What is a Viola?

A viola is a string instrument similar to a violin but larger in size, producing a deeper sound to compliment the arrangement. Two curled holes, allowing some light inside the hallowed body, just delicate enough to float, perched under the chin of its commander. [excerpt

Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by motor neuron loss, resulting in muscle wasting, paralysis and eventual death. A key pathological feature of ALS is cytoplasmically mislocalized and aggregated TDP-43 protein in >95% of cases, which is considered to have prion-like properties. Historical studies have predominantly focused on genetic forms of ALS, which represent ∼10% of cases, leaving the remaining 90% of sporadic ALS relatively understudied. Additionally, the role of astrocytes in ALS and their relationship with TDP-43 pathology is also not currently well understood. We have therefore used highly enriched human induced pluripotent stem cell (iPSC)-derived motor neurons and astrocytes to model early cell type-specific features of sporadic ALS. We first demonstrate seeded aggregation of TDP-43 by exposing human iPSC-derived motor neurons to serially passaged sporadic ALS post-mortem tissue (spALS) extracts. Next, we show that human iPSC-derived motor neurons are more vulnerable to TDP-43 aggregation and toxicity compared with their astrocyte counterparts. We demonstrate that these TDP-43 aggregates can more readily propagate from motor neurons into astrocytes in co-culture paradigms. We next found that astrocytes are neuroprotective to seeded aggregation within motor neurons by reducing (mislocalized) cytoplasmic TDP-43, TDP-43 aggregation and cell toxicity. Furthermore, we detected TDP-43 oligomers in these spALS spinal cord extracts, and as such demonstrated that highly purified recombinant TDP-43 oligomers can reproduce this observed cell-type specific toxicity, providing further support to a protein oligomer-mediated toxicity hypothesis in ALS. In summary, we have developed a human, clinically relevant, and cell-type specific modelling platform that recapitulates key aspects of sporadic ALS and uncovers both an initial neuroprotective role for astrocytes and the cell type-specific toxic effect of TDP-43 oligomers

Triangulating’ AMPATH: Demonstration of a multi-perspective strategic programme evaluation method

Clinical programmes are typically evaluated on operational performance metrics of cost, quality and outcomes. Measures of patient satisfaction are used to assess the experience of receiving care, but other perspectives, including those of staff and communities, are not often sought or used to assess and improve programmes. For strategic planning, the Kenyan HIV/AIDS programme AMPATH (Academic Model Providing Access to Healthcare) sought to evaluate its performance in 2006. The method used for this evaluation was termed ‘triangulation,’ because it used information from three different sources – patients, communities, and programme staff. From January to August 2006, Indiana University external evaluators and AMPATH staff gathered information on strengths, weaknesses and suggestions for improvement of AMPATH. Activities included in-depth key-informant semi-structured interviews of 26 AMPATH clinical and support staff, 56 patients at eight clinic sites, and seven village health dialogues (mabaraza) at five sublocations within the AMPATH catchment area. Data sources included field notes and transcripts of translated audio recordings,which were subjected to qualitative content analysis. Eighteen  recommendations for programme improvement emerged, including ten from all three respondent perspectives. Three recommendations were cited by patients and in mabaraza, but not by staff. Triangulation uncovered improvement emphases that an internal assessment would miss. AMPATH and Kenyan Ministry of Health leadership have deliberated these recommendations and accelerated strategic change actions, including rural satellite programmes, collaboration with village-based workers, and door-to-door village-based screening and counselling

3D Printed PLA Scaffolds to Promote Healing of Large Bone Defects

One challenge modern medicine faces is the ability to repair large bone defects and stimulate healing. Small defects typically heal naturally, but large bone defects do not and current solutions are to replace the missing tissue with biologically inert materials such as titanium. This limits the amount of bone healing as the defect is not repaired but rather replaced. The focus of our research is to develop a method of using 3D printing to create biodegradable scaffolds which promote bone in-growth and replacement. To accomplish this we used poly lactic acid (PLA) filament and a desktop 3D printer. To promote bone healing and provide mechanical support our team investigated different design methodologies to provide a scaffold of customizable stiffness while allowing cell attachment and in-growth. Our team used CAD modeling to create unique architecture design systems which we analyzed for stiffness using Finite Element Analysis (FEA). We developed a unit cell method of scaffold construction that allowed for customized stiffness of irregular shapes. We 3D printed our designs using a desktop 3D printer and verified our stiffness through mechanical tension and compression testing. We investigated cell viability of the scaffolds by immersing test specimens in culturing media and fibroblast cells. Fibroblast cells are from the same lineage as osteoblast cells but are much faster growing, allowing for more efficient testing. Specimens were left in the media for one week then a total cell count was performed. Scaffold designs were then evaluated based on stiffness and cell viability. We have produced several different viable models with appropriate stiffness for human trabecular bone and good cellular adhesion

Task Shifting in HIV Clinics, Western Kenya

Background: United states Agency for International development-Academic Model for Providing Accesses to Healthcare (USAID-AMPATH) cares for over 80,000 HIVinfected patients. Express care (EC) model addresses challenges of: clinically stable patient’s adherent to combined-antiretroviral-therapy with minimal need for clinician intervention and high risk patients newly initiated on cART with CD4 counts ≤100 cells/mm3 with frequent need for clinician intervention. Objective: To improve patient outcomes without increasing clinic resources. Design: A descriptive study of a clinician supervised shared nurse model. Setting: USAID-AMPATH clinics, Western Kenya. Results: Four thousand eight hundred and twenty four patients were seen during the pilot period, 90.4% were eligible for EC of whom 34.6% were enrolled. Nurses performed all traditional roles and attended to two thirds and three quarters of stable and high risk patient visits respectively. Clinicians attended to one third and one quarter of stable and high risk patient visits respectively and all visits ineligible for express care. Conclusion: The EC model is feasible. Task shifting allowed stable patients to receive visits with nurses, while clinicians had more time to concentrate on patients that were new as well as more acutely ill patients.East African Medical Journal Vol. 87 No. 7 July 201

Effects of bearing surfaces on lap joint energy dissipation

Energy is dissipated in mechanical systems in several forms. The major contributor to damping in bolted lap joints is friction, and the level of damping is a function of stress distribution in the bearing surfaces. This study examines the effects of bearing surface configuration on lap joint energy dissipation. The examination is carried out through the analysis of experimental results in a nonlinear framework. Then finite element models are constructed in a nonlinear framework to simulate the results. The experimental data were analyzed using piecewise linear log decrement. Phenomenological and non-phenomenological mathematical models were used to simulate joint behavior. Numerical results of experiments and analyses are presented

Land use not litter quality is a stronger driver of decomposition in hyperdiverse tropical forest

Funded by Natural Environment Research Council. Grant Number: NE/K016253/1Peer reviewedPublisher PD