Pregnant women\u27s alcohol consumption : the predictive utility of intention to drink and prepregnancy drinking behaviour

Objective: This study had two aims: (1) to examine pregnant women\u27s alcohol consumption across time from prepregnancy until childbirth and (2) to explore whether prepregnancy drinking and intention to drink predict prenatal alcohol consumption while controlling for relevant demographic variables.Methods: At 17&ndash;21 weeks, 248 pregnant women completed questions about demographics, intention to drink alcohol during the subsequent pregnancy, and retrospective measures of prepregnancy and early pregnancy consumption. After this time, calendars were sent fortnightly assessing daily alcohol consumption until birth.Results: For women who drank both prepregnancy and postpregnancy confirmation, average fortnight alcohol consumption in the first weeks of pregnancy was lower than during prepregnancy, and consumption continued to decrease between gestational weeks 1 and 8, particularly following pregnancy confirmation, after which it remained relatively stable. When predicting whether women drank in late pregnancy, intention accounted for unique variance after controlling for income and prepregnancy drinking. For women who drank after pregnancy confirmation, prepregnancy drinking quantity significantly predicted intention to drink, which in turn predicted fortnight alcohol consumption in later pregnancy, after controlling for prepregnancy drinking and income.Conclusions: Findings highlight the need to measure alcohol consumption at multiple time points across pregnancy, the need for educating and supporting women to reduce consumption when planning pregnancies, and the usefulness of intention to drink as a predictor of drinking during pregnancy.<br /

Macrophages Are Required for Dendritic Cell Uptake of Respiratory Syncytial Virus from an Infected Epithelium

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

The importance of post-translocation monitoring of habitat use and population growth: insights from a Seychelles Warbler (Acrocephalus sechellensis) translocation

Translocations are a valuable tool within conservation, and when performed successfully can rescue species from extinction. However, to label a translocation a success, extensive post-translocation monitoring is required, ensuring the population is growing at the expected rate. In 2011, a habitat assessment identified Frégate Island as a suitable island to host a Seychelles Warbler (Acrocephalus sechellensis) population. Later that year, 59 birds were translocated from Cousin Island to Frégate Island. Here, we determine Seychelles Warbler habitat use and population growth on Frégate Island, assessing the status of the translocation and identifying any interventions that may be required. We found that territory quality, an important predictor of fledgling production on Cousin Island, was a poor predictor of bird presence on Frégate Island. Instead, tree diversity, middle-storey vegetation density, and broad-leafed vegetation density all predicted bird presence positively. A habitat suitability map based on these results suggests most of Frégate Island contains either a suitable or a moderately suitable habitat, with patches of unsuitable overgrown coconut plantation. To achieve the maximum potential Seychelles Warbler population size on Frégate Island, we recommend habitat regeneration, such that the highly diverse subset of broad-leafed trees and a dense middle storey should be protected and replace the unsuitable coconut. Frégate Island’s Seychelles Warbler population has grown to 141 birds since the release, the slowest growth rate of all Seychelles Warbler translocations; the cause of this is unclear. This study highlights the value of post-translocation monitoring, identifying habitat use and areas requiring restoration, and ultimately ensuring that the population is growing

CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

<div><h3>Background</h3><p>TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).</p> <h3>Methodology and Principal Findings</h3><p>In the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n = 160), adalimumab (n = 56) or etanercept (n = 21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) <em>in silico</em> database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher’s exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR = 4.43, 95% CI: 1.99–10.09, p = 7.211×10⁻⁵) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29–8.99, p = 3.336×10⁻⁶). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR = 4.01, 95% CI: 1.92–8.49, p = 5.067×10⁻⁵).</p> <h3>Conclusion</h3><p>Genetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.</p> </div

Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology

<p>Abstract</p> <p>Background</p> <p>Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown.</p> <p>Objective</p> <p>This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters.</p> <p>Design</p> <p>Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs.</p> <p>Results</p> <p>Body weight decreased (<it>P <</it>0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (<it>P <</it>0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (<it>P <</it>0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (<it>P <</it>0.05, 16 ± 5%), and decreases in resistin (<it>P <</it>0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (<it>P <</it>0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin.</p> <p>Conclusion</p> <p>Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.</p

We should not forget the foot: relations between signs and symptoms, damage, and function in rheumatoid arthritis

We studied rheumatoid arthritis (RA) patients with foot complaints to address the associations between clinical signs and symptoms, radiographic changes, and function in connection with disease duration. Secondly, we describe the contribution of several foot segments to the clinical presentation and function. In 30 RA patients with complaints of their feet, attributed to either signs of arthritis and/or radiographic damage, we compared radiographic, ultrasound, clinical, and functional parameters of the feet and ankle. Pain and swelling of the ankle were correlated weakly but statistically significantly with limitation and disability (0.273 to 0.293) as measured on the 5-Foot Function Index (FFI). The clinical signs of the forefoot joints did not influence any of the functional outcome measures. Radiographic scores for both forefeet (SvdH) and hindfeet (Larsen) were correlated with the total Health Assessment Questionnaire Disability Index (HAQ DI) and the 5-FFI limitation subscale. Pain and disease duration, more than radiographic damage, influence the total HAQ DI significantly. With the progression of time, structural damage and function of the rheumatic foot worsen in RA patients. Pain and swelling of the ankle contribute more to disability than radiographic damage of the foot and ankle

Disease surveillance using a hidden Markov model

<p>Abstract</p> <p>Background</p> <p>Routine surveillance of disease notification data can enable the early detection of localised disease outbreaks. Although hidden Markov models (HMMs) have been recognised as an appropriate method to model disease surveillance data, they have been rarely applied in public health practice. We aimed to develop and evaluate a simple flexible HMM for disease surveillance which is suitable for use with sparse small area count data and requires little baseline data.</p> <p>Methods</p> <p>A Bayesian HMM was designed to monitor routinely collected notifiable disease data that are aggregated by residential postcode. Semi-synthetic data were used to evaluate the algorithm and compare outbreak detection performance with the established Early Aberration Reporting System (EARS) algorithms and a negative binomial cusum.</p> <p>Results</p> <p>Algorithm performance varied according to the desired false alarm rate for surveillance. At false alarm rates around 0.05, the cusum-based algorithms provided the best overall outbreak detection performance, having similar sensitivity to the HMMs and a shorter average time to detection. At false alarm rates around 0.01, the HMM algorithms provided the best overall outbreak detection performance, having higher sensitivity than the cusum-based Methods and a generally shorter time to detection for larger outbreaks. Overall, the 14-day HMM had a significantly greater area under the receiver operator characteristic curve than the EARS C3 and 7-day negative binomial cusum algorithms.</p> <p>Conclusion</p> <p>Our findings suggest that the HMM provides an effective method for the surveillance of sparse small area notifiable disease data at low false alarm rates. Further investigations are required to evaluation algorithm performance across other diseases and surveillance contexts.</p

Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA).</p> <p>Methods</p> <p>Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model.</p> <p>Results</p> <p>After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044).</p> <p>Conclusions</p> <p>These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA.</p