The effect of distance on observed mortality, childhood pneumonia and vaccine efficacy in rural Gambia.

We investigated whether straight-line distance from residential compounds to healthcare facilities influenced mortality, the incidence of pneumonia and vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for pneumonia was conducted on 6938 children living in the catchment areas of the two largest healthcare facilities. Deaths were monitored by three-monthly home visits. Children living >5 km from the two largest healthcare facilities had a 2·78 [95% confidence interval (CI) 1·74-4·43] times higher risk of all-cause mortality compared to children living within 2 km of these facilities. The observed rate of clinical and radiological pneumonia was lower in children living >5 km from these facilities compared to those living within 2 km [rate ratios 0·65 (95% CI 0·57-0·73) and 0·74 (95% CI 0·55-0·98), respectively]. There was no association between distance and estimated pneumococcal vaccine efficacy. Geographical access to healthcare services is an important determinant of survival and pneumonia in children in rural Gambia

Challenging Perceptions of Disability through Performance Poetry Methods: The "Seen but Seldom Heard" Project.

This paper considers performance poetry as a method to explore lived experiences of disability. We discuss how poetic inquiry used within a participatory arts-based research framework can enable young people to collectively question society’s attitudes and actions towards disability. Poetry will be considered as a means to develop a more accessible and effective arena in which young people with direct experience of disability can be empowered to develop new skills that enable them to tell their own stories. Discussion of how this can challenge audiences to critically reflect upon their own perceptions of disability will also be developed

Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer.

Background There are no established molecular biomarkers for patients with breast cancer receiving combination endocrine and CDK4/6 inhibitor (CDK4/6i). We aimed to determine whether genomic markers in circulating tumor DNA (ctDNA) can identify patients at higher risk of early progression on fulvestrant therapy with or without palbociclib, a CDK4/6i.Methods PALOMA-3 was a phase III, multicenter, double-blind randomized controlled trial of palbociclib plus fulvestrant (n = 347) vs placebo plus fulvestrant (n = 174) in patients with endocrine-pretreated estrogen receptor-positive (ER+) breast cancer. Pretreatment plasma samples from 459 patients were analyzed for mutations in 17 genes, copy number in 14 genes, and circulating tumor fraction. Progression-free survival (PFS) was compared in patients with circulating tumor fraction above or below a prespecified cutoff of 10% and with or without a specific genomic alteration. All statistical tests were 2-sided.Results Patients with high ctDNA fraction had worse PFS on both palbociclib plus fulvestrant (hazard ratio [HR] = 1.62, 95% confidence interval [CI] = 1.17 to 2.24; P = .004) and placebo plus fulvestrant (HR = 1.77, 95% CI = 1.21 to 2.59; P = .004). In multivariable analysis, high-circulating tumor fraction was associated with worse PFS (HR = 1.20 per 10% increase in tumor fraction, 95% CI = 1.09 to 1.32; P < .001), as was TP53 mutation (HR = 1.84, 95% CI = 1.27 to 2.65; P = .001) and FGFR1 amplification (HR = 2.91, 95% CI = 1.61 to 5.25; P < .001). No interaction with treatment randomization was observed.Conclusions Pretreatment ctDNA identified a group of high-risk patients with poor clinical outcome despite the addition of CDK4/6 inhibition. These patients might benefit from inclusion in future trials of escalating treatment, with therapies that may be active in these genomic contexts

Report of the Beyond the MSSM Subgroup for the Tevatron Run II SUSY/Higgs Workshop

There are many low-energy models of supersymmetry breaking parameters which are motivated by theoretical and experimental considerations. Here, we discuss some of the lesser-known theories of low-energy supersymmetry, and outline their phenomenological consequences. In some cases, these theories have more gauge symmetry or particle content than the Minimal Supersymmetric Standard Model. In other cases, the parameters of the Lagrangian are unusual compared to commonly accepted norms (e.g., Wino LSP, heavy gluino LSP, light gluino, etc.). The phenomenology of supersymmetry varies greatly between the different models. Correspondingly, particular aspects of the detectors assume greater or lesser importance. Detection of supersymmetry and the determination of all parameters may well depend upon having the widest possible view of supersymmetry phenomenology.Comment: 78 pages, 49 figures, to appear in the Proceedings of the Tevatron Run II SUSY/Higgs Workshop. Editor: J. F. Gunion; BTMSSM Convenors: M. Chertok, H. Dreiner, G. Landsberg, J. F. Gunion, J.D. Well

Correlates of Complete Childhood Vaccination in East African Countries.

Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority

Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations

Limited sensitivity of existing assays has prevented investigation of whether Adriamycin–DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin–DNA adducts/104 bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin–DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [14C]Adriamycin–DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin–DNA adducts at clinically-relevant Adriamycin concentrations. [14C]Adriamycin treatment (25 nM) resulted in 4.4 ± 1.0 adducts/107 bp (∼1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin–DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin–DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues

Experiments to Find or Exclude a Long-Lived, Light Gluino

Gluinos in the mass range ~1 1/2 - 3 1/2 GeV are absolutely excluded. Lighter gluinos are allowed, except for certain ranges of lifetime. Only small parts of the mass-lifetime parameter space are excluded for larger masses unless the lifetime is shorter than ~ 2 10^{-11} (m_{gluino}/ GeV) sec. Refined mass and lifetime estimates for R-hadrons are given, present direct and indirect experimental constraints are reviewed, and experiments to find or definitively exclude these possibilities are suggested.Comment: 27 pp, latex with 1 uufiled figure, RU-94-35. New version amplifies discussion of some points and corresponds to version for Phys. Rev.

Current applications using key mineral phases in igneous and metamorphic geology: perspectives for the future

The study of magmatic and metamorphic processes is challenged by geological complexities like geochemical variations, geochronological uncertainties and the presence/absence of fluids and/or melts. However, by integrating petrographic and microstructural studies with geochronology, geochemistry and phase equilibrium diagram investigations of different key mineral phases, it is possible to reconstruct insightful pressure–temperature–deformation–time histories. Using multiple geochronometers in a rock can provide a detailed temporal account of its evolution, as these geological clocks have different closure temperatures. Given the continuous improvement of existing and new in situ analytical techniques, this contribution provides an overview of frequently utilized petrochronometers such as garnet, zircon, titanite, allanite, rutile, monazite/xenotime and apatite, by describing the geological record that each mineral can retain and explaining how to retrieve this information. These key minerals were chosen as they provide reliable age information in a variety of rock types and, when coupled with their trace element (TE) composition, form powerful tools to investigate crustal processes at different scales. This review recommends best applications for each petrochronometer, highlights limitations to be aware of and discusses future perspectives. Finally, this contribution underscores the importance of integrating information retrieved by multi-petrochronometer studies to gain an in-depth understanding of complex thermal and deformation crustal processes