ABCB1 (MDR1) rs1045642 is associated with increased overall survival in plasma cell myeloma

Multi-drug resistance (MDR) may compromise the successful management of haematological malignancies, impairing the effectiveness of chemotherapy. The P-glycoprotein (P-gp) drug efflux pump, encoded by the gene ABCB1 (MDR1), is the most widely studied component in MDR. A single nucleotide polymorphism (SNP) has been identified within ABCB1, rs1045642 (C3435T), which may alter P-gp substrate specificity and have an impact on the effectiveness of treatment, and hence overall survival (OS). We estimated the frequency of this SNP in the Northern Irish population and investigated its impact on the OS of patients with plasma cell myeloma (PCM). There was no significant difference in the frequency of rs1045642 between the PCM cohort and an age- and gender-matched control population. Findings within the PCM cohort suggest that rs1045642 genotype influences OS (p = 2 x 10(-2)). If confirmed in larger studies, these results suggest that genotyping rs1045642 may be a useful predictor of outcome in PCM and could indicate modified treatment modalities in certain individuals.

Gamma ray-induced bystander effect in tumour glioblastoma cells: a specific study on cell survival, cytokine release and cytokine receptors.

Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

A Census-based longitudinal study of variations in survival amongst residents of nursing and residential homes in Northern Ireland

Background: despite the intensive services provided to residents of care homes, information on death rates is not routinely available for this population in the UK. Objective: to quantify mortality rates across the care home population of Northern Ireland, and assess variation by type of care home and resident characteristics. Design: a prospective, Census-based cohort study, with 5-year follow-up. Participants: all 9,072 residents of care homes for people aged 65 and over at the time of the 2001 census with a special emphasis on the 2,112 residents admitted during the year preceding census day. Measurements: age, sex, self-reported health, marital status, residence (not in care home, residential home, dual registered home, nursing home), elderly mentally infirm care provision. Results: the median survival among nursing home residents was 2.33 years (95% CI 2.25–2.59), for dual registered homes 2.75 (95% CI 2.42–3.17) and for residential homes 4.51 (95% CI 3.92–4.92) years. Age, sex and self-reported health showed weaker associations in the sicker populations in nursing homes compared to those in residential care or among the non-institutionalised. Conclusions: the high mortality in care homes indicates that places in care homes are reserved for the most severely ill and dependent. Death rates may not be an appropriate care quality measure for this population, but may serve as a useful adjunct for clinical staff and the planning of care home provision.

High density mangrove plantation enhances surface accretion, surface elevation change, and tree survival in coastal areas susceptible to sea-level rise

Survival, growth, above ground biomass accumulation, soil surface elevation dynamics and nitrogen accumulation in accreted sediments were studied in experimental treatments planted with four different densities (6.96, 3.26, 1.93 and 0.95 seedlings m-2) of the mangrove Rhizophora mucronata in Puttalam Lagoon, Sri Lanka. Measurements were taken over a period of 1171 days and were compared with those from unplanted controls. Trees at the lowest density showed significantly reduced survival, whilst measures of individual tree growth did not differ significantly among treatments. Rates of surface sediment accretion (means ± S.E.) were 13.0 (±1.3), 10.5 (±0.9), 8.4 (±0.3), 6.9 (±0.5) and 5.7 (±0.3) mm yr-1 at planting densities of 6.96, 3.26, 1.93, 0.95, and 0 (unplanted control) seedlings m-2, respectively, showing highly significant differences among treatments. Mean (± S.E.) rates of surface elevation change were much lower than rates of accretion at 2.8 (±0.2), 1.6 (±0.1), 1.1 (±0.2), 0.6 (±0.2) and -0.3 (±0.1) mm yr-1 for 6.96, 3.26, 1.93, 0.95, and 0 seedlings m-2, respectively. All planted treatments appeared to accumulate greater nitrogen concentrations in the sediment compared to the unplanted control, and suggests one potential causal mechanism for the facilitatory effects observed; high densities of plants potentially contribute to the accretion of greater amounts of nutrient rich sediment. While this potential process needs further study, this study demonstrated how higher densities of mangroves enhance rates of sediment accretion and surface elevation, processes that may be crucial in mangrove ecosystem adaptation to sea level rise. There was no evidence that increasing plant density evoked a trade-off with growth and survival of the planted trees. Rather facilitatory effects enhanced survival at high densities, suggesting that local land managers may be able to take advantage of plantation densities to help mitigate sea-level rise effects by encouraging positive soil surface elevation increment, and perhaps even greater nutrient retention to promote mangrove growth and ameliorate nearshore eutrophication in tropical island environments.

Survival of laboratory-reared juvenile European lobster (Homarus gammarus) from three brood sources in southwestern Norway

Experiments were carried out from June 2000 to April 2001 to compare survival of European lobster (Homarus gammarus) offspring (larvae and juveniles) from three brood sources, Kvitsøy Wild (KW), Kvitsøy Cultured (KC), and Rogaland Wild (RW), Norway. In the first set of experiments, newly hatched larvae (stage I) were raised in separate family tanks. All larvae groups survived to stage III/IV, although large variation in relative survival was observed among families within each of the three different female groups. Highest overall survival was observed for the RW group (12.8%), whereas no differences in overall survival were found between the KW (9.0%) and KC groups (9.6%). From stage III/IV, larvae from single family tank experiments were mixed in five “common garden” juvenile experiments. These lasted for 9 months, and the surviving juveniles were identified to family/female group using microsatellite DNA profiling. Significantly higher survival of the KW families (7.0%) was found compared with the KC (3.7%) and the RW families (3.2%), and differences in family ranking of relative survival values were evident between the KW and KC groups. The relative survival rate of the different groups was independent of female lobster size. An estimate based on only stage IV larvae reduced the difference in survival between the KW (11.4%) and KC (8.3%) group. The experiments provided evidence that cultured females (KC) are producing viable offspring with lower, but comparable survival to that of offspring from wild females (KW).

Simulating Coxian Phase-type Distributions for Patient Survival

Coxian phase-type distributions are a special type of Markov model that can be used to represent survival times in terms of phases through which an individual may progress until they eventually leave the system completely. Previous research has considered the Coxian phase-type distribution to be ideal in representing patient survival in hospital. However, problems exist in fitting the distributions. This paper investigates the problems that arise with the fitting process by simulating various Coxian phase-type models for the representation of patient survival and examining the estimated parameter values and eigenvalues obtained. The results indicate that numerical methods previously used for fitting the model parameters do not always converge. An alternative technique is therefore considered. All methods are influenced by the choice of initial parameter values. The investigation uses a data set of 1439 elderly patients and models their survival time, the length of time they spend in a UK hospital.