596 research outputs found

    The global distribution and burden of dengue.

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    Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation

    Acquiring Tetanus After Hemorrhoid Banding and Other Gastrointestinal Procedures

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    Tetanus after hemorrhoidal banding is an extremely rare but serious complication of the procedure. We describe the second reported case of this complication and review the literature concerning tetanus after different gastrointestinal procedures. Although a rare complication, practicing physicians need to be aware of the clinical presentation of this deadly disease when encountered in at-risk patient populations. Such cases also reemphasize the importance of primary tetanus immunization and follow-up boosters for all vulnerable patients

    Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect

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    The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the potential for the spread of transgenes in vivo in the mammalian gastrointestinal tract. We demonstrate the ability of GM-strains of Bacteroides to survive thymine starvation and overcome it through the exchange of genetic material. We also provide evidence for horizontal gene transfer in the mammalian gastrointestinal tract resulting in transgene-carrying wild type bacteria. These findings sound a strong note of caution on the employment of live genetically modified bacteria for the delivery of biologics

    Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus

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    BACKGROUND: Autonomic nervous system (ANS) dysfunction is present in up to one third of patients with tetanus. The prognostic value of ANS dysfunction is known in severe tetanus but its value is not well established in mild to moderate tetanus. METHODS: Medical records of all patients admitted with tetanus at two academic tertiary care centers in Karachi, Pakistan were reviewed. The demographic, clinical and laboratory data was recorded and analyzed. ANS dysfunction was defined as presence of labile or persistent hypertension or hypotension and sinus tachycardia, tachyarrythmia or bradycardia on EKG. Patients were divided into two groups based on presence of ANS dysfunction (ANS group and non ANS group). Tetanus severity was classified on the basis of Ablett criteria. RESULTS: Ninety six (64 males; 32 females) patients were admitted with the diagnosis over a period of 10 years. ANS group had 31 (32%) patients while non ANS group comprised of 65 (68%) patients. Both groups matched for age, gender, symptom severity, use of tetanus immunoglobulin and antibiotics. Twelve patients in ANS group had mild to moderate tetanus (Ablett I and II) and 19 patients had severe/very severe tetanus (Ablett III and IV). Fifteen (50%) patients in ANS group required ventilation as compared to 28 (45%) in non-ANS group (p = 0.09). Fourteen (47%) patients died in ANS group as compared to 10 (15%) in non ANS group (p= 0.002). Out of those 14 patients died in ANS group, six patients had mild to moderate tetanus and eight patients had severe/ very severe tetanus. Major cause of death was cardiac arrhythmias (13/14; 93%) in ANS group and respiratory arrest (7/10; 70%) in non ANS group. Ten (33%) patients had complete recovery in ANS group while in non ANS group 35(48%) patients had complete recovery (p= 0.05). CONCLUSIONS: ANS dysfunction was present in one third of our tetanus population. 40% patients with ANS dysfunction had only mild to moderate tetanus. ANS dysfunction, irrespective of the need of mechanical ventilation or severity of tetanus, predicted poor outcome

    Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry

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    It is well known that R-symmetric models dramatically alleviate the SUSY flavor and CP problems. We study particular modifications of existing R-symmetric models which share the solution to the above problems, and have interesting consequences for electroweak baryogenesis and the Dark Matter (DM) content of the universe. In particular, we find that it is naturally possible to have a strongly first-order electroweak phase transition while simultaneously relaxing the tension with EDM experiments. The R-symmetry (and its small breaking) implies that the gauginos (and the neutralino LSP) are pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role in making the electroweak phase transition strongly first-order. The pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac particle during freeze-out, but like a Majorana particle for annihilation today and in scattering against nuclei, thus being consistent with current constraints. Assuming a standard cosmology, it is possible to simultaneously have a strongly first-order phase transition conducive to baryogenesis and have the LSP provide the full DM relic abundance, in part of the allowed parameter space. However, other possibilities for DM also exist, which are discussed. It is expected that upcoming direct DM searches as well as neutrino signals from DM annihilation in the Sun will be sensitive to this class of models. Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure

    Patients’ preferences for osteoporosis drug treatment: a discrete choice experiment

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    Summary: Active case finding for osteoporosis is used to identify patients at high fracture risk who may benefit from preventive drug treatment. We investigated the relative weight that women place on various aspects of preventive drugs in a discrete choice experiment. Our patients said they were prepared to take preventive drugs even if side effects were expected. Int
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