Bypassing the selection rule in choosing controls for a case-control study

Objectives It has been argued that in case–control studies, controls should be drawn from the base population that gives rise to the cases. In designing a study of occupational injury and risks arising from long-term illness and prescribed medication, we lacked data on subjects' occupation, without which employed cases (typically in manual occupations) would be compared with controls from the general population, including the unemployed and a higher proportion of white-collar professions. Collecting the missing data on occupation would be costly. We estimated the potential for bias if the selection rule were ignored. Methods: We obtained published estimates of the frequencies of several exposures of interest (diabetes, mental health problems, asthma, coronary heart disease) in the general population, and of the relative risks of these diseases in unemployed versus employed individuals and in manual versus non-manual occupations. From these we computed the degree of over- or underestimation of exposure frequencies and exposure ORs if controls were selected from the general population. Results: The potential bias in the OR was estimated as likely to fall between an underestimation of 14% and an overestimation of 36.7% (95th centiles). In fewer than 6% of simulations did the error exceed 30%, and in none did it reach 50%. Conclusions: For the purposes of this study, in which we were interested only in substantial increases in risk, the potential for selection bias was judged acceptable. The rule that controls should come from the same base population as cases can justifiably be broken, at least in some circumstances. <br/

Recombinants of the major histocompatibility complex in the chicken

The primary purpose of this research was to produce and analyze recombinants of the major histocompatibility complex of the chicken in order to provide useful information concerning its structure and function. Recombinant research provides data relating to the linear order of genes and aids in elucidating gene functions. On a practical level, such knowledge bears on the health and well-being of a species. From the point of view of evolutionary origin, this information complements that already known of the mammalian major histocompatibility complex;From matings of B complex heterozygotes (B(\u271)B(\u2719)) to homozygotes (B(\u272)B(\u272)), 5 recombinants were produced in 5,584 chicks tested by hemagglutination. Analysis of the data indicates that the B(\u271) parental haplotype contributed the B-G gene and the B(\u2719) parental haplotype contributed the B-F gene to the recombinant haplotypes. The new recombinants have been designated B(\u2719r1), B(\u2719r2), B(\u2719r3), B(\u2719r4), and B(\u2719r5). The B-F region of the B(\u2719r1) haplotype controls allograft rejection, mixed lymphocyte reaction, and graft-versus-host splenomegaly. No functional properties could be assigned to the B-G region;Recombination between a locus controlling immune response to the amino acid polymer GAT and a chromosome segment containing the B-G and B-F genes has previously been reported from Iowa State University studies. Because the B(\u2719r1) haplotype confers high immune response to the amino acid polymer GAT, it was likely produced from a crossover between the B-G locus and a chromosome segment containing the B-F and Ir-GAT-Hi genes. The region controlling immune response to GAT very probably is identical to the previously described B-L region. The putative order of these regions is, therefore, B-G, B-F and B-L

Mortality from infectious pneumonia in metal workers: a comparison with deaths from asthma in occupations exposed to respiratory sensitizers

Introduction: national analyses of mortality in England and Wales have repeatedly shown excess deaths from pneumonia in welders. During 1979-1990 the excess was attributable largely to deaths from lobar pneumonia and pneumonias other than bronchopneumonia, limited to working-aged men, and apparent in other metal fume-exposed occupations. We assessed findings for 1991-2000 and compared the mortality pattern with that from asthma in occupations exposed to known respiratory sensitizers.Methods: the Office of National Statistics supplied data on deaths by underlying cause among men aged 16-74 years in England and Wales during 1991-2000, including age and last held occupation. We abstracted data on pneumonia for occupations with exposure to metal fume and on asthma for occupations commonly reported to surveillance schemes as at risk of occupational asthma. We estimated expected numbers of deaths by applying age-specific proportions of deaths by cause in the population to the total deaths by age in each occupational group. Observed and expected numbers were compared for each cause of death.Results: among working-aged men in metal fume-exposed occupations we found excesses of mortality from pneumococcal and lobar pneumonia (54 deaths vs. 27.3 expected) and from pneumonias other than bronchopneumonia (71 vs. 52.4), but no excess from these causes at older ages, or from bronchopneumonia at any age. The attributable mortality from metal fume (45.3 excess deaths) compared with an estimated 62.6 deaths from occupational asthma.Conclusion: exposure to metal fume is a material cause of occupational mortality. The hazard deserves far more attention than it presently receive

Foot and Mouth Epidemic Reduces Cases of Human Cryptosporidiosis in Scotland.

In Scotland, rates of cryptosporidiosis infection in humans peak during the spring, a peak that is coincident with the peak in rates of infection in farm animals (during lambing and calving time). Here we show that, during the outbreak of foot and mouth disease (FMD) in 2001, there was a significant reduction in human cases of cryptosporidiosis infection in southern Scotland, where FMD was present, whereas, in the rest of Scotland, there was a reduction in cases that was not significant. We associate the reduction in human cases of cryptosporidiosis infection with the reduction in the number of young farm animals, together with restrictions on movement of both farm animals and humans, during the outbreak of FMD in 2001. We further show that, during 2002, there was recovery in the rate of cryptosporidiosis infection in humans throughout Scotland, particularly in the FMD-infected area, but that rates of infection remained lower, though not significantly, than pre-2001 levels

Robust radiocarbon dating of wood samples by high-sensitivity liquid scintillation spectroscopy in the 50–70 kyr age range

Although high-sensitivity liquid scintillation (LS) spectroscopy is theoretically capable of producing finite radiocarbon ages in the 50,000- to 70,000-yr range, there is little evidence in the literature that meaningful dates in this time period have been obtained. The pressing need to undertake calibration beyond 26 kyr has resulted in the regular publication of ¹⁴C results in excess of 50 kyr, yet very little effort has been made to demonstrate their accuracy or precision. There is a paucity of systematic studies of the techniques required to produce reliable dates close to background and the methods needed to assess contamination from either in situ sources or laboratory handling and processing. We have studied the requirements for producing accurate and reliable dates beyond 50 kyr. Laboratory procedures include optimization of LS spectrometers to obtain low and stable non-¹⁴C background count rates, use of low-background counting vials, large benzene volumes, long counting times, and preconditioning of vacuum lines. We also discuss the need for multiple analyses of a suitable material containing no original ¹⁴C (background blank) and the application of an appropriate statistical model to compensate for variability in background contamination beyond counting statistics. Accurate and reproducible finite ages >60 kyr are indeed possible by high-sensitivity LS spectroscopy, but require corroborating background blank data to be defensible

Historical reconstruction of the Atlantic Meridional Overturning Circulation from the ECMWF operational ocean reanalysis

A reconstruction of the Atlantic Meridional Overturning Circulation (MOC) for the period 1959–2006 has been derived from the ECMWF operational ocean reanalysis. The reconstruction shows a wide range of time-variability, including a downward trend. At 26N, both the MOC intensity and changes in its vertical structure are in good agreement with previous estimates based on trans-Atlantic surveys. At 50N, the MOC and strength of the subpolar gyre are correlated at interannual time scales, but show opposite secular trends. Heat transport variability is highly correlated with the MOC but shows a smaller trend due to the warming of the upper ocean, which partially compensates for the weakening of the circulation. Results from sensitivity experiments show that although the time-varying upper boundary forcing provides useful MOC information, the sequential assimilation of ocean data further improves the MOC estimation by increasing both the mean and the time variability

Is primary angioplasty cost effective in the UK? Results of a comprehensive decision analysis

Objective: To assess the cost effectiveness of primary angioplasty, compared with medical management with thrombolytic drugs, to achieve reperfusion after acute myocardial infarction ( AMI) from the perspective of the UK NHS. Design: Bayesian evidence synthesis and decision analytic model. Methods: A systematic review was conducted and Bayesian statistical methods used to synthesise evidence from 22 randomised control trials. Resource utilisation was based on UK registry data, published literature and national databases, with unit costs taken from routine NHS sources and published literature. Main outcome measure: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs). Results: For the base case, the incremental cost-effectiveness ratio of primary angioplasty was pound 9241 for each additional QALY, with a probability of being cost effective of 0.90 for a cost-effectiveness threshold of pound 20 000. Results were sensitive to variations in the additional time required to initiate treatment with primary angioplasty. Conclusions: Primary angioplasty is cost effective for the treatment of AMI on the basis of threshold cost-effectiveness values used in the NHS and subject to a delay of up to about 80 minutes. These findings are mainly explained by the superior mortality benefit and the prevention of non-fatal outcomes associated with primary angioplasty for delays of up to this length

Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis

Background: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered. Objective: To extend earlier meta-analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships. Methods: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (Crl)) as a function of the additional time delay associated with angioplasty. \ Results: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean ( SE) angioplasty-related time delay ( over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis ( OR = 0.68 ( 95% Crl 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 ( 95% Crl 0.20 to 0.51); for non-fatal stroke OR = 0.24 ( 95% Crl 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation. Conclusions: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1- month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays

Multigene analyses identify the three earliest lineages of extant flowering plants

AbstractFlowering plants (angiosperms) are by far the largest, most diverse, and most important group of land plants, with over 250,000 species and a dominating presence in most terrestrial ecosystems. Understanding the origin and early diversification of angiosperms has posed a long-standing botanical challenge [1]. Numerous morphological and molecular systematic studies have attempted to reconstruct the early history of this group, including identifying the root of the angiosperm tree. There is considerable disagreement among these studies, with various groups of putatively basal angiosperms from the subclass Magnoliidae having been placed at the root of the angiosperm tree (reviewed in [2–4]). We investigated the early evolution of angiosperms by conducting combined phylogenetic analyses of five genes that represent all three plant genomes from a broad sampling of angiosperms. Amborella, a monotypic, vesselless dioecious shrub from New Caledonia, was clearly identified as the first branch of angiosperm evolution, followed by the Nymphaeales (water lilies), and then a clade of woody vines comprising Schisandraceae and Austrobaileyaceae. These findings are remarkably congruent with those from several concurrent molecular studies [5–7] and have important implications for whether or not the first angiosperms were woody and contained vessels, for interpreting the evolution of other key characteristics of basal angiosperms, and for understanding the timing and pattern of angiosperm origin and diversification

The influence of incorporating a forecutter on the performance of offshore pipeline ploughs

AbstractInstallation of offshore pipelines in the seabed can be efficiently achieved using pipeline ploughs. Increased efficiency may be achievable through incorporating a smaller forecutter in advance of the main plough share. Currently guidance is limited and conflicting as to the advantages or disadvantages of incorporating a forecutter. To investigate the effect of forecutter inclusion model tests were undertaken at 1/50th scale under laboratory conditions in sand beds prepared at different relative densities in both dry and saturated conditions. Dry sand tests were used to determine the effect of the forecutter on the static or passive components of plough tow force. The currently adopted passive pressure coefficient (Cs) did not appear to vary with relative density to the same degree as previously suggested and the forecutter increased the magnitude of the passive or static resistance to ploughing. Saturated tests were used to determine the effects of the forecutter on the rate dependant component of ploughing resistance and allow verification of a dimensionless form of rate effect representation. The forecutter acts to reduce the rate effect component of plough tow force in both fine sand (low permeability) and to a lesser extent in medium sand (higher permeability). In fine and silty sands, however, incorporating a forecutter would seem highly beneficial at all ploughing depths and soil densities but in medium sand (higher permeability) the benefits of incorporation are limited to an operating window at shallower trench depths and lower relative density