Effects of experience and commercialisation on survival in Himalayan mountaineering: retrospective cohort study

Objectives To determine whether previous Himalayan experience is associated with a decreased risk of climbing death, and whether mountaineers participating in commercial expeditions differ in their risk of death relative to those participating in traditional climbs

International Variation in Screening Mammography Interpretations in Community-Based Programs

Variations in mammography interpretations may have important clinical and economic implications. To evaluate international variability in mammography interpretation, we analyzed published reports from community-based screening programs from around the world

Direct observation of incommensurate magnetism in Hubbard chains

The interplay between magnetism and doping is at the origin of exotic strongly correlated electronic phases and can lead to novel forms of magnetic ordering. One example is the emergence of incommensurate spin-density waves with a wave vector that does not match the reciprocal lattice. In one dimension this effect is a hallmark of Luttinger liquid theory, which also describes the low energy physics of the Hubbard model. Here we use a quantum simulator based on ultracold fermions in an optical lattice to directly observe such incommensurate spin correlations in doped and spin-imbalanced Hubbard chains using fully spin and density resolved quantum gas microscopy. Doping is found to induce a linear change of the spin-density wave vector in excellent agreement with Luttinger theory predictions. For non-zero polarization we observe a decrease of the wave vector with magnetization as expected from the Heisenberg model in a magnetic field. We trace the microscopic origin of these incommensurate correlations to holes, doublons and excess spins which act as delocalized domain walls for the antiferromagnetic order. Finally, when inducing interchain coupling we observe fundamentally different spin correlations around doublons indicating the formation of a magnetic polaron

Caregiver Recognition of Childhood Diarrhea, Care Seeking Behaviors and Home Treatment Practices in Rural Burkina Faso: A Cross-Sectional Survey

Introduction: To design effective national diarrhea control programs, including oral rehydration solution (ORS) and therapeutic zinc supplementation, information is needed on local perceptions of illness, external care seeking behaviors, and home treatment practices. Methods: A cross-sectional, community-based household survey was conducted in the Orodara Health District, Burkina Faso. Caregivers of 10,490 children,27 months were interviewed to assess child diarrhea prevalence and related car

Ethics and Nanopharmacy: Value Sensitive Design of New Drugs

Although applications are being developed and have reached the market, nanopharmacy to date is generally still conceived as an emerging technology. Its concept is ill-defined. Nanopharmacy can also be construed as a converging technology, which combines features of multiple technologies, ranging from nanotechnology to medicine and ICT. It is still debated whether its features give rise to new ethical issues or that issues associated with nanopharma are merely an extension of existing issues in the underlying fields. We argue here that, regardless of the alleged newness of the ethical issues involved, developments occasioned by technological advances affect the roles played by stakeholders in the field of nanopharmacy to such an extent that this calls for a different approach to responsible innovation in this field. Specific features associated with nanopharmacy itself and features introduced to the associated converging technologies- bring about a shift in the roles of stakeholders that call for a different approach to responsibility. We suggest that Value Sensitive Design is a suitable framework to involve stakeholders in addressing moral issues responsibly at an early stage of development of new nanopharmaceuticals

17-allyamino-17-demethoxygeldanamycin treatment results in a magnetic resonance spectroscopy-detectable elevation in choline-containing metabolites associated with increased expression of choline transporter SLC44A1 and phospholipase A2

Abstract Introduction 17-allyamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is currently in clinical trials in breast cancer. However, 17-AAG treatment often results in inhibition of tumor growth rather than shrinkage, making detection of response a challenge. Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) are noninvasive imaging methods than can be used to monitor metabolic biomarkers of drug-target modulation. This study set out to examine the MRS-detectable metabolic consequences of Hsp90 inhibition in a breast cancer model. Methods MCF-7 breast cancer cells were investigated, and MRS studies were performed both on live cells and on cell extracts. 31P and 1H MRS were used to determine total cellular metabolite concentrations and 13C MRS was used to probe the metabolism of [1,2-13C]-choline. To explain the MRS metabolic findings, microarray and RT-PCR were used to analyze gene expression, and in vitro activity assays were performed to determine changes in enzymatic activity following 17-AAG treatment. Results Treatment of MCF-7 cells with 17-AAG for 48 hours caused a significant increase in intracellular levels of choline (to 266 ± 18% of control, P = 0.05) and phosphocholine (PC; to 181 ± 10% of control, P = 0.001) associated with an increase in expression of choline transporter SLC44A1 and an elevation in the de novo synthesis of PC. We also detected an increase in intracellular levels of glycerophosphocholine (GPC; to 176 ± 38% of control, P = 0.03) associated with an increase in PLA2 expression and activity. Conclusions This study determined that in the MCF-7 breast cancer model inhibition of Hsp90 by 17-AAG results in a significant MRS-detectable increase in choline, PC and GPC, which is likely due to an increase in choline transport into the cell and phospholipase activation. 1H MRSI can be used in the clinical setting to detect levels of total choline-containing metabolite (t-Cho, composed of intracellular choline, PC and GPC). As Hsp90 inhibitors enter routine clinical use, t-Cho could thus provide an easily detectable, noninvasive metabolic biomarker of Hsp90 inhibition in breast cancer patients