Microeconomic institutions and personnel economics for health care delivery: a formal exploration of what matters to health workers in Rwanda

Background: Most developing countries face important challenges regarding the quality of health care and there is a growing consensus that health workers play a key role in this process. Our understanding as to what are the key institutional challenges in human resources, and their underlying driving forces, is more limited. A conceptual framework that structures existing insights and provides concrete directions for policy making is also missing. Methods: To gain a bottom up perspective we gather qualitative data through semi-structured interviews with different levels of health workers and users of health services in rural and urban Rwanda. We conducted discussions with 48 health workers and 25 users of health services in nine different groups in 2005. We maximized within-group heterogeneity by selecting participants using specific criteria that affect health worker performance and career choice. The discussion were analysed electronically, to identify key themes and insights, and are documented with a descriptive quantitative analysis relating to the associations between quotations. The findings from this research are then revisited ten years later making use of detailed follow up studies that have been carried out since then. Findings: The original discussions identified both key challenges in human resources for health, and driving forces of these challenges, as well as possible solutions. Two sets of issues were highlighted: those related to the size and distribution of the workforce, and those related to health workers’ on-the-job performance. Among the latter, four categories were identified: health workers’ poor attitudes towards patients, absenteeism, corruption and embezzlement, and lack of medical skills among some categories of health workers. The discussion suggest that four components constitute the deeper causal factors, which are, ranked in order of ease of malleability: incentives, monitoring arrangements, professional and workplace norms and intrinsic motivation. Three institutional innovations are identified that aim at improving performance: performance pay, community health workers and increased attention to training of health workers. Revisiting the findings from this primary research making use of later in depth studies, the analysis demonstrates their continued relevance and usefulness. We discuss how the different factors affect the quality of care by impacting on health worker performance and labour market choices, making use of insights from economics and development studies on the role of institutions. Conclusion: The study results indicates that health care quality to an important degree depends on four institutional factors at the micro level that strongly impact on health workers performance and career choice, and which deserve more attention in applied research and policy reform. The analysis also helps to identify ways forwards, which fit well with the Ministry’s most recent strategic plan

Preferences and skills of Indian public sector teachers

With a sample of 700 future public sector primary teachers in India, a Discrete Choice Experiment is used to measure job preferences, particularly regarding location. General skills are also tested. Urban origin teachers and women are more averse to remote locations than rural origin teachers and men respectively. Women would require a 26-73 percent increase in salary for moving to a remote location. The results suggest that existing caste and gender quotas can be detrimental for hiring skilled teachers willing to work in remote locations. The most preferred location is home, which supports decentralised hiring, although this could compromise skills

Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNC3 expression may contribute to the ataxic phenotype

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all pat

Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric

Alzheimer's disease (AD) is characterized by deposition of beta-amyloid (Abeta) in diffuse and senile plaques, and variably in vessels. Mutations in the Abeta-encoding region of the amyloid precursor protein (APP) gene are frequently associated with very severe forms of vascular Abeta deposition, sometimes also accompanied by AD pathology. We earlier described a Flemish APP (A692G) mutation causing a form of early-onset AD with a prominent cerebral amyloid angiopathy and unusually large senile plaque cores. The pathogenic basis of Flemish AD is unknown. By image and mass spectrometric Abeta analyses, we demonstrated that in contrast to other familial AD cases with predominant brain Abeta42, Flemish AD patients predominantly deposit Abeta40. On serial histological section analysis we further showed that the neuritic senile plaques in APP692 brains were centered on vessels. Of a total of 2400 senile plaque cores studied from various brain regions from three patients, 68% enclosed a vessel, whereas the remainder were associated with vascular walls. These observations were confirmed by electron

Safe targeting of T cell acute lymphoblastic leukemia by pathology-specific NOTCH inhibition

Given the high frequency of activating NOTCH1 mutations in T cell acute lymphoblastic leukemia (T-ALL), inhibition of the γ-secretase complex remains an attractive target to prevent ligand-independent release of the cytoplasmic tail and oncogenic NOTCH1 signaling. However, four different γ-secretase complexes exist, and available inhibitors block all complexes equally. As a result, these cause severe “on-target” gastrointestinal tract, skin, and thymus toxicity, limiting their therapeutic application. Here, we demonstrate that genetic deletion or pharmacologic inhibition of the presenilin-1 (PSEN1) subclass of γ-secretase complexes is highly effective in decreasing leukemia while avoiding dose-limiting toxicities. Clinically, T-ALL samples were found to selectively express only PSEN1-containing γ-secretase complexes. The conditional knockout of Psen1 in developing T cells attenuated the development of a mutant NOTCH1-driven leukemia in mice in vivo but did not abrogate normal T cell development. Treatment of T-ALL cell lines with the selective PSEN1 inhibitor MRK-560 effectively decreased mutant NOTCH1 processing and led to cell cycle arrest. These observations were extended to T-ALL patient-derived xenografts in vivo, demonstrating that MRK-560 treatment decreases leukemia burden and increased overall survival without any associated gut toxicity. Therefore, PSEN1-selective compounds provide a potential therapeutic strategy for safe and effective targeting of T-ALL and possibly also for other diseases in which NOTCH signaling plays a role