Treating Homeless Opioid Dependent Patients with Buprenorphine in an Office-Based Setting

CONTEXT Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings in the US, its use has not been reported in homeless patients. OBJECTIVE To characterize the feasibility of OBOT-B in homeless relative to housed patients. DESIGN A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and intensity of clinical support by a nurse care manager (NCM) among homeless and housed patients in an OBOT-B program between August 2003 and October 2004. Treatment failure was defined as elopement before completing medication induction, discharge after medication induction due to ongoing drug use with concurrent nonadherence with intensified treatment, or discharge due to disruptive behavior. RESULTS Of 44 homeless and 41 housed patients enrolled over 12 months, homeless patients were more likely to be older, nonwhite, unemployed, infected with HIV and hepatitis C, and report a psychiatric illness. Homeless patients had fewer social supports and more chronic substance abuse histories with a 3- to 6-fold greater number of years of drug use, number of detoxification attempts and percentage with a history of methadone maintenance treatment. The proportion of subjects with treatment failure for the homeless (21%) and housed (22%) did not differ (P=.94). At 12 months, both groups had similar proportions with illicit opioid use [Odds ratio (OR), 0.9 (95% CI, 0.5–1.7) P=.8], utilization of counseling (homeless, 46%; housed, 49%; P=.95), and participation in mutual-help groups (homeless, 25%; housed, 29%; P=.96). At 12 months, 36% of the homeless group was no longer homeless. During the first month of treatment, homeless patients required more clinical support from the NCM than housed patients. CONCLUSIONS Despite homeless opioid dependent patients' social instability, greater comorbidities, and more chronic drug use, office-based opioid treatment with buprenorphine was effectively implemented in this population comparable to outcomes in housed patients with respect to treatment failure, illicit opioid use, and utilization of substance abuse treatment

A cohort study of the recovery of health and wellbeing following colorectal cancer (CREW study): protocol paper

Background: the number of people surviving colorectal cancer has doubled in recent years. While much of the literature suggests that most people return to near pre-diagnosis status following surgery for colorectal cancer, this literature has largely focused on physical side effects. Longitudinal studies in colorectal cancer have either been small scale or taken a narrow focus on recovery after surgery. There is a need for a comprehensive, long-term study exploring all aspects of health and wellbeing in colorectal cancer patients. The aim of this study is to establish the natural history of health and wellbeing in people who have been treated for colorectal cancer. People have different dispositions, supports and resources, likely resulting in individual differences in restoration of health and wellbeing. The protocol described in this paper is of a study which will identify who is most at risk of problems, assess how quickly people return to a state of subjective health and wellbeing, and will measure factors which influence the course of recovery. Methods: this is a prospective, longitudinal cohort study following 1000 people with colorectal cancer over a period of two years, recruiting from 30 NHS cancer treatment centres across the UK. Questionnaires will be administered prior to surgery, and 3, 9, 15 and 24 months after surgery, with the potential to return to this cohort to explore on-going issues related to recovery after cancer. Discussion: outcomes will help inform health care providers about what helps or hinders rapid and effective recovery from cancer, and identify areas for intervention development to aid this process. Once established the cohort can be followed up for longer periods and be approached to participate in related projects as appropriate and subject to funding<br/

Mendelian Randomization Analyses Suggest Childhood Body Size Indirectly Influences End Points From Across the Cardiovascular Disease Spectrum Through Adult Body Size

Background Obesity is associated with long‐term health consequences including cardiovascular disease. Separating the independent effects of childhood and adulthood obesity on cardiovascular disease risk is challenging as children with obesity typically remain overweight throughout the lifecourse. Methods and Results This study used 2‐sample univariable and multivariable Mendelian randomization to estimate the effect of childhood body size both independently and after accounting for adult body size on 12 endpoints across the cardiovascular disease disease spectrum. Univariable analyses identified strong evidence of a total effect between genetically predicted childhood body size and increased risk of atherosclerosis, atrial fibrillation, coronary artery disease, heart failure, hypertension, myocardial infarction, peripheral artery disease, and varicose veins. However, evidence of a direct effect was weak after accounting for adult body size using multivariable Mendelian randomization, suggesting that childhood body size indirectly increases risk of these 8 disease outcomes via the pathway involving adult body size. Conclusions These findings suggest that the effect of genetically predicted childhood body size on the cardiovascular disease outcomes analyzed in this study are a result of larger body size persisting into adulthood. Further research is necessary to ascertain the critical timepoints where, if ever, the detrimental impact of obesity initiated in early life begins to become immutable

Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels

<p>Abstract</p> <p>Background</p> <p>The zebrafish has been suggested as a model system for studying human diseases that affect nervous system function and motor output. However, few of the ion channels that control neuronal activity in zebrafish have been characterized. Here, we have identified zebrafish orthologs of voltage-dependent Kv3 (KCNC) K⁺channels. Kv3 channels have specialized gating properties that facilitate high-frequency, repetitive firing in fast-spiking neurons. Mutations in human Kv3.3 cause spinocerebellar ataxia type 13 (SCA13), an autosomal dominant genetic disease that exists in distinct neurodevelopmental and neurodegenerative forms. To assess the potential usefulness of the zebrafish as a model system for SCA13, we have characterized the functional properties of zebrafish Kv3.3 channels with and without mutations analogous to those that cause SCA13.</p> <p>Results</p> <p>The zebrafish genome (release Zv8) contains six Kv3 family members including two Kv3.1 genes (<it>kcnc1a </it>and <it>kcnc1b</it>), one Kv3.2 gene (<it>kcnc2</it>), two Kv3.3 genes (<it>kcnc3a </it>and <it>kcnc3b</it>), and one Kv3.4 gene (<it>kcnc4</it>). Both Kv3.3 genes are expressed during early development. Zebrafish Kv3.3 channels exhibit strong functional and structural homology with mammalian Kv3.3 channels. Zebrafish Kv3.3 activates over a depolarized voltage range and deactivates rapidly. An amino-terminal extension mediates fast, N-type inactivation. The <it>kcnc3a </it>gene is alternatively spliced, generating variant carboxyl-terminal sequences. The R335H mutation in the S4 transmembrane segment, analogous to the SCA13 mutation R420H, eliminates functional expression. When co-expressed with wild type, R335H subunits suppress Kv3.3 activity by a dominant negative mechanism. The F363L mutation in the S5 transmembrane segment, analogous to the SCA13 mutation F448L, alters channel gating. F363L shifts the voltage range for activation in the hyperpolarized direction and dramatically slows deactivation.</p> <p>Conclusions</p> <p>The functional properties of zebrafish Kv3.3 channels are consistent with a role in facilitating fast, repetitive firing of action potentials in neurons. The functional effects of SCA13 mutations are well conserved between human and zebrafish Kv3.3 channels. The high degree of homology between human and zebrafish Kv3.3 channels suggests that the zebrafish will be a useful model system for studying pathogenic mechanisms in SCA13.</p

Fate of Mercury in Synthetic Gypsum Used for Wallboard Production

This report presents and discusses results from Task 6 of the study 'Fate of Mercury in Synthetic Gypsum Used for Wallboard Production,' performed at a full-scale commercial wallboard plant. Synthetic gypsum produced by wet flue gas desulfurization (FGD) systems on coal-fired power plants is commonly used in the manufacture of wallboard. This practice has long benefited the environment by recycling the FGD gypsum byproduct, which is becoming available in increasing quantities, decreasing the need to landfill this material, and increasing the sustainable design of the wallboard product. However, new concerns have arisen as recent mercury control strategies involve the capture of mercury in FGD systems. The objective of this study is to determine whether any mercury is released into the atmosphere when the synthetic gypsum material is used as a feedstock for wallboard production. The project is being co-funded by the U.S. DOE National Energy Technology Laboratory (Cooperative Agreement DE-FC26-04NT42080), USG Corporation, and EPRI. USG Corporation is the prime contractor, and URS Group is a subcontractor. The project scope now includes six discrete tasks, each conducted at various USG wallboard plants using synthetic gypsum from different FGD systems. The project was originally composed of five tasks, which were to include (1) a baseline test, then variations representing differing power plant: (2) emissions control configurations, (3) treatment of fine gypsum particles, (4) coal types, and (5) FGD reagent types. However, Task 5, which was to include testing with an alternate FGD reagent, could not be conducted as planned. Instead, Task 5 was conducted at conditions similar to Task 3, although with gypsum from an alternate FGD system. Subsequent to conducting Task 5 under these revised conditions, an opportunity arose to test gypsum produced at the same FGD system, but with an additive (Degussa Corporation's TMT-15) being used in the FGD system. TMT-15 was expected to impact the stability of mercury in synthetic gypsum used to produce wallboard, so Task 6 was added to the project to test this theory. In this project, process stacks in the wallboard plant have been sampled using the Ontario Hydro method. For every task, the stack locations sampled have included a dryer for the wet gypsum as it enters the plant and a gypsum calciner. For Tasks 1, 4, 5 and 6, the stack of the dryer for the wet wallboard product was also tested. Also at each site, in-stream process samples were collected and analyzed for mercury concentration before and after each significant step in wallboard production. The Ontario Hydro results, process sample mercury concentration data, and process data were used to construct mercury mass balances across the wallboard plants. Task 6 was conducted at a wallboard plant processing synthetic gypsum from a power plant that fires Eastern bituminous coal. The power plant has a single-loop, open spray tower limestone forced oxidation FGD system, with the forced oxidation conducted in the reaction tank integral with the FGD absorber. The FGD system has gypsum fines blow down as part of the dewatering step. The power plant is equipped with a selective catalytic reduction (SCR) system for NOX emissions control, and the SCR was in service during the time period the gypsum tested was produced. Also, as mentioned above, Degussa additive TMT-15 was being added to the FGD system when this gypsum was produced. The results of the Task 6 stack testing, as measured by the Ontario Hydro method, detected that an average of 55% of the incoming mercury was emitted during wallboard production. These losses were distributed as about 4% across the dryer mill, 6% across the board dryer kiln, and 45% across the kettle calciner. Emissions were similar to what Task 5 results showed on a percentage basis, but about 30% lower on a mass basis. The same power plant FGD system produced the synthetic gypsum used in Task 5 (with no use of TMT-15) and in Task 6 (with TMT-15 added to the FGD system). The lower emissions on a mass basis appeared to be due to lower average mercury content in the gypsum being processed. It is not certain whether the lower average mercury content in the gypsum was an effect of TMT-15 addition to the FGD system. As was seen in the Task 1 through 5 results, most of the mercury detected in the Ontario Hydro method stack testing was in the form of elemental mercury

Cerebral perfusion in chronic stroke: Implications for lesion-symptom mapping and functional MRI

Lesion-symptom mapping studies are based upon the assumption that behavioral impairments are directly related to structural brain damage. Given what is known about the relationship between perfusion deficits and impairment in acute stroke, attributing specific behavioral impairments to localized brain damage leaves room for speculation, as impairments could also reflect abnormal neurovascular function in brain regions that appear structurally intact on traditional CT and MRI scans. Compared to acute stroke, the understanding of cerebral perfusion in chronic stroke is far less clear. Utilizing arterial spin labeling (ASL) MRI, we examined perfusion in 17 patients with chronic left hemisphere stroke. The results revealed a decrease in left hemisphere perfusion, primarily in peri-infarct tissue. There was also a strong relationship between increased infarct size and decreased perfusion. These findings have implications for lesion-symptom mapping studies as well as research that relies on functional MRI to study chronic stroke

Impact Of Redesigning A Large-Lecture Introductory Earth Science Course To Increase Student Achievement And Streamline Faculty Workload

A Geological Perspective is a general education survey course for non-science majors at a large southwestern research extensive university.  The class has traditionally served 600 students per semester in four 150-student lectures taught by faculty, and accompanied by optional weekly study groups run by graduate teaching assistants.  We radically redesigned the course to 1) improve student learning and, simultaneously, 2) reduce faculty effort.   Previously optional study groups were replaced by weekly mandatory break-out sessions, run largely by undergraduate peer mentors.  Twice weekly, lectures are brief with a large portion of class time allocated to active learning in small groups.  Completing quizzes on-line reduced grading and allowed students more flexibility.  Evaluation of the redesign (mixed methods, quasi-experimental, two-group, pre-test-post-test, multiple-measures study design) revealed no significant improvements in learner outcomes insofar as the instruments could measure. However, qualitative results reveal that overall students greatly valued their learning experience under the redesign.  In addition, the redesign reduced the departmental cost of the class offering per student by more than half.

CloneQC: lightweight sequence verification for synthetic biology

Synthetic biology projects aim to produce physical DNA that matches a designed target sequence. Chemically synthesized oligomers are generally used as the starting point for building larger and larger sequences. Due to the error rate of chemical synthesis, these oligomers can have many differences from the target sequence. As oligomers are joined together to make larger and larger synthetic intermediates, it becomes essential to perform quality control to eliminate intermediates with errors and retain only those DNA molecules that are error free with respect to the target. This step is often performed by transforming bacteria with synthetic DNA and sequencing colonies until a clone with a perfect sequence is identified. Here we present CloneQC, a lightweight software pipeline available as a free web server and as source code that performs quality control on sequenced clones. Input to the server is a list of desired sequences and forward and reverse reads for each clone. The server generates summary statistics (error rates and success rates target-by-target) and a detailed report of perfect clones. This software will be useful to laboratories conducting in-house DNA synthesis and is available at http://cloneqc.thruhere.net/ and as Berkeley Software Distribution (BSD) licensed source

Monodisperse Cylindrical Micelles and Block Comicelles of Controlled Length in Aqueous Media

Cylindrical block copolymer micelles have shown considerable promise in various fields of biomedical research. However, unlike spherical micelles and vesicles, control over their dimensions in biologically relevant solvents has posed a key challenge that potentially limits in depth studies and their optimization for applications. Here, we report the preparation of cylindrical micelles of length in the wide range of 70 nm to 1.10 μm in aqueous media with narrow length distributions (length polydispersities <1.10). In our approach, an amphiphilic linear-brush block copolymer, with high potential for functionalization, was synthesized based on poly­(ferrocenyldimethylsilane)-<i>b</i>-poly­(allyl glycidyl ether) (PFS-<i>b</i>-PAGE) decorated with triethylene glycol (TEG), abbreviated as PFS-<i>b</i>-(PEO-<i>g</i>-TEG). PFS-<i>b</i>-(PEO-<i>g</i>-TEG) cylindrical micelles of controlled length with low polydispersities were prepared in <i>N</i>,<i>N</i>-dimethylformamide using small seed initiators via living crystallization-driven self-assembly. Successful dispersion of these micelles into aqueous media was achieved by dialysis against deionized water. Furthermore, B–A–B amphiphilic triblock comicelles with PFS-<i>b</i>-poly­(2-vinylpyridine) (P2VP) as hydrophobic “B” blocks and hydrophilic PFS-<i>b</i>-(PEO-<i>g</i>-TEG) “A” segments were prepared and their hierarchical self-assembly in aqueous media studied. It was found that superstructures formed are dependent on the length of the hydrophobic blocks. Quaternization of P2VP was shown to cause the disassembly of the superstructures, resulting in the first examples of water-soluble cylindrical multiblock comicelles. We also demonstrate the ability of the triblock comicelles with quaternized terminal segments to complex DNA and, thus, to potentially function as gene vectors

A comparison of postrelease survival parameters between single and mass stranded delphinids from Cape Cod, Massachusetts, U.S.A.

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Mammal Science 32 (2016): 161–180, doi:10.1111/mms.12255.The viability of healthy single stranded dolphins as immediate release candidates has received little attention. Responders have been reluctant to release lone delphinids due to their social needs, even when they pass the same health evaluations as mass stranded animals. This study tracked postrelease success of 34 relocated and released satellite tagged delphinids from single and mass strandings. Three postrelease survival parameters (transmission duration, swim speed, and daily distance) were examined to evaluate whether they differed among single stranded/single released (SS/SR), mass stranded/single released (MS/SR), or mass stranded/mass released (MS/MR) dolphin groups. Comparisons were also made between healthy and borderline release candidates. Satellite tags transmitted for a mean of 21.2 d (SD = 19.2, range = 1–79), daily distance traveled was 42.0 km/d (11.25, 20.96–70.72), and swim speed was 4.3 km/h (1.1, 2.15–8.54). Postrelease parameters did not differ between health status groups, however, SS/SR dolphins transmitted for a shorter mean duration than MS/MR and MS/SR groups. Postrelease vessel-based surveys confirmed conspecific group location for two healthy, MS/SR dolphins. Overall, these results support the potential to release healthy stranded single delphinids; however, further refinement of health assessment protocols for these challenging cases is needed.National Oceanic and Atmospheric Administration's National Marine Fisheries Service (NOAA NMFS); John H. Prescott Marine Mammal Rescue Assistance Program Grant Numbers: NA11NMF4390078, NA11NMF4390079, NA11NMF439009