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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.
Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.
Methods
Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.
Results
The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).
Conclusions
Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.
The National Science Foundation (NSF) Daniel K. Inouye Solar Telescope (DKIST) has started operations at the summit of Haleakalā (Hawai’i). DKIST joins the nominal science phases of the NASA and ESA Parker Solar Probe and Solar Orbiter encounter missions. By combining in-situ measurements of the near-Sun plasma environment and detailed remote observations of multiple layers of the Sun, the three observatories form an unprecedented multi-messenger constellation to study the magnetic connectivity in the solar system. This work outlines the synergistic science that this multi-messenger suite enables.
Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines.
Method
This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre.
Results
A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49–44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23–121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older (p = 0.042), had a longer duration of symptoms prior to imaging (p < 0.0001) and higher C-reactive protein at diagnosis (p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days; p = 0.032), complex cases were more likely to relapse (p = 0.016).
Conclusion
A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.
Seeman, Morris, and Summers misrepresent or misunderstand the arguments we have made, as well as their own previous work. Here, we correct these inaccuracies. We also reiterate our support for hypothesis-driven and evidence-based research.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$11–18 arcsec, resulting in a catalogue of $\sim$220 000 sources, of which $\sim$180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
Objectives:
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Methods:
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Results:
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Conclusion:
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
Stone was a critical resource for prehistoric hunter-gatherers. Archaeologists, therefore, have long argued that these groups would actively have sought out stone of ‘high quality’. Although the defining of quality can be a complicated endeavour, researchers in recent years have suggested that stone with fewer impurities would be preferred for tool production, as it can be worked and used in a more controllable way. The present study shows that prehistoric hunter-gatherers at the Holocene site of Welling, in Ohio, USA, continuously selected the ‘purest’ stone for over 9000 years.
Ronald Mason’s hypothesis from the 1960s that the southeastern United States possesses greater Paleoindian projectile-point diversity than other regions is regularly cited, and often assumed to be true, but in fact has never been quantitatively tested. Even if valid, however, the evolutionary meaning of this diversity is contested. Point diversity is often linked to Clovis “origins,” but point diversity could also arise from group fissioning and drift, admixture, adaptation, or multiple founding events, among other possibilities. Before archaeologists can even begin to discuss these scenarios, it is paramount to ensure that what we think we know is representative of reality. To this end, we tested Mason’s hypothesis for the first time, using a sample of 1,056 Paleoindian points from eastern North America arui employing paradigmatic classification and rigorous statistical tools used in the quantification of ecological biodiversity. Our first set of analyses, which compared the Southeast to the Northeast, showed that the Southeast did indeed possess significantly greater point-class richness. Although this result was consistent with Mason’s hypothesis, our second set of analyses, which compared the Upper Southeast to the Lower Southeast and the Northeast showed that in terms of point-class richness the Upper Southeast > Lower Southeast > Northeast. Given current chronometrie evidence, we suggest that this latter result is consistent with the suggestion that the area of the Ohio, Cumberland, and Tennessee River valleys, as well as the mid-Atlantic coastal plain, were possible initial and secondary “staging areas” for colonizing Paleoindian foragers moving from western to eastern North America.
Recently, advocates of an “older -than- Clovis” occupation of eastern North America have suggested that bi-pointed leaf-shaped lanceolate stone bifaces provide definitive evidence of human culture on the eastern seaboard prior to the Late Glacial Maximum. This argument hinges on two suppositions : first, that points of this form are exceedingly rare in the East and second, that all known occurrences of these point forms are from landforms or depositionaI environments dating to some time before the late Pleistocene. Neither of these suppositions is supported by the archaeological record. Bi-pointed leaf shaped blades have been recoveredfrom throughout the Middle Atlantic and Northeast, where they have been repeatedly dated, either radiometrically or by association with diagnostic artifacts, to between the Late Archaic and the Early Woodland. Statistical analysis of supposed “older-than-Clovis” leaf-shaped blades demonstrates that there are no significant differences in morphology between them and unequivocally Middle Holocene leaf-shaped blades. Until such time as evidence demonstrates otherwise, there is no reason to accept that these leaf-shaped bifaces are diagnostic of a Pleistocene, much less pre-Late Glacial Maximum, occupation in eastern North America.
Electrochemical reactions at both positive and negative electrodes in a nickel metal hydride (Ni-MH) battery during charge have been investigated by in situ neutron powder diffraction. Commercially available β-Ni(OH)2 and LaNi5-based powders were used in this experiment as positive and negative electrodes, respectively. Exchange of hydrogen by deuterium for the β-Ni(OH)2 electrode was achieved by ex situ cycling of the cell prior to in situ measurements. Neutron diffraction data collected in situ show that the largest amount of deuterium contained at the positive electrode is de-intercalated from the electrode with no phase transformation involved up to ∼100 mA h/g and, in addition, the 110 peak width for the positive electrode increases on charge. The negative electrode of composition MmNi3.6Al0.4Mn0.3Co0.7, where Mm = Mischmetal, exhibits a phase transformation to an intermediate hydride γ phase first and then to the β phase on charge. Unit cell dimensions and phase fractions have been investigated by Rietveld refinement of the crystal structure.
The comments of Stanford and Bradley (above) do not address our criticisms and obfuscate the topic at hand with irrelevant data (e.g. the south-to-north movement of fluted points through the Ice Free Corridor), nonexistent data (e.g. ‘under the water’ or ‘destroyed sites’), and questionable data (e.g. Meadowcroft and Cactus Hill are by no means widely accepted, nor are Stanford and Bradley's ‘eight LGM sites’ in the mid-Atlantic region). Before touching on some of these points, we direct the reader to several recent articles (e.g. Morrow 2014; Raff & Bolnick 2014) that provide new evidence or arguments inconsistent with a trans-Atlantic migration, including the fact that DNA from the Clovis Anzick child (Montana) shows no European ancestry (Rasmussen et al. 2014). Although Stanford and Bradley describe their Solutrean ‘solution’ (Stanford & Bradley 1999) to the Pleistocene colonisation of North America as ‘testable’, their position is that the idea is correct until falsified. They propose that their colleagues have yet to provide sufficient ‘critiques’ or ‘challenges’ to discount it (see also Collins 2012; Collins et al. 2013). Yet they are the ones proposing a hypothesis inconsistent with overwhelming multidisciplinary evidence, and they ignore results of tests that do not support their claims.
Across Atlantic ice: the origin of America's Clovis culture (Stanford & Bradley 2012) is the latest iteration of a controversial proposal that North America was first colonised by people from Europe rather than from East Asia, as most researchers accept. The authors, Dennis Stanford and Bruce Bradley, argue that Solutrean groups from southern France and the Iberian Peninsula used watercraft to make their way across the North Atlantic and into North America during the Last Glacial Maximum (LGM). According to Stanford and Bradley, this 6000km journey was facilitated by a continuous ice shelf that provided fresh water and a food supply. Across Atlantic ice has received a number of positive reviews. Shea (2012: 294), for example, suggests that it is “an excellent example of hypothesis-building in the best tradition of processual archaeology. It challenges American archaeology in a way that will require serious research by its opponents”. Runnels (2012) is equally enthusiastic.