Performance-based financing as a health system reform : mapping the key dimensions for monitoring and evaluation

Peer reviewedPublisher PD

The DNA of coral reef biodiversity: predicting and protecting genetic diversity of reef assemblages

Conservation of ecological communities requires deepening our understanding of genetic diversity patterns and drivers at community-wide scales. Here, we use seascape genetic analysis of a diversity metric, allelic richness (AR), for 47 reef species sampled across 13 Hawaiian Islands to empirically demonstrate that large reefs high in coral cover harbour the greatest genetic diversity on average. We found that a species’s life history (e.g. depth range and herbivory) mediates response of genetic diversity to seascape drivers in logical ways. Furthermore, a metric of combined multi-species AR showed strong coupling to species richness and habitat area, quality and stability that few species showed individually. We hypothesize that macro-ecological forces and species interactions, by mediating species turnover and occupancy (and thus a site’s mean effective population size), influence the aggregate genetic diversity of a site, potentially allowing it to behave as an apparent emergent trait that is shaped by the dominant seascape drivers. The results highlight inherent feedbacks between ecology and genetics, raise concern that genetic resilience of entire reef communities is compromised by factors that reduce coral cover or available habitat, including thermal stress, and provide a foundation for new strategies for monitoring and preserving biodiversity of entire reef ecosystems

Munc18-1 promotes larger dense-core vesicle docking.

AbstractSecretory vesicles dock at the plasma membrane before Ca2+ triggers their exocytosis. Exocytosis requires the assembly of SNARE complexes formed by the vesicle protein Synaptobrevin and the membrane proteins Syntaxin-1 and SNAP-25. We analyzed the role of Munc18-1, a cytosolic binding partner of Syntaxin-1, in large dense-core vesicle (LDCV) secretion. Calcium-dependent LDCV exocytosis was reduced 10-fold in mouse chromaffin cells lacking Munc18-1, but the kinetic properties of the remaining release, including single fusion events, were not different from controls. Concomitantly, mutant cells displayed a 10-fold reduction in morphologically docked LDCVs. Moreover, acute overexpression of Munc18-1 in bovine chromaffin cells increased the amount of releasable vesicles and accelerated vesicle supply. We conclude that Munc18-1 functions upstream of SNARE complex formation and promotes LDCV docking

Paying health workers for performance in Battagram district, Pakistan

<p>Abstract</p> <p>Background</p> <p>There is a growing interest in using pay-for-performance mechanisms in low and middle-income countries in order to improve the performance of health care providers. However, at present there is a dearth of independent evaluations of such approaches which can guide understanding of their potential and risks in differing contexts. This article presents the results of an evaluation of a project managed by an international non-governmental organisation in one district of Pakistan. It aims to contribute to learning about the design and implementation of pay-for-performance systems and their impact on health worker motivation.</p> <p>Methods</p> <p>Quantitative analysis was conducted of health management information system (HMIS) data, financial records, and project documents covering the period 2007-2010. Key informant interviews were carried out with stakeholders at all levels. At facility level, in-depth interviews were held, as were focus group discussions with staff and community members.</p> <p>Results</p> <p>The wider project in Battagram had contributed to rebuilding district health services at a cost of less than US$4.5 per capita and achieved growth in outputs. Staff, managers and clients were appreciative of the gains in availability and quality of services. However, the role that the performance-based incentive (PBI) component played was less clear--PBI formed a relatively small component of pay, and did not increase in line with outputs. There was little evidence from interviews and data that the conditional element of the PBIs influenced behaviour. They were appreciated as a top-up to pay, but remained low in relative terms, and only slightly and indirectly related to individual performance. Moreover, they were implemented independently of the wider health system and presented a clear challenge for longer term integration and sustainability.</p> <p>Conclusions</p> <p>Challenges for performance-based pay approaches include the balance of rewarding individual versus team efforts; reflecting process and outcome indicators; judging the right level of incentives; allowing for very different starting points and situations; designing a system which is simple enough for participants to comprehend; and the tension between independent monitoring and integration in a national system. Further documentation of process and cost-effectiveness, and careful examination of the wider impacts of paying for performance, are still needed.</p

Populations of double white dwarfs in Milky Way satellites and their detectability with LISA

Context. Milky Way dwarf satellites are unique objects that encode the early structure formation and therefore represent a window into the high redshift Universe. So far, their study has been conducted using electromagnetic waves only. The future Laser Interferometer Space Antenna (LISA) has the potential to reveal Milky Way satellites through gravitational waves emitted by double white dwarf (DWD) binaries. Aims. We investigate gravitational wave signals that will be detectable by LISA as a possible tool for the identification and characterisation of the Milky Way satellites. Methods. We used the binary population synthesis technique to model the population of DWDs in dwarf satellites and we assessed the impact on the number of LISA detections when making changes to the total stellar mass, distance, star formation history, and metallicity of satellites. We calibrated predictions for the known Milky Way satellites on their observed properties. Results. We find that DWDs emitting at frequencies ≳3 mHz can be detected in Milky Way satellites at large galactocentric distances. The number of these high frequency DWDs per satellite primarily depends on its mass, distance, age, and star formation history, and only mildly depends on the other assumptions regarding their evolution such as metallicity. We find that dwarf galaxies with M⋆ >  106 M⊙ can host detectable LISA sources; the number of detections scales linearly with the satellite’s mass. We forecast that out of the known satellites, Sagittarius, Fornax, Sculptor, and the Magellanic Clouds can be detected with LISA. Conclusions. As an all-sky survey that does not suffer from contamination and dust extinction, LISA will provide observations of the Milky Way and dwarf satellites galaxies, which will be valuable for Galactic archaeology and near-field cosmology

Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-γ upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, ‘in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens

High Levels of Genetic Divergence Detected in Sacramento Perch Suggests Two Divergent Translocation Sources

Translocation has been used to conserve imperiled fishes and create new fisheries. One species for which translocation has played a significant role is the Sacramento Perch Archoplites interruptus. Extirpated from its native range, the Sacramento Perch has been introduced throughout California and Nevada through multiple translocation events, though historical records are incomplete. Recent assessments of eight previously uncharacterized Sacramento Perch populations have prompted reevaluation of range-wide population structure to inform a genetic management plan for long-term resiliency of this species. We examined Sacramento Perch genetic diversity and population structure across the current range of the species using 12 microsatellite markers. We analyzed samples from the eight uncharacterized populations and seven populations previously studied by Schwartz and May (2008). Bayesian clustering supported two distinct clusters of Sacramento Perch herein designated as A and B. Within these two clusters we detected hierarchical substructure, likely due to genetic drift after population founding. Genetic differentiation among populations within the same cluster was relatively low (FST = 0.023–0.176), while differentiation among populations from different clusters was higher (FST = 0.190–0.320). The existence of two strongly divergent genetic clusters in Sacramento Perch suggests two distinct translocation sources, and we recommend that these clusters be treated as genetic management units (GMUs). The B GMU populations had fairly low levels of genetic diversity relative to the A GMU populations. All populations showed evidence of past bottlenecks, and most had effective population sizes placing them at risk for inbreeding depression. Human-facilitated gene flow is recommended to prevent further genetic diversity loss. Due to uncertainty surrounding Sacramento Perch translocation history and strong levels of divergence between the two GMUs, translocations should be facilitated only between populations within the same GMU

Acanthaster planci, across the Hawaiian Archipelago and Johnston Atoll

The population structure of marine species is variable along the Hawaiian Archipelago; thus, it is important to understand dispersal and recruitment patterns for economically and ecologically important taxa to inform Ecosystem-based Management. Connectivity of the coral-eating crown-of-thorns sea star, Acanthaster planci, was examined from Johnston Atoll and 12 locations across the Hawaiian Archipelago. Sequences of mitochondrial DNA from 383 individuals were analyzed to infer patterns of gene flow among the Northwestern Hawaiian Islands (NWHIs), the main Hawaiian Islands, and Johnston Atoll. Population samples were genetically similar across the Hawaiian Archipelago with the exception of the west side of the Big Island of Hawaii, which was significantly differentiated from the majority of Hawaiian samples (pairwise Φ ST = 0.0607-0.1068, P &lt; .05). Although differentiated, Hawai&apos;i West shares haplotypes with every other site across the Hawaiian Archipelago. Johnston Atoll was genetically distinct from every location (pairwise Φ ST = 0.064-0.13, P &lt; .05) except French Frigate Shoals (Φ ST = 0.03, P = .10), supporting connectivity between the central NWHIs and Johnston Atoll. Taken together with the lack of geographic population structure and haplotypes shared among all populations, these results indicate widespread larval dispersal with few restrictions to gene flow along the archipelago

Widespread Dispersal of the Crown-of-Thorns Sea Star, Acanthaster planci

The population structure of marine species is variable along the Hawaiian Archipelago; thus, it is important to understand dispersal and recruitment patterns for economically and ecologically important taxa to inform Ecosystem-based Management. Connectivity of the coral-eating crown-of-thorns sea star, Acanthaster planci, was examined from Johnston Atoll and 12 locations across the Hawaiian Archipelago. Sequences of mitochondrial DNA from 383 individuals were analyzed to infer patterns of gene flow among the Northwestern Hawaiian Islands (NWHIs), the main Hawaiian Islands, and Johnston Atoll. Population samples were genetically similar across the Hawaiian Archipelago with the exception of the west side of the Big Island of Hawaii, which was significantly differentiated from the majority of Hawaiian samples (pairwise ΦST=0.0607-0.1068, <.05). Although differentiated, Hawai`i West shares haplotypes with every other site across the Hawaiian Archipelago. Johnston Atoll was genetically distinct from every location (pairwise ΦST=0.064-0.13, <.05) except French Frigate Shoals (ΦST=0.03, =.10), supporting connectivity between the central NWHIs and Johnston Atoll. Taken together with the lack of geographic population structure and haplotypes shared among all populations, these results indicate widespread larval dispersal with few restrictions to gene flow along the archipelago