The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, type of mutation, and adjuvant treatment

PURPOSE: The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups. PATIENTS AND METHODS: A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8. RESULTS: TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were associated with lymphatic invasion in proximal tumors. In distal colon tumors, deletions causing loss of amino acids were associated with worse survival. In proximal colon tumors, mutations in exon 5 showed a trend toward statistical significance (P < .05) when overall survival was considered. Dukes' C tumors with wild-type TP53 and those with mutated TP53 (proximal tumors) showed significantly better prognosis when treated with adjuvant chemotherapy. CONCLUSION: Analysis of TP53 mutations from a large cohort of CRC patients has identified tumor site, type of mutation, and adjuvant treatment as important factors in determining the prognostic significance of this genetic alteration

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Collaborative Brain-Computer Interface for Aiding Decision-Making

We look at the possibility of integrating the percepts from multiple non-communicating observers as a means of achieving better joint perception and better group decisions. Our approach involves the combination of a brain-computer interface with human behavioural responses. To test ideas in controlled conditions, we asked observers to perform a simple matching task involving the rapid sequential presentation of pairs of visual patterns and the subsequent decision as whether the two patterns in a pair were the same or different. We recorded the response times of observers as well as a neural feature which predicts incorrect decisions and, thus, indirectly indicates the confidence of the decisions made by the observers. We then built a composite neuro-behavioural feature which optimally combines the two measures. For group decisions, we uses a majority rule and three rules which weigh the decisions of each observer based on response times and our neural and neuro-behavioural features. Results indicate that the integration of behavioural responses and neural features can significantly improve accuracy when compared with the majority rule. An analysis of event-related potentials indicates that substantial differences are present in the proximity of the response for correct and incorrect trials, further corroborating the idea of using hybrids of brain-computer interfaces and traditional strategies for improving decision making

Microbial diversity arising from thermodynamic constraints

The microbial world displays an immense taxonomic diversity. This diversity is manifested also in a multitude of metabolic pathways that can utilize different substrates and produce different products. Here, we propose that these observations directly link to thermodynamic constraints that inherently arise from the metabolic basis of microbial growth. We show that thermodynamic constraints can enable coexistence of microbes that utilise the same substrate but produce different end products. We find that this thermodynamics-driven emergence of diversity is most relevant for metabolic conversions with low free energy as seen for example under anaerobic conditions, where population dynamics is governed by thermodynamic effects rather than kinetic factors such as substrate uptake rates. These findings provide a general understanding of the microbial diversity based on the first-principles of thermodynamics. As such they provide a thermodynamics-based framework for explaining the observed microbial diversity in different natural and synthetic environments

Threatened reef corals of the world

10.1371/journal.pone.0034459PLoS ONE73

Protocol for a home-based integrated physical therapy program to reduce falls and improve mobility in people with Parkinson’s disease

Background The high incidence of falls associated with Parkinson&rsquo;s disease (PD) increases the risk of injuries and immobility and compromises quality of life. Although falls education and strengthening programs have shown some benefit in healthy older people, the ability of physical therapy interventions in home settings to reduce falls and improve mobility in people with Parkinson&rsquo;s has not been convincingly demonstrated.Methods/design 180 community living people with PD will be randomly allocated to receive either a home-based integrated rehabilitation program (progressive resistance strength training, movement strategy training and falls education) or a home-based life skills program (control intervention). Both programs comprise one hour of treatment and one hour of structured homework per week over six weeks of home therapy. Blinded assessments occurring before therapy commences, the week after completion of therapy and 12 months following intervention will establish both the immediate and long-term benefits of home-based rehabilitation. The number of falls, number of repeat falls, falls rate and time to first fall will be the primary measures used to quantify outcome. The economic costs associated with injurious falls, and the costs of running the integrated rehabilitation program from a health system perspective will be established. The effects of intervention on motor and global disability and on quality of life will also be examined. Discussion This study will provide new evidence on the outcomes and cost effectiveness of home-based movement rehabilitation programs for people living with PD

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Sins of Omission

Little is known about the relative incidence of serious errors of omission versus errors of commission. Objective : To identify the most common substantive medical errors identified by medical record review. Design : Retrospective cohort study. Setting : Twelve Veterans Affairs health care systems in 2 regions. Participants : Stratified random sample of 621 patients receiving care over a 2-year period. Main Outcome Measure : Classification of reported quality problems. Methods : Trained physicians reviewed the full inpatient and outpatient record and described quality problems, which were then classified as errors of omission versus commission. Results : Eighty-two percent of patients had at least 1 error reported over a 13-month period. The average number of errors reported per case was 4.7 (95% confidence intervals [CI]: 4.4, 5.0). Overall, 95.7% (95% CI: 94.9%, 96.4%) of errors were identified as being problems with underuse. Inadequate care for people with chronic illnesses was particularly common. Among errors of omission, obtaining insufficient information from histories and physicals (25.3%), inadequacies in diagnostic testing (33.9%), and patients not receiving needed medications (20.7%) were all common. Out of the 2,917 errors identified, only 27 were rated as being highly serious, and 26 (96%) of these were errors of omission. Conclusions : While preventing iatrogenic injury resulting from medical errors is a critically important part of quality improvement, we found that the overwhelming majority of substantive medical errors identifiable from the medical record were related to people getting too little medical care, especially for those with chronic medical conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74567/1/j.1525-1497.2005.0152.x.pd