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Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.
Methods
This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).
Results
In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.
Conclusions
Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.
We investigate the concentration fluctuations of passive scalar plumes emitted from small, localised (point-like) steady sources in a neutrally stratified turbulent boundary layer over a rough wall. The study utilises high-resolution large-eddy simulations for sources of varying sizes and heights. The numerical results, which show good agreement with wind-tunnel studies, are used to estimate statistical indicators of the concentration field, including spectra and moments up to the fourth order. These allow us to elucidate the mechanisms responsible for the production, transport and dissipation of concentration fluctuations, with a focus on the very near field, where the skewness is found to have negative values – an aspect not previously highlighted. The gamma probability density function is confirmed to be a robust model for the one-point concentration at sufficiently large distances from the source. However, for ground-level releases in a well-defined area around the plume centreline, the Gaussian distribution is found to be a better statistical model. As recently demonstrated by laboratory results, for elevated releases, the peak and shape of the pre-multiplied scalar spectra are confirmed to be independent of the crosswind location for a given downwind distance. Using a stochastic model and theoretical arguments, we demonstrate that this is due to the concentration spectra being directly shaped by the transverse and vertical velocity components governing the meandering of the plume. Finally, we investigate the intermittency factor, i.e. the probability of non-zero concentration, and analyse its variability depending on the thresholds adopted for its definition.
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.
Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada.
Methods:
We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV.
Results:
We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable.
Conclusion:
PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Self-compassion (SC) describes an emotionally positive attitude extended toward ourselves when we suffer, consisting of three main components; self-kindness, common humanity, and mindfulness (Germer & Neff, 2013). SC entails being warm and understanding towards ourselves when encountering pain or personal shortcomings, rather than ignoring them or flagellating ourselves with self-criticism. SC also involves recognizing that suffering and failure are part of the shared human experience rather than isolating. In addition, SC requires taking a mindful approach to one’s feelings and thoughts, without judgment of them.
Objectives
Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing depression and anxiety in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied.
Methods
Magnetic resonance imaging data were acquired from 71 healthy participants with measured levels of SC and its six subscales. Mirroring network as WM regions of interest were analyzed using tract-based spatial statistics (TBSS). After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed.
Results
We found that self-compassion scale (SCS) total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores of SCS were also negatively correlated with FA values of the same regions. The FA values of SLF related to SC were found to be negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy.
Conclusions
Our findings suggest that levels of SC and its self-kindness and mindfulness components may be negatively associated with DMN-related WM microstructures in healthy individuals. These less WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies.
With the advent of deep, all-sky radio surveys, the need for ancillary data to make the most of the new, high-quality radio data from surveys like the Evolutionary Map of the Universe (EMU), GaLactic and Extragalactic All-sky Murchison Widefield Array survey eXtended, Very Large Array Sky Survey, and LOFAR Two-metre Sky Survey is growing rapidly. Radio surveys produce significant numbers of Active Galactic Nuclei (AGNs) and have a significantly higher average redshift when compared with optical and infrared all-sky surveys. Thus, traditional methods of estimating redshift are challenged, with spectroscopic surveys not reaching the redshift depth of radio surveys, and AGNs making it difficult for template fitting methods to accurately model the source. Machine Learning (ML) methods have been used, but efforts have typically been directed towards optically selected samples, or samples at significantly lower redshift than expected from upcoming radio surveys. This work compiles and homogenises a radio-selected dataset from both the northern hemisphere (making use of Sloan Digital Sky Survey optical photometry) and southern hemisphere (making use of Dark Energy Survey optical photometry). We then test commonly used ML algorithms such as k-Nearest Neighbours (kNN), Random Forest, ANNz, and GPz on this monolithic radio-selected sample. We show that kNN has the lowest percentage of catastrophic outliers, providing the best match for the majority of science cases in the EMU survey. We note that the wider redshift range of the combined dataset used allows for estimation of sources up to $z = 3$ before random scatter begins to dominate. When binning the data into redshift bins and treating the problem as a classification problem, we are able to correctly identify $\approx$76% of the highest redshift sources—sources at redshift $z > 2.51$—as being in either the highest bin ($z > 2.51$) or second highest ($z = 2.25$).
To investigate the association between parity and the risk of incident dementia in women.
Methods
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Results
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Conclusions
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
To assess the Framingham risk score as a prognostic tool for idiopathic sudden sensorineural hearing loss patients.
Methods
Medical records were reviewed for unilateral idiopathic sudden sensorineural hearing loss patients between January 2010 and October 2017. The 10-year risk of developing cardiovascular disease was calculated. Patients were subdivided into groups: group 1 – Framingham risk score of less than 10 per cent (n = 28); group 2 – score of 10 to less than 20 per cent (n = 6); and group 3 – score of 20 per cent or higher (n = 5).
Results
Initial pure tone average and Framingham risk score were not significantly associated (p = 0.32). Thirteen patients in group 1 recovered completely (46.4 per cent), but none in groups 2 and 3 showed complete recovery. Initial pure tone average and Framingham risk score were significantly associated in multivariable linear regression analysis (R2 = 0.36). The regression coefficient was 0.33 (p = 0.003) for initial pure tone average and −0.67 (p = 0.005) for Framingham risk score.
Conclusion
Framingham risk score may be useful in predicting outcomes for idiopathic sudden sensorineural hearing loss patients, as those with a higher score showed poorer hearing recovery.
There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.
The aim of this study was to evaluate theprevalence of night eating syndrome (NES) and its correlates in schizophrenicoutpatients.
Methods
The 14 items of self-reported night eatingquestionnaire (NEQ) was administered to 201 schizophrenic patients in psychiatricoutpatient clinic. We examined demographic and clinical characteristics, bodymass index (BMI), subjective measures of mood, sleep, binge eating, andweight-related quality of life using Beck's Depression Inventory (BDI),Pittsburgh Sleep Quality Index (PSQI), Binge Eating Scale (BES) and Koreanversion of Obesity-Related Quality of Life Scale (KOQoL), respectively.
Results
The prevalence of night eaters in schizophrenicoutpatients was 10.4% (21 of 201). Comparisons between NES group and non-NES grouprevealed no significant differences in sociodemographic characteristics, clinical status and BMI. Compared to non-NES, patients with NES reportedsignificantly greater depressed mood and sleep disturbance, more binge eatingpattern, and decreased weight-related quality of life. While 'morning anorexia'and 'delayed morning meal' (2 of 5 NES core components in NEQ) were notdiffered between groups, 'nocturnal ingestions', 'evening hyperphagia', and'mood/sleep' were more impaired in NES group.
Conclusion
These findings are the first to describe theprevalence and its correlates of night eaters in schizophrenic outpatients. These results suggest that NES has negative mental health implications, although it was not associated with obesity. Further study to generalize theseresults is required.
Thisstudy was to assess the prevalence and its correlates of restless legs syndrome(RLS) in outpatients with bipolar disorder.
Method
A total of 100clinical stabilized bipolar outpatients were examined. The presence of RLS andits severity were assessed using the International Restless Legs Sydrome StudyGroup (IRLSSG) diagnostic criteria. Beck's Depression Inventory (BDI), Spielberg's StateAnxiety Inventory (STAI-X-1), Pittsburgh Sleep Quality Index (PSQI), Koreanversion Drug Attitude Inventory (KDAI-10), Subjective Well-Beings under NeurolepticTreatment Scale-Short Form(SWN-K) and Barnes Akathisia Rating Scale (BARS) wereused to evaluate the depressive symptomatology, level of anxiety, subjectivequality of sleep, subjective feeling of well-being, drug attitude, presence ofakathisia, respectively.
Results
Of the 100 bipolar outpatients,7 (7%) were met to full criteria of IRLSSG and 36 (36%) have at least one ofthe 4 IRLSSG criterion. Because of relatively small sample size, non-parametricanalysis were done to compare the characteristics among 3 groups (full-RLS, 1≥positiveRLS-symptom and Non-RLS). There were no significant differences in sex, age, and other sociodemographic and clinical data among 3 groups. BDI, STAI-X-1 andPSQI are tended to be impaired in RLS and 1≥positive RLS-symptomgroups.
Conclusion
This is the first preliminarystudy for studying the prevalence and its correlates of RLS in bipolardisorder. The results shows that RLS was relatively smaller presentin bipolar disorder than schizophrenia. Sametendencies shown in schizophrenic patients were found that bipolar patientswith RLS had more depressive symptoms, state anxiety and poor subjective sleepquality.
Numerous studies reported on the frequency of, and factors associated with inappropriate or unnecessary emergency department (ED) visits using clinician judgment as the gold standard of appropriateness. This study evaluated the reliability of clinician judgment for assessing appropriateness of pediatric ED visit.
Methods
We conducted a retrospective cohort study comparing 3 clinicians’ determination of ED visit appropriateness with and without guidance from a three-question structured algorithm. We used a cohort of scheduled ED return visits deemed appropriate by the index treating clinician between May 1, 2012, and April 30, 2013. We measured the level of agreement among three clinician investigators with and without use of the structured algorithm.
Results
A total of 207 scheduled ED return visits were reviewed by the primary clinician reviewer who agreed with the index treating clinician for 79/207 visits (38.2%). Among a random subset of 90 return visits reviewed by all three clinicians, agreement was 67% with a Fleiss’ Kappa of 0.30 (0.17–0.44). Using a three-question algorithm based on objective criteria, agreement with the index treating provider increased to 115/207 (55.6%).
Conclusions
Although an important contributor to pediatric ED overcrowding, unnecessary or inappropriate visits are difficult to identify. We demonstrated poor reliability of clinician judgment to determine appropriateness of ED return visits, likely due to variability in clinical decision-making and risk-tolerance, social and systems factors impacting access and use of health care. We recommend that future studies evaluating the appropriateness of ED use standardized, objective criteria rather than clinician judgment alone.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The asymptotic phase θ of an initial point x in the stable manifold of a limit cycle (LC) identifies the phase of the point on the LC to which the flow φt(x) converges as t → ∞. The infinitesimal phase response curve (iPRC) quantifies the change in timing due to a small perturbation of a LC trajectory. For a stable LC in a smooth dynamical system, the iPRC is the gradient ∇x(θ) of the phase function, which can be obtained via the adjoint of the variational equation. For systems with discontinuous dynamics, the standard approach to obtaining the iPRC fails. We derive a formula for the iPRCs of LCs occurring in piecewise smooth (Filippov) dynamical systems of arbitrary dimension, subject to a transverse flow condition. Discontinuous jumps in the iPRC can occur at the boundaries separating subdomains, and are captured by a linear matching condition. The matching matrix, M, can be derived from the saltation matrix arising in the associated variational problem. For the special case of linear dynamics away from switching boundaries, we obtain an explicit expression for the iPRC. We present examples from cell biology (Glass networks) and neuroscience (central pattern generator models). We apply the iPRCs obtained to study synchronization and phase-locking in piecewise smooth LC systems in which synchronization arises solely due to the crossing of switching manifolds.
This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.