Prognostic indicators of early and late death in children admitted to district hospital in Kenya: cohort study

OBJECTIVES: To identify clinical indicators of immediate, early, and late mortality in children at admission to a sub-Saharan district hospital and to develop prognostic scores. DESIGN: Prospective cohort study. SETTING: One district hospital in Kenya. PARTICIPANTS: Children aged over 90 days admitted to hospital from 1 July 1998 to 30 June 2001. MAIN OUTCOME MEASURES: Prognostic indicators of mortality. RESULTS: Of 8091 children admitted up to 1 June 2000, 436 (5%) died. Sixty (14%) died within four hours after admission (immediate), 193 (44%) after 4-48 hours (early), and 183 (42%) after 48 hours (late). There were marked differences in the clinical features associated with immediate, early, and late death. Seven indicators (neurological status, respiratory distress (subcostal indrawing or deep breathing), nutritional status (wasting or kwashiorkor), severe anaemia, jaundice, axillary temperature, and length of history) were included in simplified prognostic scores. Data from 4802 children admitted from 1 July 2000 to 30 June 2001 were used to validate the scores. For simplified prognostic scores the areas under the receiver operating characteristic curves were 0.93 (95% confidence interval 0.92 to 0.94), 0.82 (0.80 to 0.83), and 0.82 (0.81 to 0.84) for immediate, early, and late death, respectively. CONCLUSION: In children admitted to a sub-Saharan hospital, the prognostic indicators of early and late deaths differ but a small number of simple clinical signs predict outcome wel

Native IYG: Improving Psychosocial Protective Factors for HIV/STI and Teen Pregnancy Prevention among Youth in American Indian/Alaska Native Communities

Background: Few HIV/STI and pregnancy prevention programs for youth in American Indian and Alaska Native (AI/AN) communities have been rigorously evaluated despite sexual health disparities in this population. This study reports the evaluation of a culturally adapted Internet-based HIV/STI and pregnancy prevention program for AI/AN youth, Native It’s Your Game (Native IYG). Methods: A randomized study was conducted with 523 youth (12 to 14 years old), recruited from 25 tribal sites in Alaska, Arizona, and the Pacific Northwest. Participants were surveyed at baseline and upon completion of treatment or comparison interventions. Multivariable linear regression models were used to assess impact on short term psychosocial determinants of sexual initiation. Results: A sample of 402 intervention (n=290) and comparison (n=112) youth completed the post-intervention survey (76.9% retention) from 1 to 462 days post-baseline (mean = 114, SD = ±96.67). Participants were 55.5% female, mean age of 13.0 (± 0.97) years with 86.1% self-reporting as AI/AN. Reasons not to have sex, STI knowledge, condom knowledge, condom availability self-efficacy, and condom use self-efficacy were significantly impacted (all P ≤ .01). Limitations included variability in intervention exposure and time between data collection time points. Conclusions: Native IYG demonstrated efficacy to impact short-term psychosocial determinants of sexual behavior in a sample of predominantly AI/AN middle school youth

Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

Preliminary genetic evidence of two different populations of Opisthorchis viverrini in Lao PDR

Opisthorchis viverrini is a major public health concern in Southeast Asia. Various reports have suggested that this parasite may represent a species complex, with genetic structure in the region perhaps being dictated by geographical factors and different species of intermediate hosts. We used four microsatellite loci to analyze O. viverrini adult worms originating from six species of cyprinid fish in Thailand and Lao PDR. Two distinct O. viverrini populations were observed. In Ban Phai, Thailand, only one subgroup occurred, hosted by two different fish species. Both subgroups occurred in fish from That Luang, Lao PDR, but were represented to very different degrees among the fish hosts there. Our data suggest that, although geographical separation is more important than fish host specificity in influencing genetic structure, it is possible that two species of Opisthorchis, with little interbreeding, are present near Vientiane in Lao PDR

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Single-Scale Natural SUSY

We consider the prospects for natural SUSY models consistent with current data. Recent constraints make the standard paradigm unnatural so we consider what could be a minimal extension consistent with what we now know. The most promising such scenarios extend the MSSM with new tree-level Higgs interactions that can lift its mass to at least 125 GeV and also allow for flavor-dependent soft terms so that the third generation squarks are lighter than current bounds on the first and second generation squarks. We argue that a common feature of almost all such models is the need for a new scale near 10 TeV, such as a scale of Higgsing or confinement of a new gauge group. We consider the question whether such a model can naturally derive from a single mass scale associated with supersymmetry breaking. Most such models simply postulate new scales, leaving their proximity to the scale of MSSM soft terms a mystery. This coincidence problem may be thought of as a mild tuning, analogous to the usual mu problem. We find that a single mass scale origin is challenging, but suggest that a more natural origin for such a new dynamical scale is the gravitino mass, m_{3/2}, in theories where the MSSM soft terms are a loop factor below m_{3/2}. As an example, we build a variant of the NMSSM where the singlet S is composite, and the strong dynamics leading to compositeness is triggered by masses of order m_{3/2} for some fields. Our focus is the Higgs sector, but our model is compatible with a light stop (with the other generation squarks heavy, or with R-parity violation or another mechanism to hide them from current searches). All the interesting low-energy mass scales, including linear terms for S playing a key role in EWSB, arise dynamically from the single scale m_{3/2}. However, numerical coefficients from RG effects and wavefunction factors in an extra dimension complicate the otherwise simple story.Comment: 32 pages, 3 figures; version accepted by JHE

Finite Temperature Aging Holography

We construct the gravity background which describes the dual field theory with aging invariance. We choose the decay modes of the bulk scalar field in the internal spectator direction to obtain the dissipative behavior of the boundary correlation functions of the dual scalar fields. In particular, the two-time correlation function at zero temperature has the characteristic features of the aging system: power law decay, broken time translation and dynamical scaling. We also construct the black hole backgrounds with asymptotic aging invariance. We extensively study characteristic behavior of the finite temperature two-point correlation function via analytic and numerical methods.Comment: 38 pages and 5 figures, expanded discussions on correlator, one mistake is fixed, modified discussion on shear viscosity, to appear in JHE

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg