The dynamics of centralized procurement reform in a decentralized state : evidence and lessons from Indonesia

A central policy of the Government of Indonesia's strategy for enhancing its country's economic and social development is to develop infrastructure and expand service delivery. Public procurement reform is a key component of this policy. Despite the decentralization of financial responsibility and authority to relatively autonomous local level governments, procurement reform in Indonesia is a centrally-driven effort. In this paper, we examine the extent to which procurement reform is translating into improvements in sub-national performance. Data on local government procurement expenditures point to an overall decline in the volume of procurement, especially in poorer districts. This paper uses qualitative case studies of procurement reform in six local governments and finds that local government leadership is associated with the uptake of reform. There is little evidence to suggest that procurement reform has been "demand''-led, since neither the private sector nor Civil Society Organizations (CSOs) have been active in advocating for procurement reform

Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania

Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete stages nor cell fusion events have been directly observed during parasite development in the vector, we have relied on a classical genetic analysis to determine if Leishmania has a true sexual cycle. Here, we used whole genome sequencing to follow the chromosomal inheritance patterns of experimental hybrids generated within and between different strains of L. major and L. infantum. We also generated and sequenced the first experimental hybrids in L. tropica. We found that in each case the parental somy and allele contributions matched the inheritance patterns expected under meiosis 97–99% of the time. The hybrids were equivalent to F1 progeny, heterozygous throughout most of the genome for the markers that were homozygous and different between the parents. Rare, non-Mendelian patterns of chromosomal inheritance were observed, including a gain or loss of somy, and loss of heterozygosity, that likely arose during meiosis or during mitotic divisions of the progeny clones in the fly or culture. While the interspecies hybrids appeared to be sterile, the intraspecies hybrids were able to produce backcross and outcross progeny. Analysis of 5 backcross and outcross progeny clones generated from an L. major F1 hybrid, as well as 17 progeny clones generated from backcrosses involving a natural hybrid of L. tropica, revealed genome wide patterns of recombination, demonstrating that classical crossing over occurs at meiosis, and allowed us to construct the first physical and genetic maps in Leishmania. Altogether, the findings provide strong evidence for meiosis-like sexual recombination in Leishmania, presenting clear opportunities for forward genetic analysis and positional cloning of important genes.</div

Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells

Leishmania major is the causative agent of the neglected tropical disease, cutaneous leishmaniasis. In the mouse, protective immunity to Leishmania is associated with inflammatory responses. Here, we assess the dynamics of the inflammatory responses at the lesion site during experimental long-term, low-dose intradermal infection of the ear, employing noninvasive imaging and genetically modified L. major Significant infiltrates of neutrophils and monocytes occurred at 1-4 d and 2-4 wk, whereas dermal macrophage and dendritic cell (DC) numbers were only slightly elevated in the first days. Quantitative whole-body bioluminescence imaging of myeloperoxidase activity and the quantification of parasite loads indicated that the Leishmania virulence factor, inhibitor of serine peptidase 2 (ISP2), is required to modulate phagocyte activation and is important for parasite survival at the infection site. ISP2 played a role in the control of monocyte, monocyte-derived macrophage, and monocyte-derived DC (moDC) influx, and was required to reduce iNOS expression in monocytes, monocyte-derived cells, and dermal DCs; the expression of CD80 in moDCs; and levels of IFN-γ in situ. Our findings indicate that the increased survival of L. major in the dermis during acute infection is associated with the down-regulation of inflammatory monocytes and monocyte-derived cells via ISP2.-Goundry, A., Romano, A., Lima, A. P. C. A., Mottram, J. C., Myburgh, E. Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis.

Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which Rodentibacter was specifically absent from ABX-treated hamsters, indicating this pathobiont may play a role in promoting disease progression. The results provide experimental support for antibiotic prophylaxis against secondary bacterial infections as an adjunct therapy in human VL patients

The mating competence of geographically diverse Leishmania major strains in their natural and unnatural sand fly vectors

Invertebrate stages of Leishmania are capable of genetic exchange during their extracellular growth and development in the sand fly vector. Here we explore two variables: the ability of diverse L. major strains from across its natural range to undergo mating in pairwise tests; and the timing of the appearance of hybrids and their developmental stage associations within both natural (Phlebotomus duboscqi) and unnatural (Lutzomyia longipalpis) sand fly vectors. Following co-infection of flies with parental lines bearing independent drug markers, doubly-drug resistant hybrid progeny were selected, from which 96 clonal lines were analyzed for DNA content and genotyped for parent alleles at 4-6 unlinked nuclear loci as well as the maxicircle DNA. As seen previously, the majority of hybrids showed '2n' DNA contents, but with a significant number of '3n' and one '4n' offspring. In the natural vector, 97% of the nuclear loci showed both parental alleles; however, 3% (4/150) showed only one parental allele. In the unnatural vector, the frequency of uniparental inheritance rose to 10% (27/275). We attribute this to loss of heterozygosity after mating, most likely arising from aneuploidy which is both common and temporally variable in Leishmania. As seen previously, only uniparental inheritance of maxicircle kDNA was observed. Hybrids were recovered at similar efficiencies in all pairwise crosses tested, suggesting that L. major lacks detectable 'mating types' that limit free genetic exchange. In the natural vector, comparisons of the timing of hybrid formation with the presence of developmental stages suggest nectomonads as the most likely sexually competent stage, with hybrids emerging well before the first appearance of metacyclic promastigotes. These studies provide an important perspective on the prevalence of genetic exchange in natural populations of L. major and a guide for experimental studies to understand the biology of mating

The History of Coast Salish ‘Woolly Dogs’ Revealed by Ancient Genomics and Indigenous Knowledge

Ancestral Coast Salish societies in the Pacific Northwest kept long-haired “woolly” dogs that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. Here, we analyze genomic and isotopic data from a preserved woolly dog pelt, “Mutton”, collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant pre-colonial ancestry postdating the onset of settler colonialism. We identify candidate genetic variants potentially linked with their unique woolly phenotype. We integrate these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance

The history of Coast Salish “woolly dogs” revealed by ancient genomics and Indigenous Knowledge

Ancestral Coast Salish societies in the Pacific Northwest kept long-haired “woolly dogs” that were bred and cared for over millennia. However, the dog wool–weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from “Mutton,” collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance

Replication Data for: Personnel Politics: Elections, Clientelistic Competition, and Teacher Hiring in Indonesia

What is the effect of increased electoral competition on patronage politics? If programmatic appeals are not credible, institutional reforms that move politics from an elite- to a mass-focused and more competitive environment increase patronage efforts. This leads to an overall surge and notable spike in discretionary state hiring in election years. We test this prediction in the context of Indonesia's decentralized education sector. We exploit the exogenous phasing in and timing of elections in Indonesian districts for causal identification. We find evidence for election-related increases in the number of contract teachers on local payrolls and increases in civil service teacher certifications, which dramatically increases salaries. These effects are particularly pronounced for districts in which the former authoritarian ruling party is in competition with new entrants

Replication data for: The Separation Plot: A New Visual Method for Evaluating the Fit of Binary Models

We present a visual method for assessing the predictive power of models with binary outcomes. This technique allows the analyst to evaluate model fit based upon the models' ability to consistently match high-probability predictions to actual occurrences of the event of interest, and low-probability predictions to non-occurrences of the event of interest. Unlike existing methods for assessing predictive power for logit and probit models such as Percent Correctly Predicted statistics, Brier scores and the ROC plot, our ``separation plot" has the advantage of producing a visual display that is informative and easy to explain to a general audience, while also remaining insensitive to the often arbitrary probability thresholds that are used to distinguish between predicted events and non-events. We demonstrate the effectiveness of this technique in building predictive models in a number of different areas of political research