Cost of installing and operating an electronic clinical decision support system for maternal health care: case of Tanzania rural primary health centres

Background: Poor quality of care is among the causes of high maternal and newborn disease burden in Tanzania. Potential reason for poor quality of care is the existence of a “know-do gap” where by health workers do not perform to the best of their knowledge. An electronic clinical decision support system (CDSS) for maternal health care was piloted in six rural primary health centers of Tanzania to improve performance of health workers by facilitating adherence to World Health Organization (WHO) guidelines and ultimately improve quality of maternal health care. This study aimed at assessing the cost of installing and operating the system in the health centers. Methods: This retrospective study was conducted in Lindi, Tanzania. Costs incurred by the project were analyzed using Ingredients approach. These costs broadly included vehicle, computers, furniture, facility, CDSS software, transport, personnel, training, supplies and communication. These were grouped into installation and operation cost; recurrent and capital cost; and fixed and variable cost. We assessed the CDSS in terms of its financial and economic cost implications. We also conducted a sensitivity analysis on the estimations. Results: Total financial cost of CDSS intervention amounted to 185,927.78 USD. 77% of these costs were incurred in the installation phase and included all the activities in preparation for the actual operation of the system for client care. Generally, training made the largest share of costs (33% of total cost and more than half of the recurrent cost) followed by CDSS software- 32% of total cost. There was a difference of 31.4% between the economic and financial costs. 92.5% of economic costs were fixed costs consisting of inputs whose costs do not vary with the volume of activity within a given range. Economic cost per CDSS contact was 52.7 USD but sensitive to discount rate, asset useful life and input cost variations. Conclusions: Our study presents financial and economic cost estimates of installing and operating an electronic CDSS for maternal health care in six rural health centres. From these findings one can understand exactly what goes into a similar investment and thus determine sorts of input modification needed to fit their context

Cost-effectiveness of an electronic clinical decision support system for improving quality of antenatal and childbirth care in rural Tanzania: an intervention study

Background: QUALMAT project aimed at improving quality of maternal and newborn care in selected health care facilities in three African countries. An electronic clinical decision support system was implemented to support providers comply with established standards in antenatal and childbirth care. Given that health care resources are limited and interventions differ in their potential impact on health and costs (efficiency), this study aimed at assessing cost-effectiveness of the system in Tanzania. Methods: This was a quantitative pre- and post- intervention study involving 6 health centres in rural Tanzania. Cost information was collected from health provider’s perspective. Outcome information was collected through observation of the process of maternal care. Incremental cost-effectiveness ratios for antenatal and childbirth care were calculated with testing of four models where the system was compared to the conventional paper-based approach to care. One-way sensitivity analysis was conducted to determine whether changes in process quality score and cost would impact on cost-effectiveness ratios. Results: Economic cost of implementation was 167,318 USD, equivalent to 27,886 USD per health center and 43 USD per contact. The system improved antenatal process quality by 4.5% and childbirth care process quality by 23.3% however these improvements were not statistically significant. Base-case incremental cost-effectiveness ratios of the system were 2469 USD and 338 USD per 1% change in process quality for antenatal and childbirth care respectively. Cost-effectiveness of the system was sensitive to assumptions made on costs and outcomes. Conclusions: Although the system managed to marginally improve individual process quality variables, it did not have significant improvement effect on the overall process quality of care in the short-term. A longer duration of usage of the electronic clinical decision support system and retention of staff are critical to the efficiency of the system and can reduce the invested resources. Realization of gains from the system requires effective implementation and an enabling healthcare system. Trial registration: Registered clinical trial at www.clinicaltrials.gov (NCT01409824). Registered May 2009

Cutting the Gordian knot : early and complete amino acid sequence confirmation of class II lasso peptides by HCD fragmentation

SAJ would like to thank the University of Aberdeen for an Elphinstone Scholarship. CC-A thanks CONICYT PFCHA/DOCTORADO BECAS CHILE/2016 (#21160585) fellowship and CONICYT Basal Centre Grant for the Centre for Biotechnology and Bioengineering, CeBiB (FB0001). JFC also thanks CONICYT for a National PhD Scholarship (#21110356) and a Visiting Student Scholarship.Peer reviewedPostprin

Nesting doctoral students in collaborative North-South partnerships for health systems research

Background: The European Union (EU) supports North-South Partnerships and collaborative research projects through its Framework Programmes and Horizon 2020. There is limited research on how such projects can be harnessed to provide a structured platform for doctoral level studies as a way of strengthening health system research capacity in sub-Saharan Africa (SSA). Objective: The aim of this study was to explore the challenges of, and facilitating factors for, 'nesting' doctoral students in North South collaborative research projects. The term nesting refers to the embedding of the processes of recruiting, supervising, and coordinating doctoral students in the overall research plan and processes. Design: This cross-sectional qualitative study was undertaken by the EU-funded QUALMAT Project. A questionnaire was implemented with doctoral students, supervisors, and country principal investigators (PIs), and content analysis was undertaken. Results: Completed questionnaires were received from nine doctoral students, six supervisors, and three country PIs (86% responses rate). The doctoral students from SSA described high expectations about the input they would receive (administrative support, equipment, training, supervision). This contrasted with the expectations of the supervisors for proactivity and self-management on the part of the students. The rationale for candidate selection, and understandings of the purpose of the doctoral students in the project were areas of considerable divergence. There were some challenges associated with the use of the country PIs as co-supervisors. Doctoral student progress was at times impeded by delays in the release of funding instalments from the EU. The paper provides a checklist of essential requirements and a set of recommendations for effective nesting of doctoral students in joint North-South projects. Conclusion: There are considerable challenges to the effective nesting of doctoral students within major collaborative research projects. However, ways can be found to overcome them. The nesting process ultimately helped the institutions involved in this example to take better advantage of the opportunities that collaborative projects offer to foster North-South partnerships as a contribution to the strengthening of local research capacity

Behavioral phenotype in five individuals with de novo mutations within the GRIN2B gene

Background: Intellectual disability (ID) is often associated with behavioral problems or disorders. Mutations in the GRIN2B gene (MRD6, MIM613970) have been identified as a common cause of ID (prevalence of 0.5 – 1% in individuals with ID) associated with EEG and behavioral problems. Methods: We assessed five GRIN2B mutation carriers aged between 3 and 14 years clinically and via standardized questionnaires to delineate a detailed behavioral phenotype. Parents and teachers rated problem behavior of their affected children by completing the Developmental Behavior Checklist (DBC) and the Conners’ Rating Scales Revised (CRS-R:L). Results: All individuals had mild to severe ID and needed guidance in daily routine. They showed characteristic behavior problems with prominent hyperactivity, impulsivity, distractibility and a short attention span. Stereotypies, sleeping problems and a friendly but boundless social behavior were commonly reported. Conclusion: Our observations provide an initial delineation of the behavioral phenotype of GRIN2B mutation carriers

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers

<p>Abstract</p> <p>Methods</p> <p>We examined gene expression profiles of tumor cells from 29 untreated patients with lung cancer (10 adenocarcinomas (AC), 10 squamous cell carcinomas (SCC), and 9 small cell lung cancer (SCLC)) in comparison to 5 samples of normal lung tissue (NT). The European and American methodological quality guidelines for microarray experiments were followed, including the stipulated use of laser capture microdissection for separation and purification of the lung cancer tumor cells from surrounding tissue.</p> <p>Results</p> <p>Based on differentially expressed genes, different lung cancer samples could be distinguished from each other and from normal lung tissue using hierarchical clustering. Comparing AC, SCC and SCLC with NT, we found 205, 335 and 404 genes, respectively, that were at least 2-fold differentially expressed (estimated false discovery rate: < 2.6%). Different lung cancer subtypes had distinct molecular phenotypes, which also reflected their biological characteristics. Differentially expressed genes in human lung tumors which may be of relevance in the respective lung cancer subtypes were corroborated by quantitative real-time PCR.</p> <p>Genetic programming (GP) was performed to construct a classifier for distinguishing between AC, SCC, SCLC, and NT. Forty genes, that could be used to correctly classify the tumor or NT samples, have been identified. In addition, all samples from an independent test set of 13 further tumors (AC or SCC) were also correctly classified.</p> <p>Conclusion</p> <p>The data from this research identified potential candidate genes which could be used as the basis for the development of diagnostic tools and lung tumor type-specific targeted therapies.</p

The Yin and Yang of Yeast Transcription: Elements of a Global Feedback System between Metabolism and Chromatin

When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions