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Childhood maltreatment (CM) is a risk factor for mental and physical health problems in adulthood, potentially mediated by long-term autonomic nervous system (ANS) dysregulation. To explore this link, the association between CM and vagal-sensitive heart rate variability (HRV) metrics in adults was examined, accounting for biopsychosocial factors.
Methods
Data from 4,420 participants in the Study of Health in Pomerania were analyzed, with CM assessed using the Childhood Trauma Questionnaire. HRV was derived from 10-second electrocardiograms and 5-minute pre-sleep polysomnographic recordings. Post hoc analyses examined abuse and neglect.
Results
CM was associated with reduced HRV (logRMSSD: β = −0.20 [95%-CI: −0.28, −0.12], p = 1.2e−06), driven by neglect (β = −0.27 [−0.35, −0.18], p = 1.9e−09) rather than abuse (β = 0.01 [−0.12, 0.14], p = 1). Adjustments for age, sex, and medication attenuated these effects, which remained robust after additionally controlling for socioeconomic, lifestyle, body mass index, and depressive symptoms (fully adjusted model: CM β = −0.08 [−0.15, −0.001], p = .047; neglect β = −0.11 [−0.19, −0.03], p = .009; abuse β = −0.08 [−0.20, −0.04], p = .174). Age-related differences were found, with reduced HRV in both young and older participants but not in middle-aged participants (fully adjusted: F(2,743) = 6.75, p = .001).
Conclusions
This study highlights long-term ANS dysregulation following CM, particularly neglect, indicated by altered vagal-sensitive HRV metrics. Although small in magnitude, the effect on the ANS was independent of adult biopsychosocial factors. This long-term dysregulation may contribute to an increased risk of adverse health outcomes in adulthood.
Although suicide claims more lives than war and homicide, we still have no sufficient and effective methods either for its prediction or for its prevention. Our screening methods are laborous and subjective both on the side of the patient and on the side of the clinician. Understanding the genetic background of suicidal behaviour would help identify biomarkers for screening as well as pathways as potential targets for novel intervention and prevention approaches. However, in spite of a number of GWAS studies, results are few and rarely replicate, and generally accurate phenotyping and sufficient consideration of environmental stressors is also missing.
Objectives
In our present study we performed a genome-wide analysis study for suicidal ideation in interaction with early childhood traumas in a deep-phenotyped general population sample.
Methods
Our analysis used data from 1800 volunteers in the NewMood project. As outcome phenotype the suicidal ideation item of the Brief Symptom Inventory was used. A modified version of the Childhood Trauma Questionnaire was used to assess early adverse experiences. A genome-wide association analysis was performed with Plink 1.9, including a total of 3,474,641 variants after quality control steps, followed by genome-wide by environment interaction analyses. Our models included control variables for sex, age, and the top 10 genomic principal components. Functional annotation of SNPs was carried out using FUMA v1.5.6, gene-based tests were performed using MAGMA v1.08.
Results
7 SNPs met suggestive significance in main effect analyses, of which 2 reached genome-wide significance including rs79912020 (p=3.21E-10, β=0.746) and rs10236520 (p=1.71E-08, β=0.484), with no significant findings in gene-based tests. Interaction analyses with childhood adversities yielded 31 SNPs that met genome-wide significance, including rs7983955 (p=2.28E-11, β=0.182), rs141039461 (p=3.90E-11, β=0.0541), rs12692827 (p=3.69E-10, β=0.0612) as the top SNPs. In interaction with childhood adversities, 31 genes showed a significant association in gene-based tests, including RBFOX1 (p=1.09E-10), GRM7 (p=1.20E-10), MTCH1 (p=5.59E-09), and CDH13 (p=6.60E-09) as the most significant findings.
Conclusions
Our results indicate several important novel SNPs associated with suicidal ideation when considered in interaction with the effect of childhood adversities. Furthermore, gene-based analyses replicate several genes playing a key role in central nervous system function such as GRM7 (encoding metabotropic glutamate receptor 7) or previously implicated in association with suicide (CDH13) or suicide-related factors such as aggression (RBFOX1).
Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.
Methods:
We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.
Results:
In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).
Conclusion:
Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.
Odd Radio Circles (ORCs) are a class of low surface brightness, circular objects approximately one arcminute in diameter. ORCs were recently discovered in the Australian Square Kilometre Array Pathfinder (ASKAP) data and subsequently confirmed with follow-up observations on other instruments, yet their origins remain uncertain. In this paper, we suggest that ORCs could be remnant lobes of powerful radio galaxies, re-energised by the passage of a shock. Using relativistic hydrodynamic simulations with synchrotron emission calculated in post-processing, we show that buoyant evolution of remnant radio lobes is alone too slow to produce the observed ORC morphology. However, the passage of a shock can produce both filled and edge-brightnened ORC-like morphologies for a wide variety of shock and observing orientations. Circular ORCs are predicted to have host galaxies near the geometric centre of the radio emission, consistent with observations of these objects. Significantly offset hosts are possible for elliptical ORCs, potentially causing challenges for accurate host galaxy identification. Observed ORC number counts are broadly consistent with a paradigm in which moderately powerful radio galaxies are their progenitors.
Recent research has shown the potential of speleothem δ13C to record a range of environmental processes. Here, we report on 230Th-dated stalagmite δ13C records for southwest Sulawesi, Indonesia, over the last 40,000 yr to investigate the relationship between tropical vegetation productivity and atmospheric methane concentrations. We demonstrate that the Sulawesi stalagmite δ13C record is driven by changes in vegetation productivity and soil respiration and explore the link between soil respiration and tropical methane emissions using HadCM3 and the Sheffield Dynamic Global Vegetation Model. The model indicates that changes in soil respiration are primarily driven by changes in temperature and CO2, in line with our interpretation of stalagmite δ13C. In turn, modelled methane emissions are driven by soil respiration, providing a mechanism that links methane to stalagmite δ13C. This relationship is particularly strong during the last glaciation, indicating a key role for the tropics in controlling atmospheric methane when emissions from high-latitude boreal wetlands were suppressed. With further investigation, the link between δ13C in stalagmites and tropical methane could provide a low-latitude proxy complementary to polar ice core records to improve our understanding of the glacial–interglacial methane budget.
To review methodologies and outcomes reporting among these studies and to develop a conceptual framework of outcomes to assist in guiding studies and production of clinical metrics.
Data sources:
PubMed and Embase from January 1, 2012, thru December 1, 2021.
Study eligibility criteria:
Studies evaluating highly multiplex molecular respiratory diagnostics and their impact on either clinical or economic outcomes.
Methods:
A systematic literature review (SLR) of methodologies and outcomes reporting was performed. A qualitative synthesis of identified SLRs and associated primary studies was conducted to develop conceptual framework for outcomes.
Results:
Ultimately, 4 systemic literature reviews and their 12 associated primary studies were selected for review. Most primary studies included patient outcomes focusing on antimicrobial exposure changes such as antibiotic (80%) and antiviral use (50%) or occupancy changes such as hospital length of stay (60%). Economic outcomes were infrequently reported, and societal outcomes, such as antibiotic resistance impact, were absent from the reviewed literature. Qualitative evidence synthesis of reported outcomes yielded a conceptual framework of outcomes to include operational, patient, economic, and societal domains.
Conclusions:
Our review highlights the significant heterogeneity in outcomes reporting among clinical impact studies for highly multiplex molecular respiratory diagnostics. Furthermore, we developed a conceptual framework of outcomes domains that may act as a guide to improve considerations in outcomes selection and reporting when evaluating clinical impact of these tests. These improvements may be important in synthesizing the evidence for informing clinical decision making, guidelines, and financial reimbursement.
Walking ability is related to motor co-ordination which, in rodents, can be assessed by an established test in pharmacological studies — the rotarod test. The purpose of this study was to evaluate a modified rotarod test for chickens and its relation to the often-used gait score system. At the end of their rearing period, we tested 138 male chickens (Gallus gallus domesticus) from three differing growth performance strains: Ross 308 (fast-growing; n = 46), Lohmann Dual (medium-growing; n = 46) and Lohmann Brown Plus (slow-growing; n = 46). First, the chickens’ gait scores were assessed and, immediately following this, they were placed gently onto a steady rod. The velocity of the rotating rod gradually increased, and the latency to leave the rod was recorded. By using a linear mixed model, we were able to show that the latency to leave the rotating rod was significantly predicted by the gait score. Fast-growing chickens had shorter durations on the rotating rod, and these durations were associated with gait score. We conclude that the rotarod test provides an objective alternative method for assessing walking ability in chickens without the need for intense observer training or the risk of observer biases and propose that this novel methodology has the potential to function as a precise, objective indicator of animal welfare.
The cosmic evolution of the chemical elements from the Big Bang to the present time is driven by nuclear fusion reactions inside stars and stellar explosions. A cycle of matter recurrently re-processes metal-enriched stellar ejecta into the next generation of stars. The study of cosmic nucleosynthesis and this matter cycle requires the understanding of the physics of nuclear reactions, of the conditions at which the nuclear reactions are activated inside the stars and stellar explosions, of the stellar ejection mechanisms through winds and explosions, and of the transport of the ejecta towards the next cycle, from hot plasma to cold, star-forming gas. Due to the long timescales of stellar evolution, and because of the infrequent occurrence of stellar explosions, observational studies are challenging, as they have biases in time and space as well as different sensitivities related to the various astronomical methods. Here, we describe in detail the astrophysical and nuclear-physical processes involved in creating two radioactive isotopes useful in such studies, $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$. Due to their radioactive lifetime of the order of a million years, these isotopes are suitable to characterise simultaneously the processes of nuclear fusion reactions and of interstellar transport. We describe and discuss the nuclear reactions involved in the production and destruction of $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$, the key characteristics of the stellar sites of their nucleosynthesis and their interstellar journey after ejection from the nucleosynthesis sites. This allows us to connect the theoretical astrophysical aspects to the variety of astronomical messengers presented here, from stardust and cosmic-ray composition measurements, through observation of $\gamma$ rays produced by radioactivity, to material deposited in deep-sea ocean crusts and to the inferred composition of the first solids that have formed in the Solar System. We show that considering measurements of the isotopic ratio of $^{26}\mathrm{Al}$ to $^{60}\mathrm{Fe}$ eliminate some of the unknowns when interpreting astronomical results, and discuss the lessons learned from these two isotopes on cosmic chemical evolution. This review paper has emerged from an ISSI-BJ Team project in 2017–2019, bringing together nuclear physicists, astronomers, and astrophysicists in this inter-disciplinary discussion.
Current first-line treatments for paediatric depression demonstrate mild-to-moderate effectiveness. This has spurred a growing body of literature on lifestyle recommendations pertaining to nutrition, sleep and exercise for treating paediatric depression.
Aims
Paediatric depression clinical practice guidelines (CPGs) were reviewed for quality and to catalogue recommendations on nutrition, sleep and exercise made by higher-quality CPGs.
Method
Searches were conducted in Medline, EMBASE, PsycINFO, Web of Science and CINAHL, and grey literature CPGs databases for relevant CPGs. Eligible CPGs with a minimum or high-quality level, as determined by the Appraisal of Guidelines for Research and Evaluation, Second Edition instrument, were included if they were (a) paediatric; (b) CPGs, practice parameter or consensus or expert committee recommendations; (c) for depression; (d) the latest version and (e) lifestyle recommendations for nutrition, sleep or exercise. Key information extracted included author(s), language, year of publication, country, the institutional body issuing the CPG, target disorder, age group, lifestyle recommendation and the methods used to determine CPG lifestyle recommendations.
Results
Ten paediatric CPGs for depression with a minimum or high-quality level contained recommendations on nutrition, sleep or exercise. Lifestyle recommendations were predominately qualitative, with quantitative details only outlined in two CPGs for exercise. Most recommendations were brief general statements, with 50% lacking supporting evidence from the literature.
Conclusions
Interest in lifestyle interventions for treatment in child and youth depression is growing. However, current CPG lifestyle recommendations for nutrition, sleep or exercise are based on expert opinion rather than clinical trials.
In 1968, a weapon grave with brooches was found at Suontaka Vesitorninmäki, Hattula, Finland. Since then, the grave has been interpreted as evidence of powerful women, even female warriors and leaders in early medieval Finland. Others have denied the possibility of a woman buried with a sword and tried to explain it as a double burial. We present the first modern analysis of the grave, including an examination of its context, a soil sample analysis for microremains, and an aDNA analysis. Based on these analyses, we suggest a new interpretation: the Suontaka grave possibly belonged to an individual with sex-chromosomal aneuploidy XXY. The overall context of the grave indicates that it was a respected person whose gender identity may well have been non-binary.
The coronavirus disease 2019 (COVID-19) has greatly impacted health-care systems worldwide, leading to an unprecedented rise in demand for health-care resources. In anticipation of an acute strain on established medical facilities in Dallas, Texas, federal officials worked in conjunction with local medical personnel to convert a convention center into a Federal Medical Station capable of caring for patients affected by COVID-19. A 200,000 square foot event space was designated as a direct patient care area, with surrounding spaces repurposed to house ancillary services. Given the highly transmissible nature of the novel coronavirus, the donning and doffing of personal protective equipment (PPE) was of particular importance for personnel staffing the facility. Furthermore, nationwide shortages in the availability of PPE necessitated the reuse of certain protective materials. This article seeks to delineate the procedures implemented regarding PPE in the setting of a COVID-19 disaster response shelter, including workspace flow, donning and doffing procedures, PPE conservation, and exposure event protocols.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly (e.g. increased interleukin-6 and tumour necrosis factor-alpha). COX-2 inhibitors down-regulate increased inflammatory markers and are therefore investigated as an add-on therapy in depression. Proinflammatory cytokines and/or kynurenine metabolites may predict the outcome of treatment with COX-2 inhibitors.
Objectives
To prove or disapprove the hypothesis of a better therapy response in the group of add-on celecoxib to sertraline, particularly in patients with a more pronounced proinflammatory state at baseline. The aim is to find a biological predictor (cytokines and/or kynurenine metabolites) for treatment outcome.
Design
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study. It investigates the mean change in clinical outcome and in serum cytokine and kynurenine levels from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with sertraline plus celecoxib versus sertraline plus placebo for six weeks. 51 depressed patients of both gender, aged between 18 and 60 years without any recent inflammatory disease were enrolled. The study comprises six study visits (6x ratings, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline. Cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA), kynurenine and its metabolites by High Performance Liquid Chromatography (HPLC).
Results and Conclusion
The study was completed quite recently and the results are in progress.
As German reunification took place in 1990 Eastern Germany as a former socialist country (GDR) became part of democratic Germany. It underwent dramatic changes influencing all parts of society.
Objectives
Our objective was to analyse all suicides in the Eastern German City Magdeburg based on all relevant police files.
Aims
Little is known about the former GDR and its suicide rates since no official data existed. Our aim was to investigate differences in suicide rates by age and sex in one city of the former GDR before and after reunification.
Methods
As part of GDR-time the period 1985 - 1989 (A) and as post-reunification time the period 1999 - 2004 (B) were analysed. Basis of our investigation were all police files. Absolute suicide numbers were counted. Suicide rates were calculated per 100.000 persons, sex and year. Different age structures became comparable by using the old standard population of Europe (WHO 1976).
Results
We identified 470 suicides in period A and 206 suicides in period B. For both sexes suicide rates were significantly higher in period A and increased with age. Women had generally lower suicide rates. Age-standardized rates show a reduction for males of about 50% and for females of two thirds in comparison of the two periods.
Conclusions
Suicide rates decreased in our analysed city dramatically. Women in general and particularly elder groups have lower suicide rates and thus benefited most. There are various contributing factors such as positive changes in health care and social support.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly, for example an increase in interleukin-6 and tumour necrosis factor-a is well documented. Treatment with COX-2 inhibitors down-regulate increased inflammatory markers. Therefore an adjunctive treatment of depression with COX-2 in combination with an antidepressant might lead to a better clinical outcome.
Objectives
To prove or disapprove the hypothesis of a better clinical outcome in the group with add-on celecoxib to sertraline in terms of improvement of HamD-17 and MADRS scores from baseline to endpoint.
Design
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study to investigate the mean change in clinical outcome and in serum expression of inflammation markers from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with celecoxib in combination with sertraline compared to sertraline combined with placebo. 51 depressed patients of both gender, aged between 18 and 60 without any recent inflammatory related disease were enrolled. The study comprises six study visits (6x ratings including HAMD-17 and MADRS, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline.
Results and Conclusion
The study was completed quite recently and the results are in progress.
A duality theorem for the singularity category of a finite dimensional Gorenstein algebra is proved. It complements a duality on the category of perfect complexes, discovered by Happel. One of its consequences is an analogue of Serre duality, and the existence of Auslander–Reiten triangles for the $\mathfrak{p}$-local and $\mathfrak{p}$-torsion subcategories of the derived category, for each homogeneous prime ideal $\mathfrak{p}$ arising from the action of a commutative ring via Hochschild cohomology.
Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
This research seeks to understand the economic and social interaction patterns among dispersed Piedmont Village Tradition communities in the North American Southeast, AD 1200–1600. Piedmont Village Tradition communities lived adjacent to Mississippian societies and have been categorized as a peripheral society because of this spatial relationship. We examine economic behaviors by constructing fall-off curves of local versus nonlocal lithic material proportions at settlement sites and examining the reduction behaviors and tool types at sites. The results support a possible gateway model for the acquisition and distribution of nonlocal materials that linked spatially proximate communities. To examine social interaction patterns, we conducted a Brainerd-Robinson analysis of ceramic attributes from six sites and combined our results with work by Rogers (1993). The results show sites with stylistic similarities are not the same sites that share lithic resources. We conclude that these spatially non-overlapping artifact patterns result from a heterarchical social organization with a high degree of independence between economic and social interactions. Finally, we contextualize our results within the current knowledge of Mississippian and Piedmont Village Tradition societies in the region to broaden the discussion of gateways in reciprocity-based economies, societies traditionally thought of as peripheral to complex societies, and coalescence.
A duality theorem for the stable module category of representations of a finite group scheme is proved. One of its consequences is an analogue of Serre duality, and the existence of Auslander–Reiten triangles for the $\mathfrak{p}$-local and $\mathfrak{p}$-torsion subcategories of the stable category, for each homogeneous prime ideal $\mathfrak{p}$ in the cohomology ring of the group scheme.