Search

BACKGROUND AND AIMS: Young people accessing alcohol and other drug (AOD) treatment experience high rates of treatment disengagement, contributing to poorer outcomes. To improve outcomes, it is important to identify factors associated with treatment retention. This study measured the relationships between client characteristics, treatment characteristics, clinical severity measures and completion of treatment among young people. DESIGN, SETTING AND PARTICIPANTS: This study was a retrospective analysis of routinely collected data set in residential- and community-based AOD services in New South Wales, Australia. Routinely collected data from the Network of Alcohol and Other Drug Agencies' (NADA) database were used. Included individuals were aged 10-24 years and accessed treatment between 2012 and 2023 (n = 17 474). MEASUREMENTS: Variables included client-related characteristics, service characteristics and baseline measures of clinical severity [Kessler-10 (K10), EUROHIS-QoL, severity of dependence scale (SDS)]. Multivariable binary logistic regression models assessed the relationships between these characteristics and treatment completion. FINDINGS: Rates of treatment completion were highest among adolescents in community-based treatment (57%) and lowest among young adults in residential treatment (35%). Polysubstance use was negatively associated with treatment completion among adolescents [adjusted odds ratio (adjOR) = 0.71, P < 0.001] and adults (adjOR = 0.70, P < 0.001) in community-based treatment, and adolescents in residential treatment (adjOR = 0.62, P = 0.006), as was housing insecurity (adolescents in community treatment, adjOR = 0.61, P = 0.001; adults in community treatment, adjOR = 0.77, P = 0.002; adolescents in residential treatment, adjOR = 0.42, P = 0.005). Attending youth-specific services was associated with higher treatment completion rates among adults in community-based (adjOR = 1.81, P < 0.001) and residential treatment (adjOR = 1.72, P < 0.001

Background The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study is a prospective study collecting extensive cognitive, clinical, fluid, and imaging biomarkers data from older adults living in Australia. Integration of outcomes between large prospective studies of AD will provide greater precision in models of AD brain‐behavior relationships, so it is important to align composite scores for cognitive domains between such studies. Methods Detailed methods for AIBL, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center (NACC) have been published. Briefly, AIBL participants had cognition assessed with an extensive neuropsychological test battery alongside health and biomarker assessments at entry and each 18‐months thereafter. Granular‐level cognitive data were obtained and an expert panel of two neuropsychologists and a behavioral neurologist categorized each element as assessing memory, executive functioning, language, visuospatial, or none of these, exactly as we have done previously. We also identified elements we had previously calibrated from other studies; after careful quality control and confirmation these served as anchors enabling co‐calibration. We used confirmatory factor analysis bi‐factor models to calibrate the AIBL battery with other studies. We used those calibrations to obtain co‐calibrated scores for all AIBL participants at every study visit. Here we show descriptive statistics for baseline visits, separately by diagnosis (normal cognition, mild cognitive impairment (MCI), dementia) for two enrollment waves for AIBL as well as for each phase of ADNI and across the Uniform Data Set (UDS) 1 & 2 (UDS1/2) and UDS3 time periods for NACC. Results Box plots for memory, executive functioning, language, and visuospatial for people with normal cognition are in Figure 1, MCI in Figure 2, and dementia in Figure 3. These figures show there is substantial cognitive variation across waves within these

Background Approximately 30% of older adults are cognitively normal at death despite presence of Alzheimer’s disease (AD) neuropathology at autopsy. Studying these “resilient” individuals may lead to the discovery of novel therapeutic targets. In addition, growing evidence suggests sex differences in downstream neurodegenerative consequences of AD neuropathology, with recent studies highlighting notable sex-specific genetic drivers of AD pathogenesis. We sought to extend this work by elucidating sex-specific genetic factors underlying resilience to AD. Method We used our published genetic resilience pipeline to assess sex-specific genetic predictors (Dumitrescu et al., 2020). Briefly, we used modern psychometric approaches to harmonize cognitive measures across four cohorts of cognitive aging (N=5054), in-vivo amyloid PET across two studies, and leveraged autopsy measures of amyloidosis (CERAD staging) across two studies. A continuous measure of resilience was quantified using a latent variable framework whereby higher scores reflected better-than-predicted cognitive performance given amyloidosis level and lower scores reflected worse-than-predicted performance. We then performed sex-stratified GWASs and sex-interaction GWASs, covarying for age and the first three principal components and meta-analyzed across cohorts. Finally, we performed sex-stratified genetic correlation analyses (GNOVA) between our meta-analysis results and summary statistics from 63 complex traits. Result Among individuals with normal cognition, we identified a female-specific locus on chromosome 10 (rs827389, [p(females)=7.4E-09, p(males)=0.64, p(interaction)=8.3E-05, MAF=0.46]). This variant is a modest eQTL for KIN (p=0.003), a gene encoding a DNA/RNA binding protein (http://www.braineac.org). In our genetic correlation analyses, we observed male-specific correlations between resilience and two heart rate-related traits, whereby higher resilience was associated with lower genetic risk for po

Background There are notable sex differences in the clinical manifestation of Alzheimer’s disease (AD), including differences in baseline and longitudinal changes in memory performance. However, sex-stratified models have not been routinely incorporated into genetic studies of cognitive performance or decline. We sought to identify sex-specific genetic predictors of memory performance in aging adults. Method We obtained harmonized memory scores from 11,601 females and 8,885 males from 7 cohorts of cognitive aging. We calculated scores using latent variable modeling techniques anchored on overlapping neuropsychological test items across datasets to perform both sex-stratified and sex-interaction genome-wide association studies in each cohort using mixed-effects regression models to assess genetic associations with baseline memory score and rate of memory decline. Covariates included age at baseline and population principal components. We then combined results in a fixed-effect meta-analysis. Results As expected, we observed robust associations at the APOE locus in males and females in both baseline and longitudinal models. Additionally, we identified a sex-specific locus for longitudinal memory performance (interaction-p=2.54e-6) on chromosome 7 within LINC-PINT that was genome-wide significant in males (index SNP= rs66754621; p=1.62e-8; MAF=0.20), but not females (p=0.65). This variant is in an enhancer region within several brain regions, as well as within a promoter-anchored chromatin interaction loop and a methylation eQTL in the prefrontal cortex. No female-specific loci were identified. Interestingly, we did observe nominal associations in baseline memory at some known AD loci, including male-specific effects at MS4A6A, FERMT2, and KAT8 (interaction ps=0.0026, 0.027, and 0.0058, respectively) and opposing effects between males and females at INPP5D (interaction p=0.0021). Conclusion These results highlight a novel male-specific locus of memory performance on ch

Deep learning (DL) has been shown to be effective in developing diabetic retinopathy (DR) algorithms, possibly tackling financial and manpower challenges hindering implementation of DR screening. However, our systematic review of the literature reveals few studies studied the impact of different factors on these DL algorithms, that are important for clinical deployment in real-world settings. Using 455,491 retinal images, we evaluated two technical and three image-related factors in detection of referable DR. For technical factors, the performances of four DL models (VGGNet, ResNet, DenseNet, Ensemble) and two computational frameworks (Caffe, TensorFlow) were evaluated while for image-related factors, we evaluated image compression levels (reducing image size, 350, 300, 250, 200, 150 KB), number of fields (7-field, 2-field, 1-field) and media clarity (pseudophakic vs phakic). In detection of referable DR, four DL models showed comparable diagnostic performance (AUC 0.936-0.944). To develop the VGGNet model, two computational frameworks had similar AUC (0.936). The DL performance dropped when image size decreased below 250 KB (AUC 0.936, 0.900, p < 0.001). The DL performance performed better when there were increased number of fields (dataset 1: 2-field vs 1-field-AUC 0.936 vs 0.908, p < 0.001; dataset 2: 7-field vs 2-field vs 1-field, AUC 0.949 vs 0.911 vs 0.895). DL performed better in the pseudophakic than phakic eyes (AUC 0.918 vs 0.833, p < 0.001). Various image-related factors play more significant roles than technical factors in determining the diagnostic performance, suggesting the importance of having robust training and testing datasets for DL training and deployment in the real-world settings.

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run across all participants and repeated restricting the sample to individuals with unimpaired cognition to identify variants at the earliest stages of disease. As expected, all resilience metrics were genetically correlated with cognitive performance and education attainment traits (P-values < 2.5 × 10-20), and we observed novel correlations with neuropsychiatric conditions (P-values < 7.9 × 10-4). Notably, neither resilience metric was genetically correlated with clinical Alzheimer's disease (P-values > 0.42) nor associated with APOE (P-values > 0.13). In single variant analyses, we observed a genome-wide significant locus among participants with unimpaired cognition on chromosome 18 upstream of ATP8B1 (index single nucleotide polymorphism rs2571244, minor allele frequency = 0.08, P = 2.3 × 10-8). The top variant at this locus (rs2571244) was significantly associated with methylation in prefrontal cortex tissue at multiple CpG sites, including one just upstream of ATPB81 (cg19596477; P = 2 × 10-13). Overall, this comprehensive genetic analysis of resilience implicates a putative role of vascular risk, metabolism, and mental health in protection from the cognitive consequences of neuropathology, while also providing evidence for a

This book provides an extensive guide for exercise and health professionals, students, scientists, sport coaches, athletes of various sports and those with a general interest in concurrent aerobic and strength training.

Background Palliative sedation is the widely-used intervention of administering sedating agents to induce a state of unconsciousness to take away a dying patient's perception of otherwise irrelievable symptoms. However, it remains questionable whether this ethically complex intervention is beneficial for patients and whether the associated lack of communication in the last phase of life has a negative impact on relatives' wellbeing. Methods An observational questionnaire study was conducted among relatives of a consecutive sample of patients who died a non-sudden death in the Erasmus MC Cancer Institute or in the hospice 'Laurens Cadenza' (both in Rotterdam) between 2010 and 2013. Results Relatives filled in questionnaires regarding 151 patients who had been sedated and 90 patients who had not been sedated. The median time since all patients had passed away was 21 (IQR 14-32) months. No significant differences were found in relatives 'assessments of the quality of end-of-life care, patients 'quality of life in the last week before death and their quality of dying, between patients who did and did not receive sedation, or in relatives' satisfaction with their own life, their general health and their mental wellbeing after the patient's death. Conclusions The use of sedation in these patients appears to have no negative effect on bereaved relatives' evaluation of the patient's dying phase, or on their own wellbeing after the patient's death.

OBJECTIVE: Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. RESULTS: In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber. CONCLUSIONS: Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

New clinical studies suggest that narrowing of the retinal blood vessels may be an early indicator of cardiovascular diseases. One measure to quantify the severity of retinal arteriolar narrowing is the arteriolar-to-venular diameter ratio (AVR). The manual computation of AVR is a tedious process involving repeated measurements of the diameters of all arterioles and venules in the retinal images by human graders. Consistency and reproducibility are concerns. To facilitate large-scale clinical use in the general population, it is essential to have a precise, efficient and automatic system to compute this AVR. This paper describes a new approach to obtain AVR. The starting points of vessels are detected using a matched Gaussian filter. The detected vessels are traced with the help of a combined Kalman filter and Gaussian filter. A modified Gaussian model that takes into account the central light reflection of arterioles is proposed to describe the vessel profile. The width of a vessel is obtained by data fitting. Experimental results indicate a 97.1% success rate in the identification of vessel starting points, and a 99.2% success rate in the tracking of retinal vessels. The accuracy of the AVR computation is well within the acceptable range of deviation among the human graders, with a mean relative AVR error of 4.4%. The system has interested clinical research groups worldwide and will be tested in clinical studies.

A chiral stationary phase with a silicone backbone and substituted side chains of (S)-N-1-(1-naphthyl)-4-propyloxybenzamide substitution has been introduced for open tubular column GC and SFC. The stationary phase has a broad temperature working range 20-280 degrees C), and provides highly efficient columns (> 3000 plates/meter). One of the key interactions for selectivity is the pi-pi interaction, but the stationary phase can also be used to separate enantiomers without pi electrons. The phase can be used to separate a broad range of compounds, which is demonstrated by the separation of enantiomeric compounds having aromatic rings, amino acid and terpenic alcohol groups. This stationary phase expands the use of Pirkle phases into the field of open tubular column chromatography., Addresses: Juvancz Z, Pf 27, H-1453 Budapest, Hungary. VITUKI Plc, Inst Water Pollut Control, H-1095 Budapest, Hungary. Uppsala Univ, Dept Anal Chem, S-75121 Uppsala, Sweden. Brigham Young Univ, Dept Chem, Provo, UT 84602 USA.

In this paper, polymeric hollow fibers prepared from pH-stable polypropylene were used as columns for micellar electrokinetic capillary chromatography (MECC). The electroosmotic flow (EOF) for polypropylene hollow fibers was evaluated in the pH range of 5, Addresses: UPPSALA UNIV, S-75121 UPPSALA, SWEDEN. BRIGHAM YOUNG UNIV, DEPT CHEM, PROVO, UT 84602.

The preparation of charcoal porous layer open tabular (PLOT) columns, and their application to the separation of permanent gases and light hydrocarbons are reported. Two types of charcoal, coconut and darco charcoal, were used to prepare columns from fus, Addresses: BRIGHAM YOUNG UNIV, DEPT CHEM, PROVO, UT 84602. UNIV UPPSALA, DEPT ANALYT CHEM, S-75121 UPPSALA, SWEDEN.