Incidence of malignant neoplasms among HIV-infected persons in Scotland

Among 2574 persons diagnosed with HIV throughout Scotland and observed over the period 1981-1996, cancer incidence compared to the general population was 11 times higher overall; among homosexual/bisexual males, it was 21 times higher and among injecting drug users, haemophiliacs and heterosexuals it was five times higher, mostly due to AIDS-defining neoplasms. However, liver, lung and skin cancers (all non-AIDS-defining) were also significantly increased

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Socioeconomic inequalities in cancer survival in Scotland 1986–2000

We analysed trends in 5-year survival of the 18 commonest cancers in Scotland diagnosed between 1986 and 2000 and followed up to 2004 in each of five deprivation groups based on patients postcode of residence at diagnosis. We estimated relative survival up to 5 years after diagnosis, adjusting for the different background mortality in each deprivation group by age, sex and calendar period. We estimated trends in overall survival and in the deprivation gap in survival up to 2004. Five-year survival improved for all malignancies except bladder cancer and was associated with a widening in the deprivation gap in survival. For 25 of 30 cancer–sex combinations examined, 5-year survival was lower among more deprived patients diagnosed during 1996–2000, and the deprivation gap in survival had widened since 1986–1990 for 15 of these 25 cancers, similar to the trends seen in England and Wales

The greater proportion of born-light progeny from sows mated in summer contributes to increased carcass fatness observed in spring

The backfat of pig carcasses is greater in spring than summer in Australia. The unexplained seasonal variation in carcass backfat creates complications for pig producers in supplying consistent lean carcasses. As a novel explanation, we hypothesised that the increased carcass fatness in spring was due to a greater percentage of born-light progeny from sows that were mated in summer and experienced hot conditions during early gestation. The first part of our experiment compared the birth weight of piglets born to the sows mated in summer (February, the Southern Hemisphere) with those born to sows mated in autumn (May; the Southern Hemisphere), and the second part of the experiment compared the growth performance and carcass fatness of the progeny that were stratified as born-light (0.7–1.1 kg) and born-normal (1.3–1.7 kg) from the sows mated in these two seasons. The results showed that the sows mated in summer experienced hotter conditions during early gestation as evidenced by an increased respiration rate and rectal temperature, compared with those mated in autumn. The sows mated in summer had a greater proportion of piglets that were born ≤1.1 kg (24.2% vs. 15.8%, p < 0.001), lower average piglet birth weight (1.39 kg vs. 1.52 kg, p < 0.001), lower total litter weights (18.9 kg vs. 19.5 kg, p = 0.044) and lower average placental weight (0.26 vs. 0.31 kg, p = 0.011) than those mated in autumn, although litter sizes were similar. Feed intake and growth rate of progeny from 14 weeks of age to slaughter (101 kg live weight) were greater for the born-normal than born-light pigs within the progeny from sows mated in autumn, but there was no difference between the born-light and normal progeny from sows mated in summer, as evidenced by the interaction between piglet birth weight and sow mating season (Both p < 0.05). Only the born-light piglets from the sows mated in summer had a greater backfat thickness and loin fat% than the progeny from the sows mated in autumn, as evidenced by a trend of interaction between piglet birth weight and sow mating season (Both p < 0.10). In conclusion, the increased proportion of born-light piglets (0.7–1.1 kg range) from the sows mated in summer contributed to the increased carcass fatness observed in spring

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

High-speed fixed-target serial virus crystallography

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities

Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts

Background: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge

Spatial variation in prostate cancer survival in the Northern and Yorkshire region of England using Bayesian relative survival smoothing

Primary Care Trust (PCT) estimates of survival lack robustness as there are small numbers of deaths per year in each area, even when incidence is high. We assess PCT-level spatial variation in prostate cancer survival using Bayesian spatial models of excess mortality. We extracted data on men diagnosed with prostate cancer between 1990 and 1999 from the Northern and Yorkshire Cancer Registry and Information Service database. Models were adjusted for age at diagnosis, period of diagnosis and deprivation. All covariates had a significant association with excess mortality; men from more deprived areas, older age at diagnosis and diagnosed in 1990–1994 had higher excess mortality. The unadjusted relative excess risks (RER) of death by PCT ranged from 0.75 to 1.66. After adjustment, areas of high and low excess mortality were smoothed towards the mean, and the RERs ranged from 0.74 to 1.49. Using Bayesian smoothing techniques to model cancer survival by geographic area offers many advantages over traditional methods; estimates in areas with small populations or low incidence rates are stabilised and shrunk towards local and global risk estimates improving reliability and precision, complex models are easily handled and adjustment for covariates can be made

Forecasting Non-Stationary Diarrhea, Acute Respiratory Infection, and Malaria Time-Series in Niono, Mali

BACKGROUND: Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with diarrhea, acute respiratory infection, and malaria. With the increasing awareness that the aforementioned infectious diseases impose an enormous burden on developing countries, public health programs therein could benefit from parsimonious general-purpose forecasting methods to enhance infectious disease intervention. Unfortunately, these disease time-series often i) suffer from non-stationarity; ii) exhibit large inter-annual plus seasonal fluctuations; and, iii) require disease-specific tailoring of forecasting methods. METHODOLOGY/PRINCIPAL FINDINGS: In this longitudinal retrospective (01/1996-06/2004) investigation, diarrhea, acute respiratory infection of the lower tract, and malaria consultation time-series are fitted with a general-purpose econometric method, namely the multiplicative Holt-Winters, to produce contemporaneous on-line forecasts for the district of Niono, Mali. This method accommodates seasonal, as well as inter-annual, fluctuations and produces reasonably accurate median 2- and 3-month horizon forecasts for these non-stationary time-series, i.e., 92% of the 24 time-series forecasts generated (2 forecast horizons, 3 diseases, and 4 age categories = 24 time-series forecasts) have mean absolute percentage errors circa 25%. CONCLUSIONS/SIGNIFICANCE: The multiplicative Holt-Winters forecasting method: i) performs well across diseases with dramatically distinct transmission modes and hence it is a strong general-purpose forecasting method candidate for non-stationary epidemiological time-series; ii) obliquely captures prior non-linear interactions between climate and the aforementioned disease dynamics thus, obviating the need for more complex disease-specific climate-based parametric forecasting methods in the district of Niono; furthermore, iii) readily decomposes time-series into seasonal components thereby potentially assisting with programming of public health interventions, as well as monitoring of disease dynamics modification. Therefore, these forecasts could improve infectious diseases management in the district of Niono, Mali, and elsewhere in the Sahel