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PurposeThis paper aims to explore challenges and opportunities of shifting from physical to virtual employment support delivery prompted by the Covid-19 pandemic. It investigates associated changes in the nature and balance of support and implications for beneficiary engagement with programmes and job search.Design/methodology/approachThe study draws on longitudinal interviews conducted with beneficiaries and delivery providers from a neighbourhood-based employment support initiative in an English region with a strong manufacturing heritage between 2019 and 2021. The initiative established prior to the Covid-19 pandemic involved a strong physical presence locally but switched to virtual delivery during Covid-19 lockdowns.FindingsMoving long-term to an entirely virtual model would likely benefit some beneficiaries closer to or already in employment. Conversely, others, particularly lone parents, those further from employment, some older people and those without computer/Internet access and/or digital skills are likely to struggle to navigate virtual systems. The study emphasises the importance of blending the benefits of virtual delivery with aspects of place-based physical support.Originality/valuePrevious studies of neighbourhood-based employment policies indicate the benefits of localised face-to-face support for transforming communities. These were conducted prior to the Covid-19 pandemic and the more widespread growth of virtual employment support. This study fills a gap regarding understanding the challenges and opportunities for different groups of beneficiaries when opportunities for physical encounters decline abruptly and support moves virtually.

Stellar microlensing observations tightly constrain compact object dark matter in the mass range $(10^{-11} - 10^{3}) M_{\odot}$. Primordial Black Holes (PBHs) form clusters, and it has been argued that these microlensing constraints are consequently weakened or evaded. For the most commonly studied PBH formation mechanism, the collapse of large gaussian curvature perturbations generated by inflation, the clusters are sufficiently extended that the PBHs within them act as individual lenses. We find that if the typical mass of the clusters is sufficiently large, $ \gtrsim 10^{6} M_{\odot}$, then the event duration distribution can deviate significantly from that produced by a smooth dark matter distribution, in particular at the shortest durations. As a consequence of this, the probability distribution of the number of observed events is non-Poissonian, peaking at a lower value, with an extended tail to large numbers of events. However, for PBHs formed from the collapse of large inflationary perturbations, the typical cluster is expected to contain $\sim 10^{3}$ PBHs. In this case the effect of clustering is negligibly small, apart from for the most massive PBHs probed by decade-long stellar microlensing surveys ($M_{\rm PBH} \sim 10^{3} M_{\odot}$)., Comment: 8 pages, 2 figures. v2: minor changes to method, no changes to results. v3: minor changes to formatting to comply with new UKRI Open Access rules, no changes to science. v4: version to appear in JCAP, minor changes

The management of biopsy proven atypical lobular hyperplasia (ALH) is controversial. Although upgrade rates are low, excisional biopsy is often performed to rule out occult breast cancer. In this study, we analyzed our experience with excisional biopsy for ALH diagnosed in the digital tomosynthesis era with radiographic concordance in the community hospital setting. This study included 93 consecutive patients diagnosed with pure ALH on core biopsy from January 2013–December 2017 who underwent subsequent excisional biopsy. Potential clinical, radiographic and pathologic predictors of upgrading were analyzed. At the time of excisional biopsy, five patients (5.4%) were upgraded to DCIS or invasive breast cancer. There was also a trend towards higher upgrade rates in patients with contralateral breast cancer (p = 0.06), biopsy performed by ultrasound or MRI (p = 0.07) and extensive ALH (p = 0.10). Other clinical, radiographic and pathologic variables were not predictive of upgrade rate (p > 0.1 for all). Patients with pure ALH with radiographic concordance have a low risk of pathologic upgrading on excisional biopsy. Potential predictors of upgrade rate warrant further analysis in a larger dataset.

This Report provides an extensive review of the experimental programme of direct detection searches of particle dark matter. It focuses mostly on European efforts, both current and planned, but does it within a broader context of a worldwide activity in the field. It aims at identifying the virtues, opportunities and challenges associated with the different experimental approaches and search techniques. It presents scientific and technological synergies, both existing and emerging, with some other areas of particle physics, notably collider and neutrino programmes, and beyond. It addresses the issue of infrastructure in light of the growing needs and challenges of the different experimental searches. Finally, the Report makes a number of recommendations from the perspective of a long-term future of the field. They are introduced, along with some justification, in the opening Overview and Recommendations section and are next summarised at the end of the Report. Overall, we recommend that the direct search for dark matter particle interactions with a detector target should be given top priority in astroparticle physics, and in all particle physics, and beyond, as a positive measurement will provide the most unambiguous confirmation of the particle nature of dark matter in the Universe., 106 pages

These lecture notes aim to provide an introduction to dark matter from the perspective of astrophysics/cosmology. We start with a rapid overview of cosmology, including the evolution of the Universe, its thermal history and structure formation. Then we look at the observational evidence for dark matter, from observations of galaxies, galaxy clusters, the anisotropies in the cosmic microwave background radiation and large scale structure. To detect dark matter we need to know how it's distributed, in particular in the Milky Way, so next we overview relevant results from numerical simulations and observations. Finally, we conclude by looking at what astrophysical and cosmological observations can tell us about the nature of dark matter, focusing on two particular cases: warm and self-interacting dark matter., 35 pages, 3 figures. Submitted to SciPost Physics Lecture Notes, Les Houches Summer School Series, v2: minor changes

Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4-40.1)], 55% for duplication carriers [8.3 (1.4-55.5)]) and anxiety disorders (24% [1.8 (0.4-8.4)] and 55% [10.0 (1.9-71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered.

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers’ reported impact on their dependent’s services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden. Two online questionnaires were completed by caregivers participating in Simons Searchlight in April and May 2020. Surveys were completed by caregivers of children or dependent adults with neurodevelopmental genetic conditions in Simons Searchlight. Caregivers reported that the impact of the COVID-19 pandemic moderately or severely disrupted services, therapies, or medical supports. The majority of caregivers were responsible for providing some aspect of therapy. Caregivers reported “feeling stressed but able to deal with problems as they arise,” and reported lower anxiety at follow-up. Caregivers reported that telehealth services were not meeting the needs of those with complex medical needs. Future surveys will assess if and how medical systems, educational programs, therapists, and caregivers adapt to the challenges arising during the COVID-19 pandemic.

Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4–40.1)], 55% for duplication carriers [8.3 (1.4–55.5)]) and anxiety disorders (24% [1.8 (0.4–8.4)] and 55% [10.0 (1.9–71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered.

Atypical ductal hyperplasia (ADH) is an indication for excisional biopsy to rule out occult breast cancer. We analyzed pathological findings on excisional biopsy for ADH diagnosed in a high volume breast center equipped with digital tomosynthesis. Two hundred consecutive patients were diagnosed with ADH on core biopsy with radiographic concordance followed by excisional biopsy. On excisional biopsy, 33 patients (16.5%) were diagnosed with DCIS or invasive breast cancer. Patients with a concurrent diagnosis of papilloma had a higher risk of upstaging on both univariate and multivariate analysis (41.7% vs. 14.9%, p=0.015). No other statistically significant predictors of upgrading were identified (p>0.05).

Registered nurses are required to be involved in quality improvement activities as part of delivering safe, high-quality care for patients. Graduate registered nurses often have limited knowledge a...