Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Errors in recall of age at first sex

Aims: To measure the degree and direction of errors in recall of age at first sex. Method: Participants were initially recruited in 1994–1995 (Wave I) with 3 subsequent follow-ups in: 1996 (Wave II); 2001– 2002 (Wave III); and 2007–2008 (Wave IV). Participants' individual errors in recall of their age at first sex at Wave IV were estimated by the paired difference between responses given for age at first sex in Wave I and Wave IV (recalled age at first sex obtained at Wave IV minus the age at first sex obtained at Wave I). Results: The mean of the recall-estimation of age at first sex at Wave IV was found to be slightly increased comparing to the age at first sex at Wave I (less than 1 year). The errors in the recalled age at first sex tended to increase in participants who had their first sex younger or older than the average, and the recalled age at first sex tended to bias towards the mean (i.e. participants who had first sex younger than the average were more likely to recall an age at first sex that was older than the age, and vice versa). Conclusions: In this U.S. population-based sample, the average recall error for age at first sex was small. However, the accuracy of recalled information varied significantly among subgroup populations

Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts

Angiogenesis is a multistep process that is limited and carefully regulated in normal adult tissue, but in tumours this regulation is disrupted and the process remains ‘switched on’ (Hanahan and Folkman, 1996). Ample experimental data support the fact that tumour growth requires access to blood vessels and subsequent expansion of host vessels to provide nutrients for the growing tumour mass (Folkman, 1995a). Furthermore, many studies in a variety of tumour types have reported a correlation between the extent of tumour vasculature and poor prognosis or increased metastases (Weidner et al, 1991; Folkman, 1995b; Weidner and Folkman, 1996). Thus, accurate assessment of the vasculature of tumours could provide valuable information regarding treatment outcomes and the likelihood of metastatic spread to other sites. Angiogenesis can be regulated by a variety of factors. Several cytokines produced by immune cells also have been shown to affect the process of angiogenesis. One of the most noteworthy is interleukin (IL)-12, which is produced by antigen presenting cells (APC), such as macrophages and dendritic cells (DC) in response to bacterial stimuli or other inflammatory cytokines. Thus, IL-12 plays an important role in both the innate and adaptive immune responses (Trinchieri, 1998). Owing to its central role in stimulating immunity, it has been examined for possible therapeutic effects in the treatment of tumours. In addition to its effects on the immune system, IL-12 has also been shown to inhibit angiogenesis (Voest et al, 1995; Sgadari et al, 1996). Despite studies in both experimental models and in patients (reviewed in Trinchieri and Scott, 1999), and clear demonstrations of therapeutic efficacy, relatively little is known about how it alters vessel formation within tumours. In part, this is due to the difficulty in assessing the three-dimensional structure of vessels and other cellular components within the tumour. Assessment of tumour vessels is generally based on immunohistochemistry of tumour sections. Although use of this technique has led to a great deal of important information, these procedures are extremely time consuming and provide only a limited two-dimensional view of the vessels. This makes it very difficult to visualise the structure of the microvasculature and identify differences among different tumour types or changes following treatment regimens. To more easily and accurately visualise vessels within tumours, we developed a whole-tissue mount technique that provides a three-dimensional view of the tumour vasculature relative to other components of the tumour tissue. This technique was first validated by studying vessels from transgenic mice that express green fluorescent protein (GFP) (Wu et al, 2000), and then used to investigate the mechanism by which IL-12 influences the vessel architecture within B16 tumours

Plantar plate pathology is associated with erosive disease in the painful forefoot of patients with rheumatoid arthritis

Background: Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges. Together with the transverse metatarsal ligament they prevent splaying of the forefoot and subluxation of the MTP joints. Damage to the plantar plates is a plausible mechanism therefore, through which the forefoot presentation, commonly described as ‘walking on pebbles’, may develop in patients with RA. The aims of this study were to investigate the relationship between plantar plate pathology and clinical, biomechanical and plain radiography findings in the painful forefoot of patients with RA. Secondly, to compare plantar plate pathology at the symptomatic lesser (2nd-5th) MTP joints in patients with RA, with a group of healthy age and gender matched control subjects without foot pain. Methods: In 41 patients with RA and ten control subjects the forefoot was imaged using 3T MRI. Intermediate weighted fat-suppressed sagittal and short axis sequences were acquired through the lesser MTP joints. Images were read prospectively by two radiologists and consensus reached. Plantar plate pathology in patients with RA was compared with control subjects. Multivariable multilevel modelling was used to assess the association between plantar plate pathology and the clinical, biomechanical and plain radiography findings. Results: There were significant differences between control subjects and patients with RA in the presence of plantar plate pathology at the lesser MTP joints. No substantive or statistically significant associations were found between plantar plate pathology and clinical and biomechanical findings. The presence of plantar plate pathology was independently associated with an increase in the odds of erosion (OR = 52.50 [8.38–326.97], p < 0.001). Conclusion: The distribution of plantar plate pathology at the lesser MTP joints in healthy control subjects differs to that seen in patients with RA who have the consequence of inflammatory disease in the forefoot. Longitudinal follow-up is required to determine the mechanism and presentation of plantar plate pathology in the painful forefoot of patients with RA

Concordance of sibling's recall of measures of childhood socioeconomic position

<p>Abstract</p> <p>Background</p> <p>Studies of socioeconomic determinants of health often rely on recalled information on childhood socioeconomic position, despite limited evidence of the validity of this information. This study examined concordance between siblings of recalled measures of childhood socioeconomic position.</p> <p>Methods</p> <p>This cross-sectional study examined reports by 1280 adult sibling pairs in the National Survey of Midlife Development in the United States of seven measures of childhood socioeconomic position: father's occupation (in 9 categories), father having a professional occupation, father being a supervisor at work, father's education level, mother's education level, receipt of welfare payments, and subjective appraisal of being better or worse off financially than others.</p> <p>Results</p> <p>Concordance was high for father's professional occupation (0.97; 95% confidence interval (CI) 0.96, 0.98), father's occupation in 9 categories (0.76; 95% CI 0.73, 0.80), and receipt of welfare payments (0.95; 95% CI 0.93, 0.97). Concordance was lower for father's and mother's education level, and lowest for subjective appraisal of socioeconomic position (0.60; 95% CI 0.57, 0.64). Concordance of parental education was lower for sibling pairs with high school educations or less.</p> <p>Conclusion</p> <p>Concordance of recalled measures of childhood socioeconomic position by siblings is generally but not uniformly high.</p

PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

<p>Abstract</p> <p>Background</p> <p>The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality.</p> <p>Methods</p> <p>In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor.</p> <p>Results</p> <p>Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009).</p> <p>Conclusion</p> <p>Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients.</p

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Awareness and acceptability of human papillomavirus vaccine: an application of the instrumental variables bivariate probit model

<p>Abstract</p> <p>Background</p> <p>Although lower uptake rates of the human papillomavirus (HPV) vaccine among socioeconomically disadvantaged populations have been documented, less is known about the relationships between awareness and acceptability, and other factors affecting HPV vaccine uptake.</p> <p>The current study aimed to estimate the potential effectiveness of increased HPV vaccine awareness on the acceptability of HPV vaccination in a nationally representative sample of women, using a methodology that controlled for potential non-random selection.</p> <p>Methods</p> <p>This study used a population-based sample from the 2007 Health Information National Trends Survey, a cross-sectional study of the US population aged 18 years or older, and focused on the subsample of 742 women who have any female children under the age of 18 years in the household. An instrumental variables bivariate probit model was used to jointly estimate HPV vaccine awareness and acceptability.</p> <p>Results</p> <p>The proportion of HPV vaccine acceptability among the previously aware and non-aware groups was 58% and 47%, respectively. Results from the instrumental variables bivariate probit model showed that the estimated marginal effect of awareness on acceptability was 46 percentage points, an effect that was even greater than observed.</p> <p>Conclusions</p> <p>Among populations who are not currently aware of the HPV vaccine, the potential impact of raising awareness on acceptability of HPV vaccination is substantial. This finding provides additional support to strengthening public health programs that increase awareness and policy efforts that address barriers to HPV vaccination.</p

Obesity and risk of pancreatic cancer among postmenopausal women: the Women's Health Initiative (United States)

A total of 138 503 women in the Women's Health Initiative in the United States were followed (for an average of 7.7 years) through 12 September 2005 to examine obesity, especially central obesity in relation to pancreatic cancer (n=251). Women in the highest quintile of waist-to-hip ratio had 70% (95% confidence interval 10–160%) excess risk of pancreatic cancer compared with women in the lowest quintile