The cost-effectiveness of high dose chemotherapy in the treatment of relapsed Hodgkin's disease and non-Hodgkin's lymphoma

As part of an NHS Executive Trent regional initiative we considered the role and cost-effectiveness of high dose chemotherapy in the treatment of relapsed Hodgkin's disease and non-Hodgkin's lymphoma. The key trials and case series show an additional patient benefit of 0.8–1.1 life years over standard chemotherapy. We estimate incremental cost per life year gained of £12 800–£17 600, which reduces further if long-term benefits are considered. High dose chemotherapy in these conditions is both life-saving and cost-effective. © 2000 Cancer Research Campaig

A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity

Understanding and utilization of Thematic Mapper and other remotely sensed data for vegetation monitoring

The TM Tasseled Cap transformation, which provides both a 50% reduction in data volume with little or no loss of important information and spectral features with direct physical association, is presented and discussed. Using both simulated and actual TM data, some important characteristics of vegetation and soils in this feature space are described, as are the effects of solar elevation angle and atmospheric haze. A preliminary spectral haze diagnostic feature, based on only simulated data, is also examined. The characteristics of the TM thermal band are discussed, as is a demonstration of the use of TM data in energy balance studies. Some characteristics of AVHRR data are described, as are the sensitivities to scene content of several LANDSAT-MSS preprocessing techniques

Cholesterol and coronary heart disease: screening and treatment

Coronary heart disease (CHD) is a major cause of morbidity and mortality in the United Kingdom, accounting for just under one quarter of all deaths in 1995: 27% among men and 21% among women.1 Although many CHD deaths occur among elderly people, CHD accounts for 31% of male and 13% of female deaths within the 45–64 age group

The ROTSE-III Robotic Telescope System

The observation of a prompt optical flash from GRB990123 convincingly demonstrated the value of autonomous robotic telescope systems. Pursuing a program of rapid follow-up observations of gamma-ray bursts, the Robotic Optical Transient Search Experiment (ROTSE) has developed a next-generation instrument, ROTSE-III, that will continue the search for fast optical transients. The entire system was designed as an economical robotic facility to be installed at remote sites throughout the world. There are seven major system components: optics, optical tube assembly, CCD camera, telescope mount, enclosure, environmental sensing & protection and data acquisition. Each is described in turn in the hope that the techniques developed here will be useful in similar contexts elsewhere.Comment: 19 pages, including 4 figures. To be published in PASP in January, 2003. PASP Number IP02-11

The Human Rights of Older People With Mental Health Conditions and Psychosocial Disability to a Good Death and Dying Well

The human right to a good death and dying well is as important as the right to life. At stake at the end of life are human rights to dignity, autonomy, self-determination and respect for will and preferences, equitable access to quality health care that is needs-based, and respect for family and relationships. Older people with dementia, those with serious mental illness, and those with intellectual disability are vulnerable to "bad deaths" due to violations of these rights. In this paper we explore why this is so and examine existing and potential solutions. A human rights-approach to end-of-life care and policy for older persons with mental health conditions and psychosocial disability is one that is needs-based, encompassing physical and mental health, palliative care, social, and spiritual support services provided in the context of inclusive living. Most importantly, end of life care must be self-determined, and not "one size fits all." An important remedy to existing violations is to strengthen human rights frameworks to cater specifically to older persons' needs with a UN convention on the rights of older persons. Finally, as health professionals we have important contributions to make at the coalface by accepting our responsibilities in the area of death and dying. With the concept of the palliative psychiatrist gaining traction and recognition that death is our business, we add that human rights is also our business

Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

Perspectives on open access high resolution digital elevation models to produce global flood hazard layers

Global flood hazard models have recently become a reality thanks to the release of open access global digital elevation models, the development of simplified and highly efficient flow algorithms, and the steady increase in computational power. In this commentary we argue that although the availability of open access global terrain data has been critical in enabling the development of such models, the relatively poor resolution and precision of these data now limit significantly our ability to estimate flood inundation and risk for the majority of the planet’s surface. The difficulty of deriving an accurate ‘bare-earth’ terrain model due to the interaction of vegetation and urban structures with the satellite-based remote sensors means that global terrain data are often poorest in the areas where people, property (and thus vulnerability) are most concentrated. Furthermore, the current generation of open access global terrain models are over a decade old and many large floodplains, particularly those in developing countries, have undergone significant change in this time. There is therefore a pressing need for a new generation of high resolution and high vertical precision open access global digital elevation models to allow significantly improved global flood hazard models to be developed