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Biomedical subjects

P J Solomon

Publications and source records attributed to P J Solomon.

At least 19 recordsLinked to original sources
PubMed2005

Expression profiling reveals functionally important genes and coordinately regulated signaling pathway genes during in vitro angiogenesis.

Angiogenesis is a complex multicellular process requiring the orchestration of many events including migration, alignment, proliferation, lumen formation, remodeling, and maturation. Such complexity indicates that not only individual genes but also entire signaling pathways will be crucial in angiogenesis. To define an angiogenic blueprint of regulated genes, we utilized our well-characterized three-dimensional collagen gel model of in vitro angiogenesis, in which the majority of cells synchronously progress through defined morphological stages culminating in the formation of capillary tubes. We developed a comprehensive three-tiered approach using microarray analysis, which allowed us to identify genes known to be involved in angiogenesis and genes hitherto unlinked to angiogenesis as well as novel genes and has proven especially useful for genes where the magnitude of change is small. Of interest is the ability to recognize complete signaling pathways that are regulated and genes clustering into ontological groups implicating the functional importance of particular processes. We have shown that consecutive members of the mitogen-activated protein kinase and leukemia inhibitory factor signaling pathways are altered at the mRNA level during in vitro angiogenesis. Thus, at least for the mitogen-activated protein kinase pathway, mRNA changes as well as the phosphorylation changes of these gene products may be important in the control of blood vessel morphogenesis. Furthermore, in this study, we demonstrated the power of virtual Northern blot analysis, as an alternative to quantitative RT-PCR, for measuring the magnitudes of differential gene expression.

Bayes Theorem↗
PubMed2005

Assessment of outcome over a 10-year period of patients admitted to a multidisciplinary adult intensive care unit with haematological and solid tumours.

The risk factors for time to mortality, censored at 30 days, of patients admitted to an adult teaching hospital ICU with haematological and solid malignancies were assessed in a retrospective cohort study. Patients, demographics and daily ICU patient data, from admission to day 8, were identified from a prospective computerized database and casenote review in consecutive admissions to ICU with haematological and solid tumours over a 10-year period (1989-99). The cohort, 108 ICU admissions in 89 patients was of mean age (+/-SD) 55+/-14 years; 43% were female. Patient diagnoses were leukaemia (35%), lymphoma (38%) and solid tumours (27%). Median time from hospital to ICU admission was five days (range 0-67). On ICU admission, 50% had septic shock and first day APACHE II score was 28+/-9. Forty-six per cent of patients were ventilated. ICU and 30-day mortality were 39% and 54% respectively. Multivariate Cox model predictors (P<0.05), using only ICU admission day data were: Charlson comorbidity index (CCI), time to ICU admission (days) and mechanical ventilation. For daily data (admission through day 8), predictors were: cohort effect (2nd vs 1st five-year period); CCI; time to ICU admission (days); APACHE II score and mechanical ventilation. Outcomes were considered appropriate for severity of illness and demonstrated improvement over time. Ventilation was an independent outcome determinant. Controlling for other factors, mortality has improved over time (1st vs 2nd five year period). Analysis restricted to admission data alone may be insensitive to particular covariate effects.

APACHE↗
PubMed2004

Factorial and time course designs for cDNA microarray experiments.

Microarrays are powerful tools for surveying the expression levels of many thousands of genes simultaneously. They belong to the new genomics technologies which have important applications in the biological, agricultural and pharmaceutical sciences. There are myriad sources of uncertainty in microarray experiments, and rigorous experimental design is essential for fully realizing the potential of these valuable resources. Two questions frequently asked by biologists on the brink of conducting cDNA or two-colour, spotted microarray experiments are 'Which mRNA samples should be competitively hybridized together on the same slide?' and 'How many times should each slide be replicated?' Early experience has shown that whilst the field of classical experimental design has much to offer this emerging multi-disciplinary area, new approaches which accommodate features specific to the microarray context are needed. In this paper, we propose optimal designs for factorial and time course experiments, which are special designs arising quite frequently in microarray experimentation. Our criterion for optimality is statistical efficiency based on a new notion of admissible designs; our approach enables efficient designs to be selected subject to the information available on the effects of most interest to biologists, the number of arrays available for the experiment, and other resource or practical constraints, including limitations on the amount of mRNA probe. We show that our designs are superior to both the popular reference designs, which are highly inefficient, and to designs incorporating all possible direct pairwise comparisons. Moreover, our proposed designs represent a substantial practical improvement over classical experimental designs which work in terms of standard interactions and main effects. The latter do not provide a basis for meaningful inference on the effects of most interest to biologists, nor make the most efficient use of valuable and limited resources.

Animals↗
PubMed2004

Modelling thirty-day mortality in the Acute Respiratory Distress Syndrome (ARDS) in an adult ICU.

Variables predicting thirty-day outcome from Acute Respiratory Distress Syndrome (ARDS) were analysed using Cox regression structured for time-varying covariates. Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral chest X-ray opacities, PaO2/FiO2 ratio of <200 and an acute precipitating event) were identified using a prospective computerized data base in a university teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8); ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO2/FiO2 ratio was 92 (31), 81% had four-quadrant chest X-ray opacification and lung injury score was 2.75 (0.45). Average mechanical ventilator tidal volume was 10.3 ml/predicted kg weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus indirect injury, 2.89 (1.45-5.76); PaO2/FiO2 ratio, 0.98 (0.97-0.99); operative versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were evident for PaO2/FiO2 ratio, operative versus non-operative category and ventilator tidal volume assessed as a categorical predictor with a cut-point of 8 ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg predicted weight). Thirty-day survival was improved for patients ventilated with lower tidal volumes. Survival predictors in ARDS were multifactorial and related to patient-injury-time interaction and level of mechanical ventilator tidal volume.

APACHE↗
PubMed2004

Cost calculation and prediction in adult intensive care: a ground-up utilization study.

The ability of various proxy cost measures, including therapeutic activity scores (TISS and Omega) and cumulative daily severity of illness scores, to predict individual ICU patient costs was assessed in a prospective "ground-up" utilization costing study over a six month period in 1991. Daily activity (TISS and Omega scores) and utilization in consecutive admissions to three adult university associated ICUs was recorded by dedicated data collectors. Cost prediction used linear regression with determination (80%) and validation (20%) data sets. The cohort, 1333 patients, had a mean (SD) age 57.5 (19.4) years, (41% female) and admission APACHE III score of 58 (27). ICU length of stay and mortality were 3.9 (6.1) days and 17.6% respectively. Mean total TISS and Omega scores were 117 (157) and 72 (113) respectively. Mean patient costs per ICU episode (1991 dollar AUS) were dollar 6801 (dollar 10311), with median costs of dollar 2534, range dollar 106 to dollar 95,602. Dominant cost fractions were nursing 43.3% and overheads 16.9%. Inflation adjusted year 2002 (mean) costs were dollar 9343 (dollar AUS). Total costs in survivors were predicted by Omega score, summed APACHE III score and ICU length of stay; determination R2, 0.91; validation 0.88. Omega was the preferred activity score. Without the Omega score, predictors were age, summed APACHE III score and ICU length of stay; determination R2, 0.73; validation 0.73. In non-survivors, predictors were age and ICU length of stay (plus interaction), and Omega score (determination R2, 0.97; validation 0.91). Patient costs may be predicted by a combination of ICU activity indices and severity scores.

APACHE↗
PubMed2002

Phosphate metabolism in intensive care patients with acute respiratory failure.

OBJECTIVE: To determine the variables predicting the change of plasma phosphate over the first 24 hr period in intensive care in patients with acute respiratory failure. METHODS: Fifty-seven patients were studied prospectively in a university teaching hospital intensive care unit (ICU). Thirty two patients were classified as having acute respiratory failure and a primary respiratory system diagnosis (group I), 10 were classified as having acute cardiogenic pulmonary oedema (group II) and 15 were general ICU patients (group III). Arterial blood specimens at intensive care unit admission (T0) and at 24 hr post-admission (T24) were assayed for multiple plasma biochemical parameters including phosphate (PO4) and red blood cell 2,3-diphosphoglycerate (2,3-DPG). Timed urine collections were used to determine 24 hr urine phosphate loss and renal phosphate threshold concentration (RTP). During the measurement period glucose-free fluids only were infused. RESULTS: Fifty seven patients had a mean (+/- SD) age of 67 +/- 12 years and Apache II score of 22 +/- 6. The plasma PO4 at T0 was 1.55 +/- 0.71 mmol/L and showed a significant 24 hr decrease of 0.55 mmol/L (p < 0.0001) at T24. Hypophosphataemia at T0 was observed in 26% of patients. Red blood cell 2,3-DPG was not elevated at T0 (13.5 +/- 3.3 umol/gHb) and showed a non-significant increment over 24 hr. Urine phosphate loss over the 24 hr period was 21.8 +/- 14.0 mmol with RTP being reduced below the lower reference range limit in groups I (0.65 +/- 0.29 mmol/L) and II (0.57 +/- 0.29 mmol/L). The naive form of phosphate change (PO4T24-PO4T0) was significantly related to initial plasma PO4 and was subject to regression to the mean, which was estimated to have inflated the relationship by 25%. The appropriate form of phosphate change was found to be log ratio T24/T0 phosphate. Independent predictors of log ratio T24/T0 phosphate were 24 hr change (T24-T0) in both 2,3-DPG and arterial pH, RTP, prescription of aminophylline (categorical factor) and the interaction of aminophylline and RTP (R2 = 0.65, ordinary least squares regression). CONCLUSIONS: Twenty-four hour plasma phosphate decrement in intensive care unit patients was multi-factorial and was attended by a lowered renal threshold phosphate concentration.

Journal Article↗
PubMed2000

Disease surveillance and data collection issues in epidemic modelling.

This paper is founded on a tutorial session given to the School on Modern Statistical Methods in Medical Research which was held at the International Centre for Theoretical Physics, Trieste in September 1999. We review the aims, scope and purposes of infectious disease surveillance including determining transmission information to underpin model structure and parameterization in epidemic modelling. The practical problems inherent in collecting surveillance data are illustrated by a study of HIV/AIDS in Cambodia. We also review the basic elements of mathematical models developed to represent the transmission dynamics of infectious diseases, and discuss reasons for the gap between mathematical epidemic models and available data.

Cambodia↗
PubMed1997

Truncated recurrent event survival models for methadone data.

Truncated multivariate survival models are proposed for the analysis of data from the South Australian Methadone Program. Injecting drug users may have several entries to and exists from the program. A marginal approach for recurrent events is found to provide a useful and simplified basis for modeling the retention of injecting drug users on methadone. The likelihoods and results of fitting two forms of truncated survival models are presented, together with recommendations for statistical analysis using S-PLUS. The relative merits of the marginal approach in this context and alternative ways of viewing the data are discussed.

Biometry↗