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To better understand the wide variation of performance among county health systems in Kenya, this study investigated their performance determinants. We selected five counties with varied performance and examined their performance across five domains containing 10 thematic areas. We conducted a stakeholder analysis, consisting of focus group discussions and key informant interviews, and administered a quantitative survey to quantify the magnitude of inefficiency. The study found that a shortage of funding was one of the most common complaints from counties, leading to inefficiency in the health system. Another major reason for inefficiencies was the delay in disbursing funding to health facilities, which affected the procurement of medical supplies and commodities essential for delivering healthcare to the population. In addition, lack of autonomy in procuring commodities and equipment was repeatedly mentioned as a barrier to delivering quality health services. Other reported common concerns contributing to the performance of county health systems were the lack of lab tests and equipment, low willingness to join health insurance, rigid procurement policies and lengthy procurement process, lack of motivation and incentives for service delivery, and poor economic status. Despite the common concerns among the five counties, they differed in some schematic areas, such as the county’s commitment to health and community mobilization. In summary, this study suggests various factors that determine county health system performance. Given the multifaceted nature of inefficiency drivers, it is necessary to adopt a holistic approach to address the causes of inefficiencies and improve the county health systems

During spermatogenesis, the Golgi apparatus serves important roles including the formation of the acrosome, which is a sperm-specific organelle essential for fertilization. We have previously demonstrated that D. melanogaster ATP-dependent Citrate Lyase (ATPCL) is required for spindle organization, cytokinesis, and fusome assembly during male meiosis, mainly due to is activity on fatty acid biosynthesis. Here, we show that depletion of DmATPCL also affects the organization of acrosome and suggest a role for this enzyme in the assembly of Golgi-derived structures during Drosophila spermatogenesis.

ObjectiveAssess the quality of healthcare across African countries based on health providers’ clinical knowledge, their clinic attendance and drug availability, with a focus on seven conditions accounting for a large share of child and maternal mortality in sub-Saharan Africa: malaria, tuberculosis, diarrhoea, pneumonia, diabetes, neonatal asphyxia and postpartum haemorrhage.MethodsWith nationally representative, cross-sectional data from ten countries in sub-Saharan Africa, collected using clinical vignettes (to assess provider knowledge), unannounced visits (to assess provider absenteeism) and visual inspections of facilities (to assess availability of drugs and equipment), we assess whether health providers are available and have sufficient knowledge and means to diagnose and treat patients suffering from common conditions amenable to primary healthcare. We draw on data from 8061 primary and secondary care facilities in Kenya, Madagascar, Mozambique, Nigeria, Niger, Senegal, Sierra Leone, Tanzania, Togo and Uganda, and 22 746 health workers including doctors, clinical officers, nurses and community health workers. Facilities were selected using a multistage cluster-sampling design to ensure data were representative of rural and urban areas, private and public facilities, and of different facility types. These data were gathered under the Service Delivery Indicators programme.ResultsAcross all conditions and countries, healthcare providers were able to correctly diagnose 64% (95% CI 62% to 65%) of the clinical vignette cases, and in 45% (95% CI 43% to 46%) of the cases, the treatment plan was aligned with the correct diagnosis. For diarrhoea and pneumonia, two common causes of under-5 deaths, 27% (95% CI 25% to 29%) of the providers correctly diagnosed and prescribed the appropriate treatment for both conditions. On average, 70% of health workers were present in the facilities to provide care during facility hours when those workers are scheduled to be on duty. Taken together, we estimate that the likelihood that a facility has at least one staff present with competency and key inputs required to provide child, neonatal and maternity care that meets minimum quality standards is 14%. On average, poor clinical knowledge is a greater constraint in care readiness than drug availability or health workers’ absenteeism in the 10 countries. However, we document substantial heterogeneity across countries in the extent to which drug availability and absenteeism matter quantitatively.ConclusionOur findings highlight the need to boost the knowledge of healthcare workers to achieve greater care readiness. Training programmes have shown mixed results, so systems may need to adopt a combination of competency-based preservice and in-service training for healthcare providers (with evaluation to ensure the effectiveness of the training), and hiring practices that ensure the most prepared workers enter the systems. We conclude that in settings where clinical knowledge is poor, improving drug availability or reducing health workers’ absenteeism would only modestly increase the average care readiness that meets minimum quality standards.

The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells.

The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells.

IntroductionProgress towards effective service coverage and financial protection—the two dimensions of Universal Health Coverage (UHC)—has been limited in Kenya in the last decade. The government of Kenya has embarked on a highly ambitious reform programme currently being piloted in four Kenyan counties and aiming at national rollout by 2022. This study provides an updated assessment of the performance of the Kenyan health system in terms of financial protection allowing to monitor trends over time. In light of the UHC initiative, the study provides a baseline to assess the impact of the UHC pilot programme and inform scale-up plans. It also investigates household characteristics associated with catastrophic payments.MethodsUsing data from the Kenya Household Health Expenditure and Utilization Survey (KHHEUS) 2018, we investigated the incidence and intensity of catastrophic and impoverishing health expenditure. We used a logistic regression analysis to assess households’ characteristics associated with the probability of incurring catastrophic health expenditures.ResultsThe results show that the incidence of catastrophic payments is more severe for the poorest households and in the rural areas and mainly due to outpatient services. Results for the impoverishing effect suggest that after accounting for out-of-pocket(OOP) payments, the proportion of poor people increases by 2.2 percentage points in both rural and urban areas. Thus, between 1 and 1.1 million individuals are pushed into poverty due to OOP payments. Among the characteristics associated with the probability of incurring OOP expenditures, socioeconomic conditions, the presence of elderly and of people affected by chronic conditions showed significant results.ConclusionKenya is still lagging behind in terms of protecting its citizens against financial risks associated with ill health and healthcare seeking behaviour. More effort is needed to protect the most vulnerable population groups from the high costs of illness.

The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation reactions. This renders ACL a key regulator of histone acetylation levels and gene expression in diverse organisms including humans. We have found that depletion of ATPCL, the Drosophila ortholog of human ACL, reduced levels of Acetyl CoA but, unlike its human counterpart, does not affect global histone acetylation and gene expression. Nevertheless, reduced ATPCL levels caused evident, although moderate, mitotic chromosome breakage suggesting that this enzyme plays a partial role in chromosome stability. These defects did not increase upon X-ray irradiation, indicating that they are not dependent on an impairment of DNA repair. Interestingly, depletion of ATPCL drastically increased the frequency of chromosome breaks (CBs) associated to mutations in scheggia, which encodes the ortholog of the mitochondrial citrate carrier SLC25A1 that is also required for chromosome integrity and histone acetylation. Our results indicate that ATPCL has a dispensable role in histone acetylation and prevents massive chromosome fragmentation when citrate efflux is altered.

Background Kenya is experiencing persistently high levels of inequity in health and access to care services. In 2018, decades of sustained policy efforts to promote equitable, affordable and quality health services have culminated in the launch of a universal health coverage scheme, initially piloted in four Kenyan counties and planned for national rollout by 2022. Our study aims to contribute to monitoring and evaluation efforts alongside policy implementation, by establishing a detailed, baseline assessment of socio-economic inequality and inequity in health care utilization in Kenya shortly before the policy launch. Methods We use concentration curves and corrected concentration indexes to measure socio-economic inequality in care use and the horizontal inequity index as a measure of inequity in care utilization for three types of care services: outpatient care, inpatient care and preventive and promotive care. Further insights into the individual and household level characteristics that determine observed inequality are derived through decomposition analysis. Results We find significant inequality and inequity in the use of all types of care services favouring richer population groups, with particularly pronounced levels for preventive and inpatient care services. These are driven primarily by differences in living standards and educational achievement, while the region of residence is a key driver for inequality in preventive care use only. Pro-rich inequalities are particularly pronounced for care provided in privately owned facilities, while public providers serve a much larger share of individuals from lower socio-economic groups. Conclusions Through its focus on increasing affordability of care for all Kenyans, the newly launched universal health coverage scheme represents a crucial step towards reducing disparities in health care utilization. However in order to achieve equity in health and access to care such efforts must be paralleled by multi-sectoral approaches to address all key drivers of inequity: persistent poverty, disparities in living standards and educational achievement, as well as regional differences in availability and accessibility of care.

The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation reactions. This renders ACL a key regulator of histone acetylation levels and gene expression in diverse organisms including humans. We have found that depletion of ATPCL, the Drosophila ortholog of human ACL, reduced levels of Acetyl CoA but, unlike its human counterpart, does not affect global histone acetylation and gene expression. Nevertheless, reduced ATPCL levels caused evident, although moderate, mitotic chromosome breakage suggesting that this enzyme plays a partial role in chromosome stability. These defects did not increase upon X-ray irradiation, indicating that they are not dependent on an impairment of DNA repair. Interestingly, depletion of ATPCL drastically increased the frequency of chromosome breaks (CBs) associated to mutations in scheggia, which encodes the ortholog of the mitochondrial citrate carrier SLC25A1 that is also required for chromosome integrity and histone acetylation. Our results indicate that ATPCL has a dispensable role in histone acetylation and prevents massive chromosome fragmentation when citrate efflux is altered.

Introduction Poor data quality and use have been identified as key challenges that negatively impact immunization programs in low- and middle-income countries (LMICs). In addition, many LMICs have a shortage of health personnel, and staff available have demanding workloads across several health programs. In order to address these challenges, the Better Immunization Data (BID) Initiative introduced a comprehensive suite of interventions, including an electronic immunization registry aimed at improving the quality, reliability, and use of immunization data in Arusha Region, Tanzania, and Southern Province of Zambia. The objective of this study was to assess the incremental costs of implementing the BID interventions in immunization programs in these two countries. Methods We conducted a micro-costing study to estimate the economic costs of service delivery and logistics for the immunization programs with and without the BID interventions in a sample of health facilities and district program offices in each country. Structured questionnaires were used to interview immunization program staff at baseline and post-intervention to assess annual resource utilization and costs. Cost outcomes were reported as annual cost per facility, cost per district and changes in resource costs due to the BID interventions (i.e., costs associated with health worker time, start-up costs, etc.). Sub-group analyses were conducted by health facility to assess variation in costs by volume served and location (rural versus urban). One-way sensitivity analyses were conducted to identify influential parameters. Costs were reported in 2017 US dollars. Results In Tanzania, the average annual reduction in resource costs was estimated at US$10,236 (95% confidence interval: $7,606-$14,123) per health facility, while the average annual reduction in resource costs per district was estimated at $6,542. In Zambia, reductions in resource costs were modest at an estimated annual average of $628 (95% confidence interval: $209-$1,467) per health facility and $236 per district. Resource cost reductions were mainly attributable to reductions in time required for immunization service delivery and reporting. One-way sensitivity analyses identified key cost drivers, all related to reductions in health worker time. Conclusion The introduction of electronic immunization registries and stock management systems through the BID Initiative was estimated to result in potential time savings in both countries. Health worker time was the area most impacted by the interventions, suggesting that time savings gained could be utilized for patient care. Information generated through this work provides evidence to inform stakeholder decision-making for scale-up of the BID interventions in Tanzania and Zambia and to inform other Low-to-Middle-Income Countries (LMICs) interested in similar interventions.

ObjectiveTo determine the costs to develop, roll out and maintain electronic immunisation registries (EIRs) and a related suite of data use interventions.MethodsThe Better Immunisation Data (BID) Initiative conducted the activities from 2013 to 2018 in three regions in Tanzania and one province in Zambia. The Initiative’s financial records were used to account for the financial costs of designing and developing the EIRs, BID staff time, expenditures for rolling out the EIR systems and the related suite of interventions to health facilities, and recurrent costs. Total financial costs, cost per facility and cost per child were calculated in 2018 US$.FindingsTotal expenditures were ~US$4.2 million in Tanzania and US$3.6 million in Zambia. System design and development costs accounted for ~33% and 26% of the expenditures in each country, respectively, while BID staff costs accounted for 39% and 52%, respectively. Average expenditures per health facility for rolling out the EIR system were between US$709 and US$1320 for the Tanzania regions and US$2591 for Zambia. The annualised average expenditure per child was estimated to be between US$3.30 and US$3.81 for the regions in Tanzania and US$8.46 in Zambia. Expenditures per child were higher in Zambia partly because of a much smaller birth cohort compared with Tanzania.ConclusionOther countries may benefit from the investments made and lessons learnt in Tanzania and Zambia by leveraging these now existing EIR platforms and rollout strategies, and hence may be able to implement EIRs at lower costs than reported here.

SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to progressive paralysis and death. Although SMN is required in every cell for proper RNA metabolism, the reason why its loss is especially critical in the motor system is still unclear. SMA genetic models have been employed to identify several modifiers that can ameliorate the deficits induced by SMN depletion. Here we focus on WDR79/TCAB1, a protein important for the biogenesis of several RNA species that has been shown to physically interact with SMN in human cells. We show that WDR79 depletion results in locomotion defects in both Drosophila and Caenorhabditis elegans similar to those elicited by SMN depletion. Consistent with this observation, we find that SMN overexpression rescues the WDR79 loss-of-function phenotype in flies. Most importantly, we also found that WDR79 overexpression ameliorates the locomotion defects induced by SMN depletion in both flies and worms. Our results collectively suggest that WDR79 and SMN play evolutionarily conserved cooperative functions in the nervous system and suggest that WDR79/TCAB1 may have the potential to modify SMA pathogenesis. (C) 2017 Published by Elsevier Inc.

Background Since 2000, international funding for HIV has supported scaling up antiretroviral therapy (ART) in sub-Saharan Africa. However, such funding has stagnated for years, threatening the sustainability and reach of ART programs amid efforts to achieve universal treatment. Improving health system efficiencies, particularly at the facility level, is an increasingly critical avenue for extending limited resources for ART; nevertheless, the potential impact of increased facility efficiency on ART capacity remains largely unknown. Through the present study, we sought to quantify facility-level technical efficiency across countries, assess potential determinants of efficiency, and predict the potential for additional ART expansion. Methods Using nationally-representative facility datasets from Kenya, Uganda and Zambia, and measures adjusting for structural quality, we estimated facility-level technical efficiency using an ensemble approach that combined restricted versions of Data Envelopment Analysis and Stochastic Distance Function. We then conducted a series of bivariate and multivariate regression analyses to evaluate possible determinants of higher or lower technical efficiency. Finally, we predicted the potential for ART expansion across efficiency improvement scenarios, estimating how many additional ART visits could be accommodated if facilities with low efficiency thresholds reached those levels of efficiency. Results In each country, national averages of efficiency fell below 50 % and facility-level efficiency markedly varied. Among facilities providing ART, average efficiency scores spanned from 50 % (95 % uncertainty interval (UI), 48–62 %) in Uganda to 59 % (95 % UI, 53–67 %) in Zambia. Of the facility determinants analyzed, few were consistently associated with higher or lower technical efficiency scores, suggesting that other factors may be more strongly related to facility-level efficiency. Based on observed facility resources and an efficiency improvement scenario where all facilities providing ART reached 80 % efficiency, we predicted a 33 % potential increase in ART visits in Kenya, 62 % in Uganda, and 33 % in Zambia. Given observed resources in facilities offering ART, we estimated that 459,000 new ART patients could be seen if facilities in these countries reached 80 % efficiency, equating to a 40 % increase in new patients. Conclusions Health facilities in Kenya, Uganda, and Zambia could notably expand ART services if the efficiency with which they operate increased. Improving how facility resources are used, and not simply increasing their quantity, has the potential to substantially elevate the impact of global health investments and reduce treatment gaps for people living with HIV. Electronic supplementary material The online version of this article (doi:10.1186/s12916-016-0653-z) contains supplementary material, which is available to authorized users.

Population aging is challenging governments to find new solutions to finance the increasing demand for nursing home care and slow down the increase in expenditures. In this light, many European countries are currently considering reforms to increase efficiency in the provision of nursing home services. One popular restructuring policy is the transformation of public organizations into private nonprofit organizations. The underlying assumption is that private nonprofit nursing homes are more efficient than public nursing homes. However, there is limited empirical evidence to support this view. This analysis aims to contribute to the evidence base on this issue by investigating the impact of the organizational form on the costs of nursing homes. We use a sample of 45 nursing homes from one Swiss canton over a 5-year period (2001-2005). The applied estimation strategy provides more accurate estimates as compared to previous studies. In particular, we distinguish between cost differences that are under the control of the managers from those that are not (structural). Our findings suggest that public nursing homes are more costly than private nursing homes, although the difference is small. This cost difference is mainly driven by structural rather than managerial costs. Therefore, cost-reducing policies that promote private nonprofit nursing homes are expected to reduce costs only slightly.

Engineered nanomaterials are commonly defined as materials with at least one dimension of 100 nanometers or less. Such materials typically possess nanostructure-dependent properties (e.g., chemical, mechanical, electrical, optical, magnetic, biological), which make them desiderable for commercial or medical application. However, these same proper- ties may potentially lead to nanostructure-dependent biological activity that differs from and is not directly predicted by the bulk properties of the constitutive chemicals and compounds. Nanoparticles and nanomaterials can be on the same scale of living cells components, including proteins, nucleic acids, lipids and cellular organelles. When considering nanoparticles it must be asked how man-made nanostructures can interact with or influence biological systems. Carbon nanotubes (CNTs) are an example of carbon-based nanomaterial, which has won a huge spreading in nanotechnology. The incorporation of CNTs in living systems has raised many concerns because of their hydrophobicity and tendency to ag- gregate and accumulate into cells, organs, and tissues with dangerous effects. Applications of toxicogenomics to both investigative and predictive toxicology will contribute to the in-depth investiga- tion of molecular mechanisms or the mode of nanomaterials action that is achieved by using conventional toxicological approaches. Parallel toxicogenomic technologies will promote a valuable platform for the development of biomarkers, in order to predict possible nanomaterial's toxicity. The potential of characteristic gene expression profiles ("fingerprint") of exposure or toxicological response to nanoparticles will be discussed in the review to enhance comprehension of the mo- lecular mechanism of in vivo and in vitro system exposed to nanomaterials.

Multicolor immunostaining analysis is often a desirable tool in cell biology for most researchers. Nonetheless, this is not an easy task and often not affordable by many laboratories as it might require expensive instrumentation and sophisticated analysis software. Here, we describe a simple protocol for performing sequential immunostainings on two different Drosophila specimens. Our strategy relies on an efficient and reproducible method for removal primary antibodies and/or fluorophore-conjugated secondary antibodies that does not affect antigene integrity. We show that alternation of multiple rounds of antibody incubation and removal on the same slide, followed by registration of the same DAPI-stained image, provides a simple framework for the sequential detection of several antigens in the same cell. Given that the sample fixation procedures used for Drosophila tissues are compatible with most specimen processing protocols, we can envisage that the multicolor immunostaining strategy presented here can be also adapted to different samples including mammalian tissues and/or cells.

Pressure on health care systems due to the increasing expenditures of the elderly population is pushing policy makers to adopt new regulation and payment schemes for nursing home services. We consider the behavior of nonprofit nursing homes under different payment schemes and empirically investigate the implications of prospective payments on nursing home costs under tightly regulated quality aspects. To evaluate the impact of the policy change introduced in 2006 in Southern Switzerland - from retrospective to prospective payment - we use a panel of 41 homes observed over a 10-years period (2001-2010). We employ a fixed effects model with a time trend that is allowed to change after the policy reform. There is evidence that the new payment system slightly reduces costs without impacting quality.

In Switzerland, nursing home services are mainly provided by regulated public and private nonprofit organizations. Some of them are created by local governments as foundations. This provides a unique setting to analyze the impact of the institutional form on the performance of nursing homes. We propose a model where the institutional form is represented as a legal constraint which affects managers in the decison-making process. Considering a sample of 44 Swiss Italian nursing homes over a 7-years period (1999-2005), we then disentangle persistent inefficiency due to differences in the institutional form from unobserved heterogeneity. The applied estimation strategy provides more accurate estimates of the impact of the institutional form on nursing homes efficiency, as compared to previous studies. Our results suggest that governmental nursing homes are more costly than private and public foundations. These results are consistent across different model specifications.