Organ Transplant Crisis: Should the Deficit be Eliminated Through Inter Vivos Sales?

In response to what has been characterized as the last remaining obstacle to transplantation, Senator Warren Hatch introduced a bill on October 20, 1983 which would establish a task force to investigate and make recommendations to Congress about the problem. Hearings and debate on the bill are scheduled to resume with the next Congress. Its future is bleak with the administration opposing it and the budget-cutting axe being resharpened. Regardless of the bill\u27s outcome, the problem of supplying anatomical organs will continue to present a host of moral, political, and most importantly, legal issues which must be resolved if society is to realize the full benefit of transplant science. This article will attempt to address some of these questions, exploring possibilities and obstacles presented by each

CHK1 Inhibition Synergizes with Gemcitabine Initially by Destabilizing the DNA Replication Apparatus.

Combining cell-cycle checkpoint kinase inhibitors with the DNA-damaging chemotherapeutic agent gemcitabine offers clinical appeal, with a mechanistic rationale based chiefly on abrogation of gemcitabine-induced G2-M checkpoint activation. However, evidence supporting this mechanistic rationale from chemosensitization studies has not been consistent. Here we report a systematic definition of how pancreatic cancer cells harboring mutant p53 respond to this combination therapy, by combining mathematical models with large-scale quantitative biologic analyses of single cells and cell populations. Notably, we uncovered a dynamic range of mechanistic effects at different ratios of gemcitabine and CHK1 inhibitors. Remarkably, effective synergy was attained even where cells exhibited an apparently functional G2-M surveillance mechanism, as exemplified by a lack of both overt premature CDK1 activation and S-phase mitotic entry. Consistent with these findings, S-G2 duration was extended in treated cells, leading to a definable set of lineage-dependent catastrophic fates. At synergistic drug concentrations, global replication stress was a distinct indicator of chemosensitization as characterized molecularly by an accumulation of S-phase cells with high levels of hyperphosphorylated RPA-loaded single-stranded DNA. In a fraction of these cells, persistent genomic damage was observed, including chromosomal fragmentation with a loss of centromeric regions that prevented proper kinetochore-microtubule attachment. Together, our results suggested a "foot-in-the-door" mechanism for drug synergy where cells were destroyed not by frank G2-M phase abrogation but rather by initiating a cumulative genotoxicity that deregulated DNA synthesis.This study was funded by Cancer Research UK via Institute Senior Group Leader funding (C14303/A17197) to DI Jodrell, and by Sentinel Oncology through an award from Innovate UK.This is the author accepted manuscript. The final version is available from American Association for Cancer Research via http://dx.doi.org/10.1158/0008-5472.CAN-14-334

Morphometrics predicts overall survival in patients with multiple myeloma spine metastasis: A retrospective cohort study

Background: Treatment strategies for spinal metastases for myeloma range from conservative measures (radiation and chemotherapy) to invasive (surgical). Identifying better predictors of overall survival (OS) would help in surgical decision making. Analytic morphometrics has been shown to predict survival in oncologic patients, and our study evaluates whether morphometrics is predictive of survival in patients with multiple myeloma (MM) spinal metastases. Methods: For this observational retrospective cohort study, we identified 46 patients with MM spinal metastases who had undergone stereotactic body radiation therapy. OS was the primary outcome measure. Morphometric analysis of the psoas muscle was performed using computed tomography scans of the lumbar spine. Results: OS was statistically correlated with age ( Conclusions: Morphometric analysis successfully predicts long-term survival in patients with MM. More research is needed to validate these results and to see if these methodologies can be applied to other cancer histologies

Morphometrics predicts overall survival in patients with multiple myeloma spine metastasis: A retrospective cohort study

BACKGROUND: Treatment strategies for spinal metastases for myeloma range from conservative measures (radiation and chemotherapy) to invasive (surgical). Identifying better predictors of overall survival (OS) would help in surgical decision making. Analytic morphometrics has been shown to predict survival in oncologic patients, and our study evaluates whether morphometrics is predictive of survival in patients with multiple myeloma (MM) spinal metastases. METHODS: For this observational retrospective cohort study, we identified 46 patients with MM spinal metastases who had undergone stereotactic body radiation therapy. OS was the primary outcome measure. Morphometric analysis of the psoas muscle was performed using computed tomography scans of the lumbar spine. RESULTS: OS was statistically correlated with age (P = 0.025), tumor burden (P = 0.023), and number of levels radiated (P = 0.029), but not with gender. Patients in the lowest tertile of average psoas size had significantly shorter survival compared to the highest tertile, hazard ratio (HZ) 6.87 (95% CI = 1.65-28.5, P = 0.008). When calculating the psoas size to vertebral body ratio and correlating this measure to OS, the lowest tertile again had significantly shorter OS compared to the highest tertile, HZ 6.87 (95% CI = 1.57-29.89, P = 0.010); the middle tertile also showed significantly shorter OS compared to the highest tertile, HZ 5.07 (95% CI = 1.34-19.10, P = 0.016). Kaplan-Meier survival curves were used to visually illustrate the differences in survival between different tertiles (Log-rank test P = 0.006). CONCLUSIONS: Morphometric analysis successfully predicts long-term survival in patients with MM. More research is needed to validate these results and to see if these methodologies can be applied to other cancer histologies

Doping-dependent study of the periodic Anderson model in three dimensions

We study a simple model for $f$-electron systems, the three-dimensional periodic Anderson model, in which localized $f$ states hybridize with neighboring $d$ states. The $f$ states have a strong on-site repulsion which suppresses the double occupancy and can lead to the formation of a Mott-Hubbard insulator. When the hybridization between the $f$ and $d$ states increases, the effects of these strong electron correlations gradually diminish, giving rise to interesting phenomena on the way. We use the exact quantum Monte-Carlo, approximate diagrammatic fluctuation-exchange approximation, and mean-field Hartree-Fock methods to calculate the local moment, entropy, antiferromagnetic structure factor, singlet-correlator, and internal energy as a function of the $f-d$ hybridization for various dopings. Finally, we discuss the relevance of this work to the volume-collapse phenomenon experimentally observed in f-electron systems.Comment: 12 pages, 8 figure

Are people who participate in cultural activities more satisfied with life?

The influence of various aspects of life on wellbeing has been extensively researched. However, despite little empirical evidence, participation in leisure activities has been assumed to increase subjective wellbeing. Leisure is important because it is more under personal control than other sources of life satisfaction. This study asked whether people who participate in cultural leisure activities have higher life satisfaction than people who do not, if different types of leisure have the same influence on life satisfaction and if satisfaction is dependent on the frequency of participation or the number of activities undertaken. It used data from UKHLS Survey to establish associations between type, number and frequency of participation in leisure activities and life satisfaction. Results showed an independent and positive association of participation in sport, heritage and active-creative leisure activities and life satisfaction but not for participation in popular entertainment, theatre hobbies and museum/galleries. The association of reading hobbies and sedentary-creative activities and life satisfaction was negative. High life satisfaction was associated with engaging in a number of different activities rather than the frequency of participation in each of them. The results have implications for policy makers and leisure services providers, in particular those associated with heritage recreation. Subjective wellbeing measures, such as life satisfaction, and not economic measures alone should be considered in the evaluation of services. The promotion of leisure activities which are active and promote social interaction should be considered in programmes aimed at improving the quality of life

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

A randomised controlled crossover trial investigating the short-term effects of different types of vegetables on vascular and metabolic function in middle-aged and older adults with mildly elevated blood pressure: the VEgetableS for vaScular hEaLth (VESSEL) study protocol

A diet rich in fruits and vegetables is recommended for cardiovascular health. However, the majority of Australians do not consume the recommended number of vegetable servings each day. Furthermore, intakes of vegetables considered to have the greatest cardiovascular benefit are often very low. Results from prospective observational studies indicate that a higher consumption of cruciferous vegetables (e.g. broccoli, cabbage, cauliflower) is associated with lower cardiovascular disease risk. This may be due to the presence of specific nutrients and bioactive compounds found almost exclusively, or at relatively high levels, in cruciferous vegetables. Therefore, the aim of this randomised controlled crossover trial is to determine whether regular consumption of cruciferous vegetables results in short-term improvement in measures related to cardiovascular disease risk, including ambulatory blood pressure, arterial stiffness, glycaemic control, and circulating biomarkers of oxidative stress and inflammation

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery

ACKNOWLEDGEMENTS Review and editing: S.R. Brown, Professor of Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. Email [email protected]. Patient summary: R.G. Arnott, Retired Professor, Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK. Email [email protected]. Delphi review: C.P. Macklin. BMedSci BM BS FRCS DM, Consultant Colorectal Surgeon, Mid Yorkshire Hospitals, UK. Email [email protected] reviewedPublisher PD