Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Flexibility is a particularly important biomechanical property for intracranial vascular stents. To study the flexibility of stent, the following work was carried out by using the finite element method: Four mechanical models were adopted to simulate the bending deformation of stents, and comparative studies were conducted about the distinction between cantilever beam and simply supported beam, as well as the distinction between moment-loading method and displacement-loading method. A complete process as implanting a stent including compressing, expanding and bending was also simulated, for analyzing the effects of compressing and expanding deformation on stent flexibility. At the same time, the effects of the arrangement and the number of bridges on stent flexibility were researched. The results show that: 1. A same flexibility index was obtained from cantilever beam model and simply supported beam model; displacement-loading method is better than moment-loading for simulating the bending deformation of stents. 2. The flexibility of stent with compressing and expanding deformation is lower than that in the initial form. 3. Crossly arranging the neighboring bridges in axial direction, can effectively improve the stent flexibility and reduce the flexibility difference in various bending directions; the bridge number, has proportional non-linear correlation with the stent rigidity as well as the maximum moment required for bending the stent.

Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006–2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36–27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21–36·68%) in urban area to −1·90% (95 eCI −25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1–4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4–31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.

This study aimed to comprehensively evaluate factors that influence the likelihood of syphilis infection from risk-taking behaviours and medical conditions. A retrospective case-control study was conducted by enrolling 664 syphilis inpatients (excluding 11 congenital syphilis patients) and 800 sex- and age-matched controls. Medical histories, clinical data and patient interview data were collected and subjected to logistic regression analyses. The prevalence of syphilis in the study population was 3·9% (675/17 304). By univariate analysis, syphilis infection was associated with migration between cities, marital status, smoking, reproductive history, hypertension, elevated blood urea nitrogen (BUN) and infection with hepatitis B virus (HBV) (P < 0·05). A high rate of syphilis-HBV co-infection was observed in HIV-negative patients and further research revealed an association between syphilis and specific HBV serological reactivity. Syphilis was also associated with the frequency, duration and status of tobacco use. Multivariate analysis indicated that syphilis infection was independently associated with migration between cities [adjusted odds ratio (aOR) 1·368, 95% confidence interval (CI) 1·048–1·785], current smoking (aOR 1·607, 95% CI 1·177–2·195), elevated BUN (aOR 1·782, 95% CI 1·188–2·673) and some serological patterns of HBV infection. To prevent the spread of infectious diseases, inpatients and blood donors should be tested for HIV, syphilis, HBV and HCV simultaneously.

We determined the prevalence and seasonality of infections by Fasciola of goats and bovine species (cattle and water buffalo) in Hubei and Anhui provinces of China. Faecal samples were collected at 2- to 3-month intervals from 200 goats in Hubei province and from 152 bovine species in Anhui province. All faecal samples were examined for the presence of parasites. We determined the nucleotide sequences of the first and second internal transcribed spacers (ITS-1 and ITS-2) of the nuclear ribosomal DNA (rDNA) of 39 Fasciola worms from Anhui province. The prevalence of Fasciola infection in goats ranged between 3.5 and 37.0%, with mean eggs per gram (EPG) ranging between 29.0 and 166.0. Prevalence and EPG exhibited downward trends over time with significant differences. The prevalence of Fasciola infection in cattle ranged between 13.3 and 46.2% (mean EPG, 36.4–100.0), and that of water buffalo ranged between 10.3 and 35.4% (mean EPG, 25.0–89.6), with a higher prevalence of infection and EPG from June to October compared with December to March. Analysis of ITS-1 and ITS-2 sequences revealed that F. hepatica and F. gigantica were present in all bovine species of Anhui province and that F. gigantica mainly infected water buffalo. This is the first demonstration of Fasciola infection in Hubei province and detection of F. hepatica and F. gigantica in Anhui province. The present study of Hubei province shows that mass treatment of livestock with closantel sodium injections in April and August/September controlled Fasciola infection effectively.

We conducted a systematic review to compare resistance to third-generation cephalosporins (TGCs) in Shigella strains between Europe-America and Asia-Africa from 1998 to 2012 based on a literature search of computerized databases. In Asia-Africa, the prevalence of resistance of total and different subtypes to ceftriaxone, cefotaxime and ceftazidime increased markedly, with a total prevalence of resistance up to 14·2% [95% confidence interval (CI) 3·9–29·4], 22·6% (95% CI 4·8–48·6) and 6·2% (95% CI 3·8–9·1) during 2010–2012, respectively. By contrast, resistance rates to these TGCs in Europe-America remained relatively low – less than 1·0% during the 15 years. A noticeable finding was that certain countries both in Europe-America and Asia-Africa, had a rapid rising trend in the prevalence of resistance of S. sonnei, which even outnumbered S. flexneri in some periods. Moreover, comparison between countries showed that currently the most serious problem concerning resistance to these TGCs appeared in Vietnam, especially for ceftriaxone, China, especially for cefotaxime and Iran, especially for ceftazidime. These data suggest that monitoring of the drug resistance of Shigella strains should be strengthened and that rational use of antibiotics is required.

Hospital-based studies have determined high rates of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in Indigenous populations. However, there is a paucity of community-based data. We obtained 20 years (1993–2012) of data on S. aureus isolates (N = 20 210) collected from community clinics that provide services for Indigenous communities in the Northern Territory, Australia. Methicillin resistance increased from 7% to 24%, resistance to macrolides remained stable at ~25%, and there was a slight increase in resistance to trimethoprim-sulfamethoxazole. The increase in methicillin resistance is concerning for the Indigenous communities represented by this data, but it is also of significance if virulent MRSA clones emerge and spread more widely from such settings.

Pseudorabies has become endemic and represents a widespread problem for pig production in the world, causing great economic losses associated with reproductive failure and neonatal mortality in the pig industry. Most diseases are the results of mutations of functional genes. Single-nucleotide polymorphisms (SNPs) from the coding regions of the mediators of pro-inflammatory responses or other candidate genes in pigs could indicate their potential involvement in susceptibility or resistance to PrV (pseudorabies virus) infection. There have been no previous association studies with candidate host genes that may influence PrV phenotypic traits. In order to perform association studies to identify genes contributing to PrV phenotypes, the genotypes of five SNPs from four genes (IL10, CXCL12, BAT2 and EHMT2) were determined for 178 sow samples using a high throughput microarray-based methodology. PrV antibodies were tested by enzyme-linked immunosorbent assay (ELISA) to determine whether there was an association between antibody levels and particular genotypes. The association between SNP genotypes and the PrV antibody levels were analysed using the Duncan method of one-way ANOVA procedure using the SAS (Statistical Analysis Systems) software package. The results showed that the glycoprotein E-ELISA antibody level of pigs with genotypes 11(AA) and 12(AG) was significantly higher than in pigs with genotype 22(GG) (P < 0.05) of SNP in the gene EHMT2-SNP2. The SNP of EHMT2 may be an effective potential tool to identify susceptible and resistant animals when used in conjunction with traditional selection methods.

Diversity of bugs or faults in a software system is a factor contributing to software unreliability which has not yet been appropriately emphasized. This paper is written with the intention of demonstrating the impact of fault diversity on the time to detection of software bugs. A new discrete software reliability model based on the multinomial distribution is introduced. It is shown that for models of this type, the more diverse the fault probabilities are, the longer (stochastically) it takes to detect or eliminate any n faults, while the smaller (stochastically) will be the number of faults detected or eliminated during a given amount of time (or during a given number of inputs to the system). The impact of fault diversity is also demonstrated for the Jelinski–Moranda model.

A consecutive k−out−of-n: F system is a coherent system of n-ordered components that functions if and only if there is no consecutive run of k failures among the components. Examples of such systems exist in telecommunications, oil pipelines, and integrated circuitry. Most of the research in reliability of consecutive k−out-of-n: F systems assumes that the components function independently of one another. In this paper, we develop a model incorporating positive dependence between adjacent components and show that for k ≥ (n + l)/2, the reliability of the system is a decreasing function of this dependence.

Mixture distributions are a frequently used tool in modelling random phenomena. We consider mixtures of densities from a one-parameter exponenvial family of distributions. Using the tools of totally positive functions and the variation-diminishing property of such, we study the effect of sign-crossing properties of two mixing densities μ1 and μ2 on the resulting mixture distributions f1 and f2. The results enable us to make stochastic and variability cornparisons for binomial-beta, mixed Weibull, and mixed gamma distributions.

Somatic cell nuclear transfer (SCNT) is not successful so far in non-human primates. The objective of this study was to investigate the effects of stimulation cycles (first and repeat) on oocyte retrieval and in vitro maturation (IVM) and to evaluate the effects of stimulation cycles and donor cell type (cumulus and fetal skin fibroblasts) on efficiency of SCNT with transported IVM oocytes. In this study, 369 immature oocytes were collected laparoscopically at 24 h following human chorionic gonadotrophin (hCG) treatment from 12 cynomolgus macaque (Macaca fascicularis) in 24 stimulation cycles, and shipped in pre-equilibrated IVM medium for a 5 h journey, placed in a dry portable incubator (37 °C) without CO2 supplement. A total of 70.6% (247/350) of immature oocytes reached metaphase II (MII) stage at 36 h after hCG administration, MII spindle could be seen clearly in 80.6% (104/129) of matured IVM oocytes under polarized microscopy. A total of 50.0% (37/74) of reconstructive SCNT embryos cleaved after activation; after cleavage, 37.8% (14/37) developed to the 8-cell stage and 8.1% (3/37) developed to morula, but unfortunately none developed to the blastocyst stage. Many more oocytes could be retrieved per cycle from monkeys in the first cycle than in repeated cycles (19.1 vs. 11.7, p < 0.05). There were no significant differences in the maturation rate (70.0 vs. 71.4%, p > 0.05) and MII spindle rate under polarized microscopy (76.4 vs. 86.0%, p > 0.05) between the first and repeat cycles. There were also no significant differences in the cleavage rate, and the 4-cell, 8-cell and morula development rate of SCNT embryos between the first and repeat cycles. When fibroblast cells and cumulus cells were used as the donor cells for SCNT, first cleavage rate was not significantly different, but 4-cell (50.0 vs. 88.9%, p < 0.05) and 8-cell (0 vs. 51.9%, p < 0.01) development rate were significantly lower for the former. In conclusion, the number of stimulation cycles has a significant effect on oocyte retrieval, but has no effect on maturation and SCNT embryo development; however, different donor cell types (cumulus and fibroblast) resulted in different developmental potentials of SCNT embryos.

This article describes the scientific contributions of Milton Sobel. It motivates his research by considering his family background, his war experiences, and his mentors and fellow students at Columbia University. His research in sequential analysis, selection, ranking, group testing, and probabilistic combinatorics are highlighted.

It is generally believed that hepatitis B (HBV) and C (HCV) viruses are highly prevalent in the Republic of Yemen. This study investigated the prevalence of HBV and HCV markers in 494 blood donors from Aden, 493 blood donors from Sana'a, 97 residents from an African ethnic minority in Sana'a and 99 residents of Soqotra Island. There were significant differences in the prevalence of HBV carriage (HBsAg: 6·7, 15, 19·6 and 26·3% respectively; P<0·001); past HBV infection (anti-HBc: 17·4, 18·5, 30·9 and 59·6% respectively; P<0·001); susceptibility to HBV (absence of HBV markers: 73·3, 61·9, 38·1 and 9·1% respectively; P<0·001), infectivity of HBV carriers (HBV DNA: 51·5, 33·8, 52·6 and 65·4% respectively; P=0·028) and HCV antibodies (RIBA confirmed or indeterminate: 0·6, 0·2, 5·2 and 5·1% respectively; P<0·001). A significant difference in HBV carrier rate and a borderline significant difference in the prevalence of natural infection was observed between males and females in the African community (P=0·02 and 0·06 respectively). In contrast, in Soqotra Island, there was no significant sex difference in HBV carrier rate but susceptibility was significantly more prevalent in males (P=0·03). This study illustrates that significant difference in prevalence and epidemiology exists among different communities within the same country, reflecting political, geographical and social differences. Control strategies should take these differences into account.

The influence of acute moderate haemodilution on the relation between dose and response for rocuronium was evaluated in 60 adult patients, ASA grade I, undergoing elective plastic surgery. The patients were randomly allocated to either the control or the haemodilution group. Following the induction of general anaesthesia, the status of acute moderate haemodilution in the haemodilution group was achieved by draining venous blood, and intravenous infusion of lactated Ringer's solution, 6% dextran or gelofusine, during which the levels of haemoatocrit and haemoglobin dropped from 44% to 27.5% and from 148.3 to 91.3 g L−1, respectively. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s and the percentage depression of T1 response was used as the study parameter. The relation between dose and response for rocuronium in the two groups was determined by the cumulative dose–response technique. The results showed that the dose–response curve for rocuronium during acute moderate haemodilution was shifted in a parallel fashion to the left and the potency of rocuronium was increased. There were significant differences in ED50, ED90 and ED95 between the two groups. The ED50, ED90 and ED95 of rocuronium in the haemodilution group was decreased by 28.2%, 35.4% and 38.8%, respectively, compared with the control group.

The theory of majorization is applied to investigate the effects of heterogeneity in a class of epidemics. In particular, the heterogeneity of the components of the contact vector of a given susceptible is studied. It is shown that if the heterogeneity can be partially ordered through majorization, then the probability functions of escaping infection can be similarly ordered. The results can be applied to AIDS research on the spread of the HIV virus.

We discuss a dynamo mechanism driven by weak plasma turbulence and show that turbulent plasma waves may generate and maintain cosmic magnetic field. A dynamo equation is derived from the magnetic induction equation based on mean field electrodynamics. In the usual α–ω dynamo theory, the source term in the dynamo equation arises from α–effect associated with the convective motion of the fluid. In contrast, in our theory the source term is determined by “P–effcct” associated with weakly turbulent waves (e.g. Alfvén waves) in the plasma. We suggest that “P–ω” dynamo may be operative either in the presence or absence of convection. The sole requirement for its operation is the existence of weak plasma turbulence in the source region of the cosmic magnetic field.