6 ± 3.0%. Following ingestion of lactose, hepatic DNL increased to 12.4 ± 6.9% (p=0.02 vs maltodextrin), which was comparable to sucrose [12.2 ± 6.9% (p=0.96 vs lactose)]. Exhaled 13CO2 in response to maltodextrin was 10.4 ± 4.1 mmol/kgFFM*360 min. Following ingestion of lactose, exhaled 13CO2 was 8.8 ± 4.9 mmol/kgFFM*360 min (p=0.09 vs maltodextrin), which was lower than sucrose [11.1 ± 3.9 mmol/kgFFM*360 min (p=0.01 vs lactose)].
These data are consistent with the hypothesis that hepatic de novo lipogenesis contributes to both lactose and sucrose-induced lipaemia and provide a rationale to investigate the longer-term effects of lactose and sucrose on metabolism.
The absorption of biologically important purines, pyrimidines, and nucleosides by Li-, Na-, Mg-, and Ca-montmorillonite has been studied in aqueous solutions over a range of pH values 2–12. The initial organic concentrations were about 1 m.molar. The ratio clay to organic compounds was such that only up to 25 per cent of the exchange capacity could be saturated by organic cations, but, depending on conditions, up to 100 per cent of the available organic material was absorbed. Of the nineteen compounds studied, only thymine, uracil, and their nucleosides were not absorbed under the experimental conditions. Absorption occurs primarily as a cation exchange reaction under acid conditions and varies with the basicity of the compounds, their aromatic or non-aromatic character, and the possible extent of their van der Waals interaction with the silicate layers. Nucleosides generally are less strongly absorbed than their purines or pyrimidines because their non-planar structure permits less van der Waals interaction; their absorption is influenced by the differences in swelling behavior of montmorillonite with mono- and divalent cations.
Absorptions of purine and pyrimidine derivatives by Co- and Ni- montmorillonite at pH < 6 and by Cu-montmorillonite at pH < 3 are similar to their absorption by Ca-montmorillonite and take place primarily by a cation exchange process. In the weakly acidic to weakly alkaline range, absorption is due to complex formation with the inorganic cations, and decrease in the order Cu ≫ Ni > Co ≫ Ca. Adenine, 7-methyladenine, hypoxanthine, and purine are strongly absorbed, 9-methyladenine, 6-chloropurine, and cytosine are weakly absorbed, and thymine and uracil are not absorbed. At pH < 5, the nucleosides are absorbed by Co-, Ni-, and Cu-montmorillonite in approximately the same manner as by Ca-montmorillonite, but at pH > 6 their absorptions decrease in the order Cu ≫ Ni > Co > Ca. Fe(III)-montmorillonite behaves quite differently from the other mont-morillonites studied. With purines and pyrimidines, there is strong absorption from pH 3 to pH 7–8; with the nucleosides, the absorption varies considerably with the compounds considered decreasing in the order adenosine > cytidine ≫ guanosine ≫ inosine.
Corrensite or ‘corrensite-like’ minerals occur in dike-intruded shales and siltstones of the Montana Group and Colorado Group (Early Cretaceous) in Western Montana. The < 1 μm size fraction of one specimen of this “corrensite-like” material has been studied in detail. X-ray diffraction data and chemical analysis indicate that this specimen is a regular or nearly regular interstratification of chlorite and dioctahedral smectite. Also described are other samples, which contain corrensite and additional phases. These samples were taken at several localities where basic dikes have intruded these shales and siltstones.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
The majority of excavated human remains from Neolithic Britain emanate from monumental sites. However, it is increasingly recognized that multiple funerary practices are often attested within these monuments, and that diverse treatment of the dead is evident contemporaneously at non-monumental sites. In this paper, we highlight such variation in non-monumental funerary practices in Neolithic Britain (c. 4000–2500 bc) through the biographical study of an assemblage from a large post-hole at Bridlington Boulevard, Yorkshire. Through osteological and taphonomic analysis of the human bones and technological and microwear analysis of the accompanying axehead, we infer complex funerary processes, with the expediently manufactured axehead potentially featuring in the funerary rites and subsequent post-raising before being deposited in the feature. Bridlington Boulevard represents one element of a varied funerary complex—cremations in pits and post-holes—at a time when most individuals were not deposited in monuments, or indeed were not deposited at all. Compiling these non-monumental cremations across Britain causes us to look beyond categorizing these assemblages as funerary contexts, and instead suggests important cosmological associations and forces were brought together in pit and post-and-human cremation deposits.
The research objectives were to evaluate factors that influence Canadian secondary school students’ milk and milk alternatives (MMA) consumption and to explore associations through age and gender lenses.
Design:
A qualitative design was used, consisting of semi-structured interviews and photo-elicitation methods. Analysis was guided by the Theory of Planned Behaviour (TPB). Deductive and inductive thematic analyses were used to generate themes, charting data based on attributes such as gender and age.
Setting:
Interviews were held virtually or via telephone.
Participants:
Participants were twenty-eight high school students from Ontario, Canada, diverse in terms of gender and age.
Results:
Both desirable and undesirable beliefs about the health outcomes of consuming MMA were commonly discussed. These included health benefits such as strong bones, muscular strength, and growth, and health consequences like unwanted skin conditions, weight gain, and diseases. While boys and girls associated MMA consumption with muscular strength, boys predominantly considered this favourable, while girls discussed outcomes like unwanted skin conditions and weight gain more often. Adolescents’ perspectives on taste/perceived enjoyment, environmentally friendly choices and animal welfare also influenced their MMA preferences. Parental influences were most cited among social factors, which appeared to be stronger during early adolescence. Factors involving cost, time and accessibility affected adolescents’ beliefs about how difficult it was to consume MMA.
Conclusions:
Recommendations for shifting attitudes towards MMA are provided to address unfavourable beliefs towards these products. Interventions to increase MMA consumption among adolescents should include parents and address cost barriers.
Double hydroxide solids precipitated homogeneously from three laboratory-synthesized aqueous solutions that simulated mildly contaminated surface or groundwater. Over a limited pH range, precipitates formed rapidly from dissolved ions, and more slowly by incorporating ions dissolving from other solids, including highly soluble aluminous solids. The precipitates were characterized by size and shape via transmission electron microscopy (TEM), by composition via inductively coupled plasma-mass spectrometry (ICP-MS) of mother solutions and analytical electron microscopy (AEM) of precipitates, and by structure via powder X-ray diffraction (XRD), TEM, and extended X-ray absorption fine structure (EXAFS) spectroscopy. They were identified as nanocrystalline cobalt hydrotalcite (CoHT) of the form [Co(II)1-xAl(III)x(OH)2]x+(An−x/n)·mH2O, with x = 0.17–0.25, A = CO32−, NO3−, or H3SiO4−n = anion charge and m undetermined. Complete solid solution may exist at the macroscopic level for the range of stoichiometrics reported, but clustering of Co atoms within hydroxide layers indicates a degree of immiscibility at the molecular scale. Composition evolved toward the Co-rich endmember with time for at least one precipitate. The small layer charge in the x = 0.17 precipitate caused anionic interlayers to be incomplete, producing interstratification of hydrotalcite and brucite-like layers. Solubility products estimated from solution measurements for the observed final CoHT stoichiometries suggest that CoHT is less soluble than the inactive forms of Co(OH)2 and CoCO3 near neutral pH. Low solubility and rapid formation suggest that CoHT solids may be important sinks for Co in contact with near neutral pH waters. Because hydrotalcite can incorporate a range of transition metals, precipitation of hydrotalcite may be similarly effective for removing other trace metals from natural waters.
Bulk and size-fractionated kaolinites from seven localities in Australia as well as the Clay Minerals Society Source Clays Georgia KGa-1 and KGa-2 have been studied by X-ray diffraction (XRD), laser scattering, and electron microscopy in order to understand the variation of particle characteristics across a range of environments and to correlate specific particle characteristics with intercalation behavior. All kaolinites have been intercalated with N-methyl (NMF) after pretreatment with hydrazine hydrate, and the relative efficiency of intercalation has been determined using XRD. Intercalate yields of kaolinite: NMF are consistently low for bulk samples that have a high proportion of small-sized particles (i.e., <0.5 µm) and for biphased kaolinites with a high percentage (>60%) of low-defect phase. In general, particle size appears to be a more significant controlling factor than defect distribution in determining the relative yield of kaolinite: NMF intercalate.