Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Summary
A fracture risk assessment tool (FRAX™) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK.

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FRAX™ and the assessment of fracture probability in men and women from the UK

Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. © 2010 American Society for Bone and Mineral Research.

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbmr.416

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

RAS proteins are essential components of signalling pathways that emanate from cell surface receptors. Oncogenic activation of these proteins owing to missense mutations is frequently detected in several types of cancer. A wealth of biochemical and genetic studies indicates that RAS proteins control a complex molecular circuitry that consists of a wide array of interconnecting pathways. In this Review, we describe how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes that drive tumorigenesis.

/pdf/ras-oncogenes-weaving-a-tumorigenic-web-3ae4v7jug2.pdf

RAS oncogenes: weaving a tumorigenic web

Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease

Due to the magnitude of the morbidity and mortality associated with untreated osteoporosis, it is essential that high-risk individuals be identified so that they can receive appropriate evaluation and treatment. The objective of this investigation was to develop a simple clinical assessment tool based on a small number of risk factors that could be used by women or their clinicians to assess their risk of fractures. Using data from the Study of Osteoporotic Fractures (SOF), a total of 7782 women age 65 years and older with bone mineral density (BMD) measurements and baseline risk factors were included in the analysis. A model with and without BMD T-scores was developed by identifying variables that could be easily assessed in either clinical practice or by self-administration. The assessment tool, called the FRACTURE Index, is comprised of a set of seven variables that include age, BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. The FRACTURE Index was shown to be predictive of hip fracture, as well as vertebral and nonvertebral fractures. In addition, this index was validated using the EPIDOS fracture study. The FRACTURE Index can be used either with or without BMD testing by older postmenopausal women or their clinicians to assess the 5-year risk of hip and other osteoporotic fractures, and could be useful in helping to determine the need for further evaluation and treatment of these women.

An assessment tool for predicting fracture risk in postmenopausal women.

Malignant neoplasms following bone marrow transplantation.

Summary
Using national discharge and medical claims data, we studied the epidemiology of femoral fractures from 1996 to 2006. The annual hip fracture incidence declined from 600/100,000 to 400/100,000, without decline in the more rare femur fractures. Incidence rates for subtrochanteric and femoral shaft fractures were each below 20 per 100,000.

Fragility fractures of the hip and femur: incidence and patient characteristics

Oral glucocorticoids (GCs) are widely used and despite their adverse effects on bone mineral density, the risk of sustaining osteoporotic fractures is not well addressed. The objective of this retrospective, cohort study was to assess fracture risk in patients exposed to oral GCs. Patients from an administrative claims database who were prescribed oral GCs and were enrolled 1 year before and 1 year after the initial oral GC claim were matched with a comparison population on age, sex, and date of first claim. Measurements of exposure included amount, duration, and pattern of oral GC use. The osteoporosis-related risk of fracture was based on the ratio of hazard functions estimated using a Cox proportional hazards model. The adjusted relative risk (RR) estimates (and 95% CI) for fractures were hip 1.87 (95% CI, 1.2 to 2.9), vertebral 2.92 (95% CI, 2.0 to 4.3), wrist/forearm 1.03 (95% CI, 0.8 to 1.4), nonvertebral 1.68 (95% CI, 1.5 to 1.9), any fracture 1.75 (95% CI, 1.6 to 1.9). A dose dependence of fracture risk was observed for hip, vertebral, nonvertebral, and any fractures. Long duration and continuous pattern of GC use demonstrated a significant 5-fold increased risk of hip and 5.9-fold increased risk of vertebral fracture. The combined effect of higher dose, longer duration, and continuous pattern further increased RR estimates to 7-fold for hip and 17-fold for vertebral fractures. This study confirms previous observations that suggest oral GCs have a rapid deleterious effect on trabecular-rich bone. The emerging relationship between amount, duration, and pattern of oral GC exposure and fracture risk should be considered in clinical practice and managed care settings to avoid the debilitating effects of fractures in patients.

Michael Steinbuch

Papers

Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease

An assessment tool for predicting fracture risk in postmenopausal women.

Malignant neoplasms following bone marrow transplantation.

Fragility fractures of the hip and femur: incidence and patient characteristics

Oral glucocorticoid use is associated with an increased risk of fracture