429 research outputs found
Nonlinear Control for Reconfiguration of Unmanned-Aerial-Vehicle Formation
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76757/1/AIAA-8760-121.pd
Aging and memory phenomena in magnetic and transport properties of vortex matter: a brief review
There is mounting experimental evidence that strong off-equilibrium
phenomena, such as ``memory'' or ``aging'' effects, play a crucial role in the
physics of vortices in type II superconductors. We give a short review, based
on a recently introduced schematic vortex model, of current progresses in
understanding out of equilibrium vortex behaviours. We develop a unified
description of ``memory'' phenomena in magnetic and transport properties, such
as magnetisation loops and their ``anomalous'' 2nd peak, logarithmic creep,
``anomalous'' finite creep rate in the limit of vanishing temperature,
``memory'' and ``irreversibility'' in I-V characteristics, time dependent
critical currents, ``rejuvenation'' and ``aging'' of the system response.Comment: updated versio
C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation
Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of repeat-containing C9orf72 RNA results in the production of neurotoxic dipeptide-repeat proteins (DPRs). Here, we developed a high-throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP-elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA-catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient-derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD
Cochrane rehabilitation: 2020 Annual report
during its fourth year of existence, cochrane rehabilitation went on to promote evidence-informed health decision-making in rehabilitation. in 2020, the outbreak of the coVid-19 pandemic has made it necessary to alter priorities. in these challenging times, cochrane rehabilitation has firstly changed its internal organisation and established a new relevant project in line with pandemic needs: the REH-COVER (Rehabilitation – coVid-19 evidence-based response) action. the aim was to focus on the timely collection, review and dissemination of summarised and synthesised evidence relating to COVID-19 and rehabilitation. Cochrane Rehabilitation REH-COVER action has included in 2020 five main initiatives: 1) rapid living systematic reviews on rehabilitation and coVid-19; 2) interactive living evidence map on rehabilitation and coVid-19; 3) definition of the research topics on “rehabilitation and COVID-19” in collaboration with the World Health Organization (WHO) rehabilitation programme; 4) Cochrane Library special collection on Coronavirus (COVID-19) rehabilitation; and 5) collaboration with COVID-END for the topics “rehabilitation” and “disability.” Furthermore, we are still carrying on five different special projects: Be4rehab; RCTRACK; definition of rehabilitation for research purposes; ebook project; and a prioritization exercise for Cochrane Reviews production. The Review Working Area continued to identify and “tag” the rehabilitation-relevant reviews published in the cochrane library; the publication Working area went on to publish Cochrane Corners, working more closely with the Cochrane Review Groups (CRGs) and Cochrane Networks, particularly with Cochrane Musculoskeletal, oral, skin and sensory Network; the Education Working area, the most damaged in 2020, tried to continue performing educational activities such as workshops in different online meetings; the Methodology Working area organized the third and fourth cochrane Rehabilitation Methodological (CRM) meetings respectively in Milan and Orlando; the Communication Working Area spread rehabilitation evidences through different channels and translated the contents in different languages
The effect of HIV infection on overdose mortality
Objectives: To quantify the association of HIV infection with overdose mortality and
explore the potential mechanisms.
Design: A prospective cohort study.
Methods: A total of 1927 actively injecting drug users who were HIV seronegative at
baseline, of whom 308 later HIV seroconverted, were followed semi-annually for death
from 1988 to 2001. Survival analyses using marginal structural and standard Cox
models were used to evaluate the effect of HIV infection on the risk of overdose
mortality.
Results: Overdose death rates were higher in HIV-seropositive than HIV-seronegative
drug users: 13.9 and 5.6 per 1000 person-years, respectively (P < 0.01). The hazard
ratio (HR) was 2.54 [95% confidence interval (CI) 1.47, 4.38] for the marginal structural
model and 2.06 (95% CI 1.25, 3.38) for the standard Cox model, both adjusted for
demographics, drug injection characteristics, alcohol abuse, substance abuse treatment,
and sexual orientation. Adjusting for possible time-varying mediators (i.e. drug
use, medical conditions and healthcare access) in extended marginal structural models
reduced the effect of HIV on overdose mortality by 30% (HR 1.82, 95% CI 1.01, 3.30).
Abnormal liver function was associated with a higher risk of overdose mortality (HR
2.00, 95% CI 1.05, 3.84); adjustment for this further reduced the effect of HIV on
overdose mortality.
Conclusion: HIV infection was associated with a higher risk of overdose mortality.
Drug use behavior, systematic disease and liver damage associated with HIV infection
appeared to account for a substantial portion of this association. The data suggest a
group to target with interventions to reduce overdose mortality rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40279/2/Wang_The Effect of HIV Infection on Overdose_2005.pd
Formative Assessment of ARM-U: A Modular Intervention for Decreasing Risk Behaviors Among HIV-Positive and HIV-Negative Methamphetamine-Using MSM
BACKGROUND: Methamphetamine is a major contributor to HIV transmission among men who have sex with men (MSM). Recent studies show that up to one-third of methamphetamine-using MSM (MUMSM) inject the drug. We developed a behavioral intervention for MUMSM to decrease unprotected anal intercourse and increase awareness of parenteral HIV transmission risk. This 6-session (3 in-person, 3 by telephone) modular intervention was designed to be tailored to participants' HIV (+/-) and injection drug user ([IDU] yes/no) status. We present results of formative research used to evaluate the content and to assess feasibility and acceptability of this individual-level HIV risk-reduction intervention. SETTING: HIV research clinic in a high MSM and methamphetamine prevalence neighborhood. PROJECT: Avoiding Risks from Methamphetamine-Use (ARM-U) is a brief toolbox intervention that allows counselors to select modules that suit a client's individual risk profile and intervention needs employing motivational interviewing and cognitive behavioral theory. We evaluated the format and content of the intervention through focus groups and pre-testing of the entire intervention using volunteers from the target population stratified into four groups (HIV+/IDU, HIV-/IDU, HIV+/non-IDU, HIV-/non-IDU). Four individuals in each stratum were recruited to undergo the intervention and complete a satisfaction survey at the end of each in-person session. RESULTS: In total, 25 MUMSM attended one of five focus groups. Participants thought all proposed intervention topics were important and could aid in reducing sexual risk behaviors among MUMSM. However, the neurocognitive effects of methamphetamine were reported to be a barrier to practicing safer sex, condom use negotiation or HIV status disclosure. Fifteen (94%) of 16 participants completed all 6 sessions and the satisfaction survey. On average, participants felt the intervention was useful for MUMSM, made them contemplate and move toward behavior change, and would recommend the program to their peers. LESSONS LEARNED: Based on our formative research, we revised the ARM-U intervention to emphasize pre-planning to avoid combining methamphetamine use and sex or develop strategies to avoid sex risk following methamphetamine use. We also increased emphasis on referrals for care and other requested services. Future efficacy trials are needed to evaluate the intervention's ability to reduce HIV-associated risk behaviors
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