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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.
This study utilized a novel, observational paradigm to identify functional patterns of father responsiveness to child distress. In particular, we sought to identify a pattern of caregiving deactivation characterized by parenting behavior that functioned to minimize activation of the caregiving behavioral system. We also sought to identify a pattern of caregiving hyperactivation characterized by parenting behavior that functioned to maintain or heighten caregiving system activation. In turn, we examined whether caregiving deactivation and hyperactivation were differentially associated with children’s socioemotional development over a two-year period. Participants included 235 fathers (55% White) and children (Mage = 2.97; 55% female) who visited the laboratory at two measurement occasions spaced approximately two years apart. A path model analysis revealed that caregiving deactivation was uniquely associated with decreases in children’s oppositional defiance and hostility over a two-year period. In contrast, caregiving hyperactivation was uniquely associated with increases in children’s anxiety and social disengagement two years later. The findings highlight the importance of considering both form and function in parenting behavior and provide evidence on the importance of considering fathers’ caregiving behavior.
Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.
Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021.
Methods:
CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively.
Results:
Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles.
Conclusions:
To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.
Lithofacies and biostratigraphical analysis has enabled the establishment of a stratigraphic event framework for Ludfordian and Pridoli strata in south Wales and the Welsh Borderland. In SW Wales, the Golden Grove Axis acted as a structural hinge separating the shallow marine storm-influenced Cae’r mynach Seaway from a pediment surface above which Ludfordian colluvium (Abercyfor Formation) was deposited. The Axis seeded four NW-derived river-influenced delta progrades of Leintwardinian to early Pridoli age (Tilestones Formation). A NE-sourced early Pridoli wave-influenced delta deposited the Downton Castle Sandstone Formation (DCSF), coeval to the youngest Tilestones prograde, with a lateral interface existing between Mynydd Epynt and the Clun Forest area. Except for the Malverns area, the DCSF is no longer recognized south of the Neath Disturbance. Early Pridoli forced regression promoted widespread subaerial exposure north of the Neath Disturbance, with incision into tracts close to the Welsh Borderland Fault System. The basinward-shift in facies belts resulted in marine erosion and deposition of a phosphatic ravinement pebble lag. The wave-influenced Clifford’s Mesne Sandstone Formation delta subsequently seeded on the Gorsley Axis with tidally influenced Rushall Formation accumulating in a back-barrier setting. The Pwll-Mawr Formation records the easterly advance of coeval coastal deposits on the western side of the remnant Cae’r mynach Seaway. Behind migrating delta coastlines, green muds accumulated on coastal plains (Temeside Mudstone Formation) with better drained red dryland alluvium (Moor Cliffs Formation) charting expansion of Old Red Sandstone lithofacies. Mid-Pridoli incision preserves the Pont ar Llechau Formation estuarine valley fill.
As the scale of cosmological surveys increases, so does the complexity in the analyses. This complexity can often make it difficult to derive the underlying principles, necessitating statistically rigorous testing to ensure the results of an analysis are consistent and reasonable. This is particularly important in multi-probe cosmological analyses like those used in the Dark Energy Survey (DES) and the upcoming Legacy Survey of Space and Time, where accurate uncertainties are vital. In this paper, we present a statistically rigorous method to test the consistency of contours produced in these analyses and apply this method to the Pippin cosmological pipeline used for type Ia supernova cosmology with the DES. We make use of the Neyman construction, a frequentist methodology that leverages extensive simulations to calculate confidence intervals, to perform this consistency check. A true Neyman construction is too computationally expensive for supernova cosmology, so we develop a method for approximating a Neyman construction with far fewer simulations. We find that for a simulated dataset, the 68% contour reported by the Pippin pipeline and the 68% confidence region produced by our approximate Neyman construction differ by less than a percent near the input cosmology; however, they show more significant differences far from the input cosmology, with a maximal difference of 0.05 in $\Omega_{M}$ and 0.07 in w. This divergence is most impactful for analyses of cosmological tensions, but its impact is mitigated when combining supernovae with other cross-cutting cosmological probes, such as the cosmic microwave background.
Prior to the COVID-19 pandemic, our research group initiated a pediatric practice-based randomized trial for the treatment of childhood obesity in rural communities. Approximately 6 weeks into the originally planned 10-week enrollment period, the trial was forced to pause all study activity due to the COVID-19 pandemic. This pause necessitated a substantial revision in recruitment, enrollment, and other study methods in order to complete the trial using virtual procedures. This descriptive paper outlines methods used to recruit, enroll, and manage clinical trial participants with technology to obtain informed consent, obtain height and weight measurements by video, and maintain participant engagement throughout the duration of the trial.
Methods:
The study team reviewed the IRB records, protocol team meeting minutes and records, and surveyed the site teams to document the impact of the COVID-19 shift to virtual procedures on the study. The IRB approved study changes allowed for flexibility between clinical sites given variations in site resources, which was key to success of the implementation.
Results:
All study sites faced a variety of logistical challenges unique to their location yet successfully recruited the required number of patients for the trial. Ultimately, virtual procedures enhanced our ability to establish relationships with participants who were previously beyond our reach, but presented several challenges and required additional resources.
Conclusion:
Lessons learned from this study can assist other study groups in navigating challenges, especially when recruiting and implementing studies with rural and underserved populations or during challenging events like the pandemic.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Method
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Results
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
Conclusions
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
Decumulation Pathways are proposed to help achieve better retirement outcomes for those with Defined Contribution (DC) pensions. The DC fund is split into two parts, in proportions of the consumer’s choice. Most is allocated to the Pension Fund to provide a lifetime income, while the rest is placed in the Flexible Fund for flexible access and/or to leave as a legacy. The Flexible Fund is invested in flexi-access drawdown. The Pension Fund is invested in a guaranteed annuity, Collective Defined Contribution, or a Pooled Pension Fund which maintains individual DC funds but pools longevity risk between participants. An illustrative standard Decumulation Pathway is intended as a default solution, or can be tailored by the consumer. It uses the Pooled Pension Fund, an automated withdrawal strategy which ensures a lifetime income is provided and one that aims to increase in line with inflation, and a moderate risk investment strategy. The standard approach is evaluated using various metrics, indicating that it has as a strong chance of providing a higher income than could be obtained from an annuity or drawdown, with limited downside risk.
We present Hubble Space Telescope Wide Field Camera 3 photometric and grism observations of the candidate ultra-high-redshift ($z>7$) radio galaxy, GLEAM J0917–0012. This radio source was selected due to the curvature in its 70–230 MHz, low-frequency Murchison Widefield Array radio spectrum and its faintness in K-band. Follow-up spectroscopic observations of this source with the Jansky Very Large Array and Atacama Large Millimetre Array were inconclusive as to its redshift. Our F105W and F0986M imaging observations detect the host of GLEAM J0917–0012 and a companion galaxy, $\sim$ one arcsec away. The G102 grism observations reveal a single weak line in each of the spectra of the host and the companion. To help identify these lines we utilised several photometric redshift techniques including template fitting to the grism spectra, fitting the ultraviolet (UV)-to-radio photometry with galaxy templates plus a synchrotron model, fitting of the UV-to-near-infrared photometry with EAZY, and fitting the radio data alone with RAiSERed. For the host of GLEAM J0917–0012 we find a line at $1.12\,\mu$m and the UV-to-radio spectral energy distribution (SED) fitting favours solutions at $z\sim 2$ or $z\sim 8$. While this fitting shows a weak preference for the lower redshift solution, the models from the higher redshift solution are more consistent with the strength of the spectral line. The redshift constraint by RAiSERed of $>6.5$ also supports the interpretation that this line could be Lyman$-\alpha$ at $z=8.21$; however EAZY favours the $z\sim 2$ solution. We discuss the implications of both solutions. For the companion galaxy we find a line at $0.98\,\mu$m and the SED fitting favours solutions at $z<3$ implying that the line could be the [OII]$\lambda3727$ doublet at $z=1.63$ (although the EAZY solution is $z\sim 2.6\pm 0.5$). Further observations are still required to unambiguously determine the redshift of this intriguing candidate ultra-high-redshift radio galaxy.
Building on Ellis et al.’s theorization for potent dimensions of environmental adversity, the present work sought to evaluate how environmental harshness and unpredictability might function directly and in interaction with child sensory processing sensitivity (SPS) to shape the development of child socioemotional functioning. Participants were 235 young children (Mage = 2.97 at the first measurement occasion) and their parents, who were followed for two consecutive annual measurement occasions. Child SPS was measured through behavioral observation across multiple tasks within the laboratory setting. Greater environmental unpredictability was significantly associated with the development of children’s externalizing problems over a year only for children with high SPS. Follow-up analyses indicated that the unpredictability-x-SPS interaction was consistent with differential susceptibility, such that high SPS children showed greater increases in externalizing problems under high unpredictability, but also lower increases/greater decreases in externalizing problems under low unpredictability. Such association did not apply to children with low SPS.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care.
Methods
Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3–4, 6–8,<Vinod: Please carry out the deletion of serial commas throughout the article> and 9–12 months post-baseline and remission at 3–4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/.
Results
There was no evidence of an association between age and prognosis before or after adjusting for depressive ‘disorder characteristics’ that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3–4 months post-baseline per-5-year increase in age = 0(95% CI: −0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3–4 months or 9–12 months post-baseline, but men had worse prognoses at 6–8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6–8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive ‘disorder characteristics’ and employment status (12.23% (−1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive ‘disorder characteristics’ and all available confounders.
Conclusion
Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive ‘disorder characteristics’ in clinic may be important.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
Methods:
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results:
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
Conclusions:
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
We present a detailed analysis of the radio galaxy PKS $2250{-}351$, a giant of 1.2 Mpc projected size, its host galaxy, and its environment. We use radio data from the Murchison Widefield Array, the upgraded Giant Metre-wavelength Radio Telescope, the Australian Square Kilometre Array Pathfinder, and the Australia Telescope Compact Array to model the jet power and age. Optical and IR data come from the Galaxy And Mass Assembly (GAMA) survey and provide information on the host galaxy and environment. GAMA spectroscopy confirms that PKS $2250{-}351$ lies at $z=0.2115$ in the irregular, and likely unrelaxed, cluster Abell 3936. We find its host is a massive, ‘red and dead’ elliptical galaxy with negligible star formation but with a highly obscured active galactic nucleus dominating the mid-IR emission. Assuming it lies on the local M–$\sigma$ relation, it has an Eddington accretion rate of $\lambda_{\rm EDD}\sim 0.014$. We find that the lobe-derived jet power (a time-averaged measure) is an order of magnitude greater than the hotspot-derived jet power (an instantaneous measure). We propose that over the lifetime of the observed radio emission (${\sim} 300\,$Myr), the accretion has switched from an inefficient advection-dominated mode to a thin disc efficient mode, consistent with the decrease in jet power. We also suggest that the asymmetric radio morphology is due to its environment, with the host of PKS $2250{-}351$ lying to the west of the densest concentration of galaxies in Abell 3936.
The Mediterranean diet offers a range of health benefits. However, previous studies indicate that the restricted consumption of red meat in the diet may affect long-term sustainability in non-Mediterranean countries. A 24-week randomised controlled parallel cross-over design compared a Mediterranean diet supplemented with 2–3 serves per week of fresh, lean pork (MedPork) with a low-fat control diet (LF). Thirty-three participants at risk of CVD followed each intervention for 8 weeks, with an 8-week washout period separating interventions. The primary outcome was home-measured systolic blood pressure. Secondary outcomes included diastolic blood pressure, fasting lipids, glucose, insulin, C-reactive protein (CRP), body composition and dietary adherence. During the MedPork intervention, participants achieved high adherence to dietary guidelines. Compared with the MedPork intervention, the LF intervention led to greater reductions in weight (Δ = −0·65; 95 % CI −0·04, −1·25 kg, P = 0·04), BMI (Δ = −0·25; 95 % CI −0·03, −0·47 kg/m2, P = 0·01) and waist circumference (Δ = −1·40; 95 % CI −0·45, −2·34 cm, P < 0·01). No significant differences were observed for blood pressure, lipids, glucose, insulin or CRP. These findings indicate that Australians are capable of adhering to a Mediterranean diet with 2–3 weekly serves of fresh, lean pork. Larger intervention studies are now required to demonstrate clinical efficacy of the diet in populations with elevated blood pressure.