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Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
In this paper, we investigate finite solvable tidy groups. We prove that a solvable group with order divisible by at least two primes is tidy if all of its Hall subgroups that are divisible by only two primes are tidy.
Let G be a p-group for some prime p. Recall that the Hughes subgroup of G is the subgroup generated by all of the elements of G with order not equal to p. In this paper, we prove that if the Hughes subgroup of G is cyclic, then G has exponent p or is cyclic or is dihedral. We also prove that if the Hughes subgroup of G is generalised quaternion, then G must be generalised quaternion. With these results in hand, we classify the tidy p-groups.
To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI).
Design:
Quality improvement study.
Setting:
Two urban acute care hospitals.
Interventions:
All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention.
Results:
The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022–October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021–January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73–1.05; P = .13).
Conclusions:
A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs.
We present WALLABY pilot data release 1, the first public release of H i pilot survey data from the Wide-field ASKAP L-band Legacy All-sky Blind Survey (WALLABY) on the Australian Square Kilometre Array Pathfinder. Phase 1 of the WALLABY pilot survey targeted three
$60\,\mathrm{deg}^{2}$
regions on the sky in the direction of the Hydra and Norma galaxy clusters and the NGC 4636 galaxy group, covering the redshift range of
$z \lesssim 0.08$
. The source catalogue, images and spectra of nearly 600 extragalactic H i detections and kinematic models for 109 spatially resolved galaxies are available. As the pilot survey targeted regions containing nearby group and cluster environments, the median redshift of the sample of
$z \approx 0.014$
is relatively low compared to the full WALLABY survey. The median galaxy H i mass is
$2.3 \times 10^{9}\,{\rm M}_{{\odot}}$
. The target noise level of
$1.6\,\mathrm{mJy}$
per 30′′ beam and
$18.5\,\mathrm{kHz}$
channel translates into a
$5 \sigma$
H i mass sensitivity for point sources of about
$5.2 \times 10^{8} \, (D_{\rm L} / \mathrm{100\,Mpc})^{2} \, {\rm M}_{{\odot}}$
across 50 spectral channels (
${\approx} 200\,\mathrm{km \, s}^{-1}$
) and a
$5 \sigma$
H i column density sensitivity of about
$8.6 \times 10^{19} \, (1 + z)^{4}\,\mathrm{cm}^{-2}$
across 5 channels (
${\approx} 20\,\mathrm{km \, s}^{-1}$
) for emission filling the 30′′ beam. As expected for a pilot survey, several technical issues and artefacts are still affecting the data quality. Most notably, there are systematic flux errors of up to several 10% caused by uncertainties about the exact size and shape of each of the primary beams as well as the presence of sidelobes due to the finite deconvolution threshold. In addition, artefacts such as residual continuum emission and bandpass ripples have affected some of the data. The pilot survey has been highly successful in uncovering such technical problems, most of which are expected to be addressed and rectified before the start of the full WALLABY survey.
We present the most sensitive and detailed view of the neutral hydrogen (
${\rm H\small I}$
) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal
${\rm H\small I}$
in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K (
$1.6\,\mathrm{mJy\ beam}^{-1}$
)
$\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$
spectral channel with an angular resolution of
$30^{\prime\prime}$
(
${\sim}10\,\mathrm{pc}$
). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire
${\sim}25\,\mathrm{deg}^2$
field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes
${\rm H\small I}$
test observations.
The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to
$\sim\!5$
yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of
$\sim\!162$
h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of
$0.24\ \mathrm{mJy\ beam}^{-1}$
and angular resolution of
$12-20$
arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.
Morgan and Parker proved that if G is a group with
${\textbf{Z}(G)} = 1$
, then the connected components of the commuting graph of G have diameter at most
$10$
. Parker proved that if, in addition, G is solvable, then the commuting graph of G is disconnected if and only if G is a Frobenius group or a
$2$
-Frobenius group, and if the commuting graph of G is connected, then its diameter is at most
$8$
. We prove that the hypothesis
$Z (G) = 1$
in these results can be replaced with
$G' \cap {\textbf{Z}(G)} = 1$
. We also prove that if G is solvable and
$G/{\textbf{Z}(G)}$
is either a Frobenius group or a
$2$
-Frobenius group, then the commuting graph of G is disconnected.
Sedentary behaviour is potentially a modifiable risk factor for anxiety disorders, a major source of global disability that typically starts during adolescence. This is the first prospective study of associations between repeated, device-based measures of sedentary behaviour and anxiety symptoms in adolescents.
Methods
A UK cohort with 4257 adolescents aged 12 at baseline (56% female). Main exposures were sedentary behaviour and physical activity measured using accelerometers for 7-days at ages 12, 14, and 16. Primary outcome was anxiety symptom scores at age 18 from a Clinical Interview Schedule-Revised. We used adjusted negative binomial regression and iso-temporal substitution methods to analyse the data.
Results
We found a positive association between sedentary behaviour at ages 12, 14, and 16, with anxiety symptoms at age 18, independent of total physical activity volume. Theoretically replacing an hour of daily sedentary behaviour for light activity at ages 12, 14, and 16, was associated with lower anxiety symptoms by age 18 by 15.9% (95% CI 8.7–22.4), 12.1% (95% CI 3.4–20.1), and 14.7% (95% CI 4–24.2), respectively. Whereas, theoretically replacing an hour of sedentary behaviour with moderate-to-vigorous physical activity was not associated with differences in anxiety symptoms. These results were robust to a series of sensitivity analyses.
Conclusion
Sedentary behaviour is a possible risk factor for increasing anxiety symptoms during adolescence, independent of total physical activity volume. Instead of focusing on moderate-to-vigorous activity, replacing daily sedentary behaviour with light activity during adolescence could be a more suitable method of reducing future anxiety symptoms.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
$\sim$
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
$+41^\circ$
made over a 288-MHz band centred at 887.5 MHz.
Introduction: Determining fluid status prior to resuscitation provides a more accurate guide for appropriate fluid administration in the setting of undifferentiated hypotension. Emergency Department (ED) point of care ultrasound (PoCUS) has been proposed as a potential non-invasive, rapid, repeatable investigation to ascertain inferior vena cava (IVC) characteristics. Our goal was to determine the feasibility of using PoCUS to measure IVC size and collapsibility. Methods: This was a planned secondary analysis of data from a prospective multicentre international study investigating PoCUS in ED patients with undifferentiated hypotension. We prospectively collected data on IVC size and collapsibility using a standard data collection form in 6 centres. The primary outcome was the proportion of patients with a clinically useful (determinate) scan defined as a clearly visible intrahepatic IVC, measurable for size and collapse. Descriptive statistics are provided. Results: A total of 138 scans were attempted on 138 patients; 45.7% were women and the median age was 58 years old. Overall, one hundred twenty-nine scans (93.5%; 95% CI 87.9 to 96.7%) were determinate. 131 (94.9%; 89.7 to 97.7%) were determinate for IVC size, and 131 (94.9%; 89.7 to 97.7%) were determinate for collapsibility. Conclusion: In this analysis of 138 ED patients with undifferentiated hypotension, the vast majority of PoCUS scans to investigate IVC characteristics were determinate. Future work should include analysis of the value of IVC size and collapsibility in determining fluid status in this group.
Research on at-risk states of psychosis has mainly aimed to predict conversion. Yet as a considerable number of patients does not to progress to this outcome during the investigated observation periods, the course of these non-converters (NC) is of major interest, particularly with regard to preventive interventions and treatment.
Aims
To analyze the psychopathological and functional in 18-month non-converters.
Methods
Data were derived from the prospective multicenter European Prediction of Psychosis Study with an 18-month follow-up period. Participants had to fulfill ultra-high risk criteria and/or the COGDIS criterion, which is based on a set of cognitive basic symptoms. Psychopathology was assessed with the Structure Interview for Prodromal Syndromes (SIPS), including the Global Assessment of Functioning Scale (GAF) and a short version of the Schizophrenia Proneness Instrument (SPI-A).
Results
All total and subscale scores improved significantly during follow-up. However, a more detailed analysis revealed that a considerable part of the patients showed no improvement or even a worsening of psychopathology and function.
Conclusions
Our first analysis of course on non-converters shows that a high proportion of patients improved. In the light of results from retrospective studies, however, this improvement has to be interpreted with caution, as the observation period does not allow to determine the proportion of outpost syndromes, i.e. precursors of a later prodrome. Furthermore, a considerable portion of our sample worsened functionally and/or symptomatically. With regard to retrospective schizophrenia related results, very long observation periods may be needed to characterize the patterns of course in subpsychotic syndromes.
A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.
Methods
In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).
Results
246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.
Conclusions
The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.
Ultra-high risk (UHR) criteria are defined by attenuated and/or transient full-blown psychotic symptoms and/or a combination of genetic risk factor and deterioration of functioning. To achieve a higher predictive specificity and a clear threshold of clinical importance, functional impairment has been considered as an obligate part of all UHR criteria.
Method
In the European Prediction of Psychosis Study (EPOS)N = 37 participants converted to psychosis, n = 146 completed the whole 18-month follow-up period without conversion. Assessed by the Global Assessment of Functioning Scale, modified version (GAF-M), the following functional states were considered: Considered GAF-M: ≤30%/≤10% reduction of baseline scores related to highest scores in the previous year; scores ≤70/≤60.
Results
The GAF reduction criteria led to a very unfavorable loss of sensitivity, even, if only 10% were demanded. This was accompanied by correspondingly unfavorable accuracy measures. Introducing functional impairment criteria defined by the current state reported to be predictive for psychiatric caseness (score ≤ 70) or to define serious impairment (score ≤ 60) (Kessler et al., 2002, 2003) kept sensitivity at a perfectly high level, yet did not produce any gain of specificity.
Discussion
These results were certainly be caused by the fact that the whole group showed already low GAF-M scores in the previous year. Thus, a functional impairment criterion proved not to be useful to improve prediction. However, a combination of APS or BLIPS with a ‘clinical status’ criterion of GAF-M ≤ 70 may be considerable to demonstrate a strong need for intervention.
A considerable part of clinical high-risk samples does not convert to psychosis within the studies' limited observation periods. A part of these ‘non-converters’ shows a remission of symptoms (with unknown future course). Another part, however, maintains the risk state during follow-up.
Objectives
Persistence of indicators for an increased risk of psychosis.
Aims
To investigate, if persistence of attenuated (APS) or brief limited intermittent psychotic symptoms (BLIPS), the core syndromes of ultra-high risk (UHR) criteria, can be predicted clinically.
Methods
N = 129 participants of the European Prediction of Psychosis (EPOS) Study were included into the current analysis. Persistent Risk Symptoms (pRS) were defined as an at-least ‘moderate’ level (SIPS) of at least one positive symptom at all visits (symptom had to remain the same). Functional significance was defined by a GAF-M score ≤60 at 18-month follow-up (T2).
Results
23.3% displayed persistent risk symptoms throughout follow-up. Most frequent pRS were ‘unusual thought contents’, ‘ideas of persecution’ and ‘perceptual disturbances’. In 90% of the pRS subjects, but only in 25.3% of the non-pRS subjects, GAF scores at T2 were below 60 points (p < 0.01).
Logistic regression analysis revealed that the presence of the pRS syndrome at T2 was predictable by the early course of attenuated positive symptoms with maximum accuracy when the number of at least ‘moderate’ symptoms was considered.
Conclusions
A considerable number of subjects at risk showed persistent attenuated positive symptoms associated with long-lasting functional impairments, irrespective of conversion within the foreseeable future.
The ultra-high risk state of developing a psychosis is mainly characterized by attenuated or transient full-blown psychotic symptoms. It can be assessed with the structured interview for prodromal symptoms (SIPS), comprising four domains: positive, negative, disorganization and general symptoms. As the scores of the SOPS sub-domains are regularly used to perform domain-related analyses the stability of the suggested domain structure and item composition is of major interest.
Method
SIPS (version 3.0) data from n = 243 participants of the European Prediction of Psychosis Study (EPOS) were used for the current analysis. Inclusion criteria comprised ultra-high risk criteria and the basic symptom criterion COGDIS. The EPOS investigators received extensive training by one of the scale's authors (Tandy J. Miller, PhD). Pairwise interrater concordance for SIPS was 77%, which was determined acceptable by the training team. A principal component analysis was performed (Eigenvalues > 1, varimax rotation).
Results
A five factor solution emerged. Factor 1 was primarily defined by a loss of intentionality, functioning and stress tolerance, factor 2 by anhedonia and affective blunting, factor 3 by cognitive and behavioural disorganization, factor 4 by delusions. Sleep disturbances and perceptual abnormalities/hallucinations have both been associated with dopaminergic disturbances, this may explain their common appearance on factor 5.
Discussion
The originally suggested structure of the SIPS proofed not to be stable and was replaced by a five-factor solution. Our results suggest considering a different item and factor structure in future SIPS based data analyses.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Introduction: Patients with chronic diseases are known to benefit from exercise. Such patients often visit the emergency department (ED). There are few studies examining prescribing exercise in the ED. We wished to study if exercise prescription in the ED is feasible and effective. Methods: In this pilot prospective block randomized trial, patients in the control group received routine care, whereas the intervention group received a combined written and verbal prescription for moderate exercise (150 minutes/week). Both groups were followed up by phone at 2 months. The primary outcome was achieving 150 min of exercise per week. Secondary outcomes included change in exercise, and differences in reported median weekly exercise. Comparisons were made by Mann-Whitney and Fishers tests (GraphPad). Results: Follow-up was completed for 22 patients (11 Control; 11 Intervention). Baseline reported median (with IQR) weekly exercise was similar between groups; Control 0(0-0)min; Intervention 0(0-45)min. There was no difference between groups for the primary outcome of 150 min/week at 2 months (Control 3/11; Intervention 4/11, RR 1.33 (95%CI 0.38-4.6;p=1.0). There was a significant increase in median exercise from baseline in both groups, but no difference between the groups (Control 75(10-225)min; Intervention 120(52.5-150)min;NS). 3 control patients actually received exercise prescription as part of routine care. A post-hoc comparison of patients receiving intervention vs. no intervention, revealed an increase in patients meeting the primary target of 150min/week (No intervention 0/8; Intervention 7/14, RR 2.0 (95%CI 1.2-3.4);p=0.023). Conclusion: Recruitment was feasible, however our study was underpowered to quantify an estimated effect size. As a significant proportion of the control group received the intervention (as part of standard care), any potential measurable effect was diluted. The improvement seen in patients receiving intervention and the increase in reported exercise in both groups (possible Hawthorne effect) suggests that exercise prescription for ED patients may be beneficial.