Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416

Space Efficient Breadth-First and Level Traversals of Consistent Global States of Parallel Programs

Enumerating consistent global states of a computation is a fundamental problem in parallel computing with applications to debug- ging, testing and runtime verification of parallel programs. Breadth-first search (BFS) enumeration is especially useful for these applications as it finds an erroneous consistent global state with the least number of events possible. The total number of executed events in a global state is called its rank. BFS also allows enumeration of all global states of a given rank or within a range of ranks. If a computation on n processes has m events per process on average, then the traditional BFS (Cooper-Marzullo and its variants) requires $\mathcal{O}(\frac{m^{n-1}}{n})$ space in the worst case, whereas ou r algorithm performs the BFS requires $\mathcal{O}(m^2n^2)$ space. Thus, we reduce the space complexity for BFS enumeration of consistent global states exponentially. and give the first polynomial space algorithm for this task. In our experimental evaluation of seven benchmarks, traditional BFS fails in many cases by exhausting the 2 GB heap space allowed to the JVM. In contrast, our implementation uses less than 60 MB memory and is also faster in many cases

Roughening of the (1+1) interfaces in two-component surface growth with an admixture of random deposition

We simulate competitive two-component growth on a one dimensional substrate of $L$ sites. One component is a Poisson-type deposition that generates Kardar-Parisi-Zhang (KPZ) correlations. The other is random deposition (RD). We derive the universal scaling function of the interface width for this model and show that the RD admixture acts as a dilatation mechanism to the fundamental time and height scales, but leaves the KPZ correlations intact. This observation is generalized to other growth models. It is shown that the flat-substrate initial condition is responsible for the existence of an early non-scaling phase in the interface evolution. The length of this initial phase is a non-universal parameter, but its presence is universal. In application to parallel and distributed computations, the important consequence of the derived scaling is the existence of the upper bound for the desynchronization in a conservative update algorithm for parallel discrete-event simulations. It is shown that such algorithms are generally scalable in a ring communication topology.Comment: 16 pages, 16 figures, 77 reference

Synchronization Landscapes in Small-World-Connected Computer Networks

Motivated by a synchronization problem in distributed computing we studied a simple growth model on regular and small-world networks, embedded in one and two-dimensions. We find that the synchronization landscape (corresponding to the progress of the individual processors) exhibits Kardar-Parisi-Zhang-like kinetic roughening on regular networks with short-range communication links. Although the processors, on average, progress at a nonzero rate, their spread (the width of the synchronization landscape) diverges with the number of nodes (desynchronized state) hindering efficient data management. When random communication links are added on top of the one and two-dimensional regular networks (resulting in a small-world network), large fluctuations in the synchronization landscape are suppressed and the width approaches a finite value in the large system-size limit (synchronized state). In the resulting synchronization scheme, the processors make close-to-uniform progress with a nonzero rate without global intervention. We obtain our results by ``simulating the simulations", based on the exact algorithmic rules, supported by coarse-grained arguments.Comment: 20 pages, 22 figure

The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria

The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC). The rs867186-GG genotype was more frequent in CC (4.1%) than SM (0.6%, P = 0.002). The rs867186-G variant was associated with increased sEPCR levels and sEPCR was lower in children with SM than CC (P < 0.001). Among SM children, those who had a second SM episode showed a trend toward lower plasma sEPCR both at initial admission and at 6-month follow-up compared to those without repeated SM (P = 0.06 for both). The study findings support a role for sEPCR in severe malaria pathogenesis and emphasize a distinct role of sEPCR in malaria as compared to other infectious diseases

A comparative study on the functional outcome of intertrochanteric fractures treated by proximal femoral nailing or dynamic hip screw fixation

Background: Intertrochanteric fractures are one of the commonly occurring injuries in elderly patients and are high among females and those with osteoporosis. They were treated with either dynamic hip screw (DHS) fixation or proximal femoral nailing (PFNA2) here at our institution. The study was conducted in order to find which method of surgical fixation has better functional outcome.  Methods: Total 96 patients of intertrochanteric fractures admitted during the study period of November 2017 to April 2019 were included for the study. These patients were randomly divided into two groups; DHS was used as implant in group1 and PFNA2 in group 2. Postoperatively patients were followed up after 1 month, 3months and 6 months of the surgery and were assessed using Harris hip score.Results: Harris hip score was higher with PFNA2 group compared to DHS group in all follow-ups. In unstable fractures DHS group had poor outcome compared to PFNA2. Radiological union occurred in 27.1 % cases by 3 months and 72.9% cases by 6 months with DHS whereas 70.8% and 97.9% respectively with PFNA2.  Conclusions: PFNA2 gives a better functional outcome when compared to DHS. Even though DHS gives good functional outcome in stable fractures it is not so in the case of unstable fractures. The radiological union also is faster with proximal femoral nailing. Hence in our opinion PFNA2 can be the better fixation device compared to DHS especially in unstable fractures.

The Verifying Compiler: A Grand Challenge for Computing Research

Abstract. This contribution proposes a set of criteria that distinguish a grand challenge in science or engineering from the many other kinds of short-term or long-term research problems that engage the interest of scientists and engineers. As an example drawn from Computer Science, it revives an old challenge: the construction and application of a verifying compiler that guarantees correctness of a program before running it. Introduction. The primary purpose of the formulation and promulgation of a grand challenge is the advancement of science or engineering. A grand challenge represents a commitment by a significant section of the research community to work together towards a common goal, agreed to be valuable and achievable by a team effort within a predicted timescale. The challenge is formulated by th

The extent, nature and distribution of child poverty in India

Despite a long history, research on poverty has only relatively recently examined the issue of child poverty as a distinct topic of concern. This article examines how child poverty and well-being are now conceptualized, defined and measured, and presents a portrait of child poverty in India by social and cultural groups, and by geographic area. In December 2006, the UN General Assembly adopted a definition of child poverty which noted that children living in poverty were deprived of (among other things) nutrition, water and sanitation facilities, access to basic health care services, shelter and education. The definition noted that while poverty hurts every human being ‘it is most threatening and harmful to children, leaving them unable to enjoy their rights, to reach their full potential and to participate as full members of the society’. Researchers have developed age-specific and gender-sensitive indicators of deprivation which conform to the UN definition of child poverty and which can be used to examine the extent and nature of child poverty in low and middle-income countries. These new methods have ‘transformed the way UNICEF and many of its partners both understood and measured the poverty suffered by children’ (UNICEF, 2009). This article uses these methods and presents results of child poverty in India based on nationally representative household survey data for India

Distributed Consensus, Revisited

We provide a novel model to formalize a well-known algorithm, by Chandra and Toueg, that solves Consensus among asynchronous distributed processes in the presence of a particular class of failure detectors (Diamond S or, equivalently, Omega), under the hypothesis that only a minority of processes may crash. The model is defined as a global transition system that is unambigously generated by local transition rules. The model is syntax-free in that it does not refer to any form of programming language or pseudo code. We use our model to formally prove that the algorithm is correct

The Benjamin H. Kean Travel Fellowship in Tropical Medicine: Assessment of Impact at 15 Years

Abstract. The Benjamin H. Kean Fellowship in Tropical Medicine is an American Society of Tropical Medicine and Hygiene initiative that provides medical students with funding for international clinical or research experiences lasting at least 1 month. Of the 175 Kean fellows from 1998 to 2013, 140 had current available e-mails, and 70 of the 140 (50%) responded to a survey about their fellowship experience. Alumni indicated that the Kean Fellowship had a high impact on their career plans with regard to preparation for (N = 65, 94.2%) and inspiration to pursue (N = 59, 88.1%) a career in tropical medicine and global health. Continued involvement in tropical medicine and global health was common: 52 alumni (74.3%) were currently working in tropical medicine or global health, 49 (71.0%) had done so in the interim between the Kean fellowship and their current position; and 17 of 19 Kean fellows (89.4%) who had completed all medical training and were now in professional practice continued to work in tropical medicine and global health. Alumni had been highly productive academically, publishing a total of 831 PubMed-indexed manuscripts, almost all on tropical medicine or global health topics, in the period between their fellowship year and 2013. Alumni reported strengths of the fellowship including funding, networking, and flexibility, and suggested that more networking and career mentoring would enhance the program. The Benjamin H. Kean fellowship program has been highly successful at inspiring and fostering ongoing work by trainees in tropical medicine and global health