Alien Registration- Purcell, Patrick E. (Bangor, Penobscot County)

https://digitalmaine.com/alien_docs/11305/thumbnail.jp

Evidence Map of Prevention and Treatment Interventions for Depression in Young People

Introduction. Depression in adolescents and young people is associated with reduced social, occupational, and interpersonal functioning, increases in suicide and self-harm behaviours, and problematic substance use. Age-appropriate, evidence-based treatments are required to provide optimal care. Methods. “Evidence mapping” methodology was used to quantify the nature and distribution of the extant high-quality research into the prevention and treatment of depression in young people across psychological, medical, and other treatment domains. Results. Prevention research is dominated by cognitive-behavioral- (CBT-) based interventions. Treatment studies predominantly consist of CBT and SSRI medication trials, with few trials of other psychological interventions or complementary/alternative treatments. Quality studies on relapse prevention and treatment for persistent depression are distinctly lacking. Conclusions. This map demonstrates opportunities for future research to address the numerous evidence gaps for interventions to prevent or treat depression in young people, which are of interest to clinical researchers, policy makers, and funding bodies

Evidence Map of Prevention and Treatment Interventions for Depression in Young People

Introduction. Depression in adolescents and young people is associated with reduced social, occupational, and interpersonal functioning, increases in suicide and self-harm behaviours, and problematic substance use. Age-appropriate, evidence-based treatments are required to provide optimal care. Methods. “Evidence mapping” methodology was used to quantify the nature and distribution of the extant high-quality research into the prevention and treatment of depression in young people across psychological, medical, and other treatment domains. Results. Prevention research is dominated by cognitive-behavioral- (CBT-) based interventions. Treatment studies predominantly consist of CBT and SSRI medication trials, with few trials of other psychological interventions or complementary/alternative treatments. Quality studies on relapse prevention and treatment for persistent depression are distinctly lacking. Conclusions. This map demonstrates opportunities for future research to address the numerous evidence gaps for interventions to prevent or treat depression in young people, which are of interest to clinical researchers, policy makers, and funding bodies

The effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: a factorial randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The prevalence of mental illness in young people is the highest of any age group, with the onset of depression, anxiety and substance use peaking between 18 and 24 years. Effective treatments that target sub-threshold or mild to moderate levels of disorder in young people are required to reduce the risk of persistence and recurrence. The aims of this study are to evaluate whether treatments that are less intensive than cognitive-behaviour therapy, such as problem solving therapy and exercise treatments, are acceptable and effective in managing depression and anxiety symptoms in young people and to identify possible attributes in those who are likely to respond to these treatments.</p> <p>Methods/design</p> <p>This is a factorial randomised controlled trial conducted at a large, metropolitan youth mental health service. Participants are young help-seekers aged 15-25 years with sub-threshold or mild to moderate levels of depression and anxiety (with or without comorbid substance use). The interventions comprise 4 treatment combinations delivered by psychologists over 6 sessions on a weekly basis: a psychological intervention (problem solving therapy versus supportive counselling) and an exercise intervention (behavioural exercise versus psychoeducation). Structured assessments occur at baseline, mid-point, end-point (6 weeks) and at a 6- and 12-month follow-up. The primary outcomes are depression and anxiety symptoms as measured by the Beck Depression and Anxiety Inventories. Secondary outcomes include remission (defined as no longer meeting the diagnostic criteria for a disorder if threshold level was reached at baseline, or no longer scoring in the clinical range on scale scores if sub-threshold at baseline), substance use, and functioning.</p> <p>Discussion</p> <p>The effectiveness of less complex psychological and exercise interventions in young help-seekers with sub-threshold or mild to moderate presentations of high prevalence disorders is yet to be explored. This study has been designed to examine the effectiveness of these interventions delivered alone, or in combination, in a youth-specific service. If effective, the interventions have the potential to prevent the progression of early symptoms and distress to later and potentially more serious stages of mental disorder and reduce the likelihood of ongoing problems associated with the risk of persistence and recurrence.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12608000550303.aspx">ACTRN12608000550303</a></p

Selective nanomanipulation using optical forces

We present a detailed theoretical study of the recent proposal for selective nanomanipulation of nanometric particles above a substrate using near-field optical forces [Chaumet {\it et al.} Phys. Rev. Lett. {\bf 88}, 123601 (2002)]. Evanescent light scattering at the apex of an apertureless near-field probe is used to create an optical trap. The position of the trap is controlled on a nanometric scale via the probe and small objects can be selectively trapped and manipulated. We discuss the influence of the geometry of the particles and the probe on the efficiency of the trap. We also consider the influence of multiple scattering among the particles on the substrate and its effect on the robustness of the trap.Comment: 12 pages, 17 figure

A Metabolomic Endotype of Bioenergetic Dysfunction Predicts Mortality in Critically Ill Patients with Acute Respiratory Failure

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors\u27 biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition

Origin and Examination of a Leafhopper Facultative Endosymbiont

Eukaryotes engage in intimate interactions with microbes that range in age and type of association. Although many conspicuous examples of ancient insect associates are studied (e.g., Buchneraaphidicola), fewer examples of younger associations are known. Here, we further characterize a recently evolved bacterial endosymbiont of the leafhopper Euscelidius variegatus (Hemiptera, Cicadellidae), called BEV. We found that BEV, continuously maintained in E. variegatus hosts at UC Berkeley since 1984, is vertically transmitted with high fidelity. Unlike many vertically transmitted, ancient endosymbioses, the BEV–E. variegatus association is not obligate for either partner, and BEV can be cultivated axenically. Sufficient BEV colonies were grown and harvested to estimate its genome size and provide a partial survey of the genome sequence. The BEV chromosome is about 3.8 Mbp, and there is evidence for an extrachromosomal element roughly 53 kb in size (e.g., prophage or plasmid). We sequenced 438 kb of unique short-insert clones, representing about 12% of the BEV genome. Nearly half of the gene fragments were similar to mobile DNA, including 15 distinct types of insertion sequences (IS). Analyses revealed that BEV not only shares virulence genes with plant pathogens, but also is closely related to the plant pathogenic genera Dickeya, Pectobacterium, and Brenneria. However, the slightly reduced genome size, abundance of mobile DNA, fastidious growth in culture, and efficient vertical transmission suggest that symbiosis with E. variegatus has had a significant impact on genome evolution in BEV

Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence

Background Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent. Methods We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling. Results Clonal hematopoiesis with somatic mutations was observed in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of age. Detectable clonal expansions most frequently involved somatic mutations in three genes (DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers. Clonal hematopoiesis was a strong risk factor for subsequent hematologic cancer (hazard ratio, 12.9; 95% confidence interval, 5.8 to 28.7). Approximately 42% of hematologic cancers in this cohort arose in persons who had clonality at the time of DNA sampling, more than 6 months before a first diagnosis of cancer. Analysis of bone marrow–biopsy specimens obtained from two patients at the time of diagnosis of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Conclusions Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently mutated in apparently healthy persons; these mutations may represent characteristic early events in the development of hematologic cancers. (Funded by the National Human Genome Research Institute and others.)National Human Genome Research Institute (U.S.) (Grant U54 HG003067)National Human Genome Research Institute (U.S.) (Grant R01 HG006855)Stanley Center for Psychiatric ResearchAlexander and Margaret Stewart TrustNational Institute of Mental Health (U.S.) (Grant R01 MH 077139)National Institute of Mental Health (U.S.) (Grant RC2 MH089905)Sylvan C. Herman Foundatio

A Coin Vibrational Motor Swimming at Low Reynolds Number

Low-cost coin vibrational motors, used in haptic feedback, exhibit rotational internal motion inside a rigid case. Because the motor case motion exhibits rotational symmetry, when placed into a fluid such as glycerin, the motor does not swim even though its oscillatory motions induce steady streaming in the fluid. However, a piece of rubber foam stuck to the curved case and giving the motor neutral buoyancy also breaks the rotational symmetry allowing it to swim. We measured a 1 cm diameter coin vibrational motor swimming in glycerin at a speed of a body length in 3 seconds or at 3 mm/s. The swim speed puts the vibrational motor in a low Reynolds number regime similar to bacterial motility, but because of the oscillations of the motor it is not analogous to biological organisms. Rather the swimming vibrational motor may inspire small inexpensive robotic swimmers that are robust as they contain no external moving parts. A time dependent Stokes equation planar sheet model suggests that the swim speed depends on a steady streaming velocity V stream ~ Re 1/2s U 0 where U 0 is the velocity of surface oscillations, and streaming Reynolds number Re s = U 20/(ων) for motor angular frequency ω and fluid kinematic viscosity ν

Discovery and Statistical Genotyping of Copy-Number Variation from Whole-Exome Sequencing Depth

Sequencing of gene-coding regions (the exome) is increasingly used for studying human disease, for which copy-number variants (CNVs) are a critical genetic component. However, detecting copy number from exome sequencing is challenging because of the noncontiguous nature of the captured exons. This is compounded by the complex relationship between read depth and copy number; this results from biases in targeted genomic hybridization, sequence factors such as GC content, and batching of samples during collection and sequencing. We present a statistical tool (exome hidden Markov model [XHMM]) that uses principal-component analysis (PCA) to normalize exome read depth and a hidden Markov model (HMM) to discover exon-resolution CNV and genotype variation across samples. We evaluate performance on 90 schizophrenia trios and 1,017 case-control samples. XHMM detects a median of two rare