MATERNAL PREVALENCE OF TOXOPLASMA ANTIBODY BASED ON ANONYMOUS NEONATAL SEROSURVEY - A GEOGRAPHICAL ANALYSIS

A total of 12902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London. 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission

Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia

Background: Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alterations occur in cord blood DNAs in association with EOPE and conducted a case control study to compare the genome-scale methylome differences in cord blood DNAs between 12 EOPE-associated and 8 normal births. Results: Bioinformatics analysis of methylation data from the Infinium HumanMethylation450 BeadChip shows a genome-scale hypomethylation pattern in EOPE, with 51,486 hypomethylated CpG sites and 12,563 hypermethylated sites (adjusted P <0.05). A similar trend also exists in the proximal promoters (TSS200) associated with protein-coding genes. Using summary statistics on the CpG sites in TSS200 regions, promoters of 643 and 389 genes are hypomethylated and hypermethylated, respectively. Promoter-based differential methylation (DM) analysis reveals that genes in the farnesoid X receptor and liver X receptor (FXR/LXR) pathway are enriched, indicating dysfunction of lipid metabolism in cord blood cells. Additional biological functional alterations involve inflammation, cell growth, and hematological system development. A two-way ANOVA analysis among coupled cord blood and amniotic membrane samples shows that a group of genes involved in inflammation, lipid metabolism, and proliferation are persistently differentially methylated in both tissues, including IL12B, FAS, PIK31, and IGF1. Conclusions: These findings provide, for the first time, evidence of prominent genome-scale DNA methylation modifications in cord blood DNAs associated with EOPE. They may suggest a connection between inflammation and lipid dysregulation in EOPE-associated newborns and a higher risk of cardiovascular diseases later in adulthood

Acceptability of novel lifelogging technology to determine context of sedentary behaviour in older adults

<strong>Objective:</strong> Lifelogging, using body worn sensors (activity monitors and time lapse photography) has the potential to shed light on the context of sedentary behaviour. The objectives of this study were to examine the acceptability, to older adults, of using lifelogging technology and indicate its usefulness for understanding behaviour.<strong> </strong><strong>Method:</strong> 6 older adults (4 males, mean age: 68yrs) wore the equipment (ActivPAL^TM and Vicon Revue^TM/SenseCam^TM) for 7 consecutive days during free-living activity. The older adults’ perception of the lifelogging technology was assessed through semi-structured interviews, including a brief questionnaire (Likert scale), and reference to the researcher&#39;s diary. <strong>Results:</strong> Older adults in this study found the equipment acceptable to wear and it did not interfere with privacy, safety or create reactivity, but they reported problems with the actual technical functioning of the camera. <strong>Conclusion:</strong> This combination of sensors has good potential to provide lifelogging information on the context of sedentary behaviour

Are your covariates under control? How normalization can re-introduce covariate effects

Many statistical tests rely on the assumption that the residuals of a model are normally distributed. Rank-based inverse normal transformation (INT) of the dependent variable is one of the most popular approaches to satisfy the normality assumption. Studies regularly adjust for covariates and then normalize the residuals. This study investigated the effect of regressing covariates against the dependent variable and then applying rank-based INT to the residuals. The correlation between the dependent variable and covariates at each stage of processing was assessed. An alternative approach was tested of applying rank-based INT to the dependent variable before regressing covariates was tested. Analyses based on both simulated and real data examples demonstrated that applying rank-based INT to the dependent variable residuals after regressing out covariates re-introduces a linear correlation between the dependent variable and covariates in almost all situations. This will increase type-1 errors and reduce power. Our proposed alternative approach, where rank-based INT was applied prior to controlling for covariate effects, gave residuals that were normally distributed and linearly uncorrelated with covariates. This approach is therefore recommended

Prevention of Neural-Tube Defects with Periconceptional Folic Acid, Methylfolate, or Multivitamins?

Background/Aims: To review the main results of intervention trials which showed the efficacy of periconceptional folic acid-containing multivitamin and folic acid supplementation in the prevention of neural-tube defects (NTD). Methods and Results: The main findings of 5 intervention trials are known: (i) the efficacy of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled trial resulted in an 83-91% reduction in NTD recurrence, while the results of the Hungarian (ii) randomized controlled trial and (iii) cohort-controlled trial using a multivitamin containing 0.8 mg folic acid showed 93 and 89% reductions in the first occurrence of NTD, respectively. On the other hand, (iv) another multicenter randomized controlled trial proved a 71% efficacy of 4 mg folic acid in the reduction of recurrent NTD, while (v) a public health-oriented Chinese-US trial showed a 41-79% reduction in the first occurrence of NTD depending on the incidence of NTD. Conclusions: Translational application of these findings could result in a breakthrough in the primary prevention of NTD, but so far this is not widely applied in practice. The benefits and drawbacks of 4 main possible uses of periconceptional folic acid/multivitamin supplementation, i.e. (i) dietary intake, (ii) periconceptional supplementation, (iii) flour fortification, and (iv) the recent attempt for the use of combination of oral contraceptives with 6S-5-methytetrahydrofolate (methylfolate), are discussed. Obviously, prevention of NTD is much better than the frequent elective termination of pregnancies after prenatal diagnosis of NTD fetuses

The Patients Assessment Chronic Illness Care (PACIC) questionnaire in The Netherlands: a validation study in rural general practice

BACKGROUND: Many patients with chronic illness receive health care in primary care settings, so a challenge is to provide well-structured chronic care in these settings. Our aim was to develop and test a Dutch version of the PACIC questionnaire, a measure for patient reported structured chronic care. METHODS: Observational study in 165 patients with diabetes or COPD from four general practices (72% response rate). Patients completed a written questionnaire, which included instruments for assessing chronic illness care (PACIC), evaluations of general practice (Europep), enablement (PEI), and individual characteristics. RESULTS: The patients had a mean age of 68.0 years and 47% comprised of women. Twenty-two to 35% of responding patients did not provide answers to specific items in the PACIC. In 11 items the lowest answering category was used by 30% or more of the responders and in 6 items the highest answering category was used by this number of responders. Principal factor analysis identified the previously defined five domains reasonably well. Cronbach's alpha per domain varied from 0.71 to 0.83, and the intraclass coefficient from 0.66 to 0.91. Diabetes patients reported higher presence of structured chronic care for 14 out of the 20 PACIC items. The effect of patient evaluations of general practice on the PACIC score was positive (b = 0.72, p < 0.004), but the effect of patient enablement on the PACIC score was negative (b = -1.13, p < 0.000). CONCLUSION: A translated and validated Dutch version of the PACIC questionnaire is now available. Further research on its validity is recommended

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

No imminent quantum supremacy by boson sampling

It is predicted that quantum computers will dramatically outperform their conventional counterparts. However, large-scale universal quantum computers are yet to be built. Boson sampling is a rudimentary quantum algorithm tailored to the platform of photons in linear optics, which has sparked interest as a rapid way to demonstrate this quantum supremacy. Photon statistics are governed by intractable matrix functions known as permanents, which suggests that sampling from the distribution obtained by injecting photons into a linear-optical network could be solved more quickly by a photonic experiment than by a classical computer. The contrast between the apparently awesome challenge faced by any classical sampling algorithm and the apparently near-term experimental resources required for a large boson sampling experiment has raised expectations that quantum supremacy by boson sampling is on the horizon. Here we present classical boson sampling algorithms and theoretical analyses of prospects for scaling boson sampling experiments, showing that near-term quantum supremacy via boson sampling is unlikely. While the largest boson sampling experiments reported so far are with 5 photons, our classical algorithm, based on Metropolised independence sampling (MIS), allowed the boson sampling problem to be solved for 30 photons with standard computing hardware. We argue that the impact of experimental photon losses means that demonstrating quantum supremacy by boson sampling would require a step change in technology.Comment: 25 pages, 9 figures. Comments welcom

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice