A numerical approach to C-14 wiggle-match dating of organic deposits: best fits and confidence intervals

14C wiggle-match dating (WMD) of peat deposits uses the non-linear relationship between 14C age and calendar age to match the shape of a sequence of closely spaced peat 14C dates with the 14C calibration curve. A numerical approach to WMD enables the quantitative assessment of various possible wiggle-match solutions and of calendar year confidence intervals for sequences of 14C dates. We assess the assumptions, advantages, and limitations of the method. Several case-studies show that WMD results in more precise chronologies than when individual 14C dates are calibrated. WMD is most successful during periods with major excursions in the 14C calibration curve (e.g., in one case WMD could narrow down confidence intervals from 230 to 36 yr).

Laplace transforms of probability distributions and their inversions are easy on logarithmic scales

It is shown that, when expressing arguments in terms of their logarithms, the Laplace transform of a function is related to the antiderivative of this function by a simple convolution. This allows efficient numerical computations of moment generating functions of positive random variables and their inversion. The application of the method is straightforward, apart from the necessity to implement it using high-precision arithmetics. In numerical examples the approach is demonstrated to be particularly useful for distributions with heavy tails, Such as lognormal, Weibull, or Pareto distributions, which are otherwise difficult to handle. The computational efficiency compared to other methods is demonstrated for an M/G/1 queueing problem.

Tracking leatherback turtles (Dermochelys coriacea) during consecutive inter-nesting intervals: Further support for direct transmitter attachment

Over recent years there have been substantial efforts to record and interpret the post-nesting movements of leatherback turtles (Dermochelys coriacea) breeding in tropical regions. Less well documented are the movements undertaken by individual turtles during the breeding season itself, or more specifically between sequential nesting events. Such movements are of interest for two reasons: (1) gravid female leatherbacks may range extensively into the territorial waters and nesting beaches of neighbouring countries, raising questions for conservationists and population ecologists; and (2) the magnitude of movements themselves help elucidate underlying reproductive strategies (e.g. whether to rest near to the nesting or forage extensively). Here, satellite relay data loggers are used (SRDLs) to detail the movements and behaviour of two female leatherback turtles throughout three consecutive inter-nesting intervals in the Commonwealth of Dominica, West Indies. Both near-shore residence and extensive inter-nesting movements were recorded, contrasting previous studies, with movements away from the nesting beach increasing towards the end of the nesting season. Using this behavioural study as a backdrop, the suitability of attaching satellite transmitters directly to the carapace was additionally explored as an alternative approach to conventional harness deployments. Specifically, the principal aims were to (1) gather empirical data on speed of travel and (2) assess dive performance (aerobic dive limit) to enable comparisons with turtles previously fitted with harnesses elsewhere in the Caribbean (n = 6 turtles; Grenada, WI). This produced mixed results with animals bearing directly attached transmitters travelling significantly faster (55.21 km day(-1): SD 6.68) than harnessed individuals (39.80 km day(-1); SD 6.19); whilst no discernable difference in dive performance could be found between the two groups of study animals. (C) 2009 Elsevier B.V. All rights reserved.

Water temperature and internesting intervals for loggerhead (Caretta caretta) and green (Chelonia mydas) sea turtles

Temperature loggers were attached to the carapace of green turtles (Chelonia mydas) at Ascension Island and Cyprus and to loggerhead turtles (Caretta caretta) at Cyprus, in order to record the ambient temperature experienced by individuals during the internesting interval, i.e. the period between consecutive clutches being laid. Internesting intervals were relatively short (10-14 days) and mean ambient temperatures relatively warm (27-28degreesC), compared to previous observations for these species nesting in Japan, although a single internesting interval versus temperature relationship described all the data for these two species from the different areas. The implication is that water temperature has both a common and a profound effect on the length of the internesting interval for these two species: internesting intervals are shorter when the water is warmer. (C) 2002 Elsevier Science Ltd. All rights reserved.

Age-related reference intervals for lymphocyte subsets in whole blood of healthy individuals

Enumeration of various lymphocyte subsets is used widely in the diagnosis and monitoring of various disease states. With the development of flow cytometric technology and whole blood analysis, methodologies have become more sensitive. It is therefore important to establish reference intervals in normal, healthy individuals using these techniques to give a better indication of the border between health and disease. Since some lymphocyte subpopulations are known to change with age, we have enumerated common subsets in healthy individuals from all decades of adult life, including nonagenarian subjects. We report reference intervals for these subsets in each age group, which will be of use in diagnosis and disease monitoring, particularly in elderly subjects, the most rapidly expanding group within the population today.

The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis:results of a phase II study

This study was designed to assess the potential of the continuous erythropoietin receptor activator (C.E.R.A.) to correct anemia at extended administration intervals in erythropoiesis-stimulating agent-naīve patients with chronic kidney disease (CKD) not on dialysis and to determine its optimal starting dose.

The mediastinal staging accuracy of 18F-Fluorodeoxyglycose Positron Emission Tomography/Computed Tomography in non-small cell lung cancer with variable time intervals to surgery.

BACKGROUND: PET/CT scanning can determine suitability for curative therapy and inform decision making when considering radical therapy in patients with non-small cell lung cancer (NSCLC). Metastases to central mediastinal lymph nodes (N2) may alter such management decisions. We report a 2 year retrospective series assessing N2 lymph node staging accuracy with PET/CT compared to pathological analysis at surgery.

METHODS: Patients with NSCLC attending our centre (excluding those who had induction chemotherapy) who had staging PET/CT scans and pathological nodal sampling between June 2006 and June 2008 were analysed. For each lymph node assessed pathologically, the corresponding PET/CT status was determined. 64 patients with 200 N2 lymph nodes were analysed.

RESULTS: Sensitivity of PET/CT scans for indentifying involved N2 lymph nodes was
39%, specificity 96% and overall accuracy 90%. For individual lymph node analysis, logistic regression demonstrated a significant linear association between PET/CT sensitivity and time from scanning to surgery (p=0.031) but not for specificity and accuracy. Those scanned <9 weeks before pathological sampling were significantly more sensitive (64% >9 weeks, 0% ≥ 9 weeks, p=0.013) and more accurate (94% <9 weeks, 81% ≥ 9 weeks, p=0.007). Differences in specificity were not seen (97% <9 weeks, 91% ≥ 9 weeks, p=0.228). No significant difference in specificity was found at any time point.

CONCLUSIONS: We recommend that if a PET/CT scan is older than 9 weeks, and management would be altered by the presence of N2 nodes, re-staging of the
mediastinum should be undertaken.

Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification

Aims/hypothesis: Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD. Methods: We exploited a novel algorithm, ‘Bag of Naive Bayes’, whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate association tests. The analysis was performed on a genome-wide association study of 3,464 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and subsequently replicated with 4,263 type 1 diabetes patients from the Steno Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK collection (UK–Republic of Ireland) and the Genetics of Kidneys in Diabetes US Study (GoKinD US). Results: Five genetic loci (WNT4/ZBTB40-rs12137135, RGMA/MCTP2-rs17709344, MAPRE1P2-rs1670754, SEMA6D/SLC24A5-rs12917114 and SIK1-rs2838302) were associated with ESRD in the FinnDiane study. An association between ESRD and rs17709344, tagging the previously identified rs12437854 and located between the RGMA and MCTP2 genes, was replicated in independent case–control cohorts. rs12917114 near SEMA6D was associated with ESRD in the replication cohorts under the genotypic model (p < 0.05), and rs12137135 upstream of WNT4 was associated with ESRD in Steno. Conclusions/interpretation: This study supports the previously identified findings on the RGMA/MCTP2 region and suggests novel susceptibility loci for ESRD. This highlights the importance of applying complementary statistical methods to detect novel genetic variants in diabetic nephropathy and, in general, in complex diseases.

Excess mortality in Type 1 diabetes diagnosed in childhood and adolescence: a systematic review of population-based cohorts

Aims: Systematic review of mortality in childhood-/adolescent-diagnosed Type 1 diabetes and examination of factors explaining the mortality variation between studies. 
Methods: Relevant studies were identified from systematic searches of MEDLINE and EMBASE. Observed and expected numbers of deaths were extracted, and standardised mortality ratios (SMRs) and 95 % confidence intervals (CIs) were calculated. Negative binomial regression was used to investigate association between mortality and study/country characteristics.
Results: Thirteen relevant publications with mortality data were identified describing 23 independent studies. SMRs varied markedly ranging from 0 to 854 (chi-squared = 70.68,df = 21, p<0.0001). Significant associations were observed between SMR and mid-year of follow-up [incidence rate ratio (IRR) 0.95, 95 % CI 0.91–0.99 equivalent to a 5 % decrease per year], between SMR and infant mortality rate (IRR 1.07, 95 % CI 1.02–1.12, a 7 % increase for each death per 1,000 live births) and, after omitting an outlier, between SMR and health expenditure as a percentage of gross domestic product (GDP) (IRR 0.79, 95 % CI 0.68–0.93, a 21 % decrease for each one percent increase in GDP). No relationship was detected between SMR and a country’s childhood diabetes incidence rate or GDP.
Conclusions: Excess mortality in childhood-/adolescent diagnosed Type 1 diabetes is apparent across countries worldwide. Excesses were less marked in more recent studies and in countries with lower infant mortality and higher health expenditure.

A Conditional Approach for Modelling Patient Re-admissions in Hospital using a mixture of Coxian phase-type distributions incorporating Bayes Theorem

The number of elderly patients requiring hospitalisation in Europe is rising. With a greater proportion of elderly people in the population comes a greater demand for health services and, in particular, hospital care. Thus, with a growing number of elderly patients requiring hospitalisation competing with non-elderly patients for a fixed (and in some cases, decreasing) number of hospital beds, this results in much longer waiting times for patients, often with a less satisfactory hospital experience. However, if a better understanding of the recurring nature of elderly patient movements between the community and hospital can be developed, then it may be possible for alternative provisions of care in the community to be put in place and thus prevent readmission to hospital. The research in this paper aims to model the multiple patient transitions between hospital and community by utilising a mixture of conditional Coxian phase-type distributions that incorporates Bayes' theorem. For the purpose of demonstration, the results of a simulation study are presented and the model is applied to hospital readmission data from the Lombardy region of Italy.