Intrinsic Motivation

Employs a literature review to describe intrinsic motivation as the force behind pro-social behavior, or when individuals willingly engage in behavior that is costly to them but benefits others. Regarding health workers, motivation stems from possible appreciation of provision of health care, experiencing a warm glow from helping people, or earning esteem from being seen to have helped people. A typology, focusing on the sources of motivation and social preferences, leads to classification of eight categories of intrinsically motivated physicians ranging from status seeking to altruistic and to approval seeking. Intrinsic motivation plays an important role in the decision to become a health worker, what sector to work in, whether to exert effort, and what services to provide, while questions remain about extrinsic incentives' possibly negative effect on intrinsically motivated workers

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

Computational Analysis of Alzheimer Amyloid Plaque Composition in 2D- and Elastically Reconstructed 3D-MALDI MS Images

MALDI mass spectrometry imaging (MSI) enables label-free, spatially resolved analysis of a wide range of analytes in tissue sections. Quantitative analysis of MSI datasets is typically performed on single pixels or manually assigned regions of interest (ROIs). However, many sparse, small objects such as Alzheimer’s disease (AD) brain deposits of amyloid peptides called plaques are neither single pixels nor ROIs. Here, we propose a new approach to facilitate the comparative computational evaluation of amyloid plaque-like objects by MSI: a fast PLAQUE PICKER tool that enables a statistical evaluation of heterogeneous amyloid peptide composition. Comparing two AD mouse models, APP NL-G-F and APP PS1, we identified distinct heterogeneous plaque populations in the NL-G-F model but only one class of plaques in the PS1 model. We propose quantitative metrics for the comparison of technical and biological MSI replicates. Furthermore, we reconstructed a high-accuracy 3D-model of amyloid plaques in a fully automated fashion, employing rigid and elastic MSI image registration using structured and plaque-unrelated reference ion images. Statistical single-plaque analysis in reconstructed 3D-MSI objects revealed the Aβ1–42Arc peptide to be located either in the core of larger plaques or in small plaques without colocalization of other Aβ isoforms. In 3D, a substantially larger number of small plaques were observed than that indicated by the 2D-MSI data, suggesting that quantitative analysis of molecularly diverse sparsely-distributed features may benefit from 3D-reconstruction. Data are available via ProteomeXchange with identifier PXD020824

Hypoxic cancer–associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling

Intratumoral hypoxia causes the formation of dysfunctional blood vessels, which contribute to tumor metastasis and reduce the efficacy of therapeutic treatments. Blood vessels are embedded in the tumor stroma of which cancer-associated fibroblasts (CAFs) constitute a prominent cellular component. We found that hypoxic human mammary CAFs promoted angiogenesis in CAF-endothelial cell cocultures in vitro. Mass spectrometry–based proteomic analysis of the CAF secretome unraveled that hypoxic CAFs contributed to blood vessel abnormalities by altering their secretion of various pro- and anti-angiogenic factors. Hypoxia induced pronounced remodeling of the CAF proteome, including proteins that have not been previously related to this process. Among those, the uncharacterized protein NCBP2-AS2 that we renamed HIAR (hypoxia-induced angiogenesis regulator) was the protein most increased in abundance in hypoxic CAFs. Silencing of HIAR abrogated the pro-angiogenic and pro-migratory function of hypoxic CAFs by decreasing secretion of the pro-angiogenic factor VEGFA and consequently reducing VEGF/VEGFR downstream signaling in the endothelial cells. Our study has identified a regulator of angiogenesis and provides a map of hypoxia-induced molecular alterations in mammary CAFs

The γ-secretase substrate proteome and its role in cell signaling regulation

γ-Secretases mediate the regulated intramembrane proteolysis (RIP) of more than 150 integral membrane proteins. We developed an unbiased γ-secretase substrate identification (G-SECSI) method to study to what extent these proteins are processed in parallel. We demonstrate here parallel processing of at least 85 membrane proteins in human microglia in steady-state cell culture conditions. Pharmacological inhibition of γ-secretase caused substantial changes of human microglial transcriptomes, including the expression of genes related to the disease-associated microglia (DAM) response described in Alzheimer disease (AD). While the overall effects of γ-secretase deficiency on transcriptomic cell states remained limited in control conditions, exposure of mouse microglia to AD-inducing amyloid plaques strongly blocked their capacity to mount this putatively protective DAM cell state. We conclude that γ-secretase serves as a critical signaling hub integrating the effects of multiple extracellular stimuli into the overall transcriptome of the cell.</p