Instructional constraints faced by learners with duchenne muscular dystrophy: A case study of Joy Town Special Primary School, Thika, Kenya.

The study is about the instructional constraints facing learners with Duchenne muscular dystrophy (DMD) at Salvation Army (SA) Joy Town special primary school, Thika, Kenya. Instructional constraints in this study are the academic challenges encountered by the learners that include: poor teaching methods, inappropriate curriculum, and lack of a modified learning and teaching environment among others. The study adopted a descriptive design because it aims at getting a true picture of a situation, behavior or attitude of individuals and the community at large. The target population was 43, and the study population was 23. The researcher used interviews and observation guide to collect data. Piloting was done at Dagoretti special school for the physically handicapped (PH), content-related validity was used as a measure to determine validity, and descriptive statistics where tables of frequencies and percentages were used in analyzing data. Results revealed that there were major instructional constraints facing learners with DMD.Keywords: Instructional constraints, Duchenne muscular dystrophy, learners with special educational needs

Disclosing HIV-Positive Status: What Do Questions Have to Do with It?

This article discussed the need to ask questions among people living with HIV to facilitate disclosure. This is because disclosure of a HIV-positive status is an important tool for prevention of HIV and early treatment, many people who know their status do not disclose to their spouse or sexual partners. Disclosure would not only protect the spouse from risk of infection and if already infected be able to access treatment, support and care  but also promote adherence to antiretroviral therapy. The paper looked at questioning as an important communication skill that can facilitate disclosure. This paper is based on a larger qualitative study that investigated the factors influencing disclosure of HIV-positive status to spouses among people living with HIV in Kirinyaga County in Kenya. Data was collected using semistructured In-Depth Interviews. The paper argued that questions play a crucial role in disclosure of a HIV-positive status in accessing information which would otherwise be unavailable about the HIV-positive status of their spouses and suggests incorporation of communication skills on questioning and disclosure at the comprehensive care  Centre services. Key Words: HIV disclosure, person living with HIV, questioning, spouses, psychological safet

The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria

Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 (PfHRP2) have diagnostic and prognostic value in severe malaria. We investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of PfHRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma PfHRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4

Institutional Innovations for Building Impact-oriented Agricultural Research, Knowledge and Development Institutions

The central development question in African agriculture is how to catalyze a more competitive, equitable and sustainable agricultural growth within the context of smallholder production systems, inefficient agricultural marketing, inefficient investments by private sector amidst degradation prone natural resources base (Lynam and Blackie, 1994; IAC, 2004; World bank, 2006 ). Concerted scholarly analyses of Science and Technology (S&T) strategies have given birth to Integrated Agricultural Research for Development (IAR4D) an organizing concept of the Innovation Systems Approach (ISA) as the promise holder. It is hypothesized that the generation, diffusion and application of impactful innovations critically depend on systemic integration of knowledge systems that promote communication, interaction and cooperation between agricultural research, education, extension, farmers, private sector and policy regulatory systems. This paper examines how the different institutional innovations arising from various permutations of linkages and interactions of ARD organizations (national, international advanced agricultural research centres and universities) influenced the different outcomes in addressing identified ARD problems. A multi-institutional, multi-disciplinary phased Participatory Action Research approach was used to pool knowledge to address outstanding and emerging challenges in three countries (DRC, Rwanda and Uganda) with 2, 16 and 24 years out of conflict, respectively) of the Lake Kivu Pilot Learning Site. A landmark institutional innovation was the participatory establishment of twelve (12) Innovation Platforms as tools for pooling knowledge across the agricultural business, education, research and extension systems. The knowledge “pool” was to generate, diffuse and apply innovations to reduce transactions costs and create value chain based “win-win” situations. A number of innovations (e.g. International Public Goods-IPGs, market binding contracts, registered brands and/or certification processes, diversity, density and quality of networks/collective action, bulking centres, ICT application and depth of knowledge pools) were initiated. There were major breakthroughs which included bringing on board non-traditional private sector and policy maker partners, overcoming the predominant “farmer handout syndrome”, building consensus and addressing common interest challenge. Making markets work, bringing various stakeholders including universities to the community and vice-versa, appreciation of indigenous knowledge system, propelling collective soil and water conservation and demand/utilization of technologies hitherto on-shelf were other very significant breakthroughs. Sustainable operations of the Innovation Systems knowledge “pool” nurturing institutional learning were ensured through the availability of a “functional body”. The body undertook the social enterprise of organizing farmers and traders, facilitating/brokering ARD organization linkages by using multi-media to build social capital to overcome emergent knowledge, credit, market, technology and resource degradation challenges under different policy regulatory systems

Reference values for body composition and associations with blood pressure in Kenyan adults aged ≥50 years old

Objectives: To develop age and sex-specific centile reference curves for fat free mass (FFM) and fat mass (FM) adjusted for height in an adult Kenyan population and to investigate the association between FM, FFM and blood pressure (BP). Methods: Measures of body composition from bioimpedance analyses and BP were collected in 1,995 participants aged ≥50y in Nakuru County, Kenya. Reference curves were produced using the LMS method. Multivariable linear regression models were used to test the cross-sectional association between body composition indexes and BP. Results: The age and sex-specific reference curves for body composition (FMI and FFMI) confirm that FFMI is lower in both men and women with increasing age. FMI declines with age in women while among men the decline starts after 70 years. FFM was higher in men (47.4 ± 7.2 kg) than in women (38.8 ± 5.5 kg), while FM was lower in men (17.3 ± 8.1 kg) than in women (24.4 ± 10.2 kg). FMI, FFMI and BMI were all positively associated with systolic and diastolic BP, and after adjusting for body weight, FFMI remained positively associated with systolic BP and the FMI remained positively associated with diastolic BP. There was no evidence to suggest that FMI and FFMI were superior to measurement of BMI alone. Conclusion: These body composition reference curves provide normative data on body composition for older adults in Kenya. Further research should consider the prospective associations with health, including frailty-related outcomes

Arabidopsis leucine-rich repeat receptor–like kinase NILR1 is required for induction of innate immunity to parasitic nematodes

Plant-parasitic nematodes are destructive pests causing losses of billions of dollars annually. An effective plant defence against pathogens relies on the recognition of pathogen-associated molecular patterns (PAMPs) by surface-localised receptors leading to the activation of PAMP-triggered immunity (PTI). Extensive studies have been conducted to characterise the role of PTI in various models of plant-pathogen interactions. However, far less is known about the role of PTI in roots in general and in plant-nematode interactions in particular. Here we show that nematode-derived proteinaceous elicitor/s is/are capable of inducing PTI in Arabidopsis in a manner dependent on the common immune co-receptor BAK1. Consistent with the role played by BAK1, we identified a leucine-rich repeat receptor-like kinase, termed NILR1 that is specifically regulated upon infection by nematodes. We show that NILR1 is essential for PTI responses initiated by nematodes and nilr1 loss-of-function mutants are hypersusceptible to a broad category of nematodes. To our knowledge, NILR1 is the first example of an immune receptor that is involved in induction of basal immunity (PTI) in plants or in animals in response to nematodes. Manipulation of NILR1 will provide new options for nematode control in crop plants in future

Principles, design and processes of integrated agricultural research for development: experiences and lessons from LKPLS under the SSACP

With increasing recognition holding the promise of overcoming the outstanding problems faced byAfrican agriculture, IAR4D faces the danger of being ‘blurred’ by past approaches and falling short of its potential to deliver the desired impacts in diverse multi-stakeholder, biophysical, socio- economic, cultural, technological and market contexts unless its actualisation and working is clearly understood. In this paper, we present the conceptualisation and principles of and knowledge-based experiences and lessons from the implementation of the sub-Saharan Africa Challenge Programme (SSACP) in the Lake Kivu Pilot Learning Site (LKPLS). The presentation covers the formation and facilitation of IPs for the actualisation of IAR4D to evolve mechanisms for the early recognition of interlinked issues in natural resource management, productivity and value addition technologies, markets, gender and policy arrangements. These have autonomously triggered flexible, locally directed interactions to innovate options from within or outside their environment for resolving the challenges, and have moved along a new institutional and technological change trajectory. Emerging lessons point to the endowment of IP members with selfhelp knowledge interactions, training in IAR4D, quality of facilitation and research to be key determinants of the power behind of self-regulating mechanisms

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation