Prevalence of asymptomatic malaria infections in selected military camps in Tanzania

Background: Despite a decrease in malaria burden reported between 2000 and 2015, an increasing trend of malaria transmission has been recently reported in some endemic countries including Tanzania. Periodic monitoring to identify pocket areas for asymptomatic Plasmodium falciparum infection   is vital for malaria elimination efforts. The objective of this study was to determine prevalence of asymptomatic malaria infections among military recruits in selected camps in Tanzania. Methods: A cross-sectional study was conducted in 2015 at four military camps (Bulombora, Mgambo, Ruvu, and Rwamkoma) of National Service located in regions with varying malaria endemicity in Tanzania.  Finger prick blood samples collected from asymptomatic military recruits who had been at the camps for over two months were simultaneously tested using microscopy and malaria rapid diagnostic tests (mRDTs) to detect malaria parasite infections. Results: Malaria parasite prevalence among asymptomatic recruits was 20.3% and 19.4% by microscopy and mRDT respectively. There was moderate agreement (Kappa=0.724) between microscopy and mRDT test results. A significant difference (p<0.001) of malaria parasite prevalence among the four study camps was observed; ranging from 1.9% in Bulombora to 39.4% in Rwamkoma. The geometric mean parasite density was 11,053 asexual parasites/µl and most recruits (56.8%) had 200 to 1999 asexual parasites/µl. P. falciparum was the predominant (99.2%) malaria parasite species. Conclusion: Our study found high prevalence of asymptomatic malaria infections among military recruits in the selected camps, and this varied from one camp to another. The study has highlighted that public residence institutions such as military camps can be potential hotspots for malaria infection and therefore should not be skipped in routine national malaria surveillance system for monitoring trends of infection

Route map for the discovery and pre-clinical development of new drugs and treatments for cutaneous leishmaniasis.

Although there have been significant advances in the treatment of visceral leishmaniasis (VL) and several novel compounds are currently in pre-clinical and clinical development for this manifestation of leishmaniasis, there have been limited advances in drug research and development (R & D) for cutaneous leishmaniasis (CL). Here we review the need for new treatments for CL, describe in vitro and in vivo assays, models and approaches taken over the past decade to establish a pathway for the discovery, and pre-clinical development of new drugs for CL. These recent advances include novel mouse models of infection using bioluminescent Leishmania, the introduction of PK/PD approaches to skin infection, and defined pre-clinical candidate profiles

Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis.

OBJECTIVES: Drugs for Neglected Diseases initiative (DNDi) has identified three chemical lead series, the nitroimidazoles, benzoxaboroles and aminopyrazoles, as innovative treatments for visceral leishmaniasis. The leads discovered using phenotypic screening, were optimised following disease- and compound-specific criteria. Several leads of each series were progressed and preclinical drug candidates have been nominated. Here we evaluate the efficacy of the lead compounds of each of these three chemical classes in in vitro and in vivo models of cutaneous leishmaniasis. METHODS: The in vitro activity of fifty-five compounds was evaluated against the intracellular amastigotes of L. major, L. aethiopica, L. amazonensis, L. panamensis, L. mexicana and L. tropica. The drugs demonstrating potent activity (EC50 < 5 μM) against at least 4 of 6 species were subsequently evaluated in vivo in different L. major - BALB/c mouse models using a 5 or 10-day treatment with either the oral or topical formulations. Efficacy was expressed as lesion size (measured daily using callipers), parasite load (by quantitative PCR - DNA) and bioluminescence signal reduction relative to the untreated controls. RESULTS: The selected drug compounds (3 nitroimidazoles, 1 benzoxaborole and 3 aminopyrazoles) showed consistent and potent activity across a range of Leishmania species that are known to cause CL with EC50 values ranging from 0.29 to 18.3 μM. In all cases, this potent in vitro antileishmanial activity translated into high levels of efficacy with a linear dose-response against murine CL. When administered at 50 mg/kg/day, DNDI-0690 (nitroimidazole), DNDI-1047 (aminopyrazole) and DNDI-6148 (benzoxaborole) all resulted in a significant lesion size reduction (no visible nodule) and an approximate 2-log-fold reduction of the parasite load as measured by qPCR compared to the untreated control. CONCLUSIONS: The lead compounds DNDI-0690, DNDI-1047 and DNDI-6148 showed excellent activity across a range of Leishmania species in vitro and against L. major in mice. These compounds offer novel potential drugs for the treatment of CL

10 kW SOFC Power System Commercialization

Cummins Power Generation (CPG) as the prime contractor and SOFCo-EFS Holdings LLC (SOFCo), as their subcontractor, teamed under the Solid-state Energy Conversion Alliance (SECA) program to develop 3-10kW solid oxide fuel cell systems for use in recreational vehicles, commercial work trucks and stand-by telecommunications applications. The program goal is demonstration of power systems that meet commercial performance requirements and can be produced in volume at a cost of $400/kW. This report summarizes the team's activities during the seventh six-month period (July-December 2005) of the four-year Phase I effort. While there has been significant progress in the development of the SOFC subsystems that can support meeting the program Phase 1 goals, the SOFCo ceramic stack technology has progressed significantly slower than plan and CPG consider it unlikely that the systemic problems encountered will be overcome in the near term. SOFCo has struggled with a series of problems associated with inconsistent manufacturing, inadequate cell performance, and the achievement of consistent, durable, low resistance inter-cell connections with reduced or no precious materials. A myriad of factors have contributed to these problems, but the fact remains that progress has not kept pace with the SECA program. A contributing factor in SOFCo's technical difficulties is attributed to their significantly below plan industry cost share spending over the last four years. This has resulted in a much smaller SOFC stack development program, has contributed to SOFCo not being able to aggressively resolve core issues, and clouds their ability to continue into a commercialization phase. In view of this situation, CPG has conducted an independent assessment of the state-of-the-art in planar SOFC's stacks and have concluded that alternative technology exists offering the specific performance, durability, and low cost needed to meet the SECA objectives. We have further concluded that there is insufficient evidence to reliably predict that SOFCo will be able to achieve the SECA performance and cost goals on a schedule consistent with SECA or CPG commercialization goals. CPG believes SOFCo have made a good faith effort consistent with the available resources, but have repeatedly fallen short of achieving the programs scheduled targets. CPG has therefore initiated a process of application for extension of Phase 1 of our SECA program with the intent of transitioning to an alternative stack supplier with more mature SOFC technology, and demonstrating a system meeting the SECA Phase 1 goals by the end of calendar 2006. We have identified an alternative supplier and will be reporting the progress on transition and program planning in monthly technical reports, reviews, and in the next semiannual report

Eosinophils in glioblastoma biology

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Cummins Power Generation SECA Phase 1

The following report documents the progress of the Cummins Power Generation (CPG) SECA Phase 1 SOFC development and final testing under the U.S. Department of Energy Solid State Energy Conversion Alliance (SECA) contract DE-FC26-01NT41244. This report overviews and summarizes CPG and partner research development leading to successful demonstration of the SECA Phase 1 objectives and significant progress towards SOFC commercialization. Significant Phase 1 Milestones: (1) Demonstrated: (a) Operation meeting Phase 1 requirements on commercial natural gas. (b) LPG and Natural Gas CPOX fuel reformers. (c) SOFC systems on dry CPOX reformate. (c) Steam reformed Natural Gas operation. (d) Successful start-up and shut-down of SOFC system without inert gas purge. (e) Utility of stack simulators as a tool for developing balance of plant systems. (2) Developed: (a) Low cost balance of plant concepts and compatible systems designs. (b) Identified low cost, high volume components for balance of plant systems. (c) Demonstrated high efficiency SOFC output power conditioning. (d) Demonstrated SOFC control strategies and tuning methods. The Phase 1 performance test was carried out at the Cummins Power Generation facility in Minneapolis, Minnesota starting on October 2, 2006. Performance testing was successfully completed on January 4, 2007 including the necessary steady-state, transient, efficiency, and peak power operation tests

Diesel Fueled SOFC for Class 7/Class 8 On-Highway Truck Auxiliary Power

The following report documents the progress of the Cummins Power Generation (CPG) Diesel Fueled SOFC for Class 7/Class 8 On-Highway Truck Auxiliary Power (SOFC APU) development and final testing under the U.S. Department of Energy (DOE) Energy Efficiency and Renewable Energy (EERE) contract DE-FC36-04GO14318. This report overviews and summarizes CPG and partner development leading to successful demonstration of the SOFC APU objectives and significant progress towards SOFC commercialization. Significant SOFC APU Milestones: Demonstrated: Operation meeting SOFC APU requirements on commercial Ultra Low Sulfur Diesel (ULSD) fuel. SOFC systems operating on dry CPOX reformate. Successful start-up and shut-down of SOFC APU system without inert gas purge. Developed: Low cost balance of plant concepts and compatible systems designs. Identified low cost, high volume components for balance of plant systems. Demonstrated efficient SOFC output power conditioning. Demonstrated SOFC control strategies and tuning methods

10kW SOFC POWER SYSTEM COMMERCIALIZATION

Participants in the SECA 10 kW SOFC Power System Commercialization project include Cummins Power Generation (CPG), the power generation arm of Cummins, Inc., SOFCo-EFS Holdings, LLC (formerly McDermott Technology, Inc.), the fuel cell and fuel processing research and development arm of McDermott International Inc., M/A-COM, the Multi-Layer Ceramics (MLC) processing and manufacturing arm of Tyco Electronics, and Ceramatec, a materials technology development company. CPG functions in the role of prime contractor and system integrator. SOFCo-EFS is responsible for the design and development of the hot box assembly, including the SOFC stack(s), heat exchanger(s), manifolding, and fuel reformer. M/A-COM and SOFCo-EFS are jointly responsible for development of the MLC manufacturing processes, and Ceramatec provides technical support in materials development. In October 2002, McDermott announced its intention to cease operations at McDermott Technology, Inc. (MTI) as of December 31, 2002. This decision was precipitated by several factors, including the announced tentative settlement of the B&amp;W Bankruptcy which would result in all of the equity of B&amp;W being conveyed to a trust, thereby eliminating McDermott's interest in the company, and the desire to create a separate fuel cell entity to facilitate its commercial development. The new fuel cell entity is named SOFCo-EFS Holdings, LLC. All of McDermott's solid oxide fuel cell and fuel processing work will be conducted by SOFCo-EFS, using personnel previously engaged in that work. SOFCo-EFS will continue to be located in the Alliance, OH facility and use the existing infrastructure and test facilities for its activities. While the effort needed to accomplish this reorganization has detracted somewhat from SOFCo's efficiency during the fourth quarter, we believe the improved focus on the core fuel cell and fuel reformation resulting from the reorganization will have a positive impact on the SECA project in the long run. The program is organized into three developmental periods. In Phase 1 the team will develop and demonstrate a proof-of-concept prototype design and develop the manufacturing plan to substantiate potential producibility at a target cost level of $800/kW factory manufacturing cost. Phase 2 will further develop the design and reduce the projected manufacturing cost to$600 kW. Depending on an assessment of the maturity of the technology at the end of Phase 1, Phase 2 may be structured and supplemented to develop a limited production capability. Finally, in Phase 3, a full Value Package Introduction (VPI) Program will be integrated with the SECA program to develop a mass-producible design, with a factory manufacturing cost of $400/kW, and with full cross-functional support for unrestricted commercial sales

GLUT1-induced cFLIP expression promotes proliferation and prevents apoptosis in vascular smooth muscle cells

Enhanced expression of the facilitative glucose transporter, GLUT1, has been shown to inhibit apoptosis in several cell systems including vascular smooth muscle cells (VSMCs). A decrease in apoptosis could lead to increased VSMC numbers in neointimal and medial arterial layers under several pathologic conditions. The hypothesis underlying these studies is that GLUT1 induces expression of antiapoptotic and prosurvival genes that increase VSMC survival. Transcriptomic analysis of A7r5 VSMCs, in which GLUT1 was acutely overexpressed, showed a 2.14-fold increase in c-FLICE inhibitory protein (cFLIP), which promotes cellular growth and prevents apoptosis through caspase 8 binding. We confirmed that overexpression of GLUT1 induced mRNA and protein expression of both the long and short isoforms of cFLIP (cFLIPL and cFLIPS) in primary and stable immortalized VSMC lines as well as in aortas from GLUT1 transgenic mice. Increased GLUT1 reduced VSMC death by more than twofold after serum withdrawal, as evidenced by decreased caspase 3 activity and Trypan blue exclusion studies. GLUT1 overexpression resulted in a greater than twofold increase in proliferating cell nuclear antigen expression and live cell numbers, consistent with augmented VSMC proliferation. Lentiviral knockdown of cFLIPL showed that cFLIPL was necessary for the proproliferative and antiapoptotic effects of GLUT1 overexpression. Taken together, these data suggest that GLUT1 induction of cFLIPL expression augments proliferation and prevents apoptosis in VSMCs