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Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.
Methods
Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.
Results
k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.
Conclusions
Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.
This inductive examination of the topics in the public administration literature using computational social science and corpus linguistics (17 journals, N=12,760 articles, 1991–2019) reveals a new landscape of public administration topics, changes in topics over time and their distribution: Topic modelling of the stock of the whole corpus identifies 50 topics: the top ten topics included health care, federal government, performance management, environmental regulation, HRM and networks and accounted for just over a third of scholarship between 1991–2019. Focal topics identified in individual journals identified similarities with popular topics in the whole corpus – networks, health care, HRM – and less frequently examined topics including gender and diversity and partnerships. Analysis of topics over time shows a substantial flow in topics moving from a country and practice focus in the early stages of our study period to concepts such as governance, networks and citizens in the late stages (2015–2019).
Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting.
Method:
This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history.
Results:
Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70–0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background.
Conclusions:
A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.
With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist.
Methods:
HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions?
Results:
This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected.
Conclusion:
This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.
In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania.
Method:
Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus.
Results:
Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant.
Conclusion:
In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent ‘rule out’ value in this setting.
Cognitive stimulation therapy (CST) is the only non-pharmacological, treatment for dementia recommended by the UK National Institute for Health and Care Excellence, following multiple international trials demonstrating beneficial cognitive outcomes in people with mild-to-moderate dementia. However, there is limited understanding of whether treatment prognosis is influenced by sociodemographic and clinical variables (such as dementia subtype and gender), information which could inform clinical decision-making.
Aim
We describe the protocol for a systematic review and individual patient data meta-analysis assessing the prognostic factors related to CST. In publishing this protocol, we hope to increase the transparency of our work, and keep healthcare professionals aware of the latest evidence for effective CST.
Method
A systematic review will be conducted with searches of the bibliographic databases Medline, EMBASE and PsycINFO, from inception to 7 February 2023. Studies will be included if they are clinical trials of CST, use the Alzheimer's Disease Assessment Scale – Cognitive Subscale (gold-standard measure of cognition in dementia in clinical trials) and include participants with mild-to-moderate dementia. Following harmonisation of the data-set, mixed-effect models will be constructed to explore the relationship between the prognostic indicators and change scores post-treatment.
Conclusions
This is the first individual patient data meta-analyses on CST, and has the potential to significantly optimise patient care. Previous analyses suggest people with advanced dementia could benefit more from CST treatment. Given that CST is currently used post-diagnosis in people with mild-to-moderate dementia, the implications of confirming this finding, among identifying other prognostic indicators, are profound.
Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.
Studies show ethnic inequalities in rates of involuntary admission and types of clinical care (such as psychological therapies). However, few studies have investigated if there is a relationship between clinical care practices and ethnic inequalities in involuntary admission.
Aims
This study investigated the impact of ethnicity and clinical care on involuntary admission and the potential mediation effects of prior clinical care.
Method
In this retrospective cohort study, we used data from the electronic records of the South London and Maudsley NHS Foundation Trust and identified patients with a first hospital admission between January 2008 and May 2021. Logistic regression and mediation analyses were used to investigate the association between ethnicity and involuntary admission, and whether clinical care, in the 12 months preceding admission, mediates the association.
Results
Compared with White British people, higher odds of involuntary admission were observed among 10 of 14 minority ethnic groups; with more than twice the odds observed among people of Asian Chinese, of Asian Bangladeshi and of any Black background. There were some ethnic differences in clinical care prior to admission, but these had a minimal impact on the inequalities in involuntary admission. More out-patient appointments and home treatment were associated with higher odds of involuntary admission, whereas psychological therapies and having a care plan were associated with reduced odds of involuntary admission.
Conclusions
Ethnic inequalities in involuntary admission persist after accounting for potential mediating effects of several types and frequencies of clinical care. Promoting access to psychological therapies and ensuring that care plans are in place may reduce involuntary admissions.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
Design:
Longitudinal study
Participants:
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
Measurements:
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
Results:
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
Conclusions:
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
The adult population of repaired tetralogy of Fallot is increasing and at risk of pre-mature death and arrhythmia. This study evaluates risk factors for adverse outcome and the effect of pulmonary valve replacement within a national cohort.
Methods:
A retrospective cohort study of 341 adult repaired tetralogy of Fallot (16–72 years) managed through a single national service was undertaken incorporating over 1200 patient-years of follow-up. Demographics, cardiopulmonary exercise testing, cardiac magnetic resonance, reintervention (including pulmonary valve replacement), and clinical events were analysed. The influence of these parameters on a primary outcome (death or arrhythmia) was evaluated.
Results:
Compared with an age-/gender-matched population, patients experienced a reduced survival, particularly males over 55 years (standardised mortality ratio : 6.12, 95% CI: 1.64–15.66, p = 0.004). Cox proportional hazards modelling identified increased indexed right ventricle (RV) end-diastolic volume (hazard ratio (HR): 2.86, 95% CI: 1.4–5.85, p = 0.004) and female gender (HR (male): 0.37, 95% CI: 0.14–0.98, p = 0.045) to be predictors significantly associated with the primary outcome. Pulmonary valve replacement undertaken at indexed RV end-diastolic volume = 145 ml/m2 reduced RV volumes and QRS duration but did not improve cardiopulmonary exercise testing nor NYHA class. Pulmonary valve replacement during cohort period was associated with increased risk of primary outcome (HR: 2.82, 95% CI: 1.36–5.86, p = 0.005).
Conclusions:
Although the majority of adult tetralogy of Fallot were asymptomatic in NYHA 1, cardiopulmonary exercise testing revealed important deficits. Tetralogy of Fallot survival was reduced compared to the general population. Female gender and increasing RV end-diastolic volume predicted adverse events. Pulmonary valve replacement reduced RV volumes and QRS duration but did not improve primary outcome.
Common mental disorders (CMDs), particularly depression, are major contributors to the global mental health burden. South Asia, while diverse, has cultural, social, and economic challenges, which are common across the region, not least an aging population. This creates an imperative to better understand how CMD affects older people in this context, which relies on valid and culturally appropriate screening and research tools. This review aims to scope the availability of CMD screening tools for older people in South Asia. As a secondary aim, this review will summarize the use of these tools in epidemiology, and the extent to which they have been validated or adapted for this population.
Design:
A scoping review was performed, following PRISMA guidelines. The search strategy was developed iteratively in Medline and translated to Embase, PsychInfo, Scopus, and Web of Science. Data were extracted from papers in which a tool was used to identify CMD in a South Asian older population (50+), including validation, adaptation, and use in epidemiology. Validation studies meeting the criteria were critically appraised using the Quality Assessment of Diagnostic Accuracy Studies – version 2 (QUADAS-2) tool.
Results:
Of the 4694 papers identified, 176 met the selection criteria at full-text screening as relevant examples of diagnostic or screening tool use. There were 15 tool validation studies, which were critically appraised. Of these, 10 were appropriate to evaluate as diagnostic tests. All of these tools assessed for depression. Geriatric Depression Scale (GDS)-based tools were predominant with variable diagnostic accuracy across different settings. Methodological issues were substantial based on the QUADAS-2 criteria. In the epidemiological studies identified (n = 160), depression alone was assessed for 82% of the studies. Tools lacking cultural validation were commonly used (43%).
Conclusions:
This review identifies a number of current research gaps including a need for culturally relevant validation studies, and attention to other CMDs such as anxiety.
Around 8150 BP, the Storegga tsunami struck North-west Europe. The size of this wave has led many to assume that it had a devastating impact upon contemporaneous Mesolithic communities, including the final inundation of Doggerland, the now submerged Mesolithic North Sea landscape. Here, the authors present the first evidence of the tsunami from the southern North Sea, and suggest that traditional notions of a catastrophically destructive event may need rethinking. In providing a more nuanced interpretation by incorporating the role of local topographic variation within the study of the Storegga event, we are better placed to understand the impact of such dramatic occurrences and their larger significance in settlement studies.
Late Pleistocene and Early Holocene aeolian deposits in Tasmania are extensive in the present subhumid climate zone but also occur in areas receiving >1000 mm of rain annually. Thermoluminescence, optically stimulated luminescence, and radiocarbon ages indicate that most of the deposits formed during periods of cold climate. Some dunes are remnants of longitudinal desert dunes sourced from now-inundated continental shelves which were previously semi-arid. Others formed near source, often in the form of lunettes east of seasonally-dry lagoons in the previously semi-arid Midlands and southeast of Tasmania, or as accumulations close to floodplains of major rivers, or as sandsheets in exposed areas. Burning of vegetation by the Aboriginal population after 40 ka is likely to have influenced sediment supply. A key site for determining climate variability in southern Tasmania is Maynes Junction which records three periods of aeolian deposition (at ca. 90, 32 and 20 ka), interspersed with periods of hillslope instability. Whether wind speeds were higher than at present during the last glacial period is uncertain, but shells in the Mary Ann Bay sandsheet near Hobart and particle size analysis of the Ainslie dunes in northeast Tasmania suggest stronger winds during the last glacial period than at present.
OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.
The Murchison Widefield Array (MWA) has observed the entire southern sky (Declination,
$\delta< 30^{\circ}$
) at low radio frequencies, over the range 72–231MHz. These observations constitute the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey, and we use the extragalactic catalogue (EGC) (Galactic latitude,
$|b| >10^{\circ}$
) to define the GLEAM 4-Jy (G4Jy) Sample. This is a complete sample of the ‘brightest’ radio sources (
$S_{\textrm{151\,MHz}}>4\,\text{Jy}$
), the majority of which are active galactic nuclei with powerful radio jets. Crucially, low-frequency observations allow the selection of such sources in an orientation-independent way (i.e. minimising the bias caused by Doppler boosting, inherent in high-frequency surveys). We then use higher-resolution radio images, and information at other wavelengths, to morphologically classify the brightest components in GLEAM. We also conduct cross-checks against the literature and perform internal matching, in order to improve sample completeness (which is estimated to be
$>95.5$
%). This results in a catalogue of 1863 sources, making the G4Jy Sample over 10 times larger than that of the revised Third Cambridge Catalogue of Radio Sources (3CRR;
$S_{\textrm{178\,MHz}}>10.9\,\text{Jy}$
). Of these G4Jy sources, 78 are resolved by the MWA (Phase-I) synthesised beam (
$\sim2$
arcmin at 200MHz), and we label 67% of the sample as ‘single’, 26% as ‘double’, 4% as ‘triple’, and 3% as having ‘complex’ morphology at
$\sim1\,\text{GHz}$
(45 arcsec resolution). We characterise the spectral behaviour of these objects in the radio and find that the median spectral index is
$\alpha=-0.740 \pm 0.012$
between 151 and 843MHz, and
$\alpha=-0.786 \pm 0.006$
between 151MHz and 1400MHz (assuming a power-law description,
$S_{\nu} \propto \nu^{\alpha}$
), compared to
$\alpha=-0.829 \pm 0.006$
within the GLEAM band. Alongside this, our value-added catalogue provides mid-infrared source associations (subject to 6” resolution at 3.4
$\mu$
m) for the radio emission, as identified through visual inspection and thorough checks against the literature. As such, the G4Jy Sample can be used as a reliable training set for cross-identification via machine-learning algorithms. We also estimate the angular size of the sources, based on their associated components at
$\sim1\,\text{GHz}$
, and perform a flux density comparison for 67 G4Jy sources that overlap with 3CRR. Analysis of multi-wavelength data, and spectral curvature between 72MHz and 20GHz, will be presented in subsequent papers, and details for accessing all G4Jy overlays are provided at https://github.com/svw26/G4Jy.
The entire southern sky (Declination,
$\delta< 30^{\circ}$
) has been observed using the Murchison Widefield Array (MWA), which provides radio imaging of
$\sim$
2 arcmin resolution at low frequencies (72–231 MHz). This is the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey, and we have previously used a combination of visual inspection, cross-checks against the literature, and internal matching to identify the ‘brightest’ radio-sources (
$S_{\mathrm{151\,MHz}}>4$
Jy) in the extragalactic catalogue (Galactic latitude,
$|b| >10^{\circ}$
). We refer to these 1 863 sources as the GLEAM 4-Jy (G4Jy) Sample, and use radio images (of
${\leq}45$
arcsec resolution), and multi-wavelength information, to assess their morphology and identify the galaxy that is hosting the radio emission (where appropriate). Details of how to access all of the overlays used for this work are available at https://github.com/svw26/G4Jy. Alongside this we conduct further checks against the literature, which we document here for individual sources. Whilst the vast majority of the G4Jy Sample are active galactic nuclei with powerful radio-jets, we highlight that it also contains a nebula, two nearby, star-forming galaxies, a cluster relic, and a cluster halo. There are also three extended sources for which we are unable to infer the mechanism that gives rise to the low-frequency emission. In the G4Jy catalogue we provide mid-infrared identifications for 86% of the sources, and flag the remainder as: having an uncertain identification (129 sources), having a faint/uncharacterised mid-infrared host (126 sources), or it being inappropriate to specify a host (2 sources). For the subset of 129 sources, there is ambiguity concerning candidate host-galaxies, and this includes four sources (B0424–728, B0703–451, 3C 198, and 3C 403.1) where we question the existing identification.
The “Turn on the Night” associated event had presentations on the latest dark skies protection issues considered by the IAU’s Dark and Quiet Skies working groups. Presentations were also made on dark skies education programs and cultural/scientific heritage.
Depression in older people is likely to become a growing global health problem with aging populations. Significant cultural variation exists in beliefs about depression (terminology, symptomatology, and treatments) but data from sub-Saharan Africa are minimal. Low-resource interventions for depression have been effective in low-income settings but cannot be utilized without accurate diagnosis. This study aimed to achieve a shared understanding of depression in Tanzania in older people.
Methods:
Using a qualitative design, focus groups were conducted with participants aged 60 and over. Participants from rural villages of Kilimanjaro, Tanzania, were selected via randomized sampling using census data. Topic guides were developed including locally developed case vignettes. Transcripts were translated into English from Swahili and thematic analysis conducted.
Findings:
Ten focus groups were held with 81 participants. Three main themes were developed: a) conceptualization of depression by older people and differentiation from other related conditions (“too many thoughts,” cognitive symptoms, affective and biological symptoms, wish to die, somatic symptoms, and its difference to other concepts); b) the causes of depression (inability to work, loss of physical strength and independence, lack of resources, family difficulties, chronic disease); c) management of depression (love and comfort, advice, spiritual support, providing help, medical help).
Conclusions:
This research expands our understanding of how depression presents in older Tanzanians and provides information about lay beliefs regarding causes and management options. This may allow development of culturally specific screening tools for depression that, in turn, increase diagnosis rates, support accurate diagnosis, improve service use, and reduce stigma.