Early prediction of circulatory failure in the intensive care unit using machine learning.

Intensive-care clinicians are presented with large quantities of measurements from multiple monitoring systems. The limited ability of humans to process complex information hinders early recognition of patient deterioration, and high numbers of monitoring alarms lead to alarm fatigue. We used machine learning to develop an early-warning system that integrates measurements from multiple organ systems using a high-resolution database with 240 patient-years of data.

CASMAP: detection of statistically significant combinations of SNPs in association mapping.

Summary: Combinatorial association mapping aims to assess the statistical association of higher-order interactions of genetic markers with a phenotype of interest. This article presents combinatorial association mapping (CASMAP), a software package that leverages recent advances in significant pattern mining to overcome the statistical and computational challenges that have hindered combinatorial association mapping. CASMAP can be used to perform region-based association studies and to detect higher-order epistatic interactions of genetic variants.

Genome-wide genetic heterogeneity discovery with categorical covariates.

Motivation: Genetic heterogeneity is the phenomenon that distinct genetic variants may give rise to the same phenotype. The recently introduced algorithm Fast Automatic Interval Search ( FAIS ) enables the genome-wide search of candidate regions for genetic heterogeneity in the form of any contiguous sequence of variants, and achieves high computational efficiency and statistical power. Although FAIS can test all possible genomic regions for association with a phenotype, a key limitation is its inability to correct for confounders such as gender or population structure, which may lead to numerous false-positive associations.

Genome-wide detection of intervals of genetic heterogeneity associated with complex traits.

Motivation: Genetic heterogeneity, the fact that several sequence variants give rise to the same phenotype, is a phenomenon that is of the utmost interest in the analysis of complex phenotypes. Current approaches for finding regions in the genome that exhibit genetic heterogeneity suffer from at least one of two shortcomings: (i) they require the definition of an exact interval in the genome that is to be tested for genetic heterogeneity, potentially missing intervals of high relevance, or (ii) they suffer from an enormous multiple hypothesis testing problem due to the large number of potential candidate intervals being tested, which results in either many false positives or a lack of power to detect true intervals.

Results: Here, we present an approach that overcomes both problems: it allows one to automatically find all contiguous sequences of single nucleotide polymorphisms in the genome that are jointly associated with the phenotype.

Screening for job loss: development of a work instability scale for traumatic brain injury.

Objective: The objective of this study was to explore the concept of work instability (a mis-match between an individual's functional and cognitive abilities and the demands of their job) following traumatic brain injury (TBI) and develop a work instability scale specific to this population.

Method: Work instability (WI) following TBI was explored through qualitative interviews which were then used to generate items for a work instability scale (WIS). Rasch analysis was used to examine the scaling properties of the TBI-WIS which was then validated against a gold standard of expert vocational assessment by occupational psychologists.

McIndoe Memorial Lecture, 1980. In quest of perfection: training in plastic surgery.

The history, organisation, and present pattern of training in plastic surgery in the United Kingdom are outlined and suggestions made for its future development.

Thymosin-inducible lymphocytes in the peripheral blood of patients with malignant melanoma.

E rosette-forming (T) lymphocytes and surface immunoglobulin-bearing lymphocytes were estimated in 85 patients with malignant melanoma. The melanoma patient group had lower mean levels of T lymphocytes and higher mean levels of immunoglobulin-bearing (? B) lymphocytes than did normal subjects. The absolute and percentage depressions of T-cell levels in the melanoma patients were stage-related, as was the depression of total lymphocyte and B-lymphocyte levels.

A clinical trial of BCG immunotherapy as an adjunct to surgery in the treatment of primary malignant melanoma.

A preliminary analysis of a controlled trial of BCG immunotherapy as an adjunct to surgery in the treatment of primary malignant melanoma has been carried out. The length of follow-up varied from 5 years to 6 months. No obvious benefit from BCG immunotherapy has been found so far.

Autoimmunization with irradiated tumour cells in human malignant melanoma.

Thirteen patients have been immunized with their own irradiated melanoma cells on one or more occasions. Following these autografts tumour-specific cytotoxic antibodies were produced, the longest response lasting 14 days. This procedure had no apparent effect on the course of the disease in these patients.

Tumour-specific antibodies in human malignant melanoma and their relationship to the extent of the disease.

Biopsy specimens and sera were obtained from 103 melanoma patients. Autoantibodies were demonstrated by (1) complement-dependent cytotoxicity of autologous melanoma cells in short-term culture; (2) complement-dependent inhibition of ribonucleic acid synthesis; (3) immunofluorescent staining of the cytoplasm of killed melanoma cells and of the surface membrane of viable melanoma cells. Over one-third of the sera studied had antibodies to autologous melanoma cells.