Feasibility of identifying families for genetic studies of birth defects using the National Health Interview Survey

BACKGROUND: The purpose of this study was to determine whether the National Health Interview Survey is a useful source to identify informative families for genetic studies of birth defects. METHODS: The 1994/1995 National Health Interview Survey (NHIS) was used to identify households where individuals with two or more birth defects reside. Four groups of households were identified: 1) single non-familial (one individual with one birth defect); 2) single familial (more than one individual with one birth defect); 3) multiple non-familial (one individual with more than one birth defect), and 4) multiple familial (more than one individual with more than one birth defect). The March 2000 U.S. Census on households was used to estimate the total number of households in which there are individuals with birth defects. RESULTS: Of a total of 28,094 households and surveyed about birth defects and impairments, 1,083 single non-familial, 55 multiple non-familial, 54 single familial, and 8 multiple familial households were identified. Based on the 2000 U.S. census, it is estimated that there are 4,472,385 households where at least one person has one birth defect in the United States and in 234,846 of them there are at least two affected individuals. Western states had the highest prevalence rates. CONCLUSIONS: Population-based methods, such as the NHIS, are modestly useful to identify the number and the regions where candidate families for genetic studies of birth defects reside. Clinic based studies and birth defects surveillance systems that collect family history offer better probability of ascertainment

Survey context and question wording affects self reported annoyance due to road traffic noise: a comparison between two cross-sectional studies

<p>Abstract</p> <p>Background</p> <p>Surveys are a common way to measure annoyance due to road traffic noise, but the method has some draw-backs. Survey context, question wording and answer alternatives could affect participation and answers and could have implications when comparing studies and/or performing pooled analyses. The aim of this study was to investigate the difference in annoyance reporting due to road traffic noise in two types of surveys of which one was introduced broadly and the other with the clearly stated aim of investigating noise and health.</p> <p>Methods</p> <p>Data was collected from two surveys carried out in the municipality of Malmö, southern Sweden in 2007 and 2008 (n = 2612 and n = 3810). The first survey stated an aim of investigating residential environmental exposure, especially noise and health. The second survey was a broad public health survey stating a broader aim. The two surveys had comparable questions regarding noise annoyance, although one used a 5-point scale and the other a 4-point scale. We used geographic information systems (GIS) to assess the average road and railway noise (L_Aeq,24h) at the participants' residential address. Logistic regression was used to calculate odds ratios for annoyance in relation to noise exposure.</p> <p>Results</p> <p>Annoyance at least once a week due to road traffic noise was significantly more prevalent in the survey investigating environment and health compared to the public health survey at levels > 45 dB(A), but not at lower exposure levels. However no differences in annoyance were found when comparing the extreme alternatives "never" and "every day". In the study investigating environment and health, "Noise sensitive" persons were more likely to readily respond to the survey and were more annoyed by road traffic noise compared to the other participants in that survey.</p> <p>Conclusions</p> <p>The differences in annoyance reporting between the two surveys were mainly due to different scales, suggesting that extreme alternatives are to prefer before dichotomization when comparing results between the two. Although some findings suggested that noise-sensitive individuals were more likely to respond to the survey investigating noise and health, we could not find convincing evidence that contextual differences affected either answers or participation.</p

Direct Measurement of Nuclear Dependence of Charged Current Quasielastic-like Neutrino Interactions using MINERvA

Charged-current $\nu_{\mu}$ interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear environment on quasielastic-like interactions. The transfered four-momentum squared to the target nucleus, $Q^2$, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus $Q^2$ and the cross-section ratios of iron, lead and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on atomic number. While the quasielastic-like scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral bloo

A systematic review of correlates of sedentary behaviour in adults aged 18–65 years: a socio-ecological approach

Background: Recent research shows that sedentary behaviour is associated with adverse cardio-metabolic consequences even among those considered sufficiently physically active. In order to successfully develop interventions to address this unhealthy behaviour, factors that influence sedentariness need to be identified and fully understood. The aim of this review is to identify individual, social, environmental, and policy-related determinants or correlates of sedentary behaviours among adults aged 18-65 years. Methods: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between January 2000 and September 2015. The search strategy was based on four key elements and their synonyms: (a) sedentary behaviour (b) correlates (c) types of sedentary behaviours (d) types of correlates. Articles were included if information relating to sedentary behaviour in adults (18-65 years) was reported. Studies on samples selected by disease were excluded. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42014009823). Results: 74 original studies were identified out of 4041: 71 observational, two qualitative and one experimental study. Sedentary behaviour was primarily measured as self-reported screen leisure time and total sitting time. In 15 studies, objectively measured total sedentary time was reported: accelerometry (n = 14) and heart rate (n = 1). Individual level factors such as age, physical activity levels, body mass index, socio-economic status and mood were all significantly correlated with sedentariness. A trend towards increased amounts of leisure screen time was identified in those married or cohabiting while having children resulted in less total sitting time. Several environmental correlates were identified including proximity of green space, neighbourhood walkability and safety and weather. Conclusions: Results provide further evidence relating to several already recognised individual level factors and preliminary evidence relating to social and environmental factors that should be further investigated. Most studies relied upon cross-sectional design limiting causal inference and the heterogeneity of the sedentary measures prevented direct comparison of findings. Future research necessitates longitudinal study designs, exploration of policy-related factors, further exploration of environmental factors, analysis of inter-relationships between identified factors and better classification of sedentary behaviour domains

Benefits and barriers among volunteer teaching faculty: comparison between those who precept and those who do not in the core pediatrics clerkship

Background: Community-based outpatient experiences are a core component of the clinical years in medical school. Central to the success of this experience is the recruitment and retention of volunteer faculty from the community. Prior studies have identified reasons why some preceptors volunteer their time however, there is a paucity of data comparing those who volunteer from those who do not. Methods: A survey was developed following a review of previous studies addressing perceptions of community-based preceptors. A non-parametric, Mann&#x2013;Whitney U test was used to compare active preceptors (APs) and inactive preceptors (IPs) and all data were analyzed in SPSS 20.0. Results: There was a 28% response rate. Preceptors showed similar demographic characteristics, valued intrinsic over extrinsic benefits, and appreciated Continuing Medical Education (CME)/Maintenance of Certification (MOC) opportunities as the highest extrinsic reward. APs were more likely to also precept at the M1/M2 level and value recognition and faculty development opportunities (p&#x3C;0.05). IPs denoted time as the most significant barrier and, in comparison to APs, rated financial compensation as more important (p&#x3C;0.05). Conclusions: Community preceptors are motivated by intrinsic benefits of teaching. Efforts to recruit should initially focus on promoting awareness of teaching opportunities and offering CME/MOC opportunities. Increasing the pool of preceptors may require financial compensation

Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women

<p>Abstract</p> <p>Background</p> <p>In 2009 the Uterine Bleeding and Pain Women's Research Study (UBP-WRS) was conducted interviewing 21,479 women across 8 countries in order to gain patient-based prevalence data on uterine pain and bleeding indications and investigate uterine symptoms and women's treatment experiences. This article shows relevant results of the study for the indication uterine fibroids providing data on self-reported prevalence, symptomatology and management of uterine fibroids.</p> <p>Methods</p> <p>2,500 women (USA: 4,500 women) in each country (Brazil, Canada, France, Germany, Italy, South Korea, the UK, the USA) completed an online survey. Women included were in their reproductive age (age group 15-49 years; USA: 18-49 years) and had ever experienced menstrual bleedings. Quotas were applied for age, region, level of education and household income of respondents. Variables have been analyzed descriptively and exploratory statistical tests have been performed.</p> <p>Results</p> <p>The self-reported prevalence of uterine fibroids ranged from 4.5% (UK) to 9.8% (Italy), reaching 9.4% (UK) to 17.8% (Italy) in the age group of 40-49 years. Women with a diagnosis of uterine fibroids reported significantly more often about bleeding symptoms than women without a diagnosis: heavy bleedings (59.8% vs. 37.4%), prolonged bleedings (37.3% vs. 15.6%), bleeding between periods (33.3% vs. 13.5%), frequent periods (28.4% vs. 15.2%), irregular and predictable periods (36.3% vs. 23.9%). Furthermore women with diagnosed uterine fibroids reported significantly more often about the following pain symptoms: pressure on the bladder (32.6% vs. 15.0%), chronic pelvic pain (14.5% vs. 2.9%), painful sexual intercourse (23.5% vs. 9.1%) and pain occurring mid-cycle, after and during menstrual bleeding (31.3%, 16.7%, 59.7%, vs. 17.1%, 6.4%, 52.0%). 53.7% of women reported that their symptoms had a negative impact on their life in the last 12 month, influencing their sexual life (42.9%), performance at work (27.7%) and relationship & family (27.2%).</p> <p>Conclusions</p> <p>Uterine fibroid is a common concern in women at fertile age causing multiple bleeding and pain symptoms which can have a negative impact on different aspects in women's life.</p

SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation

<p>Abstract</p> <p>Background</p> <p>Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.</p> <p>Design</p> <p>Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.</p> <p>Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.</p> <p>Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.</p> <p>Discussion</p> <p>The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01392586">NCT01392586</a>.</p

Differentiation of Glioma and Radiation Injury in Rats Using In Vitro Produce Magnetically Labeled Cytotoxic T-Cells and MRI

A limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be attained by sensitized T-cells following vaccination of primed dendritic cells (DCs). The purpose of this study was to determine whether cord blood T-cells can be sensitized against glioma cells (U-251) and if these sensitized cytotoxic T-cells (CTLs) can be used as cellular magnetic resonance imaging probes to identify and differentiate glioma from radiation necrosis in rodent models.Cord blood T and CD14+ cells were collected. Isolated CD14+ cells were then converted to dendritic cells (DCs), primed with glioma cell lysate and used to sensitize T-cells. Phenotypical expression of the generated DCs were analyzed to determine the expression level of CD14, CD86, CD83 and HLA-DR. Cells positive for CD25, CD4, CD8 were determined in generated CTLs. Specificity of cytotoxicity of the generated CTLs was also determined by lactate dehydrogenase (LDH) release assay. Secondary proliferation capacity of magnetically labeled and unlabeled CTLs was also determined. Generated CTLs were magnetically labeled and intravenously injected into glioma bearing animals that underwent MRI on days 3 and 7 post- injection. CTLs were also administered to animals with focal radiation injury to determine whether these CTLs accumulated non-specifically to the injury sites. Multi-echo T2- and T2*-weighted images were acquired and R2 and R2* maps created. Our method produced functional, sensitized CTLs that specifically induced U251 cell death in vitro. Both labeled and unlabeled CTLs proliferated equally after the secondary stimulation. There were significantly higher CD25 positive cells (p = <0.006) in CTLs. In addition, T2- and T2*-weighted MR images showed increased low signal intensity areas in animals that received labeled CTLs as compared to the images from animals that received control cells. Histological analysis confirmed the presence of iron positive cells in sites corresponding to MRI low signal intensity regions. Significant differences (p = <0.001) in tumor R2 and R2* values were observed among the groups of animals. Animals with radiation injury exhibited neither MRI hypointense areas nor presence of iron positive cells.Our results indicate that T-cells can be effectively sensitized by in vitro methods and used as cellular probes to identify and differentiate glioma from radiation necrosis