Native American Tribes in Wisconsin Improve Health Care Delivery

This program report discusses the results and lessons learned from an Inter-Tribal managed care demonstration project in Wisconsin. The project was implemented from 1996 to 2000 to develop a more coordinated, cost-effective approach to health care among the nine Wisconsin Indian tribes belonging to GLITC, a nonprofit organization that aids tribes in delivery of health and other tribal services.

EFFECTS OF CHEMISTRY AND OTHER VARIABLES ON CORROSION AND STRESS CORROSION CRACKING IN HANFORD DOUBLE SHELL TANKS

Laboratory testing was performed to develop a comprehensive understanding of the corrosivity of the tank wastes stored in Double-Shell Tanks using simulants primarily from Tanks 241-AP-105, 241-SY-103 and 241-AW-105. Additional tests were conducted using simulants of the waste stored in 241-AZ-102, 241-SY-101, 241-AN-107, and 241-AY-101. This test program placed particular emphasis on defining the range of tank waste chemistries that do not induce the onset of localized forms of corrosion, particularly pitting and stress corrosion cracking. This document summarizes the key findings of the research program

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Friedreich's Ataxia Frequency in a Large Cohort of Genetically Undetermined Ataxia Patients

Background: Patients with suspected genetic ataxia are often tested for Friedreich's ataxia (FRDA) and/or a variety of spinocerebellar ataxias (SCAs). FRDA can present with atypical, late-onset forms and so may be missed in the diagnostic process. We aimed to determine FRDA-positive subjects among two cohorts of patients referred to a specialist ataxia centre either for FRDA or SCA testing to determine the proportion of FRDA cases missed in the diagnostic screening process. Methods: 2000 SCA-negative ataxia patients, not previously referred for FRDA testing (group A), were tested for FRDA expansions and mutations. This group was compared with 1768 ataxia patients who had been previously referred for FRDA testing (group B) and were therefore more likely to have a typical presentation. The phenotypes of positive cases were assessed through review of the clinical case notes. Results: Three patients (0.2%) in group A had the FRDA expansion on both alleles, compared with 207 patients (11.7%) in group B. The heterozygous carrier rate across both cohorts was of 41 out of 3,768 cases (1.1%). The size of the expansions in the three FRDA-positive cases in group A was small, and their presentation atypical with late-onset. Conclusions: This study demonstrates that FRDA is very rare among patients who were referred purely for SCA testing without the clinical suspicion of FRDA. Such cases should be referred to specialist ataxia centres for more extensive testing to improve patient management and outcomes

Insolubility Theorems and EPR Argument

I wish to thank in particular Arthur Fine for very perceptive comments on a previous draft of this paper. Many thanks also to Theo Nieuwenhuizen for inspiration, to Max Schlosshauer for correspondence, to two anonymous referees for shrewd observations, and to audiences at Aberdeen, Cagliari and Oxford (in particular to Harvey Brown, Elise Crull, Simon Saunders, Chris Timpson and David Wallace) for stimulating questions. This paper was written during my tenure of a Leverhulme Grant on ‘The Einstein Paradox’: The Debate on Nonlocality and Incompleteness in 1935 (Project Grant nr. F/00 152/AN), and it was revised for publication during my tenure of a Visiting Professorship in the Doctoral School of Philosophy and Epistemology, University of Cagliari (Contract nr. 268/21647).Peer reviewedPostprin

Is there a no-go theorem for superradiant quantum phase transitions in cavity and circuit QED ?

In cavity quantum electrodynamics (QED), the interaction between an atomic transition and the cavity field is measured by the vacuum Rabi frequency $\Omega_0$. The analogous term "circuit QED" has been introduced for Josephson junctions, because superconducting circuits behave as artificial atoms coupled to the bosonic field of a resonator. In the regime with $\Omega_0$ comparable to the two-level transition frequency, "superradiant" quantum phase transitions for the cavity vacuum have been predicted, e.g. within the Dicke model. Here, we prove that if the time-independent light-matter Hamiltonian is considered, a superradiant quantum critical point is forbidden for electric dipole atomic transitions due to the oscillator strength sum rule. In circuit QED, the capacitive coupling is analogous to the electric dipole one: yet, such no-go property can be circumvented by Cooper pair boxes capacitively coupled to a resonator, due to their peculiar Hilbert space topology and a violation of the corresponding sum rule

Preparing medical students for clinical practice: easing the transition

The transition from medical student to junior doctor is a challenge; the UK General Medical Council has issued guidance emphasizing the importance of adequate preparation of medical students for clinical practice. This study aimed to determine whether a junior doctor-led simulation-based course is an effective way of preparing final year medical students for practice as a junior doctor. We piloted a new 'preparation for practice' course for final year medical students prior to beginning as Foundation Year 1 (first year of practice) doctors. The course ran over three days and consisted of four simulated stations: ward round, prescribing, handover, and lessons learnt. Quantitative and qualitative feedback was obtained .A total of 120 students attended (40 on each day) and feedback was collected from 95 of them. Using a scale of 1 (lowest) to 5 (highest), feedback was positive, with 99% and 96% rating 4 or 5 for the overall quality of the program and the relevance of the program content, respectively. A score of 5 was awarded by 67% of students for the ward round station; 58% for the handover station; 71% for the prescribing station, and 35% for the lessons learnt station. Following the prescribing station, students reported increased confidence in their prescribing. Preparation for practice courses and simulation are an effective and enjoyable way of easing the transition from medical student to junior doctor. Together with 'on-the-job' shadowing time, such programs can be used to improve students' confidence, competence, and ultimately patient safety and quality of care

Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer

A de Sitter Hoedown

Rotating black holes in de Sitter space are known to have interesting limits where the temperatures of the black hole and cosmological horizon are equal. We give a complete description of the thermal phase structure of all allowed rotating black hole configurations. Only one configuration, the rotating Nariai limit, has the black hole and cosmological horizons both in thermal and rotational equilibrium, in that both the temperatures and angular velocities of the two horizons coincide. The thermal evolution of the spacetime is shown to lead to the pure de Sitter spacetime, which is the most entropic configuration. We then provide a comprehensive study of the wave equation for a massless scalar in the rotating Nariai geometry. The absorption cross section at the black hole horizon is computed and a condition is found for when the scattering becomes superradiant. The boundary-to-boundary correlators at finite temperature are computed at future infinity. The quasinormal modes are obtained in explicit form. Finally, we obtain an expression for the expectation value of the number of particles produced at future infinity starting from a vacuum state with no incoming particles at past infinity. Some of our results are used to provide further evidence for a recent holographic proposal between the rotating Nariai geometry and a two-dimensional conformal field theory.Comment: 35 + 1 pages, 9 figures; v3: typos correcte

Changes in the Prevalence of Child and Youth Mental Disorders and Perceived Need for Professional Help between 1983 and 2014: Evidence from the Ontario Child Health Study

© The Author(s) 2019. Objectives: To examine: 1) changes in the prevalence of mental disorders and perceived need for professional help among children (ages 4 to 11) and youth (ages 12 to 16) between 1983 and 2014 in Ontario and 2) whether these changes vary by age and sex, urban-rural residency, poverty, lone-parent status, and immigrant background. Methods: The 1983 (n = 2836) and 2014 (n = 5785) Ontario Child Health Studies are provincially representative cross-sectional surveys with identical self-report checklist measures of conduct disorder, hyperactivity, and emotional disorder, as well as perceived need for professional help, assessed by integrating parent and teacher responses (ages 4 to 11) and parent and youth responses (ages 12 to 16). Results: The overall prevalence of perceived need for professional help increased from 6.8% to 18.9% among 4- to 16-year-olds. An increase in any disorder among children (15.4% to 19.6%) was attributable to increases in hyperactivity among males (8.9% to 15.7%). Although the prevalence of any disorder did not change among youth, conduct disorder decreased (7.2% to 2.5%) while emotional disorder increased (9.2% to 13.2%). The prevalence of any disorder increased more in rural and small to medium urban areas versus large urban areas. The prevalence of any disorder decreased for children and youth in immigrant but not nonimmigrant families. Conclusions: Although there have been decreases in the prevalence of conduct disorder, increases in other mental disorders and perceived need for professional help underscore the continued need for effective prevention and intervention programs