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There is considerable interest in the role of neuroimmune processes in neuropsychiatric presentations among young people seeking mental health, neurological, paediatric and rheumatological services. The increasing availability of new immunotherapies, particularly monoclonal antibodies, introduces challenges in effectively and appropriately selecting candidates for immunotherapies. Neuroimmune-mediated neuropsychiatric syndromes (NIMNPS) typically include two broad types: i) ‘autoimmune encephalitis’, characterised by acute or subacute onset, neurological signs such as seizures, delirium or motor features and severe psychotic or major mood phenomena. Anti-N-methyl-D-aspartate receptor encephalitis was a pioneering clinical example, but various other autoantibodies have since been associated with this phenotype; and ii) atypical mood or psychotic syndromes with sub-acute or insidious onset, moderately severe atypical mood or psychotic symptoms, autonomic dysregulation, narcolepsy-like features, poor response to conventional treatments and adverse (notably motor) effects from psychotropic medications. Diagnosis of NIMNPS requires clinical or laboratory evidence of direct brain involvement, though autoantibodies are not always detectable. Given the broad and controversial diagnostic criteria for NIMNPS, we propose standardised clinical criteria for identifying ‘possible cases’, followed by laboratory, neuropsychological and brain imaging tests to confirm ‘probable’ cases suitable for immunotherapy. We emphasise rapid clinical and informed co-decision-making with young people and their families and loved ones. While immunotherapy holds promise for symptom alleviation, highly-personalised approaches and long-term management are essential. Future research should validate our proposed criteria, establish optimal, standardised yet personalised immunotherapy strategies that balance between clinical benefit and risks, and identify predictive markers of treatment response.
Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.
Although food insecurity affects a significant proportion of young children in New Zealand (NZ)(1), evidence of its association with dietary intake and sociodemographic characteristics in this population is lacking. This study aims to assess the household food security status of young NZ children and its association with energy and nutrient intake and sociodemographic factors. This study included 289 caregiver and child (1-3 years old) dyads from the same household in either Auckland, Wellington, or Dunedin, NZ. Household food security status was determined using a validated and NZ-specific eight-item questionnaire(2). Usual dietary intake was determined from two 24-hour food recalls, using the multiple source method(3). The prevalence of inadequate nutrient intake was assessed using the Estimated Average Requirement (EAR) cut-point method and full probability approach. Sociodemographic factors (i.e., socioeconomic status, ethnicity, caregiver education, employment status, household size and structure) were collected from questionnaires. Linear regression models were used to estimate associations with statistical significance set at p <0.05. Over 30% of participants had experienced food insecurity in the past 12 months. Of all eight indicator statements, “the variety of foods we are able to eat is limited by a lack of money,” had the highest proportion of participants responding “often” or “sometimes” (35.8%). Moderately food insecure children exhibited higher fat and saturated fat intakes, consuming 3.0 (0.2, 5.8) g/day more fat, and 2.0 (0.6, 3.5) g/day more saturated fat compared to food secure children (p<0.05). Severely food insecure children had lower g/kg/day protein intake compared to food secure children (p<0.05). In comparison to food secure children, moderately and severely food insecure children had lower fibre intake, consuming 1.6 (2.8, 0.3) g/day and 2.6 (4.0, 1.2) g/day less fibre, respectively. Severely food insecure children had the highest prevalence of inadequate calcium (7.0%) and vitamin C (9.3%) intakes, compared with food secure children [prevalence of inadequate intakes: calcium (2.3%) and vitamin C (2.8%)]. Household food insecurity was more common in those of Māori or Pacific ethnicity; living in areas of high deprivation; having a caregiver who was younger, not in paid employment, or had low educational attainment; living with ≥2 other children in the household; and living in a sole-parent household. Food insecure young NZ children consume a diet that exhibits lower nutritional quality in certain measures compared to their food-secure counterparts. Food insecurity was associated with various sociodemographic factors that are closely linked with poverty or low income. As such, there is an urgent need for poverty mitigation initiatives to safeguard vulnerable young children from the adverse consequences of food insecurity.
Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) (n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17–28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15–23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30–67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.
Derived from the National Pediatric Cardiology Quality Improvement Collaborative registry, the NEONATE risk score predicted freedom from interstage mortality or heart transplant for patients with single ventricle CHD and aortic arch hypoplasia discharged home following Stage 1 palliation.
Objectives:
We sought to validate the score in an external, modern cohort.
Methods:
This was a retrospective cohort analysis of single ventricle CHD and aortic arch hypoplasia patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry from 2016 to 2020, who were discharged home after Stage 1 palliation. Points were allocated per the NEONATE score (Norwood type—Norwood/Blalock–Taussig shunt: 3, Hybrid: 12; extracorporeal membrane oxygenation post-op: 9, Opiates at discharge: 6, No Digoxin at discharge: 9, Arch Obstruction on discharge echo: 9, Tricuspid regurgitation ≥ moderate on discharge echo: 12; Extra oxygen plus ≥ moderate tricuspid regurgitation: 28). The composite primary endpoint was interstage mortality or heart transplant.
Results:
In total, 1026 patients met inclusion criteria; 61 (6%) met the primary outcome. Interstage mortality occurred in 44 (4.3%) patients at a median of 129 (IQR 62,195) days, and 17 (1.7%) were referred for heart transplant at a 167 (114,199) days of life. The median NEONATE score was 0(0,9) in those who survived to Stage 2 palliation compared to 9(0,15) in those who experienced interstage mortality or heart transplant (p < 0.001). Applying a NEONATE score cut-off of 17 points that separated patients into low- and high-risk groups in the learning cohort provided 91% specificity, negative predictive value of 95%, and overall accuracy of 87% (85.4–89.5%).
Conclusion:
In a modern cohort of patients with single ventricle CHD and aortic arch hypoplasia, the NEONATE score remains useful at discharge post-Stage 1 palliation to predict freedom from interstage mortality or heart transplant.
In both population-based and clinical cohorts, cross-sectional and longitudinal studies have reported associations between a range of non-specific markers of immune activation (e.g., pro-inflammatory cytokines) or chronic inflammation (e.g., C-reactive protein [CRP]) and depressive and other mood disorders (Dowlati et al. 2010; Hickie et al. 2018; Khandaker et al. 2017; Orsolini et al. 2022; Valkanova et al. 2013). The clinico-pathological significance, and directional relationships, of these associations tended to be downplayed as the systemic levels of these inflammatory markers were not in the ranges typical of active infective, inflammatory or significant autoimmune diseases.
The Wisconsin high-temperature superconductor axisymmetric mirror experiment (WHAM) will be a high-field platform for prototyping technologies, validating interchange stabilization techniques and benchmarking numerical code performance, enabling the next step up to reactor parameters. A detailed overview of the experimental apparatus and its various subsystems is presented. WHAM will use electron cyclotron heating to ionize and build a dense target plasma for neutral beam injection of fast ions, stabilized by edge-biased sheared flow. At 25 keV injection energies, charge exchange dominates over impact ionization and limits the effectiveness of neutral beam injection fuelling. This paper outlines an iterative technique for self-consistently predicting the neutral beam driven anisotropic ion distribution and its role in the finite beta equilibrium. Beginning with recent work by Egedal et al. (Nucl. Fusion, vol. 62, no. 12, 2022, p. 126053) on the WHAM geometry, we detail how the FIDASIM code is used to model the charge exchange sources and sinks in the distribution function, and both are combined with an anisotropic magnetohydrodynamic equilibrium solver method to self-consistently reach an equilibrium. We compare this with recent results using the CQL3D code adapted for the mirror geometry, which includes the high-harmonic fast wave heating of fast ions.
The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) lacks a rigorous enrollment audit process, unlike other collaborative networks. Most centers require individual families to consent to participate. It is unknown whether there is variation across centers or biases in enrollment.
Methods:
We used the Pediatric Cardiac Critical Care Consortium (PC4) registry to assess enrollment rates in NPC-QIC for those centers participating in both registries using indirect identifiers (date of birth, date of admission, gender, and center) to match patient records. All infants born 1/1/2018–12/31/2020 and admitted 30 days of life were eligible. In PC4, all infants with a fundamental diagnosis of hypoplastic left heart or variant or who underwent a surgical or hybrid Norwood or variant were eligible. Standard descriptive statistics were used to describe the cohort and center match rates were plotted on a funnel chart.
Results:
Of 898 eligible NPC-QIC patients, 841 were linked to 1,114 eligible PC4 patients (match rate 75.5%) in 32 centers. Match rates were lower in patients of Hispanic/Latino ethnicity (66.1%, p = 0.005), and those with any specified chromosomal abnormality (57.4%, p = 0.002), noncardiac abnormality (67.8%, p = 0.005), or any specified syndrome (66.5%, p = 0.001). Match rates were lower for patients who transferred to another hospital or died prior to discharge. Match rates varied from 0 to 100% across centers.
Conclusions:
It is feasible to match patients between the NPC-QIC and PC4 registries. Variation in match rates suggests opportunities for improvement in NPC-QIC patient enrollment.
The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ($\Sigma_{\star}$), H i ($\Sigma_{\text{H}\,{\small\text{I}}}$), and molecular gas ($\Sigma_{\text{mol}}$) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$-to-$\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.
Critical consciousness (CC) theory emphasizes a form of reflection on social, political, and economic conditions that analyzes the historical root causes of inequity and the ways these inequities are systemically perpetuated and magnified through laws, policies, and institutions. Despite the theoretical centrality of structural and historical thinking in CC, most empirical work on the topic has not incorporated these constructs into measures of critical reflection. The current chapter explores the rationale for measuring structural and historical thinking in critical reflection and considers challenges to doing so. We present factor analytic work showing how new measures of structural and historical attributions can be incorporated into existing measurement of critical reflection. We discuss strengths and weaknesses of this approach and explore the implications of this expanded measure.
The surge in critically ill patients has pressured hospitals to expand their intensive care unit capacities and critical care staff. This was difficult given the country’s shortage of intensivists. This paper describes the implementation of a multidisciplinary central line placement team and its impact in reducing the vascular access workload of ICU physicians during the height of the COVID-19 pandemic.
Methods:
Vascular surgeons, interventionalists, and anesthesiologists, were redeployed to the ICU Access team to place central and arterial lines. Nurses with expertise in vascular access were recruited to the team to streamline consultation and assist with line placement.
Results:
While 51 central and arterial lines were placed per 100 ICU patients in 2019, there were 87 central and arterial lines placed per 100 COVID-19 ICU patients in the sole month of April, 2020. The ICU Access Team placed 107 of the 226 vascular access devices in April 2020, reducing the procedure-related workload of ICU treating teams by 46%.
Conclusions:
The ICU Access Team was able to complete a large proportion of vascular access insertions without reported complications. Given another mass casualty event, this ICU Access Team could be reassembled to rapidly meet the increased vascular access needs of patients.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Methods
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
Results
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
Conclusions
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
When presenting with a first episode of psychosis (FEP), migrants can have different demographic and clinical characteristics to the native-born population and this was examined in an Irish Early Intervention for Psychosis service.
Methods:
All cases of treated FEP from three local mental health services within a defined catchment area were included. Psychotic disorder diagnoses were determined using the SCID and symptom and functioning domains were measured using validated and reliable measures.
Results:
From a cohort of 612 people, 21.1% were first-generation migrants and there was no difference in the demographic characteristics, diagnoses, symptoms or functioning between migrants and those born in the Republic of Ireland, except that migrants from Africa presented with less insight. Of those admitted, 48.6% of admissions for migrants were involuntary compared to 37.7% for the native-born population (p = 0.09).
Conclusions:
First-generation migrants now make up a significant proportion of people presenting with a FEP to an Irish EI for psychosis service. Broadly the demographic and clinical characteristics of migrants and those born in the Republic of Ireland are similar, except for less insight in migrants from Africa and a trend for a higher proportion of involuntary admissions in the total migrant group.
Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
Aims
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
Method
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
Conclusions
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Individuals who experience serious mental health disorders are at an increased risk of physical illness co-morbidity and early intervention is crucial. Recommendations to embed an exercise physiologist service into a mental health service have not been fully evaluated.
Objectives
This study aimed to determine (i) demographics and clinical characteristics of the young people referred to exercise physiology, (ii) adherence to metabolic monitoring, (iii) baseline physical health and (iv) level of engagement after referral.
Methods
This is a naturalistic cohort study and included all young people referred to the exercise physiology service between 2015 and 2019 at Orygen, a specialist youth mental health service in the north-western region of Melbourne.
Results
During the study period of 45 months, 312 young people were referred to exercise physiology, and of those, 51.3% were male. The mean age was 19.8 years. In regard to primary diagnoses, 47.4% had a psychotic disorder and 33.7% an affective disorder. Baseline weight measurements were completed for 71.8% of young people. The proportion of young people who were classified as overweight or obese increased from 55.1% to 70.4% (p < 0.001). For those referred, 61.5% attended either an individual session or a group session. A total of 29.5% did not attend their appointment following referral.
Conclusions
As over half of young people had poor physical health at presentation, integrating an exercise physiology service into a youth mental health service is a novel and needed intervention. However, there still needs to be an emphasis on metabolic monitoring and engagement.