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The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.
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.
People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.
Methods:
We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.
Results:
Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.
Conclusions:
CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
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.
Indian adolescents experience body dissatisfaction. However, empirically supported interventions are lacking, particularly in lower socio-economic regions of India. This paper describes the acceptability testing of a six-session teacher-led comics-based intervention, aiming to improve body image and related outcomes among adolescents in Indian Hindi medium schools.
Methods
Thirty-five students (50% girls; Mage, girls = 12.3 years; Mage, boys = 13 years) and nine teachers (11% women) from Hindi medium schools in Rajasthan, India, completed a quantitative acceptability questionnaire regarding comics that target body dissatisfaction and associated risk factors. They also participated in online or telephone semi-structured interviews to share in-depth feedback, with teachers providing additional feedback on an accompanying teacher guide. The quantitative data were analysed descriptively, with the interviews analysed using qualitative codebook thematic analysis.
Results
Quantitative analyses revealed that 73% of students felt the comics made them feel good about themselves. Qualitative analyses revealed four themes: (1) body dissatisfaction is a concern; (2) the comics are powerful; (3) increasing ease of understanding; (4) a teacher guide to aid delivery.
Conclusion
This study demonstrates acceptability of a novel teacher-led comics-based body image intervention for adolescents in Indian Hindi medium schools from lower socio-economic settings. These findings are currently informing intervention optimizations, which will be evaluated in a randomized controlled effectiveness trial. If found to be effective, this intervention will be disseminated across eight Indian states by UNICEF. Trial registration. This trial has been registered with ClinicalTrials.gov; a database of privately and publicly funded studies conducted around the world. Registration date: 2nd May 2020; Registration ID: (NCT04317755). https://clinicaltrials.gov/ct2/show/NCT04317755?term=NCT04317755&draw=2&rank=1.
Long Acting Buprenorphine (LAB) – Buvidal (CAM2038) – is a prolonged release treatment for opioid dependence in adults. Its extensive use was funded by Welsh Government during the pandemic in Wales and it has been found to be a significantly better than oral medications in improving quality of life, possibly through providing allostatic craving and anxiety reduction
Objectives
This is a case series of 10 patients who were referred to Community Addiction Services in North and South West Wales with OAD.
Methods
Patients were mainly using Codeine or Tramadol and were referred due to either ongoing illicit use or via primary care services requesting support. As part of the pandemic initiative, they were initiated on Buvidal and followed up.
Results
All ten patients successfully started on Buvidal without significant issues. As a group, if transferred straight to Buvidal, they tended to have fewer significant withdrawal symptoms prior to starting on the Buvidal compared to those on Methadone or Heroin. They were treated on the usual range of Buvidal doses (1 on 64mg, the others on 96-128mg monthly). They have all stabilised and successfully moved on with their lives on Buvidal. One has used the time on Buvidal to have psychological input around past traumas and successfully detoxified in the community using Buvidal.
Conclusions
Recommendations for services considering OAD - it is a surprisingly effective treatment which is easy to start. It has the scope for being both an effective OAD recovery medication and a potentially simple detoxification strategy for this patient group.
Disclosure
Professor Melichar has provided consultancy work, presentations, training and chaired panel discussions for all the companies in this area in the UK and some outside the UK. Recent work includes Althea (UK), Britannia (UK), Camurus (UK and Global), Martin
The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis and may have affected healthcare-associated infection (HAI) prevention strategies. We evaluated the impact of the COVID-19 pandemic on HAI incidence in Brazilian intensive care units (ICUs).
Methods:
In this ecological study, we compared adult patients admitted to the ICU from April through June 2020 (pandemic period) with the same period in 2019 (prepandemic period) in 21 Brazilian hospitals. We used the Wilcoxon signed rank-sum test in a pairwise analysis to compare the following differences between the pandemic and the prepandemic periods: microbiologically confirmed central-line–associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) incidence density (cases per 1,000 central line and ventilator days, respectively), the proportion of organisms that caused HAI, and antibiotic consumption (DDD).
Results:
We detected a significant increase in median CLABSI incidence during the pandemic: 1.60 (IQR, 0.44–4.20) vs 2.81 (IQR, 1.35–6.89) (P = .002). We did not detect a significant difference in VAP incidence between the 2 periods. In addition, we detected a significant increase in the proportion of CLABSI caused by Enterococcus faecalis and Candida spp during the pandemic, although only the latter retained statistical significance after correction for multiple comparisons. We did not detect a significant change in ceftriaxone, piperacillin–tazobactam, meropenem, or vancomycin consumption between the studied periods.
Conclusions:
There was an increase in CLABSI incidence in Brazilian ICUs during the first months of COVID-19 pandemic. Additionally, we detected an increase in the proportion of CLABSI caused by E. faecalis and Candida spp during this period. CLABSI prevention strategies must be reinforced in ICUs during the COVID-19 pandemic.
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.
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.
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.
The relative burden and risk of readmission for people with personality disorders in hospital settings is unknown.
Aims
To compare hospital use of people with personality disorder with that of people with other mental health diagnoses, such as psychoses and affective disorders.
Method
Naturalistic study of hospital presentations for mental health in a large community catchment. Mixed-effects Cox regression and survival curves were generated to examine risk of readmission for each group.
Results
Of 2894 people presenting to hospital, patients with personality disorder represented 20.5% of emergency and 26.6% of in-patients. Patients with personality disorder or psychoses were 2.3 times (95% CI 1.79–2.99) more likely than others to re-present within 28 days. Personality disorder diagnosis increases rate of readmission by a factor of 8.7 (s.e. = 0.31), marginally lower than psychotic disorders (10.02, s.e. = 0.31).
Conclusions
Personality disorders place significant demands on in-patient and emergency departments, similar to that of psychoses in terms of presentation and risk of readmission.