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A comprehensive guide on Atomic-Scale Analytical Tomography (ASAT) that discusses basic concepts and implications of the technique in areas such as material sciences, microscopy, engineering sciences and several interdisciplinary avenues. The title interrogates how to successfully achieve ASAT at the intersection of transmission electron microscopy and atom probe microscopy. This novel concept is capable of identifying individual atoms in large volumes as well as in 3D, with high spatial resolution. Written by leading experts from academia and industry, this book serves as a guide with real-world applications on cutting-edge research problems. An essential reading for researchers, engineers and practitioners interested in nanoscale characterisation, this book introduces the reader to a new direction for atomic-scale microscopy.
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurity that typically develops after the administration of infant formula, suggesting a link between nutritional components and disease development. One of the most significant complications that develops in patients with NEC is severe lung injury. We have previously shown that the administration of a nutritional formula that is enriched in pre-digested triglycrides that do not require lipase action can significantly reduce the severity of NEC in a mouse model. We now hypothesize that this 'pre-digested fat system (PDF)' may reduce NEC-associated lung injury. In support of this hypothesis, we now show that rearing newborn mice on a nutritional formula based on the 'pre-digested fat (PDF) system’ promotes lung development, as evidenced by increased tight junctions and surfactant protein expression. Mice who were administered this 'PDF fat system’ were significantly less vulnerable to the development of NEC-induced lung inflammation, and the administration of the 'PDF fat system’ conferred lung protection. In seeking to define the mechanisms involved, the administration of the PDF system’ significantly enhanced lung maturation and reduced the production of reactive oxygen species (ROS). These findings suggest that the PDF system protects the development of NEC-induced lung injury through effects on lung maturation and reduced reactive oxygen species in the lung, and also increase lung maturation in non-NEC mice.
Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D v. healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case–control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B1, B6, B12, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B1 was higher (148⋅9 v. 131⋅7; P 0⋅01) and B6 lower (37⋅3 v. 52⋅9; P 0⋅01) in T2D v. controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B1, B6, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D.
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
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
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.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The approach of functional integration has the potential to solve challenges regarding lightweight design and resource efficiency since the number of parts and therefore the weight and needed installation space can be reduced. One important step in developing integrative concepts is the pre-selection of suitable functions or components. Previous methods of pre-selection take various aspects into account. However, pre-selection based on these methods usually requires additional tables and forms, whose preparation and editing quickly becomes time-consuming. At the same time, most of the development engineers are working on CAD models. However, their use in the selection of suitable integration partners is not yet supported sufficiently. The development of more than 80 concepts on five different vehicles has shown that the consideration of geometric properties (position, orientation, size) is effective, as they can be identified with minimal analysis effort while working on CAD. In this paper a four-step procedure is presented how integration partners can be identified directly on the basis of CAD models. A following evaluation with development engineers in practice completes the research.
Violent criminal offenders with personality disorders (PD's) can cause immense harm, but are often deemed untreatable. This study aimed to conduct a randomized clinical trial to test the effectiveness of long-term psychotherapy for rehabilitating offenders with PDs.
We compared schema therapy (ST), an evidence-based psychotherapy for PDs, to treatment-as-usual (TAU) at eight high-security forensic hospitals in the Netherlands. Patients in both conditions received multiple treatment modalities and differed only in the individual, study-specific therapy they received. One-hundred-three male offenders with antisocial, narcissistic, borderline, or paranoid PDs, or Cluster B PD-not-otherwise-specified, were assigned to 3 years of ST or TAU and assessed every 6 months. Primary outcomes were rehabilitation, involving gradual reintegration into the community, and PD symptoms.
Patients in both conditions showed moderate to large improvements in outcomes. ST was superior to TAU on both primary outcomes – rehabilitation (i.e. attaining supervised and unsupervised leave) and PD symptoms – and six of nine secondary outcomes, with small to moderate advantages over TAU. ST patients moved more rapidly through rehabilitation (supervised leave, treatment*time: F(5308) = 9.40, p < 0.001; unsupervised leave, treatment*time: F(5472) = 3.45, p = 0.004), and showed faster improvements on PD scales (treatment*time: t(1387) = −2.85, p = 0.005).
These findings contradict pessimistic views on the treatability of violent offenders with PDs, and support the effectiveness of long-term psychotherapy for rehabilitating these patients, facilitating their re-entry into the community.
Nightmares are a hallmark symptom of posttraumatic stress disorder (PTSD). This strong association may reflect a shared pathophysiology in the form of altered autonomic activity and increased reactivity. Using an acoustic startle paradigm, we investigated the interrelationships of psychophysiological measures during wakefulness and PTSD diagnosis, posttraumatic nightmares, and nontraumatic nightmares.
A community sample of 122 trauma survivors were presented with a series of brief loud tones, while heart rate (HRR), skin conductance (SCR), and orbicularis oculi electromyogram (EMGR) responses were measured. Prior to the tone presentations, resting heart rate variability (HRV) was assessed. Nightmares were measured using nightmare logs. Three dichotomous groupings of participants were compared: (1) current PTSD diagnosis (n = 59), no PTSD diagnosis (n = 63), (2) those with (n = 26) or without (n = 96) frequent posttraumatic nightmares, and (3) those with (n = 22) or without (n = 100) frequent nontraumatic nightmares.
PTSD diagnosis was associated with posttraumatic but not with nontraumatic nightmares. Both PTSD and posttraumatic nightmares were associated with a larger mean HRR to loud tones, whereas nontraumatic nightmare frequency was associated with a larger SCR. EMGR and resting HRV were not associated with PTSD diagnosis or nightmares.
Our findings suggest a shared pathophysiology between PTSD and posttraumatic nightmares in the form of increased HR reactivity to startling tones, which might reflect reduced parasympathetic tone. This shared pathophysiology could explain why PTSD is more strongly related to posttraumatic than nontraumatic nightmares, which could have important clinical implications.
Typically, the WTO Arbitrator, when charged with evaluating the permissible level of countermeasures (suspension of concessions), has chosen a counterfactual state of the world where the challenged (illegal) measure has not been adopted at all. The Arbitrator then would calculate the trade lost because of the adopted (illegal) measure, and thus, decide on the level of permissible countermeasures. In US–Washing Machines (Article 22.6-US), deviating from this custom, the Arbitrator adopted a different counterfactual, assuming that the complainant had adopted a different, ‘reasonable’ measure. The Arbitrator then evaluated the trade lost based on the distance between the adopted (illegal) and the ‘reasonable’ measure and calculated the level of countermeasures. In this paper, we explain the multitude of perils facing dispute settlement if this approach is adopted in future disputes. We also advance a few thoughts on rethinking the workings of the Arbitrator when measuring the level of permissible countermeasures, since similar slippery slopes risk being reproduced in future cases.
In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.
Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.
Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.
These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.
Classical results about peaking from complex interpolation theory are extended to polynomials on a closed disk, and on the complement of its interior. New results are obtained concerning interpolation by univalent polynomials on a Jordan domain whose boundary satisfies certain smoothness conditions.
The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population.
The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics.
Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories.
A low-stable profile characterised by little-to-no psychological distress (‘resilient’ class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.
Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
For people in mental health crisis, acute day units (ADUs) provide daily structured sessions and peer support in non-residential settings, often as an addition or alternative to crisis resolution teams (CRTs). There is little recent evidence about outcomes for those using ADUs, particularly compared with those receiving CRT care alone.
We aimed to investigate readmission rates, satisfaction and well-being outcomes for people using ADUs and CRTs.
We conducted a cohort study comparing readmission to acute mental healthcare during a 6-month period for ADU and CRT participants. Secondary outcomes included satisfaction (Client Satisfaction Questionnaire), well-being (Short Warwick–Edinburgh Mental Well-being Scale) and depression (Center for Epidemiologic Studies Depression Scale).
We recruited 744 participants (ADU: n = 431, 58%; CRT: n = 312, 42%) across four National Health Service trusts/health regions. There was no statistically significant overall difference in readmissions: 21% of ADU participants and 23% of CRT participants were readmitted over 6 months (adjusted hazard ratio 0.78, 95% CI 0.54–1.14). However, readmission results varied substantially by setting. At follow-up, ADU participants had significantly higher Client Satisfaction Questionnaire scores (2.5, 95% CI 1.4–3.5, P < 0.001) and well-being scores (1.3, 95% CI 0.4–2.1, P = 0.004), and lower depression scores (−1.7, 95% CI −2.7 to −0.8, P < 0.001), than CRT participants.
Patients who accessed ADUs demonstrated better outcomes for satisfaction, well-being and depression, and no significant differences in risk of readmission, compared with those who only used CRTs. Given the positive outcomes for patients, and the fact that ADUs are inconsistently provided in the National Health Service, their value and place in the acute care pathway needs further consideration and research.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
The coronavirus disease 2019 (COVID-19) emergency has led to numerous attempts to assess the impact of the pandemic on population mental health. The findings indicate an increase in depression and anxiety but have been limited by the lack of specificity about which aspects of the pandemic (e.g. viral exposure or economic threats) have led to adverse mental health outcomes.
Network analyses were conducted on data from wave 1 (N = 2025, recruited 23 March–28 March 2020) and wave 2 (N = 1406, recontacts 22 April–1 May 2020) of the COVID-19 Psychological Research Consortium Study, an online longitudinal survey of a representative sample of the UK adult population. Our models included depression (PHQ-9), generalized anxiety (GAD-7) and trauma symptoms (ITQ); and measures of COVID-specific anxiety, exposure to the virus in self and close others, as well as economic loss due to the pandemic.
A mixed graphical model at wave 1 identified a potential pathway from economic adversity to anxiety symptoms via COVID-specific anxiety. There was no association between viral exposure and symptoms. Ising network models using clinical cut-offs for symptom scores at each wave yielded similar findings, with the exception of a modest effect of viral exposure on trauma symptoms at wave 1 only. Anxiety and depression symptoms formed separate clusters at wave 1 but not wave 2.
The psychological impact of the pandemic evolved in the early phase of lockdown. COVID-related anxiety may represent the mechanism through which economic consequences of the pandemic are associated with psychiatric symptoms.