41 research outputs found

    Strategies For Campers With Sensory Challenges

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    The OTS partnered with a summer camp agency to understand their needs for camp programming. The executive director informed the OTS that this camp would benefit from programming recommendations as they would like to be more inclusive toward campers of all abilities. Pfeiffer, Clark, and Arbesman (2018) explain that sensory challenges can exist in children/adolescents with or without an existing diagnosis. Children and adolescents who have difficulty regulating and responding to sensory input impedes their ability to participate in meaningful occupations. The OTS decided to provide the agency with programming recommendations to serve campers with sensory challenges in order to achieve the camp’s goal of increasing inclusivity. Having strategies in place for campers with sensory challenges will help to improve occupational engagement and improve one’s overall camp experience. The OTS utilized the person-environment-occupation model (PEO) (Law et al., 1996) and Dunn’s Model of Sensory Processing (1997) to provide this agency sensory based strategies for campers. The results of this DEP included the dissemination of a staff education packet intended to educate camp staff on the importance of considering camper’s sensory needs. This product contained sensory-based strategies that could be implemented in the camp environment as well as weekly programming recommendations. Having strategies in place to help campers cope with sensory challenges allows for successful participation in meaningful occupations in the variety of environments offered at this summer camp

    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

    The surgical management and prevention of laparoscopic cholecystectomy associated bile duct injuries

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    Laparoscopic cholecystectomy (LC) is considered the gold standard in the surgical management of gallstone disease and is one of the most commonly performed general surgery operations worldwide. Bile duct injury (BDI) in LC remains a feared complication as it is associated with significant morbidity, prolonged hospital stay, increased costs, and reduced quality of life for patients, as well as the risk of litigation for the injuring surgeon. The initial incidence of BDI after the introduction of LC was reported to be between 0.4 and 0.8%, which was higher than the estimated 0.2% reported during the open cholecystectomy era. However, recent reports from the United States and Europe suggest a return to open cholecystectomy rates. Despite being a frequently performed operation in both the private and public health sectors in South Africa, there is a paucity of data on the incidence of BDI. In the only study to date reporting the frequency of BDI in South Africa, a single centre incidence of 1.2% was documented over an 18-month period, which is significantly higher than previous reports. No data have been published on the implications of BDI for patients treated within the South African healthcare system. This thesis describes the surgical management of BDI at an academic referral centre over a thirty-year period. Potential factors influencing treatment and patient outcome after BDI are investigated. These include the influence of geographic distance from referral centre on the timing of referral and repair, and subsequent long-term patient outcomes. The influence of dual healthcare sectors (public vs. private) on access to diagnostic and interventional modalities, and eventual outcome is also investigated, and the evolution in the management of BDIs over the three studied decades is documented. Factors associated with loss of patency following surgical repair of LC-BDIs are also determined. Based on the findings of this detailed review of the management and outcomes of LC-BDIs, a treatment algorithm for management in resource-constrained environments is proposed. Establishing the optimal management of LC-BDIs in a developing country healthcare setting is important but does not address the source of the problem. In an effort to make LC-BDI a near-never event, a standardized method of performing, documenting and monitoring the quality of LC was developed and implemented for all LCs performed in the Cape Metro West health district. Prospective data collection is scheduled to continue to the end of 2020; however, an interim analysis is presented. A previously published scoring system for assessing quality of the critical view of safety achieved during LC, a critical component of a safe LC, is applied and validated in a large cohort of LC patients. A prospective database was created for data capture along with a Standard Operating Procedure, both designed with the goal of expanding the intervention and database nationally. The studies reported in this thesis make a substantial contribution to the literature and will have a beneficial impact on patient care in two important ways. Firstly, the management of BDI in South Africa is described and a treatment algorithm for resource-constrained environments is proposed, based on local experience. Secondly, a change of practice was implemented and a LC database was established with the possibility of expanding the effort to the national level. Locally, the change in practice has thus far resulted in identification of areas of improvement to limit BDI and increased knowledge about the appropriate steps to take to avoid causing a LC-BDI

    The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy

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    LAQ824 and LBH589 (panobinostat) are histone deacetylase inhibitors (HDACi) developed as cancer therapeutics and we have used the EΌ-myc lymphoma model to identify the molecular events required for their antitumor effects. Induction of tumor cell death

    Accurate detection of low prevalence AKT1 E17K mutation in tissue or plasma from advanced cancer patients.

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    Personalized healthcare relies on accurate companion diagnostic assays that enable the most appropriate treatment decision for cancer patients. Extensive assay validation prior to use in a clinical setting is essential for providing a reliable test result. This poses a challenge for low prevalence mutations with limited availability of appropriate clinical samples harboring the mutation. To enable prospective screening for the low prevalence AKT1 E17K mutation, we have developed and validated a competitive allele-specific TaqMan¼ PCR (castPCRℱ) assay for mutation detection in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Analysis parameters of the castPCRℱ assay were established using an FFPE DNA reference standard and its analytical performance was assessed using 338 breast cancer and gynecological cancer FFPE samples. With recent technical advances for minimally invasive mutation detection in circulating tumor DNA (ctDNA), we subsequently also evaluated the OncoBEAMℱ assay to enable plasma specimens as additional diagnostic opportunity for AKT1 E17K mutation testing. The analysis performance of the OncoBEAMℱ test was evaluated using a novel AKT1 E17K ctDNA reference standard consisting of sheared genomic DNA spiked into human plasma. Both assays are employed at centralized testing laboratories operating according to quality standards for prospective identification of the AKT1 E17K mutation in ER+ breast cancer patients in the context of a clinical trial evaluating the AKT inhibitor AZD5363 in combination with endocrine (fulvestrant) therapy

    Phototrophic biofilm assembly in microbial-mat-derived unicyanobacterial consortia: model systems for the study of autotroph-heterotroph interactions

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    Microbial autotroph-heterotroph interactions influence biogeochemical cycles on a global scale, but the diversity and complexity of natural systems and their intractability to in situ manipulation make it challenging to elucidate the principles governing these interactions. The study of assembling phototrophic biofilm communities provides a robust means to identify such interactions and evaluate their contributions to the recruitment and maintenance of phylogenetic and functional diversity over time. To examine primary succession in phototrophic communities, we isolated two unicyanobacterial consortia from the microbial mat in Hot Lake, Washington, characterizing the membership and metabolic function of each consortium. We then analyzed the spatial structures and quantified the community compositions of their assembling biofilms. The consortia retained the same suite of heterotrophic species, identified as abundant members of the mat and assigned to Alphaproteobacteria , Gammaproteobacteria , and Bacteroidetes. Autotroph growth rates dominated early in assembly, yielding to increasing heterotroph growth rates late in succession. The two consortia exhibited similar assembly patterns, with increasing relative abundances of members from Bacteroidetes and Alphaproteobacteria concurrent with decreasing relative abundances of those from Gammaproteobacteria . Despite these similarities at higher taxonomic levels, the relative abundances of individual heterotrophic species were substantially different in the developing consortial biofilms. This suggests that, although similar niches are created by the cyanobacterial metabolisms, the resulting webs of autotroph-heterotroph and heterotroph-heterotroph interactions are specific to each primary producer. The relative simplicity and tractability of the Hot Lake unicyanobacterial consortia make them useful model systems for deciphering interspecies interactions and assembly principles relevant to natural microbial communities

    The epsomitic phototrophic microbial mat of Hot Lake, Washington: community structural responses to seasonal cycling

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    Phototrophic microbial mats are compact ecosystems composed of highly interactive organisms in which energy and element cycling take place over millimeter-to-centimeter-scale distances. Although microbial mats are common in hypersaline environments, they have not been extensively characterized in systems dominated by divalent ions. Hot Lake is a meromictic, epsomitic lake that occupies a small, endorheic basin in north-central Washington. The lake harbors a benthic, phototrophic mat that assembles each spring, disassembles each fall, and is subject to greater than tenfold variation in salinity (primarily Mg 2+ and SO 2− 4 ) and irradiation over the annual cycle. We examined spatiotemporal variation in the mat community at five time points throughout the annual cycle with respect to prevailing physicochemical parameters by amplicon sequencing of the V4 region of the 16S rRNA gene coupled to near-full-length 16S RNA clone sequences. The composition of these microbial communities was relatively stable over the seasonal cycle and included dominant populations of Cyanobacteria , primarily a group IV cyanobacterium ( Leptolyngbya ), and Alphaproteobacteria (specifically, members of Rhodobacteraceae and Geminicoccus ). Members of Gammaproteobacteria (e.g., Thioalkalivibrio and Halochromatium ) and Deltaproteobacteria (e.g., Desulfofustis ) that are likely to be involved in sulfur cycling peaked in summer and declined significantly by mid-fall, mirroring larger trends in mat community richness and evenness. Phylogenetic turnover analysis of abundant phylotypes employing environmental metadata suggests that seasonal shifts in light variability exert a dominant influence on the composition of Hot Lake microbial mat communities. The seasonal development and organization of these structured microbial mats provide opportunities for analysis of the temporal and physical dynamics that feed back to community function
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