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An analysis of the divertor designs for the Infinity Two Fusion Pilot Plant (FPP) Baseline Plasma Design is presented. The divertor uses an m = 5, n = 4 magnetic island chain. Two divertor designs are presented. A classical divertor that is similar to the W7-X island divertor is analyzed using diffusive field line following and the fluid code EMC3-Lite. For a baseline 800 MW operating point in Infinity Two, the conditions where the heat flux on the divertor plate remains in the acceptable region are analyzed. In addition a related, but different and novel Large Island Backside Divertor (LIBD) design is shown. The LIBD promises improved neutral pumping by closing the divertor through the use of baffling and with a structure inside the island, thus preventing neutralized plasma particles from reentering the plasma.
The integration of geotechnical and geophysical well logs, along with biostratigraphic and sediment analyses of borehole Schoten (northern Belgium), provides a better characterization of the glauconite-rich sandy Miocene successions near their type sections. It also provides a way to correlate the latter with more distal areas along the southern North Sea Basin. In the Schoten area, the Rupelian Boom Formation is unconformably overlain by the Lower to Middle Miocene Berchem Formation, which is in turn unconformably overlain by the Upper Miocene Diest Formation (Borsbeek Member). The Berchem Formation is formally subdivided into the Edegem, Kiel and Antwerpen members, which can be identified on the gamma-ray log of borehole Schoten. Sediment analyses show that the glauconite content and the local presence of phosphatic nodules are the main factors contributing to the fluctuating gamma-ray values. For the first time, the geophysical log signatures of the members of the Berchem Formation were correlated across large areas and major fault systems, which shows the regional significance of the boundaries between these members. Indeed, the boundary between the Edegem Member and the Kiel Member corresponds with the boundary between the Dutch Veldhoven and Groote Heide formations, known as the Early Miocene Unconformity. The overall higher gamma-ray values for the middle Miocene Antwerpen Member and equivalents in the upper part of the Dutch Groote Heide Formation are likely related to the eustatic sea level highs during the Miocene Climatic Optimum.
While early intervention in psychosis (EIP) programs have been increasingly implemented across the globe, many initiatives from Africa, Asia and Latin America are not widely known. The aims of the current review are (a) to describe population-based and small-scale, single-site EIP programs in Africa, Asia and Latin America, (b) to examine the variability between programs located in low-and-middle income (LMIC) and high-income countries in similar regions and (c) to outline some of the challenges and provide recommendations to overcome existing obstacles.
Methods
EIP programs in Africa, Asia and Latin America were identified through experts from the different target regions. We performed a systematic search in Medline, Embase, APA PsycInfo, Web of Science and Scopus up to February 6, 2024.
Results
Most EIP programs in these continents are small-scale, single-site programs that serve a limited section of the population. Population-based programs with widespread coverage and programs integrated into primary health care are rare. In Africa, EIP programs are virtually absent. Mainland China is one of the only LMICs that has begun to take steps toward developing a population-based EIP program. High-income Asian countries (e.g. Hong Kong and Singapore) have well-developed, comprehensive programs for individuals with early psychosis, while others with similar economies (e.g. South Korea and Japan) do not. In Latin America, Chile is the only country in the process of providing population-based EIP care.
Conclusions
Financial resources and integration in mental health care, as well as the availability of epidemiological data on psychosis, impact the implementation of EIP programs. Given the major treatment gap of early psychosis in Africa, Latin America and large parts of Asia, publicly funded, locally-led and accessible community-based EIP care provision is urgently needed.
Developmental studies of mental disorders based on epidemiological data are often based on cross-sectional retrospective surveys. Under such designs, observations are right-censored, causing underestimation of lifetime prevalences and correlations, and inducing bias in latent trait models on the observations. In this paper we propose a Partial Likelihood (PL) method to estimate unbiased IRT models of lifetime predisposition to develop a certain outcome. A two-step estimation procedure corrects the IRT likelihood of outcome appearance with a function depending on (a) projected outcome frequencies at the end of the risk period, and (b) outcome censoring status at the time of the observation. Simulation results showed that the PL method yielded good recovery of true frequencies and intercepts. Slopes were best estimated when events were sufficiently correlated. When PL is applied to lifetime mental health disorders (assessed in the ESEMeD project surveys), estimated univariate prevalences were, on average, 1.4 times above raw estimates, and 2.06 higher in the case of bivariate prevalences.
Galaxy Zoo is an online project to classify morphological features in extra-galactic imaging surveys with public voting. In this paper, we compare the classifications made for two different surveys, the Dark Energy Spectroscopic Instrument (DESI) imaging survey and a part of the Kilo-Degree Survey (KiDS), in the equatorial fields of the Galaxy And Mass Assembly (GAMA) survey. Our aim is to cross-validate and compare the classifications based on different imaging quality and depth. We find that generally the voting agrees globally but with substantial scatter, that is, substantial differences for individual galaxies. There is a notable higher voting fraction in favour of ‘smooth’ galaxies in the DESI+zoobot classifications, most likely due to the difference between imaging depth. DESI imaging is shallower and slightly lower resolution than KiDS and the Galaxy Zoo images do not reveal details such as disc features and thus are missed in the zoobot training sample. We check against expert visual classifications and find good agreement with KiDS-based Galaxy Zoo voting. We reproduce the results from Porter-Temple+ (2022), on the dependence of stellar mass, star formation, and specific star formation on the number of spiral arms. This shows that once corrected for redshift, the DESI Galaxy Zoo and KiDS Galaxy Zoo classifications agree well on population properties. The zoobot cross-validation increases confidence in its ability to compliment Galaxy Zoo classifications and its ability for transfer learning across surveys.
The relevance of education and outreach (E&O) activities about the Antarctic Treaty has been recognized at the Antarctic Treaty Consultative Meetings (ATCM) and at the Committee for Environmental Protection (CEP). This study examines the key topics and the target audiences detailed in papers submitted to the ATCM on E&O. Since the Antarctic Treaty entered into force in 1961, a total of 216 ATCM papers on E&O have been produced. The number of papers has increased substantially since the mid-1990s. ‘Science’ (76.9%) and ‘Wildlife/Biodiversity/Environment’ (75.5%) were the most addressed topics in these papers, while the ‘Public’ (81.0%) and those attending ‘Schools’ (69.0%) are the main target audiences. ‘Science’ in ATCM papers increased ~120-fold from 1961–1997 to 2015–2023, while ATCM papers discussing engagement with the ‘Public’ increased ~40-fold during the same period. ‘Climate change’ was first mentioned in 2006, and the number of papers per year increased fourfold by 2015–2023. This study shows the increasing interest in E&O through time, addressing key topics to relevant audiences related to the Antarctic region. From an educational perspective, attention should be paid to emerging topics (e.g. equity, diversity and inclusion), and the engagement of early-career professionals and educators should be made a priority.
According to International Union for the Conservation of Nature (IUCN) guidelines, all species must be assessed against all criteria during the Red Listing process. For organismal groups that are diverse and understudied, assessors face considerable challenges in assembling evidence due to difficulty in applying definitions of key terms used in the guidelines. Challenges also arise because of uncertainty in population sizes (Criteria A, C, D) and distributions (Criteria A2/3/4c, B). Lichens, which are often small, difficult to identify, or overlooked during biodiversity inventories, are one such group for which specific difficulties arise in applying Red List criteria. Here, we offer approaches and examples that address challenges in completing Red List assessments for lichens in a rapidly changing arena of data availability and analysis strategies. While assessors still contend with far from perfect information about individual species, we propose practical solutions for completing robust assessments given the currently available knowledge of individual lichen life-histories.
Problem Management Plus (PM+) has been effective in reducing mental health problems among refugees at three-month follow-up, but there is a lack of research on its long-term effectiveness. This study examined the effectiveness of PM+ in reducing symptoms of common mental disorders at 12-month follow-up among Syrian refugees in the Netherlands.
Methods
This single-blind, parallel, controlled trial randomised 206 adult Syrians who screened positive for psychological distress and impaired functioning to either PM+ in addition to care as usual (PM+/CAU) or CAU alone. Assessments were at baseline, 1 week and 3 months after the intervention and 12 months after baseline. Outcomes were psychological distress (Hopkins Symptom Checklist [HSCL-25]), depression (HSCL-25 subscale), anxiety (HSCL-25 subscale), posttraumatic stress disorder symptoms (PCL-5), functional impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS).
Results
In March 2019–December 2022, 103 participants were assigned to PM+/CAU and 103 to CAU of which 169 (82.0%) were retained at 12 months. Intention-to-treat analyses showed greater reductions in psychological distress at 12 months for PM+/CAU compared to CAU (adjusted mean difference −0.17, 95% CI −0.310 to −0.027; p = 0.01, Cohen’s d = 0.28). Relative to CAU, PM+/CAU participants also showed significant reductions on anxiety (−0.19, 95% CI −0.344 to −0.047; p = 0.01, d = 0.31) but not on any of the other outcomes.
Conclusions
PM+ is effective in reducing psychological distress and symptoms of anxiety over a period up to 1 year. Additional support such as booster sessions or additional (trauma-focused) modules may be required to prolong and consolidate benefits gained through PM+ on other mental health and psychosocial outcomes.
The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID).
Methods
We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as “minimal improvement”).
Results
We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4–5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms.
Conclusions
By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.
Social determinants of health (SDoH), such as food and financial insecurity and food assistance, are potentially modifiable factors that may influence breastfeeding initiation and duration. Knowledge gaps exist regarding the relationship between these SDoH and infant feeding practices. We explored the relationships of food and financial insecurity and food assistance with the continuation of breastfeeding at four months postpartum among mothers and whether race and ethnicity modified these associations.
Design:
Mothers retrospectively reported food and financial insecurity and receipt of food assistance (e.g. Women, Infants and Children and Supplemental Nutrition Assistance Program) during pregnancy with their first child and infant feeding practices (exclusive/mostly breastfeeding v. exclusive/mostly formula feeding) following the birth of their first child. Sociodemographic-adjusted modified Poisson regressions estimated prevalence ratios and 95 % CI.
Setting:
Minneapolis-St. Paul, Minnesota.
Participants:
Mothers who participated in the Life-course Experiences And Pregnancy study (LEAP) (n 486).
Results:
Ten percent of mothers reported food insecurity, 43 % financial insecurity and 22 % food assistance during their pregnancies. At four months postpartum, 63 % exclusively/mostly breastfed and 37 % exclusively/mostly formula-fed. We found a lower adjusted prevalence of breastfeeding at four months postpartum for mothers who reported experiencing food insecurity (0·65; 0·43–0·98) and receiving food assistance (0·66; 0·94–0·88) relative to those who did not. For financial insecurity (aPR 0·92; 0·78, 1·08), adjusted estimates showed little evidence of an association.
Conclusions:
We found a lower level of breastfeeding among mothers experiencing food insecurity and using food assistance. Resources to support longer breastfeeding duration for mothers are needed. Moreover, facilitators, barriers and mechanisms of breastfeeding initiation and duration must be identified.
High-fat diet (HFD) consumption during pregnancy can shape fetal brain development, increasing susceptibility to mental disorders. Nevertheless, the mechanisms underlying these negative outcomes remain unclear.
Objectives
We hypothesize that mHFD induces inflammation and oxidative stress (OS) in the fetal brain, disrupting excitatory/inhibitory (E/I) balance in the adult brain. This results in altered hypothalamic-pituitary-adrenal (HPA) axis reactivity, emotional regulation, and cognitive function. We tested the ability of N-acetyl-cysteine (NAC) - a powerful anti-oxidant and anti-inflammatory compound - to counteract mHFD effects.
Methods
Our mHFD model consists of female C57BL/6N mice fed either HFD (fat 58%, carbohydrate 25.5%, and protein 16.4%) or control diet (CD, fat 10.5%, carbohydrate 73.1% and protein 16.4%) before and during pregnancy (13 weeks). After 5 weeks on diets, half of them received NAC (1g/kg) for 8 weeks, until delivery.
Gene expression of Il-1b, Cd68, Tmem119, iNOS, and Arg1 was measured in fetal brains. Cognitive function and emotional phenotype were assessed in adult male and female offspring through the Morris Water Maze (MWM) and the Emergence test, respectively. HPA axis functionality was assessed by measuring plasma corticosterone levels by ELISA following acute stress. Gene expression of vesicular glutamate transporter 1 (Vglut1) and vesicular GABA transporter (Vgat) were assessed as markers of E/I balance.
Results
Exposure to mHFD induced inflammation and OS in the fetal brain of both sexes, by increasing Il-1b and iNOS/Arg1. Additionally, Cd68 and Tmem119 were specifically increased in females. In adulthood, mHFD reduced latency to emerge from the shelter in the Emergence test in both sexes. In females, mHFD impaired cognitive function, reducing time spent in the MWM target zone, and increased HPA reactivity in response to acute stress. Furthermore, mHFD decreased Vgat expression in both sexes, resulting in an imbalanced Vglut1/Vgat ratio towards excessive excitatory input. Maternal NAC supplementation rescued this imbalance.
Conclusions
Overall, these data show that mHFD increases inflammation and OS in fetal brains, with greater effects in female offspring, inducing alterations in the E/I neuronal balance with concomitant disruptions of the neuroendocrine system and the emotional and cognitive profiles during adulthood. The supplementation with NAC was effective in rescuing the E/I imbalance as well as the behavioral phenotype.
There is a relative lack of research, targeted models and tools to manage beaches in estuaries and bays (BEBs). Many estuaries and bays have been highly modified and urbanised, for example port developments and coastal revetments. This paper outlines the complications and opportunities for conserving and managing BEBs in modified estuaries. To do this, we focus on eight diverse case studies from North and South America, Asia, Europe, Africa and Australia combined with the broader global literature. Our key findings are as follows: (1) BEBs are diverse and exist under a great variety of tide and wave conditions that differentiate them from open-coast beaches; (2) BEBs often lack statutory protection and many have already been sacrificed to development; (3) BEBs lack specific management tools and are often managed using tools developed for open-coast beaches; and (4) BEBs have the potential to become important in “nature-based” management solutions. We set the future research agenda for BEBs, which should include broadening research to include greater diversity of BEBs than in the past, standardising monitoring techniques, including the development of global databases using citizen science and developing specific management tools for BEBs. We must recognise BEBs as unique coastal features and develop the required fundamental knowledge and tools to effectively manage them, so they can continue providing their unique ecosystem services.
Electroconvulsive therapy (ECT) is a psychiatric intervention that has proven effectiveness and safety in various psychiatric conditions, such as major depressive disorder, prolonged or severe manic episodes and catatonia. Despite positive scientific evidence, ECT was always seen as controversial by patients, caregivers, and even some psychiatrists, which lead to a decrease in its use over the years.
Objectives
To investigate the way young psychiatrists view the place of ECT in modern psychiatry by assessing their knowledge, attitude and access to training opportunities in ECT.
Methods
An anonymous survey was disseminated online among early career psychiatrists and psychiatric trainees. The questionnaire consisted of 36 multiple-choice and Likert scale questions.
Results
Most of our respondents consider ECT both an effective and a safe treatment option and would recommend ECT to their patients when indicated. Early career psychiatrists who had access to ECT training are more knowledgeable about the indications, precautions and side effects of this method, but more than half of the participants mentioned ECT training was unavailable during their residency programme. Almost all respondents stated that they are interested in enhancing their theoretical and practical competencies in ECT.
Conclusions
Early career psychiatrists have a positive attitude towards ECT but express the need of targeted education aimed at improving levels of knowledge about ECT.
A review of fabric studies of clays suggests the need for relating those fabric characteristics which are revealed at the two levels of magnification provided by optical and electron microscopy, and a technique to achieve this has been developed and is described within the context of the initial stages of a long term study of the interrelation between fabric and engineering behaviour. Two kaolinitic clays with contrived fabrics were prepared by controlling particle size, moisture content and pH of suspension, and consolidation load and were subjected to shear loading to failure. Resin impregnation techniques which permit the kaolinite to be cut into thin sections for transmission electron microscopy have been optimized with the object of minimizing fabric strain and damage during ultratomy.
The fabrics of the hard and soft ambient material are qualitatively compared by means of electron micrographs and are explained in terms of the preparatory procedures adopted for fabric control. The fabrics of the two types of shear induced structures are also qualitatively compared and explained in terms of the original fabrics and the subsequent shear loading.
The adsorption of 1,10-phenanthroline (OP) onto some clays and oxides was studied as a function of concentration, pH, and time. The adsorption was found to be irreversible and the isotherms, except for silica gel, were hyperbolic and gave rise to plots similar to that of Langmuir. Kinetic and light scattering studies show that OP is adsorbed as a micellar unit composed on the average of 3.5 molecules/micelle. This fact explains the overestimation observed in the surface areas of some sorbents since no true monomolecular layer of OP is formed on the surfaces. The adsorption was also found to be pH dependent, attaining a maximum, independent of the sorbent, at about pH 6. This maximum was approximately at the same pH in which only the molecular form of OP began to be present. The partial desorption of OP as the pH increased beyond 6 is possibly associated with the aggregation of micelles on the surfaces.
Background: Zilucoplan, a macrocyclic peptide complement component 5 inhibitor, sustained efficacy for up to 60 weeks of treatment, with a favourable safety profile in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis in an interim analysis of RAISE-XT (NCT04225871). We evaluate the safety and efficacy of zilucoplan up to 96 weeks. Methods: RAISE-XT, a Phase 3, multicentre, open-label extension study, included patients who participated in the double-blind Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg injections. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: At data cut-off (11 May 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years (N=200). TEAEs occurred in 191 (95.5%) patients; the most common TEAE was COVID-19 (n=64; 32.0%). At Week 96, mean (standard error) change in MG-ADL score from double-blind study baseline was –6.33 (0.49) and –7.83 (0.60) for patients who received zilucoplan 0.3mg/kg and placebo in the double-blind studies, respectively. Conclusions: Zilucoplan demonstrated a favourable long-term safety profile. Efficacy was sustained for 96 weeks in patients who had previously received zilucoplan and who switched from placebo.
Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.
Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.
By examining the shared neuro-cognitive correlates of curiosity and creativity, we better understand the brain basis of creativity. However, by only examining shared components, important neuro-cognitive correlates are overlooked. Here, we argue that any comprehensive brain model of creativity should consider multiple cognitive processes and, alongside the interplay between brain networks, also the neurochemistry and neural oscillations that underly creativity.
Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown.
Methods
A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies.
Results
Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations.
Conclusions
Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.