Open Questions in Classical Gravity

We discuss some outstanding open questions regarding the validity and uniqueness of the standard second order Newton-Einstein classical gravitational theory. On the observational side we discuss the degree to which the realm of validity of Newton's Law of Gravity can actually be extended to distances much larger than the solar system distance scales on which the law was originally established. On the theoretical side we identify some commonly accepted but actually still open to question assumptions which go into the formulating of the standard second order Einstein theory in the first place. In particular, we show that while the familiar second order Poisson gravitational equation (and accordingly its second order covariant Einstein generalization) may be sufficient to yield Newton's Law of Gravity they are not in fact necessary. The standard theory thus still awaits the identification of some principle which would then make it necessary too. We show that current observational information does not exclusively mandate the standard theory, and that the conformal invariant fourth order theory of gravity considered recently by Mannheim and Kazanas is also able to meet the constraints of data, and in fact to do so without the need for any so far unobserved non-luminous or dark matter.Comment: UCONN-93-1, plain TeX format, 22 pages (plus 7 figures - send requests to [email protected]). To appear in a special issue of Foundations of Physics honoring Professor Fritz Rohrlich on the occasion of his retirement, L. P. Horwitz and A. van der Merwe Editors, Plenum Publishing Company, N.Y., Fall 199

Long Term Effects of Radiation and Combined Modalities on Mouse Lung

The lung appears to be the major dose-limiting organ in radiation of the thorax. Early responses (\u3c1 week) involve the type II pneumocyte and increased surfactant biosynthesis and secretion. Later changes, which appear to be related to the surfactant response, lead to classical radiation pneumonitis, which is often fatal. Animals which survive radiation pneumonitis develop progressive fibrosis, a late-appearing response, which reduces compliance and available air space, and is usually fatal. This study centers on the fine structural changes in the lungs of LAF1 mice, 63 weeks following various radiation exposures (5-13 Gy). Doses which are subthreshold in evoking surfactant and pneumonitic responses precipitate fibrosis and atelectasis by 63 weeks, and involve type II pneumocyte sloughing and degeneration. Of the two major deterrents to lung irradiation (pneumonitis and fibrosis), these results suggest that fibrosis always follows pneumonitis, but pneumonitis is not a necessary preliminary step to fibrosis. Bleomycin elicits several morphological alterations characteristic of radiation, and, when combined with the latter, appears to exacerbate radiation effects

Doubleâ blind, randomized phase 3 trial of lowâ dose 13â cis retinoic acid in the prevention of second primaries in head and neck cancer: Longâ term followâ up of a trial of the Eastern Cooperative Oncology Groupâ ACRIN Cancer Research Group (C0590)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139904/1/cncr30920.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139904/2/cncr30920_am.pd

Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings.</p> <p>Methods</p> <p>Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.</p> <p>Results</p> <p>Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.</p> <p>Conclusions</p> <p>In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.</p

Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma

The molecular basis for the inverse relationship between differentiation and tumorigenesis is unknown. The function of runx2, a master regulator of osteoblast differentiation belonging to the runt family of tumor suppressor genes, is consistently disrupted in osteosarcoma cell lines. Ectopic expression of runx2 induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and leading to the dephosphorylation of the retinoblastoma tumor suppressor protein (pRb) and a G1 cell cycle arrest. Runx2 physically interacts with the hypophosphorylated form of pRb, a known coactivator of runx2, thereby completing a feed-forward loop in which progressive cell cycle exit promotes increased expression of the osteoblast phenotype. Loss of p27KIP1 perturbs transient and terminal cell cycle exit in osteoblasts. Consistent with the incompatibility of malignant transformation and permanent cell cycle exit, loss of p27KIP1 expression correlates with dedifferentiation in high-grade human osteosarcomas. Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is mediated through runx2 and p27KIP1, and these processes are disrupted in osteosarcoma

Directly Observed Therapy and Improved Tuberculosis Treatment Outcomes in Thailand

BACKGROUND: The World Health Organization (WHO) recommends that tuberculosis (TB) patients receive directly observed therapy (DOT). Randomized controlled trials have not consistently shown that this practice improves TB treatment success rates. In Thailand, one of 22 WHO-designated high burden TB countries, patients may have TB treatment observed by a health care worker (HCW), family member, or no one. We studied whether DOT improved TB treatment outcomes in a prospective, observational cohort. METHODS AND FINDINGS: We prospectively collected epidemiologic data about TB patients treated at public and private facilities in four provinces in Thailand and the national infectious diseases hospital from 2004-2006. Public health staff recorded the type of observed therapy that patients received during the first two months of TB treatment. We limited our analysis to pulmonary TB patients never previously treated for TB and not known to have multidrug-resistant TB. We analyzed the proportion of patients still on treatment at the end of two months and with treatment success at the end of treatment according to DOT type. We used propensity score analysis to control for factors associated with DOT and treatment outcome. Of 8,031 patients eligible for analysis, 24% received HCW DOT, 59% family DOT, and 18% self-administered therapy (SAT). Smear-positive TB was diagnosed in 63%, and 21% were HIV-infected. Of patients either on treatment or that defaulted at two months, 1601/1636 (98%) patients that received HCW DOT remained on treatment at two months compared with 1096/1268 (86%) patients that received SAT (adjusted OR [aOR] 3.8; 95% confidence interval [CI] 2.4-6.0) and 3782/3987 (95%) patients that received family DOT (aOR 2.1; CI, 1.4-3.1). Of patients that had treatment success or that defaulted at the end of treatment, 1369/1477 (93%) patients that received HCW DOT completed treatment compared with 744/1074 (69%) patients that received SAT (aOR 3.3; CI, 2.4-4.5) and 3130/3529 (89%) patients that received family DOT (aOR 1.5; 1.2-1.9). The benefit of HCW DOT compared with SAT was similar, but smaller, when comparing patients with treatment success to those with death, default, or failure. CONCLUSIONS: In Thailand, two months of DOT was associated with lower odds of default during treatment. The magnitude of benefit was greater for DOT provided by a HCW compared with a family member. Thailand should consider increasing its use of HCW DOT during TB treatment

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Clinical capabilities of graduates of an outcomes-based integrated medical program

<p>Abstract</p> <p>Background</p> <p>The University of New South Wales (UNSW) Faculty of Medicine replaced its old content-based curriculum with an innovative new 6-year undergraduate entry outcomes-based integrated program in 2004. This paper is an initial evaluation of the perceived and assessed clinical capabilities of recent graduates of the new outcomes-based integrated medical program compared to benchmarks from traditional content-based or process-based programs.</p> <p>Method</p> <p>Self-perceived capability in a range of clinical tasks and assessment of medical education as preparation for hospital practice were evaluated in recent graduates after 3 months working as junior doctors. Responses of the 2009 graduates of the UNSW’s new outcomes-based integrated medical education program were compared to those of the 2007 graduates of UNSW’s previous content-based program, to published data from other Australian medical schools, and to hospital-based supervisor evaluations of their clinical competence.</p> <p>Results</p> <p>Three months into internship, graduates from UNSW’s new outcomes-based integrated program rated themselves to have good clinical and procedural skills, with ratings that indicated significantly greater capability than graduates of the previous UNSW content-based program. New program graduates rated themselves significantly more prepared for hospital practice in the confidence (reflective practice), prevention (social aspects of health), interpersonal skills (communication), and collaboration (teamwork) subscales than old program students, and significantly better or equivalent to published benchmarks of graduates from other Australian medical schools. Clinical supervisors rated new program graduates highly capable for teamwork, reflective practice and communication.</p> <p>Conclusions</p> <p>Medical students from an outcomes-based integrated program graduate with excellent self-rated and supervisor-evaluated capabilities in a range of clinically-relevant outcomes. The program-wide curriculum reform at UNSW has had a major impact in developing capabilities in new graduates that are important for 21^st century medical practice.</p