Surrogate endpoints in clinical trials of chronic kidney disease progression: moving from single to multiple risk marker response scores.

PubMed

Schievink, Bauke; Mol, Peter G M; Lambers Heerspink, Hiddo J

2015-11-01

There is increased interest in developing surrogate endpoints for clinical trials of chronic kidney disease progression, as the established clinically meaningful endpoint end-stage renal disease requires large and lengthy trials to assess drug efficacy. We describe recent developments in the search for novel surrogate endpoints. Declines in estimated glomerular filtration rate (eGFR) of 30% or 40% and albuminuria have been proposed as surrogates for end-stage renal disease. However, changes in eGFR or albuminuria may not be valid under all circumstances as drugs always have effects on multiple renal risk markers. Changes in each of these other 'off-target' risk markers can alter renal risk (either beneficially or adversely), and can thereby confound the relationship between surrogates that are based on single risk markers and renal outcome. Risk algorithms that integrate the short-term drug effects on multiple risk markers to predict drug effects on hard renal outcomes may therefore be more accurate. The validity of these risk algorithms is currently investigated. Given that drugs affect multiple renal risk markers, risk scores that integrate these effects are a promising alternative to using eGFR decline or albuminuria. Proper validation is required before these risk scores can be implemented.

Mitigating Risks to Pregnant Teens from Zika Virus.

PubMed

Maynard, Andrew D; Bowman, Diana M; Hodge, James G

2016-12-01

Zika infection in pregnant women is associated with an elevated probability of giving birth to a child with microcephaly and multiple other disabilities. Public health messaging on Zika prevention has predominantly targeted women who know they are pregnant or intend to become pregnant, but not teenage females for whom unintended pregnancy is more likely. Vulnerabilities among this population to reproductive risks associated with Zika are further amplified by restrictive abortion laws in several Zika-impacted states. Key to prevention is enhanced, targeted public health messaging centered on teens nationally and particularly in certain high-risk regions.

Evaluation of volumetric modulated arc therapy for cranial radiosurgery using multiple noncoplanar arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Audet, Chantal; Poffenbarger, Brett A.; Chang, Pauling

2011-11-15

Purpose: To evaluate a commercial volumetric modulated arc therapy (VMAT), using multiple noncoplanar arcs, for linac-based cranial radiosurgery, as well as evaluate the combined accuracy of the VMAT dose calculations and delivery. Methods: Twelve patients with cranial lesions of variable size (0.1-29 cc) and two multiple metastases patients were planned (Eclipse RapidArc AAA algorithm, v8.6.15) using VMAT (1-6 noncoplanar arcs), dynamic conformal arc (DCA, {approx}4 arcs), and IMRT (nine static fields). All plans were evaluated according to a conformity index (CI), healthy brain tissue doses and volumes, and the dose to organs at risk. A 2D dose distribution was measuredmore » (Varian Novalis Tx, HD120 MLC, 1000 MU/min, 6 MV beam) for the {approx}4 arc VMAT treatment plans using calibrated film dosimetry. Results: The CI (0-1 best) average for all plans was best for {approx}4 noncoplanar arc VMAT at 0.86 compared with {approx}0.78 for IMRT and a single arc VMAT and 0.68 for DCA. The volumes of healthy brain receiving 50% of the prescribed target coverage dose or more (V{sub 50%}) were lowest for the four arc VMAT [RA(4)] and DCA plans. The average ratio of the V{sub 50%} for the other plans to the RA(4) V{sub 50%} were 1.9 for a single noncoplanar arc VMAT [RA(1nc)], 1.4 for single full coplanar arc VMAT [RA(1f)] and 1.3 for IMRT. The V{sub 50%} improved significantly for single isocenter multiple metastases plan when two noncoplanar VMAT arcs were added to a full single coplanar one. The maximum dose to 5 cc of the outer 1 cm rim of healthy brain which one may want to keep below nonconsequential doses of 300-400 cGy, was 2-3 times greater for IMRT, RA(1nc) and RA(1f) plans compared with the multiple noncoplanar arc DCA and RA(4) techniques. Organs at risk near (0-4 mm) to targets were best spared by (i) single noncoplanar arcs when the targets are lateral to the organ at risk and (ii) by skewed nonvertical planes of IMRT fields when the targets are not lateral to the organ at risk. The highest dose gradient observed between an organ at risk and a target at the edge of a VMAT arc plane or plane of IMRT fields was 17%/mm. The average absolute percent difference between the measured and calculated central axis dose for all the VMAT plans was 3.6 {+-} 2.2%. The measured perpendicular profile widths and shifts were on average within 0.5 mm of planned values. The average total MUs for VMAT plans was double the DCA average and similar to the IMRT average. Conclusions: For the aforementioned planning and delivery system and cranial lesions greater than 7 mm in diameter, multiple noncoplanar arc VMAT consistently provides accurate and high quality cranial radiosurgery dose distributions with low doses to healthy brain tissue and high dose conformity to the target. These qualities may make multiple noncoplanar arc VMAT suitable for a greater range of prescription doses or larger and more irregular lesions. For smaller and/or rounder lesions there are other clinically acceptable treatment techniques that may involve fewer couch angles or arcs and reduce treatment times.« less

Combining qualitative and quantitative operational research methods to inform quality improvement in pathways that span multiple settings

PubMed Central

Crowe, Sonya; Brown, Katherine; Tregay, Jenifer; Wray, Jo; Knowles, Rachel; Ridout, Deborah A; Bull, Catherine; Utley, Martin

2017-01-01

Background Improving integration and continuity of care across sectors within resource constraints is a priority in many health systems. Qualitative operational research methods of problem structuring have been used to address quality improvement in services involving multiple sectors but not in combination with quantitative operational research methods that enable targeting of interventions according to patient risk. We aimed to combine these methods to augment and inform an improvement initiative concerning infants with congenital heart disease (CHD) whose complex care pathway spans multiple sectors. Methods Soft systems methodology was used to consider systematically changes to services from the perspectives of community, primary, secondary and tertiary care professionals and a patient group, incorporating relevant evidence. Classification and regression tree (CART) analysis of national audit datasets was conducted along with data visualisation designed to inform service improvement within the context of limited resources. Results A ‘Rich Picture’ was developed capturing the main features of services for infants with CHD pertinent to service improvement. This was used, along with a graphical summary of the CART analysis, to guide discussions about targeting interventions at specific patient risk groups. Agreement was reached across representatives of relevant health professions and patients on a coherent set of targeted recommendations for quality improvement. These fed into national decisions about service provision and commissioning. Conclusions When tackling complex problems in service provision across multiple settings, it is important to acknowledge and work with multiple perspectives systematically and to consider targeting service improvements in response to confined resources. Our research demonstrates that applying a combination of qualitative and quantitative operational research methods is one approach to doing so that warrants further consideration. PMID:28062603

The Dual Participants: A High Risk Drinking Driver Target Group.

ERIC Educational Resources Information Center

Kline, Michael V.; And Others

1988-01-01

Studied dual participants (N=2,525), multiple offender drinking driver program participants who also attend non-drinking driver alcohol treatment programs. Findings support need for drinking driver programs to be aware of high risk dual participants and for alcohol-related treatment programs to provide drinking and driving education to all dual…

A Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine.

PubMed

Patel, Kershaw V; Pandey, Ambarish; de Lemos, James A

2018-04-11

Until recently, therapies to mitigate atherosclerotic cardiovascular disease (ASCVD) risk have been limited to lifestyle interventions, blood pressure lowering medications, high intensity statin therapy, antiplatelet agents, and in select patients, coronary artery revascularization. Despite administration of these evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly among individuals with known ASCVD. Moreover, the current guideline-based approach does not adequately account for patient-specific, causal pathways that lead to ASCVD progression and complications. In the past few years, multiple new pharmacological agents, targeting conceptually distinct pathophysiological targets, have been shown in large and well-conducted clinical trials to lower cardiovascular risk among patients with established ASCVD receiving guideline directed medical care. These evidenced-based therapies reduce event rates, and in some cases all-cause and cardiovascular mortality; these benefits confirm important new disease targets and challenge the adequacy of the current "standard of care" for secondary prevention.

Longitudinal Prediction of Disruptive Behavior Disorders in Adolescent Males from Multiple Risk Domains

PubMed Central

Trentacosta, Christopher J.; Hyde, Luke W.; Goodlett, Benjamin D.; Shaw, Daniel S.

2012-01-01

The disruptive behavior disorders are among the most prevalent youth psychiatric disorders, and they predict numerous problematic outcomes in adulthood. This study examined multiple domains of risk during early childhood and early adolescence as longitudinal predictors of disruptive behavior disorder diagnoses among adolescent males. Early adolescent risks in the domains of sociodemographic factors, the caregiving context, and youth attributes were examined as mediators of associations between early childhood risks and disruptive behavior disorder diagnoses. Participants were 309 males from a longitudinal study of low-income mothers and their sons. Caregiving and youth risk during early adolescence each predicted the likelihood of receiving a disruptive behavior disorder diagnosis. Furthermore, sociodemographic and caregiving risk during early childhood were indirectly associated with disruptive behavior disorder diagnoses via their association with early adolescent risk. The findings suggest that preventive interventions targeting risk across domains may reduce the prevalence of disruptive behavior disorders. PMID:23239427

Is Adolescent Poly-tobacco Use Associated with Alcohol and Other Drug Use?

PubMed Central

Creamer, MeLisa R.; Portillo, Gabriela V.; Clendennen, Stephanie L.; Perry, Cheryl L.

2016-01-01

Objectives To examine associations between current multiple tobacco product use, and current use of alcohol and marijuana, binge drinking, and lifetime use of marijuana, alcohol, and other drugs among US high school students. Methods Using 2013 Youth Risk Behavior Survey data (N = 13,583 high school students), logistic regression analyses were conducted to determine if single tobacco product or multiple tobacco product users are more likely to engage in other risk behaviors than zero tobacco product users, controlling for demographic variables. Results Overall, 23% of the sample used tobacco products and 10% of students reported current use of at least 2 tobacco products. Among single tobacco product users, the odds for engaging in risk behaviors ranged from 3.3 to 9.9 compared to non-tobacco users (p < .0001). Among multiple tobacco product users, the odds ranged from 1.5 to 4.7 (p < .01) compared to single tobacco product users. Conclusions Results suggest dual users are significantly more likely to engage in risk behavior than non-users and single product users. Future interventions should consider identifying dual-users as at higher risk, and targeting multiple risk behaviors. PMID:26685820

Improving health outcomes for youth living with the human immunodeficiency virus: a multisite randomized trial of a motivational intervention targeting multiple risk behaviors.

PubMed

Naar-King, Sylvie; Parsons, Jeffrey T; Murphy, Debra A; Chen, Xinguang; Harris, D Robert; Belzer, Marvin E

2009-12-01

To determine if Healthy Choices, a motivational interviewing intervention targeting multiple risk behaviors, improved human immunodeficiency virus (HIV) viral load. A randomized, 2-group repeated measures design with analysis of data from baseline and 6- and 9-month follow-up collected from 2005 to 2007. Five US adolescent medicine HIV clinics. A convenience sample with at least 1 of 3 risk behaviors (nonadherence to HIV medications, substance abuse, and unprotected sex) was enrolled. The sample was aged 16 to 24 years and primarily African American. Of the 205 enrolled, 19 did not complete baseline data collections, for a final sample size of 186. Young people living with HIV were randomized to the intervention plus specialty care (n = 94) or specialty care alone (n = 92). The 3- and 6-month follow-up rates, respectively, were 86% and 82% for the intervention group and 81% and 73% for controls. Intervention Healthy Choices was a 4-session individual clinic-based motivational interviewing intervention delivered during a 10-week period. Motivational interviewing is a method of communication designed to elicit and reinforce intrinsic motivation for change. Outcome Measure Plasma viral load. Youth randomized to Healthy Choices showed a significant decline in viral load at 6 months postintervention compared with youth in the control condition (beta = -0.36, t = -2.15, P = .03), with those prescribed antiretroviral medications showing the lowest viral loads. Differences were no longer significant at 9 months. A motivational interviewing intervention targeting multiple risk behaviors resulted in short-term improvements in viral load for youth living with HIV. Trial Registration clinicaltrials.gov Identifier: NCT00103532.

Healthy Choices: Motivational Enhancement Therapy for Health Risk Behaviors in HIV-Positive Youth

ERIC Educational Resources Information Center

Naar-King, Sylvie; Wright, Kathryn; Parsons, Jeffrey T.; Frey, Maureen; Templin, Thomas; Lam, Phebe; Murphy, Debra

2006-01-01

This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16-25. Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention. Youth were randomized to receive a four-session motivational…

Effects of a Narrative Intervention on Story Retelling in At-Risk Young Children

ERIC Educational Resources Information Center

Brown, Jennifer A.; Garzarek, Jessica E.; Donegan, Katharine L.

2014-01-01

The purpose of this multiple baseline study across participants was to examine a narrative retell intervention with guided self-monitoring on narrative macrostructure skills in low-income African American young children at risk for language disorders. Three target 4-year-old children in a mixed-age kindergarten class of nine students participated…

Multi-target detection and positioning in crowds using multiple camera surveillance

NASA Astrophysics Data System (ADS)

Huang, Jiahu; Zhu, Qiuyu; Xing, Yufeng

2018-04-01

In this study, we propose a pixel correspondence algorithm for positioning in crowds based on constraints on the distance between lines of sight, grayscale differences, and height in a world coordinates system. First, a Gaussian mixture model is used to obtain the background and foreground from multi-camera videos. Second, the hair and skin regions are extracted as regions of interest. Finally, the correspondences between each pixel in the region of interest are found under multiple constraints and the targets are positioned by pixel clustering. The algorithm can provide appropriate redundancy information for each target, which decreases the risk of losing targets due to a large viewing angle and wide baseline. To address the correspondence problem for multiple pixels, we construct a pixel-based correspondence model based on a similar permutation matrix, which converts the correspondence problem into a linear programming problem where a similar permutation matrix is found by minimizing an objective function. The correct pixel correspondences can be obtained by determining the optimal solution of this linear programming problem and the three-dimensional position of the targets can also be obtained by pixel clustering. Finally, we verified the algorithm with multiple cameras in experiments, which showed that the algorithm has high accuracy and robustness.

Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

NASA Astrophysics Data System (ADS)

Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

2016-07-01

Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency.

Individual and social determinants of multiple chronic disease behavioral risk factors among youth.

PubMed

Alamian, Arsham; Paradis, Gilles

2012-03-22

Behavioral risk factors are known to co-occur among youth, and to increase risks of chronic diseases morbidity and mortality later in life. However, little is known about determinants of multiple chronic disease behavioral risk factors, particularly among youth. Previous studies have been cross-sectional and carried out without a sound theoretical framework. Using longitudinal data (n = 1135) from Cycle 4 (2000-2001), Cycle 5 (2002-2003) and Cycle 6 (2004-2005) of the National Longitudinal Survey of Children and Youth, a nationally representative sample of Canadian children who are followed biennially, the present study examines the influence of a set of conceptually-related individual/social distal variables (variables situated at an intermediate distance from behaviors), and individual/social ultimate variables (variables situated at an utmost distance from behaviors) on the rate of occurrence of multiple behavioral risk factors (physical inactivity, sedentary behavior, tobacco smoking, alcohol drinking, and high body mass index) in a sample of children aged 10-11 years at baseline. Multiple behavioral risk factors were assessed using a multiple risk factor score. All statistical analyses were performed using SAS, version 9.1, and SUDAAN, version 9.01. Multivariate longitudinal Poisson models showed that social distal variables including parental/peer smoking and peer drinking (Log-likelihood ratio (LLR) = 187.86, degrees of freedom (DF) = 8, p < .001), as well as individual distal variables including low self-esteem (LLR = 76.94, DF = 4, p < .001) increased the rate of occurrence of multiple behavioral risk factors. Individual ultimate variables including age, sex, and anxiety (LLR = 9.34, DF = 3, p < .05), as well as social ultimate variables including family socioeconomic status, and family structure (LLR = 10.93, DF = 5, p = .05) contributed minimally to the rate of co-occurrence of behavioral risk factors. The results suggest targeting individual/social distal variables in prevention programs of multiple chronic disease behavioral risk factors among youth.

Evaluating risk communication: examining target audience perceptions about four presentation formats for fish consumption health advisory information.

PubMed

Connelly, N A; Knuth, B A

1998-10-01

Information format can influence the extent to which target audiences understand and respond to risk-related information. This study examined four elements of risk information presentation format. Using printed materials, we examined target audience perceptions about: (a) reading level; (b) use of diagrams vs. text; (c) commanding versus cajoling tone; and (d) use of qualitative vs. quantitative information presented in a risk ladder. We used the risk communication topic of human health concerns related to eating noncommercial Great Lakes fish affected by chemical contaminants. Results from the comparisons of specific communication formats indicated that multiple formats are required to meet the needs of a significant percent of anglers for three of the four format types examined. Advisory text should be reviewed to ensure the reading level is geared to abilities of the target audience. For many audiences, a combination of qualitative and quantitative information, and a combination of diagrams and text may be most effective. For most audiences, a cajoling rather than commanding tone better provides them with the information they need to make a decision about fish consumption. Segmenting audiences regarding information needs and communication formats may help clarify which approaches to take with each audience.

[Estimates of Target Population for Pneumococcal Vaccination in People over 50 years in Catalonia and Spain].

PubMed

Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Satué, Eva; de Diego, Cinta; Vila-Rovira, Marc; Jariod, Manel

2017-03-15

Published data about prevalence of distinct risk condictions for pneumococcal disease is scarce. This study investigated the prevalence of distinct risk conditions for pneumococal disease in Catalonian adults and stimated the potential size of target population for pneumococcal vaccination in Catalonia and Spain. Cross-sectional population-based study that included 2,033,465 individuals older than 49 years-old assigned to the Catalonian Health Institute (Catalonia, Spain) at 01/01/2015. The Catalonian Health Institute Information System for the Development of Research in Primary Care (SIDIAP) was used to identify comorbidities and/or underlying conditions in each subject and establish potential target population for pneumococcal vaccination on the basis of their risk for suffering pneumococcal infections: 1) immunocompromised subjects; 2) immunocompetents subjects with any risk condition; 3) immunocompetents subjects without risk conditions. Of the 2,033,465 study subjects, 1,053,155 (51.8%) had no risk conditions, 649,014 (31.9%) had one risk condition and 331,296 (16.3%) had multiple risk conditions (11.4% in 50-64 years vs 21.2% in people older than 65 years, p smaller than 0.001; 21.8% in men vs 11.6% in women, p smaller than 0.001). Overall, 176,600 (8.7%) and 803,710 (39.5%) were classified in risk stratum 1 and 2, respectively. According to distinct risk strata considered, the target population for pneumococcal vaccination varied between 0.2-1.9 million in Catalonia and 1.5-2.3 million in Spain. In our setting, almost fifty percent of people ≥50 years have at least one risk condition to suffert pneumococcal disease. Adult population susceptible for pneumococal vaccination largely varies depending on the risk stratum considered as targeted people for pneumococcal vaccination.

Randomised Controlled Trial of Parent Groups for Child Antisocial Behaviour Targeting Multiple Risk Factors: The SPOKES Project

ERIC Educational Resources Information Center

Scott, Stephen; Sylva, Kathy; Doolan, Moira; Price, Jenny; Jacobs, Brian; Crook, Carolyn; Landau, Sabine

2010-01-01

Background: There is a pressing need for cost-effective population-based interventions to tackle early-onset antisocial behaviour. As this is determined by many factors, it would seem logical to devise interventions that address several influences while using an efficient means of delivery. The aim of this trial was to change four risk factors…

Assessing the impacts induced by global climate change through a multi-risk approach: lessons learned from the North Adriatic coast (Italy)

NASA Astrophysics Data System (ADS)

Gallina, Valentina; Torressan, Silvia; Zabeo, Alex; Critto, Andrea; Glade, Thomas; Marcomini, Antonio

2015-04-01

Climate change is expected to pose a wide range of impacts on natural and human systems worldwide, increasing risks from long-term climate trends and disasters triggered by weather extremes. Accordingly, in the future, one region could be potentially affected by interactions, synergies and trade-offs of multiple hazards and impacts. A multi-risk risk approach is needed to effectively address multiple threats posed by climate change across regions and targets supporting decision-makers toward a new paradigm of multi-hazard and risk management. Relevant initiatives have been already developed for the assessment of multiple hazards and risks affecting the same area in a defined timeframe by means of quantitative and semi-quantitative approaches. Most of them are addressing the relations of different natural hazards, however, the effect of future climate change is usually not considered. In order to fill this gap, an advanced multi-risk methodology was developed at the Euro-Mediterranean Centre on Climate Change (CMCC) for estimating cumulative impacts related to climate change at the regional (i.e. sub-national) scale. This methodology was implemented into an assessment tool which allows to scan and classify quickly natural systems and human assets at risk resulting from different interacting hazards. A multi-hazard index is proposed to evaluate the relationships of different climate-related hazards (e.g. sea-level rise, coastal erosion, storm surge) occurring in the same spatial and temporal area, by means of an influence matrix and the disjoint probability function. Future hazard scenarios provided by regional climate models are used as input for this step in order to consider possible effects of future climate change scenarios. Then, the multi-vulnerability of different exposed receptors (e.g. natural systems, beaches, agricultural and urban areas) is estimated through a variety of vulnerability indicators (e.g. vegetation cover, sediment budget, % of urbanization), tailored case by case to different sets of natural hazards and elements at risk. Finally, the multi-risk assessment integrates the multi-hazard with the multi-vulnerability index of exposed receptors, providing a relative ranking of areas and targets potentially affected by multiple risks in the considered region. The methodology was applied to the North Adriatic coast (Italy) producing a range of GIS-based multi-hazard, exposure, multi-vulnerability and multi-risk maps that can be used by policy-makers to define risk management and adaptation strategies. Results show that areas affected by higher multi-hazard scores are located close to the coastline where all the investigated hazards are present. Multi-vulnerability assumes relatively high scores in the whole case study, showing that beaches, wetlands, protected areas and river mouths are the more sensible targets. The final estimate of multi-risk for coastal municipalities provides useful information for local public authorities to set future priorities for adaptation and define future plans for shoreline and coastal management in view of climate change.

Combining qualitative and quantitative operational research methods to inform quality improvement in pathways that span multiple settings.

PubMed

Crowe, Sonya; Brown, Katherine; Tregay, Jenifer; Wray, Jo; Knowles, Rachel; Ridout, Deborah A; Bull, Catherine; Utley, Martin

2017-08-01

Improving integration and continuity of care across sectors within resource constraints is a priority in many health systems. Qualitative operational research methods of problem structuring have been used to address quality improvement in services involving multiple sectors but not in combination with quantitative operational research methods that enable targeting of interventions according to patient risk. We aimed to combine these methods to augment and inform an improvement initiative concerning infants with congenital heart disease (CHD) whose complex care pathway spans multiple sectors. Soft systems methodology was used to consider systematically changes to services from the perspectives of community, primary, secondary and tertiary care professionals and a patient group, incorporating relevant evidence. Classification and regression tree (CART) analysis of national audit datasets was conducted along with data visualisation designed to inform service improvement within the context of limited resources. A 'Rich Picture' was developed capturing the main features of services for infants with CHD pertinent to service improvement. This was used, along with a graphical summary of the CART analysis, to guide discussions about targeting interventions at specific patient risk groups. Agreement was reached across representatives of relevant health professions and patients on a coherent set of targeted recommendations for quality improvement. These fed into national decisions about service provision and commissioning. When tackling complex problems in service provision across multiple settings, it is important to acknowledge and work with multiple perspectives systematically and to consider targeting service improvements in response to confined resources. Our research demonstrates that applying a combination of qualitative and quantitative operational research methods is one approach to doing so that warrants further consideration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparing strategies to assess multiple behavior change in behavioral intervention studies.

PubMed

Drake, Bettina F; Quintiliani, Lisa M; Sapp, Amy L; Li, Yi; Harley, Amy E; Emmons, Karen M; Sorensen, Glorian

2013-03-01

Alternatives to individual behavior change methods have been proposed, however, little has been done to investigate how these methods compare. To explore four methods that quantify change in multiple risk behaviors targeting four common behaviors. We utilized data from two cluster-randomized, multiple behavior change trials conducted in two settings: small businesses and health centers. Methods used were: (1) summative; (2) z-score; (3) optimal linear combination; and (4) impact score. In the Small Business study, methods 2 and 3 revealed similar outcomes. However, physical activity did not contribute to method 3. In the Health Centers study, similar results were found with each of the methods. Multivitamin intake contributed significantly more to each of the summary measures than other behaviors. Selection of methods to assess multiple behavior change in intervention trials must consider study design, and the targeted population when determining the appropriate method/s to use.

Numerical study of impact erosion of multiple solid particle

NASA Astrophysics Data System (ADS)

Zheng, Chao; Liu, Yonghong; Chen, Cheng; Qin, Jie; Ji, Renjie; Cai, Baoping

2017-11-01

Material erosion caused by continuous particle impingement during hydraulic fracturing results in significant economic loss and increased production risks. The erosion process is complex and has not been clearly explained through physical experiments. To address this problem, a multiple particle model in a 3D configuration was proposed to investigate the dynamic erosion process. This approach can significantly reduce experiment costs. The numerical model considered material damping and elastic-plastic material behavior of target material. The effects of impact parameters on erosion characteristics, such as plastic deformation, contact time, and energy loss rate, were investigated. Based on comprehensive studies, the dynamic erosion mechanism and geometry evolution of eroded crater was obtained. These findings can provide a detailed erosion process of target material and insights into the material erosion caused by multiple particle impingement.

Overexpression of the Cytokine BAFF and Autoimmunity Risk.

PubMed

Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

2017-04-27

Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

Number of Sexual Partners and Relationship Status Are Associated With Unprotected Sex Across Emerging Adulthood

PubMed Central

Wilhite, Emily R.; Harden, K. Paige; Fromme, Kim

2018-01-01

Sex with multiple partners, consecutively or concurrently, is a risk factor for contracting sexually transmitted infections (STIs) as multiple partner–partner contacts present increased opportunity for transmission. It is unclear, however, if individuals who tend to have more partners also use protection less reliably than those with sexual histories of fewer partners. Longitudinal data can elucidate whether an individual shows a consistent pattern of sex with multiple partners. We used latent class growth analyses to examine emerging adult survey data (N = 2244) spanning 10 waves of assessment across 6 years. We identified three trajectory classes described with respect to number of partners as (a) Multiple, (b) Single, and (c) Rare. Trajectory group, relationship status, and their interactions were tested as predictors of using protection against STIs and pregnancy at each wave. The Multiple Partners class had the greatest odds ratio of reporting sex without protection against STIs and pregnancy, followed by the Single and Rare classes. Exclusive relationship status was a risk factor for unprotected sex at earlier waves, but a protective factor at most later waves. There was no significant interaction between relationship status and trajectory class in predicting use of protection. The Multiple Partners class reported more permissive values on sex and an elevated proportion of homosexual behavior. This group overlaps with an already identified at-risk population, men who have sex with men. Potential mechanisms explaining the increased risk for sex without protection, including communication, risk assessment, and co-occurring risk behaviors are discussed as targets for intervention. PMID:26940966

Number of Sexual Partners and Relationship Status Are Associated With Unprotected Sex Across Emerging Adulthood.

PubMed

Ashenhurst, James R; Wilhite, Emily R; Harden, K Paige; Fromme, Kim

2017-02-01

Sex with multiple partners, consecutively or concurrently, is a risk factor for contracting sexually transmitted infections (STIs) as multiple partner-partner contacts present increased opportunity for transmission. It is unclear, however, if individuals who tend to have more partners also use protection less reliably than those with sexual histories of fewer partners. Longitudinal data can elucidate whether an individual shows a consistent pattern of sex with multiple partners. We used latent class growth analyses to examine emerging adult survey data (N = 2244) spanning 10 waves of assessment across 6 years. We identified three trajectory classes described with respect to number of partners as (a) Multiple, (b) Single, and (c) Rare. Trajectory group, relationship status, and their interactions were tested as predictors of using protection against STIs and pregnancy at each wave. The Multiple Partners class had the greatest odds ratio of reporting sex without protection against STIs and pregnancy, followed by the Single and Rare classes. Exclusive relationship status was a risk factor for unprotected sex at earlier waves, but a protective factor at most later waves. There was no significant interaction between relationship status and trajectory class in predicting use of protection. The Multiple Partners class reported more permissive values on sex and an elevated proportion of homosexual behavior. This group overlaps with an already identified at-risk population, men who have sex with men. Potential mechanisms explaining the increased risk for sex without protection, including communication, risk assessment, and co-occurring risk behaviors are discussed as targets for intervention.

Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

DTIC Science & Technology

2014-05-01

syndrome (MDS) [36-41]. Multiple Phase III trials of tipifarnib monotherapy in acute myeloid leukemia (AML) and in refractory advanced colorectal...cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome . Cancer 2011;117(6):1236-44 42. Harousseau JL...multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome . Blood 2007;109(10):4158

Clustering of health behaviours in adult survivors of childhood cancer and the general population.

PubMed

Rebholz, C E; Rueegg, C S; Michel, G; Ammann, R A; von der Weid, N X; Kuehni, C E; Spycher, B D

2012-07-10

Little is known about engagement in multiple health behaviours in childhood cancer survivors. Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20-35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. The model identified four health behaviour patterns: 'risk-avoidance', with a generally healthy behaviour; 'moderate drinking', with higher levels of sporting activities, but moderate alcohol-consumption; 'risk-taking', engaging in several risk behaviours; and 'smoking', smoking but not drinking. Similar proportions of survivors and controls fell into the 'risk-avoiding' (42% vs 44%) and the 'risk-taking' cluster (14% vs 12%), but more survivors were in the 'moderate drinking' (39% vs 28%) and fewer in the 'smoking' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.

Neural reactivity to reward in school-age offspring of depressed mothers.

PubMed

Wiggins, Jillian Lee; Schwartz, Karen T G; Kryza-Lacombe, Maria; Spechler, Philip A; Blankenship, Sarah L; Dougherty, Lea R

2017-05-01

Identifying neural profiles predictive of future psychopathology in at-risk individuals is important to efficiently direct preventive care. Alterations in reward processing may be a risk factor for depression. The current study characterized neural substrates of reward processing in children at low- and high-risk for psychopathology due to maternal depression status. Children with (n=27) and without (n=19) maternal depression (ages 5.9-9.6 years) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during fMRI acquisition. Multiple dorsal prefrontal, temporal, and striatal regions showed significant Group (high- vs. low-risk)×Performance (hit vs. miss)×Condition (no reward vs. reward) interactions in a whole-brain analysis. All regions exhibited similar patterns, whereby the high-risk group showed blunted activation differences between trials with vs. without rewards when participants hit the target. Moreover, high-risk children showed activation differences between trials with vs. without rewards in the opposite direction, compared to the low-risk group, when they missed the target. This study had a modest sample size, though larger than existing studies. Children with maternal depression are at elevated risk for future psychopathology, yet not all experience clinically significant symptoms; longitudinal research is necessary to fully track the pathway from risk to disorder. Children of depressed mothers exhibited attenuated neural activation differences and activation patterns opposite to children without depressed mothers. Our findings may provide targets for hypothesis-driven preventive interventions and lead to earlier identification of individuals at risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Hierarchy for targeting prosurvival BCL2 family proteins in multiple myeloma: pivotal role of MCL1.

PubMed

Gong, Jia-Nan; Khong, Tiffany; Segal, David; Yao, Yuan; Riffkin, Chris D; Garnier, Jean-Marc; Khaw, Seong Lin; Lessene, Guillaume; Spencer, Andrew; Herold, Marco J; Roberts, Andrew W; Huang, David C S

2016-10-06

New therapeutic targets are needed to address the poor prognosis of patients with high-risk multiple myeloma. Myeloma cells usually express a range of the prosurvival BCL2 proteins. To define the hierarchy of their relative importance for maintaining the survival of myeloma cells, we targeted each of them in a large panel of cell lines, using pharmacological inhibitors or gene editing or by peptide-based approaches, alone or in combination. The majority of well-established immortalized cell lines (17/25) or low-passage myeloma cell lines (5/7) are readily killed when MCL1 is targeted, even including those cell lines sensitive to BCL2 inhibition. Targeting MCL1 also constrained the growth of myeloma in vivo. We also identified a previously unrecognized subset of myeloma that is highly BCLXL-dependent, and has the potential for cotargeting MCL1 and BCLXL. As MCL1 is pivotal for maintaining survival of most myelomas, it should be prioritized for targeting in the clinic once high-quality, validated inhibitors become available. © 2016 by The American Society of Hematology.

Competing targets of microRNA-608 affect anxiety and hypertension

PubMed Central

Hanin, Geula; Shenhar-Tsarfaty, Shani; Yayon, Nadav; Hoe, Yau Yin; Bennett, Estelle R.; Sklan, Ella H.; Rao, Dabeeru. C.; Rankinen, Tuomo; Bouchard, Claude; Geifman-Shochat, Susana; Shifman, Sagiv; Greenberg, David S.; Soreq, Hermona

2014-01-01

MicroRNAs (miRNAs) can repress multiple targets, but how a single de-balanced interaction affects others remained unclear. We found that changing a single miRNA–target interaction can simultaneously affect multiple other miRNA–target interactions and modify physiological phenotype. We show that miR-608 targets acetylcholinesterase (AChE) and demonstrate weakened miR-608 interaction with the rs17228616 AChE allele having a single-nucleotide polymorphism (SNP) in the 3′-untranslated region (3′UTR). In cultured cells, this weakened interaction potentiated miR-608-mediated suppression of other targets, including CDC42 and interleukin-6 (IL6). Postmortem human cortices homozygote for the minor rs17228616 allele showed AChE elevation and CDC42/IL6 decreases compared with major allele homozygotes. Additionally, minor allele heterozygote and homozygote subjects showed reduced cortisol and elevated blood pressure, predicting risk of anxiety and hypertension. Parallel suppression of the conserved brain CDC42 activity by intracerebroventricular ML141 injection caused acute anxiety in mice. We demonstrate that SNPs in miRNA-binding regions could cause expanded downstream effects changing important biological pathways. PMID:24722204

A prospective study of risk-based colposcopy demonstrates improved detection of cervical precancers.

PubMed

Wentzensen, Nicolas; Walker, Joan; Smith, Katie; Gold, Michael A; Zuna, Rosemary; Massad, L Stewart; Liu, Angela; Silver, Michelle I; Dunn, S Terence; Schiffman, Mark

2018-06-01

Sensitivity for detection of precancers at colposcopy and reassurance provided by a negative colposcopy are in need of systematic study and improvement. We sought to evaluate whether selecting the appropriate women for multiple targeted cervical biopsies based on screening cytology, human papillomavirus testing, and colposcopic impression could improve accuracy and efficiency of cervical precancer detection. In all, 690 women aged 18-67 years referred to colposcopy subsequent to abnormal cervical cancer screening results were included in the study (ClinicalTrials.gov: NCT00339989). Up to 4 cervical biopsies were taken during colposcopy to evaluate the incremental benefit of multiple biopsies. Cervical cytology, human papillomavirus genotyping, and colposcopy impression were used to establish up to 24 different risk strata. Outcomes for the primary analysis were cervical precancers, which included p16 + cervical intraepithelial neoplasia 2 and all cervical intraepithelial neoplasia 3 that were detected by colposcopy-guided biopsy during the colposcopy visit. Later outcomes in women without cervical intraepithelial neoplasia 2 + at baseline were abstracted from electronic medical records. The risk of detecting precancer ranged from 2-82% across 24 strata based on colposcopy impression, cytology, and human papillomavirus genotyping. The risk of precancer in the lowest stratum increased only marginally with multiple biopsies. Women in the highest-risk strata had risks of precancer consistent with immediate treatment. In other risk strata, multiple biopsies substantially improved detection of cervical precancer. Among 361 women with cervical intraepithelial neoplasia <2 at baseline, 195 (54%) had follow-up cytology or histology data with a median follow-up time of 508 days. Lack of detection of precancer at initial colposcopy that included multiple biopsies predicted low risk of precancer during follow-up. Risk assessment at the colposcopy visit makes identification of cervical precancers more effective and efficient. Not finding precancer after a multiple-biopsy protocol provides high reassurance and allows releasing women back to regular screening. Published by Elsevier Inc.

Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction☆

PubMed Central

Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

2010-01-01

Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Cumulative Risk Assessment

EPA Science Inventory

Simultaneous or sequential exposure to multiple chemicals may cause interactions in the pharmacokinetics (PK) and/or pharmacodynamics (PD) of the individual chemicals. Such interactions can cause modification of the internal or target dose/response of one chemical in the mixture ...

Management of severe asthma: targeting the airways, comorbidities and risk factors.

PubMed

Gibson, Peter G; McDonald, Vanessa M

2017-06-01

Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA. © 2017 Royal Australasian College of Physicians.

Design of a randomized controlled trial for multiple cancer risk behaviors among Spanish-speaking Mexican-origin smokers.

PubMed

Castro, Yessenia; Basen-Engquist, Karen; Fernandez, Maria E; Strong, Larkin L; Eakin, Elizabeth G; Resnicow, Ken; Li, Yisheng; Wetter, David W

2013-03-18

Smoking, poor diet, and physical inactivity account for as much as 60% of cancer risk. Latinos experience profound disparities in health behaviors, as well as the cancers associated with them. Currently, there is a dearth of controlled trials addressing these health behaviors among Latinos. Further, to the best of our knowledge, no studies address all three behaviors simultaneously, are culturally sensitive, and are guided by formative work with the target population. Latinos represent 14% of the U.S. population and are the fastest growing minority group in the country. Efforts to intervene on these important lifestyle factors among Latinos may accelerate the elimination of cancer-related health disparities. The proposed study will evaluate the efficacy of an evidence-based and theoretically-driven Motivation And Problem Solving (MAPS) intervention, adapted and culturally-tailored for reducing cancer risk related to smoking, poor diet, and physical inactivity among high-risk Mexican-origin smokers who are overweight/obese (n = 400). Participants will be randomly assigned to one of two groups: Health Education (HE) or MAPS (HE + up to 18 MAPS counseling calls over 18 months). Primary outcomes are smoking status, servings of fruits and vegetables, and both self-reported and objectively measured physical activity. Outcome assessments will occur at baseline, 6 months, 12 months, and 18 months. The current study will contribute to a very limited evidence base on multiple risk factor intervention studies on Mexican-origin individuals and has the potential to inform both future research and practice related to reducing cancer risk disparities. An effective program targeting multiple cancer risk behaviors modeled after chronic care programs has the potential to make a large public health impact because of the dearth of evidence-based interventions for Latinos and the extended period of support that is provided in such a program. National Institutes of Health Clinical Trials Registry # NCT01504919.

Dual task cost of walking is related to fall risk in persons with multiple sclerosis.

PubMed

Wajda, Douglas A; Motl, Robert W; Sosnoff, Jacob J

2013-12-15

Persons with multiple sclerosis (MS) commonly have walking and cognitive impairments. While walking with a simultaneous cognitive task, persons with MS experience a greater decline in walking performance than healthy controls. This change in performance is termed dual task cost or dual task interference and has been associated with fall risk in older adults. We examined whether dual task cost during walking was related to fall risk in persons with MS. Thirty-three ambulatory persons with MS performed walking tasks with and without a concurrent cognitive task (dual task condition) as well as underwent a fall risk assessment. Dual task cost was operationalized as the percent change in velocity from normal walking conditions to dual task walking conditions. Fall risk was quantified using the Physiological Profile Assessment. A Spearman correlation analysis revealed a significant positive correlation between dual task cost of walking velocity and fall risk as well as dual task cost of stride length and fall risk. Overall, the findings indicate that dual task cost is associated with fall risk and may be an important target for falls prevention strategies. © 2013.

Factors associated with sexual risk behavior among persons living with HIV: gender and sexual identity group differences.

PubMed

Courtenay-Quirk, Cari; Pals, Sherri L; Colfax, Grant; McKirnan, David; Gooden, Lauren; Eroğlu, Doğan

2008-09-01

Factors associated with HIV transmission risk may differ between subgroups of persons living with HIV/AIDS (PLWHA). This study examined such factors in a sample of PLWHA recruited in 3 US metropolitan areas. Sexually active participants were categorized as gay or bisexual men (GBM) (n = 545), heterosexual men (HSM, n = 223), or women (n = 214). Of 982 participants, 27.1% reported serodiscordant unprotected anal or vaginal sex (SDUAV). SDUAV was associated with multiple (2 or more) partners, using poppers, and lower safer sex self-efficacy among GBM. SDUAV was associated with multiple partners among HSM. Among women, factors examined were not associated with SDUAV. These findings are consistent with prior research and facilitate our ability to target those who may be most at risk for transmitting HIV among HIV-positive GBM. More research must be conducted to identify factors associated with risk behavior among HSM and women.

Multiple Peer Group Self-Identification and Adolescent Tobacco Use

PubMed Central

Fuqua, Juliana L.; Gallaher, Peggy E.; Unger, Jennifer B.; Trinidad, Dennis R.; Sussman, Steve; Ortega, Enrique; Johnson, C. Anderson

2014-01-01

Associations between peer group self-identification and smoking were examined among 2,698 ethnically diverse middle school students in Los Angeles who self-identified with groups such as Rockers, Skaters, and Gamers. The sample was 47.1% male, 54.7% Latino, 25.4% Asian, 10.8% White, 9.1% Other ethnicity, and 59.3% children of immigrant parents. Multiple group self-identification was common: 84% identified with two or more groups and 65% identified with three or more groups. Logistic regression analyses indicated that as students endorsed more high-risk groups, the greater their risk of tobacco use. A classification tree analysis identified risk groups based on interactions among ethnicity, gender, and group self-identification. Psychographic targeting based on group self-identification could be useful to design more relevant smoking prevention messages for adolescents who identify with high-risk peer groups. PMID:22458850

Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital.

PubMed

Teh, Benjamin W; Worth, Leon J; Harrison, Simon J; Thursky, Karin A; Slavin, Monica A

2015-07-01

Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.

Multiple health behaviours: overview and implications

PubMed Central

Spring, Bonnie; Moller, Arlen C.; Coons, Michael J.

2012-01-01

Background More remains unknown than known about how to optimize multiple health behaviour change. Methods After reviewing the prevalence and comorbidities among major chronic disease risk behaviours for adults and youth, we consider the origins and applicability of high-risk and population strategies to foster multiple health behaviour change. Results Findings indicate that health risk behaviours are prevalent, increase with age and co-occur as risk behaviour clusters or bundles. Conclusions We conclude that both population and high-risk strategies for health behaviour intervention are warranted, potentially synergistic and need intervention design that accounts for substitute and complementary relationships among bundled health behaviours. To maximize positive public health impact, a pressing need exists for bodies of basic and translational science that explain health behaviour bundling. Also needed is applied science that elucidates the following: (1) the optimal number of behaviours to intervene upon; (2) how target behaviours are best selected (e.g. greatest health impact; patient preference or positive effect on bundled behaviours); (3) whether to increase healthy or decrease unhealthy behaviours; (4) whether to intervene on health behaviours simultaneously or sequentially and (5) how to achieve positive synergies across individual-, group- and population-level intervention approaches. PMID:22363028

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

PubMed

Painter, Jodie N; Kaufmann, Susanne; O'Mara, Tracy A; Hillman, Kristine M; Sivakumaran, Haran; Darabi, Hatef; Cheng, Timothy H T; Pearson, John; Kazakoff, Stephen; Waddell, Nicola; Hoivik, Erling A; Goode, Ellen L; Scott, Rodney J; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; French, Juliet D; Salvesen, Helga B; Pollock, Pamela M; Thompson, Deborah J; Spurdle, Amanda B; Edwards, Stacey L

2016-06-02

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The additive effect of adherence to multiple healthy lifestyles on subclinical atherosclerosis: Insights from the AWHS.

PubMed

Uzhova, Irina; Mateo-Gallego, Rocio; Moreno-Franco, Belén; Molina-Montes, Esther; Leon-Latre, Montserrat; Casasnovas Lenguas, José A; Civeira, Fernando; Peñalvo, José L

2018-03-28

Public health strategies targeting multiple healthy behaviors, rather than individual factors, have been proposed as more efficient strategies to promote cardiovascular health. However, the additive effect of multiple targets on primary prevention has not been fully characterized. To examine how adherence to multiple healthy behaviors is associated with the presence of subclinical atherosclerosis, a measure of early cardiovascular disease. Analysis of a baseline data from 1798 middle-aged men from the Aragon Workers Health Study conducted between 2009 and 2010. Healthy behaviors were defined according to American Heart Association recommendations, aligned with Spanish Nutritional recommendations and included moderate alcohol consumption, smoking abstinence, no abdominal adiposity, decreased sedentarism, and adherence to Alternate Mediterranean Dietary Index. Presence of coronary artery calcium and plaques in femoral and carotid was quantified by a 16-slice computed tomography scanner and 2D ultrasound. Moderate alcohol consumption, as well as adherence to Mediterranean diet is independently associated with a 6% lower risk of having subclinical atherosclerosis. Smoking abstinence is associated with a 11% lower risk of subclinical atherosclerosis. Those who follow 3 lifestyle behaviors (Mediterranean diet, nonsmoking, and moderate alcohol intake) have 18% lower odds of presenting subclinical atherosclerosis compared with those who do not follow these protective lifestyle habits. Adoption of multiple healthy lifestyle behaviors early in life could be a key strategy to tackle the onset of atherosclerosis and reduce cardiovascular disease burden. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Habitat risk assessment for regional ocean planning in the U.S. Northeast and Mid-Atlantic.

PubMed

Wyatt, Katherine H; Griffin, Robert; Guerry, Anne D; Ruckelshaus, Mary; Fogarty, Michael; Arkema, Katie K

2017-01-01

Coastal habitats provide important benefits to people, including habitat for species targeted by fisheries and opportunities for tourism and recreation. Yet, such human activities also can imperil these habitats and undermine the ecosystem services they provide to people. Cumulative risk assessment provides an analytical framework for synthesizing the influence of multiple stressors across habitats and decision-support for balancing human uses and ecosystem health. To explore cumulative risk to habitats in the U.S. Northeast and Mid-Atlantic Ocean Planning regions, we apply the open-source InVEST Habitat Risk Assessment model to 13 habitats and 31 stressors in an exposure-consequence framework. In doing so, we advance the science priorities of EBM and both regional planning bodies by synthesizing the wealth of available data to improve our understanding of human uses and how they affect marine resources. We find that risk to ecosystems is greatest first, along the coast, where a large number of stressors occur in close proximity and secondly, along the continental shelf, where fewer, higher consequence activities occur. Habitats at greatest risk include soft and hard-bottom nearshore areas, tidal flats, soft-bottom shelf habitat, and rocky intertidal zones-with the degree of risk varying spatially. Across all habitats, our results indicate that rising sea surface temperatures, commercial fishing, and shipping consistently and disproportionally contribute to risk. Further, our findings suggest that management in the nearshore will require simultaneously addressing the temporal and spatial overlap as well as intensity of multiple human activities and that management in the offshore requires more targeted efforts to reduce exposure from specific threats. We offer a transparent, generalizable approach to evaluating cumulative risk to multiple habitats and illustrate the spatially heterogeneous nature of impacts along the eastern Atlantic coast and the importance of spatial scale in estimating such impacts. These results offer a valuable decision-support tool by helping to constrain the decision space, focus attention on habitats and locations at the greatest risk, and highlight effect management strategies.

Habitat risk assessment for regional ocean planning in the U.S. Northeast and Mid-Atlantic

PubMed Central

Guerry, Anne D.; Ruckelshaus, Mary; Fogarty, Michael; Arkema, Katie K.

2017-01-01

Coastal habitats provide important benefits to people, including habitat for species targeted by fisheries and opportunities for tourism and recreation. Yet, such human activities also can imperil these habitats and undermine the ecosystem services they provide to people. Cumulative risk assessment provides an analytical framework for synthesizing the influence of multiple stressors across habitats and decision-support for balancing human uses and ecosystem health. To explore cumulative risk to habitats in the U.S. Northeast and Mid-Atlantic Ocean Planning regions, we apply the open-source InVEST Habitat Risk Assessment model to 13 habitats and 31 stressors in an exposure-consequence framework. In doing so, we advance the science priorities of EBM and both regional planning bodies by synthesizing the wealth of available data to improve our understanding of human uses and how they affect marine resources. We find that risk to ecosystems is greatest first, along the coast, where a large number of stressors occur in close proximity and secondly, along the continental shelf, where fewer, higher consequence activities occur. Habitats at greatest risk include soft and hard-bottom nearshore areas, tidal flats, soft-bottom shelf habitat, and rocky intertidal zones—with the degree of risk varying spatially. Across all habitats, our results indicate that rising sea surface temperatures, commercial fishing, and shipping consistently and disproportionally contribute to risk. Further, our findings suggest that management in the nearshore will require simultaneously addressing the temporal and spatial overlap as well as intensity of multiple human activities and that management in the offshore requires more targeted efforts to reduce exposure from specific threats. We offer a transparent, generalizable approach to evaluating cumulative risk to multiple habitats and illustrate the spatially heterogeneous nature of impacts along the eastern Atlantic coast and the importance of spatial scale in estimating such impacts. These results offer a valuable decision-support tool by helping to constrain the decision space, focus attention on habitats and locations at the greatest risk, and highlight effect management strategies. PMID:29261672

Bridging the gap between individual-level risk for HIV and structural determinants: using root cause analysis in strategic planning.

PubMed

Willard, Nancy; Chutuape, Kate; Stines, Stephanie; Ellen, Jonathan M

2012-01-01

HIV prevention efforts have expanded beyond individual-level interventions to address structural determinants of risk. Coalitions have been an important vehicle for addressing similar intractable and deeply rooted health-related issues. A root cause analysis process may aid coalitions in identifying fundamental, structural-level contributors to risk and in identifying appropriate solutions. For this article, strategic plans for 13 coalitions were analyzed both before and after a root cause analysis approach was applied to determine the coalitions' strategic plans potential impact and comprehensiveness. After root cause analysis, strategic plans trended toward targeting policies and practices rather than on single agency programmatic changes. Plans expanded to target multiple sectors and several changes within sectors to penetrate deeply into a sector or system. Findings suggest that root cause analysis may be a viable tool to assist coalitions in identifying structural determinants and possible solutions for HIV risk.

The need to increase awareness of the risk factors of COPD.

PubMed

Roche, Nicolas

2016-07-01

COPD is a heterogeneous disease responsible for a major burden on public and individual health. A wide variety of intrinsic and environmental risk factors are involved, and exert their influence at various time points during the life span of individuals. Knowledge of these factors is of utmost importance to develop appropriate screening and prevention programs, and may help improving the pathophysiological knowledge of the disease. Accordingly, there are multiple targets of information and education on risk factors for COPD, including the general population and patients, workers and employers, doctors and other healthcare professionals, researchers, policy-makers, payers, etc. Gender and socioeconomic factors need to be specifically considered. Importantly, it is likely that increasing the specific knowledge of COPD risk factors among the above-mentioned targets cannot not be obtained without increasing the general knowledge of COPD in the population, which at present is dramatically low.

Sick Populations and Sick Subpopulations: Reducing Disparities in Cardiovascular Disease Between Blacks and Whites in the United States.

PubMed

Lu, Yuan; Ezzati, Majid; Rimm, Eric B; Hajifathalian, Kaveh; Ueda, Peter; Danaei, Goodarz

2016-08-09

Cardiovascular disease (CVD) death rates are much higher in blacks than whites in the United States. It is unclear how CVD risk and events are distributed among blacks versus whites and how interventions reduce racial disparities. We developed risk models for fatal and for fatal and nonfatal CVD using 8 cohorts in the United States. We used 6154 adults who were 50 to 69 years of age in the National Health and Nutrition Examination Survey 1999 to 2012 to estimate the distributions of risk and events in blacks and whites. We estimated the total and disparity impacts of a range of population-wide, targeted, and risk-based interventions on 10-year CVD risks and event rates. Twenty-five percent (95% confidence interval [CI], 22-28) of black men and 12% (95% CI, 10-14) of black women were at ≥6.67% risk of fatal CVD (almost equivalent to 20% risk of fatal or nonfatal CVD) compared with 10% (95% CI, 8-12) of white men and 3% (95% CI, 2-4) of white women. These high-risk individuals accounted for 55% (95% CI, 49-59) of CVD deaths among black men and 42% (95% CI, 35-46) in black women compared with 30% (95% CI, 24-35) in white men and 18% (95% CI, 13-22) in white women. We estimated that an intervention that treated multiple risk factors in high-risk individuals could reduce black-white difference in CVD death rate from 1659 to 1244 per 100 000 in men and from 1320 to 897 in women. Rates of fatal and nonfatal CVD were generally similar between black and white men. In women, a larger proportion of women were at ≥7.5% risk of CVD (30% versus 19% in whites), and an intervention that targeted multiple risk factors among this group was estimated to reduce black-white differences in CVD rates from 1688 to 1197 per 100 000. A substantially larger proportion of blacks have a high risk of fatal CVD and bear a large share of CVD deaths. A risk-based intervention that reduces multiple risk factors could substantially reduce overall CVD rates and racial disparities in CVD death rates. © 2016 American Heart Association, Inc.

Germline genetic variants with implications for disease risk and therapeutic outcomes.

PubMed

Pasternak, Amy L; Ward, Kristen M; Luzum, Jasmine A; Ellingrod, Vicki L; Hertz, Daniel L

2017-10-01

Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care. Copyright © 2017 the American Physiological Society.

Added value of second biopsy target in screen-detected widespread suspicious breast calcifications.

PubMed

Falkner, Nathalie M; Hince, Dana; Porter, Gareth; Dessauvagie, Ben; Jeganathan, Sanjay; Bulsara, Max; Lo, Glen

2018-06-01

There is controversy on the optimal work-up of screen-detected widespread breast calcifications: whether to biopsy a single target or multiple targets. This study evaluates agreement between multiple biopsy targets within the same screen-detected widespread (≥25 mm) breast calcification to determine if the second biopsy adds value. Retrospective observational study of women screened in a statewide general population risk breast cancer mammographic screening program from 2009 to 2016. Screening episodes recalled for widespread calcifications where further views indicated biopsy, and two or more separate target areas were sampled within the same lesion were included. Percentage agreement and Cohen's Kappa were calculated. A total of 293317 women were screened during 761124 separate episodes with recalls for widespread calcifications in 2355 episodes. In 171 women, a second target was biopsied within the same lesion. In 149 (86%) cases, the second target biopsy result agreed with the first biopsy (κ = 0.6768). Agreement increased with increasing mammography score (85%, 86% and 92% for score 3, 4 and 5 lesions). Same day multiple biopsied lesions were three times more likely to yield concordant results compared to post-hoc second target biopsy cases. While a single target biopsy is sufficient to discriminate a benign vs. malignant diagnosis in most cases, in 14% there is added value in performing a second target biopsy. Biopsies performed prospectively are more likely to yield concordant results compared to post-hoc second target biopsy cases, suggesting a single prospective biopsy may be sufficient when results are radiological-pathological concordant; discordance still requires repeat sampling. © 2018 The Royal Australian and New Zealand College of Radiologists.

General strategy for the protection of organs at risk in IMRT therapy of a moving body

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abolfath, Ramin M.; Papiez, Lech

2009-07-15

We investigated protection strategies of organs at risk (OARs) in intensity modulated radiation therapy (IMRT). These strategies apply to delivery of IMRT to moving body anatomies that show relative displacement of OAR in close proximity to a tumor target. We formulated an efficient genetic algorithm which makes it possible to search for global minima in a complex landscape of multiple irradiation strategies delivering a given, predetermined intensity map to a target. The optimal strategy was investigated with respect to minimizing the dose delivered to the OAR. The optimization procedure developed relies on variability of all parameters available for control ofmore » radiation delivery in modern linear accelerators, including adaptation of leaf trajectories and simultaneous modification of beam dose rate during irradiation. We showed that the optimization algorithms lead to a significant reduction in the dose delivered to OAR in cases where organs at risk move relative to a treatment target.« less

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease.

PubMed

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S; Johnson, Kipp W; Ze, Yi; Tomlinson, Max S; Readhead, Ben; Dudley, Joel T; Kullo, Iftikhar J

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease.

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease

PubMed Central

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S.; Johnson, Kipp W.; Ze, Yi; Tomlinson, Max S.; Readhead, Ben; Dudley, Joel T.; Kullo, Iftikhar J.

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease. PMID:29888052

Accidental Water Pollution Risk Analysis of Mine Tailings Ponds in Guanting Reservoir Watershed, Zhangjiakou City, China.

PubMed

Liu, Renzhi; Liu, Jing; Zhang, Zhijiao; Borthwick, Alistair; Zhang, Ke

2015-12-02

Over the past half century, a surprising number of major pollution incidents occurred due to tailings dam failures. Most previous studies of such incidents comprised forensic analyses of environmental impacts after a tailings dam failure, with few considering the combined pollution risk before incidents occur at a watershed-scale. We therefore propose Watershed-scale Tailings-pond Pollution Risk Analysis (WTPRA), designed for multiple mine tailings ponds, stemming from previous watershed-scale accidental pollution risk assessments. Transferred and combined risk is embedded using risk rankings of multiple routes of the "source-pathway-target" in the WTPRA. The previous approach is modified using multi-criteria analysis, dam failure models, and instantaneous water quality models, which are modified for application to multiple tailings ponds. The study area covers the basin of Gutanting Reservoir (the largest backup drinking water source for Beijing) in Zhangjiakou City, where many mine tailings ponds are located. The resultant map shows that risk is higher downstream of Gutanting Reservoir and in its two tributary basins (i.e., Qingshui River and Longyang River). Conversely, risk is lower in the midstream and upstream reaches. The analysis also indicates that the most hazardous mine tailings ponds are located in Chongli and Xuanhua, and that Guanting Reservoir is the most vulnerable receptor. Sensitivity and uncertainty analyses are performed to validate the robustness of the WTPRA method.

APPLICATION OF A MULTIROUTE HUMAN PBPK MODEL FOR BROMODICHLOROMETHANE (BDCM)

EPA Science Inventory

Due to its presence in water as a volatile disinfection byproduct, BDCM poses a risk for exposure via multiple routes. Mechanistic data suggest target tissue metabolism could be important for some types of BDCM-induced toxicity. Utilizing our refined PBPK model for BDCM, the impa...

Multiple sex partner behavior in female undergraduate students in China: a multi-campus survey.

PubMed

Yan, Hong; Chen, Weiqi; Wu, Haocheng; Bi, Yongyi; Zhang, Miaoxuan; Li, Shiyue; Braun, Kathryn L

2009-08-22

China is realizing increases in women engaged in premarital sex and multiple sex partner behavior. Our aim was to examine prevalence and determinants of multiple sex partner behavior among female undergraduates in China. Anonymously completed questionnaires were received from 4,769 unmarried female undergraduates, recruited using randomized cluster sampling by type of university and students' major and grade. Items captured demographic, family, peer and work influence, and student factors (major, academic performance, and sex-related knowledge and attitudes). To examine risk factors for sexual behaviors, we used multi-level logistic regression, yielding odds ratios (OR) and 95% confidence intervals (95% CI). Of 4,769 female students, 863 (18.10%) reported ever having sexual intercourse, and 5.31% reported having multiple sex partners (29.32% of all women having sexual intercourse). Several demographic, family, peer and work influences, and student factors (including major, performance, knowledge, and attitude toward sex) were risk factors for ever having sex. However, risk factors for multiple sex partners only included working in a place of entertainment, having current close friends that were living with boyfriends, poor academic performance, and positive attitudes toward multiple partners. These women also were more likely to practice masturbation, start having sex at a younger age, have sex with married men and/or men not their "boyfriends" at first coitus, and not use condoms consistently. A small but important subset of Chinese female undergraduates is engaged in unprotected sex with multiple sex partners. Interventions need to target at risk women, stressing the importance of consistent condom use.

Multiple sex partner behavior in female undergraduate students in China: A multi-campus survey

PubMed Central

Yan, Hong; Chen, Weiqi; Wu, Haocheng; Bi, Yongyi; Zhang, Miaoxuan; Li, Shiyue; Braun, Kathryn L

2009-01-01

Background China is realizing increases in women engaged in premarital sex and multiple sex partner behavior. Our aim was to examine prevalence and determinants of multiple sex partner behavior among female undergraduates in China. Methods Anonymously completed questionnaires were received from 4,769 unmarried female undergraduates, recruited using randomized cluster sampling by type of university and students' major and grade. Items captured demographic, family, peer and work influence, and student factors (major, academic performance, and sex-related knowledge and attitudes). To examine risk factors for sexual behaviors, we used multi-level logistic regression, yielding odds ratios (OR) and 95% confidence intervals (95% CI). Results Of 4,769 female students, 863 (18.10%) reported ever having sexual intercourse, and 5.31% reported having multiple sex partners (29.32% of all women having sexual intercourse). Several demographic, family, peer and work influences, and student factors (including major, performance, knowledge, and attitude toward sex) were risk factors for ever having sex. However, risk factors for multiple sex partners only included working in a place of entertainment, having current close friends that were living with boyfriends, poor academic performance, and positive attitudes toward multiple partners. These women also were more likely to practice masturbation, start having sex at a younger age, have sex with married men and/or men not their "boyfriends" at first coitus, and not use condoms consistently. Conclusion A small but important subset of Chinese female undergraduates is engaged in unprotected sex with multiple sex partners. Interventions need to target at risk women, stressing the importance of consistent condom use. PMID:19698132

Clustering of health behaviours in adult survivors of childhood cancer and the general population

PubMed Central

Rebholz, C E; Rueegg, C S; Michel, G; Ammann, R A; von der Weid, N X; Kuehni, C E; Spycher, B D

2012-01-01

Background: Little is known about engagement in multiple health behaviours in childhood cancer survivors. Methods: Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20–35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. Results: The model identified four health behaviour patterns: ‘risk-avoidance', with a generally healthy behaviour; ‘moderate drinking', with higher levels of sporting activities, but moderate alcohol-consumption; ‘risk-taking', engaging in several risk behaviours; and ‘smoking', smoking but not drinking. Similar proportions of survivors and controls fell into the ‘risk-avoiding' (42% vs 44%) and the ‘risk-taking' cluster (14% vs 12%), but more survivors were in the ‘moderate drinking' (39% vs 28%) and fewer in the ‘smoking' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. Conclusion: A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions. PMID:22722311

Innovative model uses a new brand of specialist to target the high-risk chronically ill.

PubMed

2002-06-01

Some patients simply can't be taken care of in your typical 15-minute office visit. That's why a Houston-based organization developed a new model--and a new specialist--to deal with the growing number of patients affected by multiple diagnoses and other factors putting them at high risk for hospital utilization. With early success, the approach has now attracted the attention of Medicare and other insurers.

A Systematic Review of Interventions to Improve Adherence to Melanoma Preventive Behaviors for Individuals at Elevated Risk

PubMed Central

Wu, Yelena P.; Aspinwall, Lisa G.; Conn, Bridgid M.; Stump, Tammy; Grahmann, Bridget; Leachman, Sancy A.

2016-01-01

Background and Objectives To examine the effectiveness of behavioral interventions for melanoma prevention targeted to individuals at elevated risk due to personal and/or family history. Methods Through literature searches in 5 search databases (through July 2014), 20 articles describing 14 unique interventions focused on melanoma prevention among individuals at elevated risk for the disease were identified. Interventions targeting only patients undergoing active treatment for melanoma were excluded. Results The average study quality was moderate. The majority of interventions (6 out of 9, 66% of studies) led to improvements in one or more photoprotective behaviors, particularly for improvements in use of protective clothing (3 out of 5, 60% of studies), and frequency and/or thoroughness of skin self-examinations (9 out of 12, 75%). Fewer interventions (5 out of 14, 36%) targeted uptake of total body skin examinations (60% led to improvements). Also, fewer interventions targeted all three preventive behaviors (5 out of 14, 36%). Conclusions Findings suggest future interventions should aim to improve adherence across multiple preventive behaviors, over a longer time period (past 8 months post-intervention), and target high-risk children. Studies should include adequate sample sizes to investigate moderators and mediators of intervention effectiveness. Interventions may be strengthened by new techniques, such as incorporating family members (e.g., to improve thoroughness of skin self-examinations) and eHealth technology. PMID:27090434

Endocannabinoid system: potential novel targets for treatment of schizophrenia.

PubMed

Saito, Atsushi; Ballinger, Michael D L; Pletnikov, Mikhail V; Wong, Dean F; Kamiya, Atsushi

2013-05-01

Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

Application of portfolio theory to risk-based allocation of surveillance resources in animal populations.

PubMed

Prattley, D J; Morris, R S; Stevenson, M A; Thornton, R

2007-09-14

Distribution of finite levels of resources between multiple competing tasks can be a challenging problem. Resources need to be distributed across time periods and geographic locations to increase the probability of detection of a disease incursion or significant change in disease pattern. Efforts should focus primarily on areas and populations where risk factors for a given disease reach relatively high levels. In order to target resources into these areas, the overall risk level can be evaluated periodically across locations to create a dynamic national risk landscape. Methods are described to integrate the levels of various risk factors into an overall risk score for each area, to account for the certainty or variability around those measures and then to allocate surveillance resources across this risk landscape. In addition to targeting resources into high risk areas, surveillance continues in lower risk areas where there is a small yet positive chance of disease occurrence. In this paper we describe the application of portfolio theory concepts, routinely used in finance, to design surveillance portfolios for a series of examples. The appropriate level of resource investment is chosen for each disease or geographical area and time period given the degree of disease risk and uncertainty present.

Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: multi-institutional retrospective analysis of 389 patients.

PubMed

Mariotti, Guilherme C; Costa, Daniel N; Pedrosa, Ivan; Falsarella, Priscila M; Martins, Tatiana; Roehrborn, Claus G; Rofsky, Neil M; Xi, Yin; M Andrade, Thais C; Queiroz, Marcos R; Lotan, Yair; Garcia, Rodrigo G; Lemos, Gustavo C; Baroni, Ronaldo H

2016-09-01

To determine the incremental diagnostic value of targeted biopsies added to an extended sextant biopsy scheme on a per-patient, risk-stratified basis in 2 academic centers using different multiparametric magnetic resonance imaging (MRI) protocols, a large group of radiologists, multiple biopsy systems, and different biopsy operators. All patients with suspected prostate cancer (PCa) who underwent multiparametric MRI of the prostate in 2 academic centers between February 2013 and January 2015 followed by systematic and targeted MRI-transrectal ultrasound fusion biopsy were reviewed. Risk-stratified detection rate using systematic biopsies was compared with targeted biopsies on a per-patient basis. The McNemar test was used to compare diagnostic performance of the 2 approaches. A total of 389 men met eligibility criteria. PCa was diagnosed in 47% (182/389), 52%(202/389), and 60%(235/389) of patients using the targeted, systematic, and combined (targeted plus systematic) approach, respectively. Compared with systematic biopsy, targeted biopsy diagnosed 11% (37 vs. 26) more intermediate-to-high risk (P<0.0001) and 16% (10 vs. 16) fewer low-risk tumors (P<0.0001). These results were replicated when data from each center, biopsy-naïve patients, and men with previous negative biopsies were analyzed separately. Targeted MRI-transrectal ultrasound fusion biopsy consistently improved the detection of clinically significant PCa in a large patient cohort with diverse equipment, protocols, radiologists, and biopsy operators as can be encountered in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Ready, set, go: a cross-sectional survey to understand priorities and preferences for multiple health behaviour change in a highly disadvantaged group.

PubMed

Noble, Natasha; Paul, Christine; Sanson-Fisher, Robert; Turon, Heidi; Turner, Nicole; Conigrave, Katherine

2016-09-13

Socially disadvantaged groups, such as Aboriginal Australians, tend to have a high prevalence of multiple lifestyle risk factors, increasing the risk of disease and underscoring the need for services to address multiple health behaviours. The aims of this study were to explore, among a socially disadvantaged group of people attending an Aboriginal Community Controlled Health Service (ACCHS): a) readiness to change health behaviours; b) acceptability of addressing multiple risk factors sequentially or simultaneously; and c) preferred types of support services. People attending an ACCHS in regional New South Wales (NSW) completed a touchscreen survey while waiting for their appointment. The survey assessed participant health risk status, which health risks they would like to change, whether they preferred multiple health changes to be made together or separately, and the types of support they would use. Of the 211 participants who completed the survey, 94 % reported multiple (two or more) health risks. There was a high willingness to change, with 69 % of current smokers wanting to cut down or quit, 51 % of overweight or obese participants wanting to lose weight and 44 % of those using drugs in the last 12 months wanting to stop or cut down. Of participants who wanted to make more than one health change, over half would be willing to make simultaneous or over-lapping health changes. The most popular types of support were help from a doctor or Health Worker and seeing a specialist, with less than a quarter of participants preferring telephone or electronic (internet or smart phone) forms of assistance. The importance of involving family members was also identified. Strategies addressing multiple health behaviour changes are likely to be acceptable for people attending an ACCHS, but may need to allow flexibility in the choice of initial target behaviour, timing of changes, and the format of support provided.

Sexual Initiation, Parent Practices, and Acculturation in Hispanic Seventh Graders

ERIC Educational Resources Information Center

Morales-Campos, Daisy Y.; Markham, Christine; Peskin, Melissa Fleschler; Fernandez, Maria E.

2012-01-01

Background: Hispanic youths have high rates of sexually transmitted infections and pregnancies, yet little research has targeted multiple protective/risk factors for early sexual initiation in this group. This study examined two main factors--parenting practices and acculturation--on early sexual initiation among Hispanic middle school students in…

Anatomy-driven multiple trajectory planning (ADMTP) of intracranial electrodes for epilepsy surgery.

PubMed

Sparks, Rachel; Vakharia, Vejay; Rodionov, Roman; Vos, Sjoerd B; Diehl, Beate; Wehner, Tim; Miserocchi, Anna; McEvoy, Andrew W; Duncan, John S; Ourselin, Sebastien

2017-08-01

Epilepsy is potentially curable with resective surgery if the epileptogenic zone (EZ) can be identified. If non-invasive imaging is unable to elucidate the EZ, intracranial electrodes may be implanted to identify the EZ as well as map cortical function. In current clinical practice, each electrode trajectory is determined by time-consuming manual inspection of preoperative imaging to find a path that avoids blood vessels while traversing appropriate deep and superficial regions of interest (ROIs). We present anatomy-driven multiple trajectory planning (ADMTP) to find safe trajectories from a list of user-defined ROIs within minutes rather than the hours required for manual planning. Electrode trajectories are automatically computed in three steps: (1) Target Point Selection to identify appropriate target points within each ROI; (2) Trajectory Risk Scoring to quantify the cumulative distance to critical structures (blood vessels) along each trajectory, defined as the skull entry point to target point. (3) Implantation Plan Computation: to determine a feasible combination of low-risk trajectories for all electrodes. ADMTP was evaluated on 20 patients (190 electrodes). ADMTP lowered the quantitative risk score in 83% of electrodes. Qualitative results show ADMTP found suitable trajectories for 70% of electrodes; a similar portion of manual trajectories were considered suitable. Trajectory suitability for ADMTP was 95% if traversing sulci was not included in the safety criteria. ADMTP is computationally efficient, computing between 7 and 12 trajectories in 54.5 (17.3-191.9) s. ADMTP efficiently compute safe and surgically feasible electrode trajectories.

SU-E-J-57: First Development of Adapting to Intrafraction Relative Motion Between Prostate and Pelvic Lymph Nodes Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ge, Y; Colvill, E; O’Brien, R

2015-06-15

Purpose Large intrafraction relative motion of multiple targets is common in advanced head and neck, lung, abdominal, gynaecological and urological cancer, jeopardizing the treatment outcomes. The objective of this study is to develop a real-time adaptation strategy, for the first time, to accurately correct for the relative motion of multiple targets by reshaping the treatment field using the multi-leaf collimator (MLC). Methods The principle of tracking the simultaneously treated but differentially moving tumor targets is to determine the new aperture shape that conforms to the shifted targets. Three dimensional volumes representing the individual targets are projected to the beam’s eyemore » view. The leaf openings falling inside each 2D projection will be shifted according to the measured motion of each target to form the new aperture shape. Based on the updated beam shape, new leaf positions will be determined with optimized trade-off between the target underdose and healthy tissue overdose, and considerations of the physical constraints of the MLC. Taking a prostate cancer patient with pelvic lymph node involvement as an example, a preliminary dosimetric study was conducted to demonstrate the potential treatment improvement compared to the state-of- art adaptation technique which shifts the whole beam to track only one target. Results The world-first intrafraction adaptation system capable of reshaping the beam to correct for the relative motion of multiple targets has been developed. The dose in the static nodes and small bowel are closer to the planned distribution and the V45 of small bowel is decreased from 110cc to 75cc, corresponding to a 30% reduction by this technique compared to the state-of-art adaptation technique. Conclusion The developed adaptation system to correct for intrafraction relative motion of multiple targets will guarantee the tumour coverage and thus enable PTV margin reduction to minimize the high target dose to the adjacent organs-at-risk. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: a Case-Control and Genotype-Phenotype Study.

PubMed

Křenek, Pavel; Benešová, Yvonne; Bienertová-Vašků, Julie; Vašků, Anna

2018-04-01

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, p a = 0.02; Taq, p g = 0.02, p a = 0.02; BsmI, p g = 0.02, p a = 0.04; ApaI, p g = 0.008, p a = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: p g = 0.01, p a = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT p corr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.

Molecular profiling of multiple myeloma: from gene expression analysis to next-generation sequencing.

PubMed

Agnelli, Luca; Tassone, Pierfrancesco; Neri, Antonino

2013-06-01

Multiple myeloma is a fatal malignant proliferation of clonal bone marrow Ig-secreting plasma cells, characterized by wide clinical, biological, and molecular heterogeneity. Herein, global gene and microRNA expression, genome-wide DNA profilings, and next-generation sequencing technology used to investigate the genomic alterations underlying the bio-clinical heterogeneity in multiple myeloma are discussed. High-throughput technologies have undoubtedly allowed a better comprehension of the molecular basis of the disease, a fine stratification, and early identification of high-risk patients, and have provided insights toward targeted therapy studies. However, such technologies are at risk of being affected by laboratory- or cohort-specific biases, and are moreover influenced by high number of expected false positives. This aspect has a major weight in myeloma, which is characterized by large molecular heterogeneity. Therefore, meta-analysis as well as multiple approaches are desirable if not mandatory to validate the results obtained, in line with commonly accepted recommendation for tumor diagnostic/prognostic biomarker studies.

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation

NASA Astrophysics Data System (ADS)

Treuer, U.; Treuer, H.; Hoevels, M.; Müller, R. P.; Sturm, V.

1998-01-01

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

Adjuvant therapy for advanced renal cell carcinoma.

PubMed

Meissner, Matthew A; McCormick, Barrett Z; Karam, Jose A; Wood, Christopher G

2018-07-01

Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear. Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors. Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.

Mass Spectrometric Immunoassay and Multiple Reaction Monitoring as Targeted MS-based Quantitative Approaches in Biomarker Development: Potential Applications to Cardiovascular Disease and Diabetes

PubMed Central

Yassine, Hussein; Borges, Chad R.; Schaab, Matthew R.; Billheimer, Dean; Stump, Craig; Reaven, Peter; Lau, Serrine S.; Nelson, Randall

2014-01-01

Type 2 diabetes (T2DM) is an important risk factor for cardiovascular disease (CVD)—the leading cause of death in the US. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed towards treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary mass spectrometry-based approaches—Mass Spectrometric Immunoassay (MSIA) and tandem mass spectrometry as multiple reaction monitoring (MRM)—for the analysis of plasma proteins and post translational modifications (PTMs) of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the HDL proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on high density lipoprotein (HDL) proteins from T2DM patients to provide examples of how these mass spectrometry approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice. PMID:23696124

HIV Risk Perception, Sexual Behavior, and HIV Prevalence among Men-Who-Have-Sex-with-Men at a Community-Based Voluntary Counseling and Testing Center in Kuala Lumpur, Malaysia.

PubMed

Koh, Kwee Choy; Yong, Lit Sin

2014-01-01

We describe the HIV risk perception, sexual behavior, and HIV prevalence among 423 men-who-have-sex-with-men (MSM) clients who received voluntary counseling and testing (VCT) services at a community-based center in Kuala Lumpur, Malaysia. The mean age was 29 years old. One hundred one (23.9%) clients rated themselves as low risk, 118 (27.9%) as medium risk, 36 (8.5%) as high risk, and 168 (39.7%) were unsure of their risk. Twenty-four (9.4%) clients tested HIV positive (4 (4%) low risk, 9 (7.6%) medium risk, 11 (30.6%) high risk, and 13 (7.7%) unsure risk). We found a positive correlation between risk perception and HIV infection in this study. Clients with high HIV risk perception have 17x the odds of testing HIV positive compared to low risk clients. High HIV risk perception was significantly associated with multiple sex partners, multiple types of sex partners, alcohol use before intercourse, unprotected sex beyond 6 months, and inconsistent condom use during anal sex compared to low risk clients. There were no statistically significant differences between medium risk and unsure risk clients compared to low risk clients. Strategies should be targeted towards change in sexual practices among those who are perceived to be at high risk.

Sexual Orientation Disparities in Sexually Transmitted Infection Risk Behaviors and Risk Determinants Among Sexually Active Adolescent Males: Results From a School-Based Sample

PubMed Central

Schnarrs, Phillip W.; Rosario, Margaret; Garofalo, Robert; Mustanski, Brian

2014-01-01

Objectives. We examined disparities in risk determinants and risk behaviors for sexually transmitted infections (STIs) between gay-identified, bisexual-identified, and heterosexual-identified young men who have sex with men (YMSM) and heterosexual-identified young men who have sex with women (YMSW) using a school-based sample of US sexually active adolescent males. Methods. We analyzed a pooled data set of Youth Risk Behavior Surveys from 2005 and 2007 that included information on sexual orientation identity, sexual behaviors, and multiple STI risk factors. Results. Bisexual-identified adolescents were more likely to report multiple STI risk behaviors (number of sex partners, concurrent sex partners, and age of sexual debut) compared with heterosexual YMSW as well as heterosexual YMSM and gay-identified respondents. Gay, bisexual, and heterosexual YMSM were significantly more likely to report forced sex compared with heterosexual YMSW. Conclusions. Our results provide evidence that sexual health disparities emerge early in the life course and vary by both sexual orientation identity and sexual behaviors. In particular, they show that bisexual-identified adolescent males exhibit a unique risk profile that warrants targeted sexual health interventions. PMID:24825214

Adaptation of a Counseling Intervention to Address Multiple Cancer Risk Factors Among Overweight/Obese Latino Smokers

PubMed Central

Castro, Yessenia; Fernández, Maria E.; Strong, Larkin L.; Stewart, Diana W.; Krasny, Sarah; Robles, Eden Hernandez; Heredia, Natalia; Spears, Claire A.; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W.

2015-01-01

More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social cognitive theory and principles of motivational interviewing originally developed for smoking cessation to also address physical activity and fruit/vegetable consumption among Latinos exhibiting multiple health risk behaviors. Literature reviews, focus groups, expert consultation, pretesting, and pilot testing were used to inform adaptation decisions. We identified common mechanisms underlying change in smoking, physical activity, and diet used as treatment targets; identified practical models of patient-centered cross-cultural service provision; and identified that family preferences and support as particularly strong concerns among the priority population. Adaptations made to the original intervention are described. The current study is a practical example of how an intervention can be adapted to maximize relevance and acceptability and also maintain the core elements of the original evidence-based intervention. The intervention has significant potential to influence cancer prevention efforts among Latinos in the United States and is being evaluated in a sample of 400 Latino overweight/obese smokers. PMID:25527143

Epigenetic polypharmacology: from combination therapy to multitargeted drugs.

PubMed

de Lera, Angel R; Ganesan, A

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed.

Too many targets, not enough patients: rethinking neuroblastoma clinical trials.

PubMed

Fletcher, Jamie I; Ziegler, David S; Trahair, Toby N; Marshall, Glenn M; Haber, Michelle; Norris, Murray D

2018-06-01

Neuroblastoma is a rare solid tumour of infancy and early childhood with a disproportionate contribution to paediatric cancer mortality and morbidity. Combination chemotherapy, radiation therapy and immunotherapy remains the standard approach to treat high-risk disease, with few recurrent, actionable genetic aberrations identified at diagnosis. However, recent studies indicate that actionable aberrations are far more common in relapsed neuroblastoma, possibly as a result of clonal expansion. In addition, although the major validated disease driver, MYCN, is not currently directly targetable, multiple promising approaches to target MYCN indirectly are in development. We propose that clinical trial design needs to be rethought in order to meet the challenge of providing rigorous, evidence-based assessment of these new approaches within a fairly small patient population and that experimental therapies need to be assessed at diagnosis in very-high-risk patients rather than in relapsed and refractory patients.

Novel biomarkers for cardiovascular risk assessment: current status and future directions.

PubMed

MacNamara, James; Eapen, Danny J; Quyyumi, Arshed; Sperling, Laurence

2015-09-01

Cardiovascular disease (CVD) is the leading cause of mortality in the modern world. Traditional risk algorithms may miss up to 20% of CVD events. Therefore, there is a need for new cardiac biomarkers. Many fields of research are dedicated to improving cardiac risk prediction, including genomics, transcriptomics and proteomics. To date, even the most promising biomarkers have only demonstrated modest associations and predictive ability. Few have undergone randomized control trials. A number of biomarkers are targets to new therapies aimed to reduce cardiovascular risk. Currently, some of the most promising risk prediction has been demonstrated with panels of multiple biomarkers. This article reviews the current state and future of proteomic biomarkers and aggregate biomarker panels.

Allowable carbon emissions lowered by multiple climate targets.

PubMed

Steinacher, Marco; Joos, Fortunat; Stocker, Thomas F

2013-07-11

Climate targets are designed to inform policies that would limit the magnitude and impacts of climate change caused by anthropogenic emissions of greenhouse gases and other substances. The target that is currently recognized by most world governments places a limit of two degrees Celsius on the global mean warming since preindustrial times. This would require large sustained reductions in carbon dioxide emissions during the twenty-first century and beyond. Such a global temperature target, however, is not sufficient to control many other quantities, such as transient sea level rise, ocean acidification and net primary production on land. Here, using an Earth system model of intermediate complexity (EMIC) in an observation-informed Bayesian approach, we show that allowable carbon emissions are substantially reduced when multiple climate targets are set. We take into account uncertainties in physical and carbon cycle model parameters, radiative efficiencies, climate sensitivity and carbon cycle feedbacks along with a large set of observational constraints. Within this framework, we explore a broad range of economically feasible greenhouse gas scenarios from the integrated assessment community to determine the likelihood of meeting a combination of specific global and regional targets under various assumptions. For any given likelihood of meeting a set of such targets, the allowable cumulative emissions are greatly reduced from those inferred from the temperature target alone. Therefore, temperature targets alone are unable to comprehensively limit the risks from anthropogenic emissions.

Multiple Logistic Regression Analysis of Cigarette Use among High School Students

ERIC Educational Resources Information Center

Adwere-Boamah, Joseph

2011-01-01

A binary logistic regression analysis was performed to predict high school students' cigarette smoking behavior from selected predictors from 2009 CDC Youth Risk Behavior Surveillance Survey. The specific target student behavior of interest was frequent cigarette use. Five predictor variables included in the model were: a) race, b) frequency of…

Factors perceived as being related to accidental falls by persons with multiple sclerosis.

PubMed

Nilsagård, Ylva; Denison, Eva; Gunnarsson, Lars-Gunnar; Boström, Katrin

2009-01-01

This study explores and describes factors that persons with multiple sclerosis (MS) perceive as being related to accidental falls. A qualitative content analysis with primarily deductive approach was conducted using the International Classification of Functioning, Disability and Health. Twelve persons with MS, and identified as fallers, were interviewed. Factors perceived to cause accidental falls that had not previously been targeted in MS populations in relation to falls were identified as divided attention, reduced muscular endurance, fatigue and heat sensitivity. Previously reported risk factors such as changed gait pattern, limited walking ability, impaired proprioception, vision and spasticity were supported. Activities involving walking, recreation and leisure, maintaining and changing body position, lifting or carrying, taking care of the home, washing the body, moving around, preparing meals and housekeeping were limited and considered to be risk activities. Supportive persons and assistive device reduced falls, and unsuitable physical environments and climate conditions induced falls. Several preventative strategies were described as partially compensating for the impairments, limitations and restrictions. Investigating accidental falls using the perspective of the patient gave important information about variables not earlier targeted in MS research.

Volcano warning systems: Chapter 67

USGS Publications Warehouse

Gregg, Chris E.; Houghton, Bruce F.; Ewert, John W.

2015-01-01

Messages conveying volcano alert level such as Watches and Warnings are designed to provide people with risk information before, during, and after eruptions. Information is communicated to people from volcano observatories and emergency management agencies and from informal sources and social and environmental cues. Any individual or agency can be both a message sender and a recipient and multiple messages received from multiple sources is the norm in a volcanic crisis. Significant challenges to developing effective warning systems for volcanic hazards stem from the great diversity in unrest, eruption, and post-eruption processes and the rapidly advancing digital technologies that people use to seek real-time risk information. Challenges also involve the need to invest resources before unrest to help people develop shared mental models of important risk factors. Two populations of people are the target of volcano notifications–ground- and aviation-based populations, and volcano warning systems must address both distinctly different populations.

Application of High-Throughput In Vitro Assays for Risk-Based ...

EPA Pesticide Factsheets

Multiple drivers shape the types of human-health assessments performed on chemicals by U.S. EPA resulting in chemical assessments are “fit-for-purpose” ranging from prioritization for further testing to full risk assessments. Layered on top of the diverse assessment needs are the resource intensive nature of traditional toxicological studies used to test chemicals and the lack of toxicity information on many chemicals. To address these challenges, the Agency initiated the ToxCast program to screen thousands of chemicals across hundreds of high-throughput screening assays in concentrations-response format. One of the findings of the project has been that the majority of chemicals interact with multiple biological targets within a narrow concentration range and the extent of interactions increases rapidly near the concentration causing cytotoxicity. This means that application of high-throughput in vitro assays to chemical assessments will need to identify both the relative selectivity at chemicals interact with biological targets and the concentration at which these interactions perturb signaling pathways. The integrated analyses will be used to both define a point-of-departure for comparison with human exposure estimates and identify which chemicals may benefit from further studies in a mode-of-action or adverse outcome pathway framework. The application of new technologies in a risk-based, tiered manner provides flexibility in matching throughput and cos

Molecular Mechanisms and Management of a Cutaneous Inflammatory Disorder: Psoriasis

PubMed Central

Cho, Dae Ho; Park, Hyun Jeong

2017-01-01

Psoriasis is a complex chronic inflammatory cutaneous disorder. To date, robust molecular mechanisms of psoriasis have been reported. Among diverse aberrant immunopathogenetic mechanisms, the current model emphasizes the role of Th1 and the IL-23/Th17 axis, skin-resident immune cells and major signal transduction pathways involved in psoriasis. The multiple genetic risk loci for psoriasis have been rapidly revealed with the advent of a novel technology. Moreover, identifying epigenetic modifications could bridge the gap between genetic and environmental risk factors in psoriasis. This review will provide a better understanding of the pathogenesis of psoriasis by unraveling the complicated interplay among immunological abnormalities, genetic risk foci, epigenetic modification and environmental factors of psoriasis. With advances in molecular biology, diverse new targets are under investigation to manage psoriasis. The recent advances in treatment modalities for psoriasis based on targeted molecules are also discussed. PMID:29232931

Multi-target QSPR modeling for simultaneous prediction of multiple gas-phase kinetic rate constants of diverse chemicals

NASA Astrophysics Data System (ADS)

Basant, Nikita; Gupta, Shikha

2018-03-01

The reactions of molecular ozone (O3), hydroxyl (•OH) and nitrate (NO3) radicals are among the major pathways of removal of volatile organic compounds (VOCs) in the atmospheric environment. The gas-phase kinetic rate constants (kO3, kOH, kNO3) are thus, important in assessing the ultimate fate and exposure risk of atmospheric VOCs. Experimental data for rate constants are not available for many emerging VOCs and the computational methods reported so far address a single target modeling only. In this study, we have developed a multi-target (mt) QSPR model for simultaneous prediction of multiple kinetic rate constants (kO3, kOH, kNO3) of diverse organic chemicals considering an experimental data set of VOCs for which values of all the three rate constants are available. The mt-QSPR model identified and used five descriptors related to the molecular size, degree of saturation and electron density in a molecule, which were mechanistically interpretable. These descriptors successfully predicted three rate constants simultaneously. The model yielded high correlations (R2 = 0.874-0.924) between the experimental and simultaneously predicted endpoint rate constant (kO3, kOH, kNO3) values in test arrays for all the three systems. The model also passed all the stringent statistical validation tests for external predictivity. The proposed multi-target QSPR model can be successfully used for predicting reactivity of new VOCs simultaneously for their exposure risk assessment.

A Case Report of Salvage Radiotherapy for a Patient with Recurrent Gastric Cancer and Multiple Comorbidities Using Real-time MRI-guided Adaptive Treatment System

PubMed Central

Jeon, Seung Hyuck; Chie, Eui Kyu

2018-01-01

The stomach is one of the most deforming organs caused by respiratory motions and daily variation by food intake. Applying radiotherapy has been quite a challenge due to the high risk of missing the target as well as radiation exposure to large volumes of normal tissue. However, real-time magnetic resonance (MR)-guided radiotherapy with adaptive planning could focus the high dose radiation to the target area while minimizing neighboring normal tissue exposure and compensate for not only daily but real-time variation. Here is a case report of a patient with recurrent gastric cancer and multiple co-morbidities, unsuitable for both resection and chemotherapy, who underwent MR guided adaptive radiotherapy. PMID:29900091

A review of multi-risk methodologies for natural hazards: Consequences and challenges for a climate change impact assessment.

PubMed

Gallina, Valentina; Torresan, Silvia; Critto, Andrea; Sperotto, Anna; Glade, Thomas; Marcomini, Antonio

2016-03-01

This paper presents a review of existing multi-risk assessment concepts and tools applied by organisations and projects providing the basis for the development of a multi-risk methodology in a climate change perspective. Relevant initiatives were developed for the assessment of multiple natural hazards (e.g. floods, storm surges, droughts) affecting the same area in a defined timeframe (e.g. year, season, decade). Major research efforts were focused on the identification and aggregation of multiple hazard types (e.g. independent, correlated, cascading hazards) by means of quantitative and semi-quantitative approaches. Moreover, several methodologies aim to assess the vulnerability of multiple targets to specific natural hazards by means of vulnerability functions and indicators at the regional and local scale. The overall results of the review show that multi-risk approaches do not consider the effects of climate change and mostly rely on the analysis of static vulnerability (i.e. no time-dependent vulnerabilities, no changes among exposed elements). A relevant challenge is therefore to develop comprehensive formal approaches for the assessment of different climate-induced hazards and risks, including dynamic exposure and vulnerability. This requires the selection and aggregation of suitable hazard and vulnerability metrics to make a synthesis of information about multiple climate impacts, the spatial analysis and ranking of risks, including their visualization and communication to end-users. To face these issues, climate impact assessors should develop cross-sectorial collaborations among different expertise (e.g. modellers, natural scientists, economists) integrating information on climate change scenarios with sectorial climate impact assessment, towards the development of a comprehensive multi-risk assessment process. Copyright © 2015 Elsevier Ltd. All rights reserved.

A simple rapid approach using coupled multivariate statistical methods, GIS and trajectory models to delineate areas of common oil spill risk

NASA Astrophysics Data System (ADS)

Guillen, George; Rainey, Gail; Morin, Michelle

2004-04-01

Currently, the Minerals Management Service uses the Oil Spill Risk Analysis model (OSRAM) to predict the movement of potential oil spills greater than 1000 bbl originating from offshore oil and gas facilities. OSRAM generates oil spill trajectories using meteorological and hydrological data input from either actual physical measurements or estimates generated from other hydrological models. OSRAM and many other models produce output matrices of average, maximum and minimum contact probabilities to specific landfall or target segments (columns) from oil spills at specific points (rows). Analysts and managers are often interested in identifying geographic areas or groups of facilities that pose similar risks to specific targets or groups of targets if a spill occurred. Unfortunately, due to the potentially large matrix generated by many spill models, this question is difficult to answer without the use of data reduction and visualization methods. In our study we utilized a multivariate statistical method called cluster analysis to group areas of similar risk based on potential distribution of landfall target trajectory probabilities. We also utilized ArcView™ GIS to display spill launch point groupings. The combination of GIS and multivariate statistical techniques in the post-processing of trajectory model output is a powerful tool for identifying and delineating areas of similar risk from multiple spill sources. We strongly encourage modelers, statistical and GIS software programmers to closely collaborate to produce a more seamless integration of these technologies and approaches to analyzing data. They are complimentary methods that strengthen the overall assessment of spill risks.

Defining subgroups of low socioeconomic status women at risk for depressive symptoms: the importance of perceived stress and cumulative risks.

PubMed

van der Waerden, Judith E B; Hoefnagels, Cees; Hosman, Clemens M H; Jansen, Maria W J

2014-12-01

Most disadvantaged women are exposed to risk factors for depression, but not all necessarily have an identical risk for this mental health problem. A better prediction of which low socioeconomic status (SES) women are most at risk for depressive symptoms can help target preventive interventions at high-risk subgroups most in need of support. Exploring which demographic, socioeconomic and psychological risk factors are associated with self-reported depressive symptoms in a sample of low-SES women and whether the number of risk factors might expose them to an accumulated risk. Between April 2005 and November 2007, 519 disadvantaged women from urban neighbourhoods in Maastricht, a southern Dutch city, participated in a cross-sectional survey on stress and depressive symptoms. Lower education levels, no current employment and lower net monthly family incomes were socioeconomic risk factors associated with higher scores for depressive symptoms. The psychological risk factor 'perceived stress' had the highest explained variance and was most strongly associated with depressive symptoms. Women exposed to multiple risk factors across domains had a cumulated risk for depressive symptomatology. Low-SES women who seem most eligible for targeted preventive action are those with cumulative risks. Depression prevention strategies for this population may benefit from focusing on perceived stress since this is an important modifiable risk factor. © The Author(s) 2014.

The evolution of systolic blood pressure as a strong predictor of cardiovascular risk and the effectiveness of fixed-dose ARB/CCB combinations in lowering levels of this preferential target

PubMed Central

Mourad, Jean-Jacques

2008-01-01

Elevated blood pressure is an important cardiovascular risk factor. Although targets for both diastolic blood pressure (DBP) and systolic blood pressure (SBP) are defined by current guidelines, DBP has historically taken precedence in hypertension management. However, there is strong evidence that SBP is superior to DBP as a predictor of cardiovascular events. Moreover, achieving control of SBP is assuming greater importance amongst an aging population. In spite of the growing recognition of the importance of SBP in reducing cardiovascular risk and the emphasis by current guidelines on SBP control, a substantial proportion of patients still fail to achieve SBP targets, and SBP control is achieved much less frequently than DBP control. Thus, new approaches to the management of hypertension are required in order to control SBP and minimize cardiovascular risk. Fixed-dose combination (FDC) therapy is an approach that offers the advantages of multiple drug administration and a reduction in regimen complexity that favors compliance. We have reviewed the latest evidence demonstrating the efficacy in targeting SBP of the most recent FDC products; combinations of the calcium channel blocker (CCB), amlodipine, with angiotensin receptor blockers (ARBs), valsartan or olmesartan. In addition, results from studies with new classes of agent are outlined. PMID:19337545

Review of clinical practice guidelines for the management of LDL-related risk.

PubMed

Morris, Pamela B; Ballantyne, Christie M; Birtcher, Kim K; Dunn, Steven P; Urbina, Elaine M

2014-07-15

Managing risk related to low-density lipoprotein (LDL) is vital in therapy for patients at risk for atherosclerotic cardiovascular disease (ASCVD) events given its important etiologic role in atherogenesis. Despite decades of research showing reduction of ASCVD risk with multiple approaches to lowering of LDL cholesterol, there continue to be significant gaps in care with inadequate numbers of patients receiving standard of care lipid-lowering therapy. Confusion regarding implementation of the multiple published clinical practice guidelines has been identified as one contributor to suboptimal management of LDL-related risk. This review summarizes the current guidelines for reduction of LDL-related cardiovascular risk provided by a number of major professional societies, which have broad applicability to diverse populations worldwide. Statements have varied in the process and methodology of development of recommendations, the grading system for level and strength of evidence, the inclusion or exclusion of expert opinion, the suggested ASCVD risk assessment tool, the lipoproteins recommended for risk assessment, and the lipoprotein targets of therapy. The similarities and differences among important guidelines in the United States and internationally are discussed, with recommendations for future strategies to improve consistency in approaches to LDL-related ASCVD risk and to reduce gaps in implementation of evidence-based therapies. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The relationship between health risks and health and productivity costs among employees at Pepsi Bottling Group.

PubMed

Henke, Rachel M; Carls, Ginger S; Short, Meghan E; Pei, Xiaofei; Wang, Shaohung; Moley, Susan; Sullivan, Mark; Goetzel, Ron Z

2010-05-01

To evaluate relationships between modifiable health risks and costs and measure potential cost savings from risk reduction programs. Health risk information from active Pepsi Bottling Group employees who completed health risk assessments between 2004 and 2006 (N = 11,217) were linked to medical care, workers' compensation, and short-term disability cost data. Ten health risks were examined. Multivariate analyses were performed to estimate costs associated with having high risk, holding demographics, and other risks constant. Potential savings from risk reduction were estimated. High risk for weight, blood pressure, glucose, and cholesterol had the greatest impact on total costs. A one-percentage point annual reduction in the health risks assessed would yield annual per capita savings of $83.02 to $103.39. Targeted programs that address modifiable health risks are expected to produce substantial cost reductions in multiple benefit categories.

Incidence of listeriosis and related mortality among groups at risk of acquiring listeriosis.

PubMed

Goulet, Véronique; Hebert, Marjolaine; Hedberg, Craig; Laurent, Edith; Vaillant, Véronique; De Valk, Henriette; Desenclos, Jean-Claude

2012-03-01

Listeriosis is a foodborne disease of significant public health concern that primarily affects persons with recognized underlying conditions or diseases that impair cell-mediated immunity. The degree of risk posed by the different underlying conditions is crucial to prioritize prevention programs that target the highest risk populations. We reviewed cases of listeriosis reported in France from 2001 to 2008. Numbers of cases and deaths were tabulated by age and underlying condition. Measures of the impact of specific underlying conditions on the occurrence of listeriosis were calculated. For estimating the total number of persons living with specific diseases, we applied prevalence estimates of these diseases to the French population. Underlying conditions were ranked by the degree to which they increased the risk of listeriosis. From 2001 to 2008, 1959 cases of listeriosis were reported in France (mean annual incidence 0.39 per 100,000 residents). Compared with persons <65 years with no underlying conditions, those with chronic lymphocytic leukemia had a >1000-fold increased risk of acquiring listeriosis, and those with liver cancer; myeoloproliferative disorder; multiple myeloma; acute leukemia; giant cell arteritis; dialysis; esophageal, stomach, pancreas, lung, and brain cancer; cirrhosis; organ transplantation; and pregnancy had a 100-1000-fold increased risk of listeriosis. To be effective and acceptable to physicians and patients, listeriosis prevention strategies should be targeted based on evidence of increased risk. Stringent dietary guidance, to avoid specific foods with a high risk for Listeria contamination, should be targeted to pregnant women and to others at highest risk of listeriosis.

Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription

NASA Astrophysics Data System (ADS)

Jang, Mihue; Kim, Jong Hwan; Nam, Hae Yun; Kwon, Ick Chan; Ahn, Hyung Jun

2015-08-01

For therapeutic applications of siRNA, there are technical challenges with respect to targeted and systemic delivery. We here report a new siRNA carrier, RNAtr NPs, in a way that multiple tandem copies of RNA hairpins as a result of rolling circle transcription (RCT) can be readily adapted in tumour-targeted and systemic siRNA delivery. RNAtr NPs provide a means of condensing large amounts of multimeric RNA transcripts into the compact nanoparticles, especially without the aid of polycationic agents, and thus reduce the risk of immunogenicity and cytotoxicity by avoiding the use of synthetic polycationic reagents. This strategy allows the design of a platform technology for systemic delivery of siRNA to tumour sites, because RCT reaction, which enzymatically generates RNA polymers in multiple copy numbers at low cost, can lead to directly accessible routes to targeted and systemic delivery. Therefore, RNAtr NPs suggest great potentials as the siRNA therapeutics for cancer treatment.

Integrating geological uncertainty in long-term open pit mine production planning by ant colony optimization

NASA Astrophysics Data System (ADS)

Gilani, Seyed-Omid; Sattarvand, Javad

2016-02-01

Meeting production targets in terms of ore quantity and quality is critical for a successful mining operation. In-situ grade uncertainty causes both deviations from production targets and general financial deficits. A new stochastic optimization algorithm based on ant colony optimization (ACO) approach is developed herein to integrate geological uncertainty described through a series of the simulated ore bodies. Two different strategies were developed based on a single predefined probability value (Prob) and multiple probability values (Pro bnt) , respectively in order to improve the initial solutions that created by deterministic ACO procedure. Application at the Sungun copper mine in the northwest of Iran demonstrate the abilities of the stochastic approach to create a single schedule and control the risk of deviating from production targets over time and also increase the project value. A comparison between two strategies and traditional approach illustrates that the multiple probability strategy is able to produce better schedules, however, the single predefined probability is more practical in projects requiring of high flexibility degree.

Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

PubMed Central

Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

2015-01-01

The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

School Dropout Prevention: What Arts-Based Community and Out-of-School-Time Programs Can Contribute

ERIC Educational Resources Information Center

Charmaraman, Linda; Hall, Georgia

2011-01-01

Out-of-school-time programs, especially arts-based programs, can be critical players in a community's efforts to prevent school dropout. This research review suggests the following approaches for arts-based programs: (1) recruitment and retention of target populations with multiple risk factors; (2) long-term skill development that engages youth…

Patterns of multiple health risk-behaviours in university students and their association with mental health: application of latent class analysis.

PubMed

Kwan, M Y; Arbour-Nicitopoulos, K P; Duku, E; Faulkner, G

2016-08-01

University and college campuses may be the last setting where it is possible to comprehensively address the health of a large proportion of the young adult population. It is important that health promoters understand the collective challenges students are facing, and to better understand the broader lifestyle behavioural patterning evident during this life stage. The purpose of this study was to examine the clustering of modifiable health-risk behaviours and to explore the relationship between these identified clusters and mental health outcomes among a large Canadian university sample. Undergraduate students (n = 837; mean age = 21 years) from the University of Toronto completed the National College Health Assessment survey. The survey consists of approximately 300 items, including assessments of student health status, mental health and health-risk behaviours. Latent class analysis was used to identify patterning based on eight salient health-risk behaviours (marijuana use, other illicit drug use, risky sex, smoking, binge drinking, poor diet, physical inactivity, and insufficient sleep). A three-class model based on student behavioural patterns emerged: "typical," "high-risk" and "moderately healthy." Results also found high-risk students reporting significantly higher levels of stress than typical students (χ2(1671) = 7.26, p < .01). Students with the highest likelihood of engaging in multiple health-risk behaviours reported poorer mental health, particularly as it relates to stress. Although these findings should be interpreted with caution due to the 28% response rate, they do suggest that interventions targeting specific student groups with similar patterning of multiple health-risk behaviours may be needed.

Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes

PubMed Central

Dong, Tao; He, Jing; Wang, Shiqing; Wang, Lianzhang; Cheng, Yuqi; Zhong, Yi

2016-01-01

The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes. PMID:27335463

Adverse effects of anticancer agents that target the VEGF pathway.

PubMed

Chen, Helen X; Cleck, Jessica N

2009-08-01

Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed.

Risk Prediction Score for HIV Infection: Development and Internal Validation with Cross-Sectional Data from Men Who Have Sex with Men in China.

PubMed

Yin, Lu; Zhao, Yuejuan; Peratikos, Meridith Blevins; Song, Liang; Zhang, Xiangjun; Xin, Ruolei; Sun, Zheya; Xu, Yunan; Zhang, Li; Hu, Yifei; Hao, Chun; Ruan, Yuhua; Shao, Yiming; Vermund, Sten H; Qian, Han-Zhu

2018-05-21

Receptive anal intercourse, multiple partners, condomless sex, sexually transmitted infections (STIs), and drug/alcohol addiction are familiar factors that correlate with increased human immunodeficiency virus (HIV) risk among men who have sex with men (MSM). To improve estimation to HIV acquisition, we created a composite score using questions from routine survey of 3588 MSM in Beijing, China. The HIV prevalence was 13.4%. A risk scoring tool using penalized maximum likelihood multivariable logistic regression modeling was developed, deploying backward step-down variable selection to obtain a reduced-form model. The full penalized model included 19 sexual predictors, while the reduced-form model had 12 predictors. Both models calibrated well; bootstrap-corrected c-indices were 0.70 (full model) and 0.71 (reduced-form model). Non-Beijing residence, short-term living in Beijing, illegal drug use, multiple male sexual partners, receptive anal sex, inconsistent condom use, alcohol consumption before sex, and syphilis infection were the strongest predictors of HIV infection. Discriminating higher-risk MSM for targeted HIV prevention programming using a validated risk score could improve the efficiency of resource deployment for educational and risk reduction programs. A valid risk score can also identify higher risk persons into prevention and vaccine clinical trials, which would improve trial cost-efficiency.

Occupational Risks and Exposures Among Wildlife Health Professionals.

PubMed

Garland-Lewis, Gemina; Whittier, Christopher; Murray, Suzan; Trufan, Sally; Rabinowitz, Peter M

2017-03-01

Most emerging infectious diseases are zoonotic in origin, with wildlife a frequent source of zoonotic disease events. Although individuals with extensive wildlife contact may be at the greatest risk of contracting novel infectious agents, the occupational risk of those working closely with wildlife has not been well studied. This study assessed the occupational exposures among wildlife health professionals working in multiple countries worldwide. An occupational risk survey of past and present exposures was developed and administered online in a confidential manner to wildlife workers recruited through an ongoing international wildlife pathogen surveillance project. Surveys were completed by 71 participants in 14 countries. Significant lifetime exposures reported included bites from bats and rodents and touching dead animals. Completion of training in occupational safety was reported by 75% of respondents. While gloves were used for most tasks, use of N95 respirators and other personal protective equipment varied by task. Eighty percent of workers reported rabies vaccination. Some respondents indicated interest in enhanced occupational health services targeting their unique needs. Wildlife workers represent an occupational population at risk of zoonotic infection and injury. Enhanced occupational health services targeting wildlife workers could reduce the risk and sequelae of zoonotic exposure and infection.

Spatially-Distributed Cost–Effectiveness Analysis Framework to Control Phosphorus from Agricultural Diffuse Pollution

PubMed Central

Geng, Runzhe; Wang, Xiaoyan; Sharpley, Andrew N.; Meng, Fande

2015-01-01

Best management practices (BMPs) for agricultural diffuse pollution control are implemented at the field or small-watershed scale. However, the benefits of BMP implementation on receiving water quality at multiple spatial is an ongoing challenge. In this paper, we introduce an integrated approach that combines risk assessment (i.e., Phosphorus (P) index), model simulation techniques (Hydrological Simulation Program–FORTRAN), and a BMP placement tool at various scales to identify the optimal location for implementing multiple BMPs and estimate BMP effectiveness after implementation. A statistically significant decrease in nutrient discharge from watersheds is proposed to evaluate the effectiveness of BMPs, strategically targeted within watersheds. Specifically, we estimate two types of cost-effectiveness curves (total pollution reduction and proportion of watersheds improved) for four allocation approaches. Selection of a ‘‘best approach” depends on the relative importance of the two types of effectiveness, which involves a value judgment based on the random/aggregated degree of BMP distribution among and within sub-watersheds. A statistical optimization framework is developed and evaluated in Chaohe River Watershed located in the northern mountain area of Beijing. Results show that BMP implementation significantly (p >0.001) decrease P loss from the watershed. Remedial strategies where BMPs were targeted to areas of high risk of P loss, deceased P loads compared with strategies where BMPs were randomly located across watersheds. Sensitivity analysis indicated that aggregated BMP placement in particular watershed is the most cost-effective scenario to decrease P loss. The optimization approach outlined in this paper is a spatially hierarchical method for targeting nonpoint source controls across a range of scales from field to farm, to watersheds, to regions. Further, model estimates showed targeting at multiple scales is necessary to optimize program efficiency. The integrated model approach described that selects and places BMPs at varying levels of implementation, provides a new theoretical basis and technical guidance for diffuse pollution management in agricultural watersheds. PMID:26313561

Spatially-Distributed Cost-Effectiveness Analysis Framework to Control Phosphorus from Agricultural Diffuse Pollution.

PubMed

Geng, Runzhe; Wang, Xiaoyan; Sharpley, Andrew N; Meng, Fande

2015-01-01

Best management practices (BMPs) for agricultural diffuse pollution control are implemented at the field or small-watershed scale. However, the benefits of BMP implementation on receiving water quality at multiple spatial is an ongoing challenge. In this paper, we introduce an integrated approach that combines risk assessment (i.e., Phosphorus (P) index), model simulation techniques (Hydrological Simulation Program-FORTRAN), and a BMP placement tool at various scales to identify the optimal location for implementing multiple BMPs and estimate BMP effectiveness after implementation. A statistically significant decrease in nutrient discharge from watersheds is proposed to evaluate the effectiveness of BMPs, strategically targeted within watersheds. Specifically, we estimate two types of cost-effectiveness curves (total pollution reduction and proportion of watersheds improved) for four allocation approaches. Selection of a ''best approach" depends on the relative importance of the two types of effectiveness, which involves a value judgment based on the random/aggregated degree of BMP distribution among and within sub-watersheds. A statistical optimization framework is developed and evaluated in Chaohe River Watershed located in the northern mountain area of Beijing. Results show that BMP implementation significantly (p >0.001) decrease P loss from the watershed. Remedial strategies where BMPs were targeted to areas of high risk of P loss, deceased P loads compared with strategies where BMPs were randomly located across watersheds. Sensitivity analysis indicated that aggregated BMP placement in particular watershed is the most cost-effective scenario to decrease P loss. The optimization approach outlined in this paper is a spatially hierarchical method for targeting nonpoint source controls across a range of scales from field to farm, to watersheds, to regions. Further, model estimates showed targeting at multiple scales is necessary to optimize program efficiency. The integrated model approach described that selects and places BMPs at varying levels of implementation, provides a new theoretical basis and technical guidance for diffuse pollution management in agricultural watersheds.

Modelling the impact of correlations between condom use and sexual contact pattern on the dynamics of sexually transmitted infections.

PubMed

Yamamoto, Nao; Ejima, Keisuke; Nishiura, Hiroshi

2018-05-31

It is believed that sexually active people, i.e. people having multiple or concurrent sexual partners, are at a high risk of sexually transmitted infections (STI), but they are likely to be more aware of the risk and may exhibit greater fraction of the use of condom. The purpose of the present study is to examine the correlation between condom use and sexual contact pattern and clarify its impact on the transmission dynamics of STIs using a mathematical model. The definition of sexual contact pattern can be broad, but we focus on two specific aspects: (i) type of partnership (i.e. steady or casual partnership) and (ii) existence of concurrency (i.e. with single or multiple partners). Systematic review and meta-analysis of published studies are performed, analysing literature that epidemiologically examined the relationship between condom use and sexual contact pattern. Subsequently, we employ an epidemiological model and compute the reproduction number that accounts for with and without concurrency so that the corresponding coverage of condom use and its correlation with existence of concurrency can be explicitly investigated using the mathematical model. Combining the model with parameters estimated from the meta-analysis along with other assumed parameters, the impact of varying the proportion of population with multiple partners on the reproduction number is examined. Based on systematic review, we show that a greater number of people used condoms during sexual contact with casual partners than with steady partners. Furthermore, people with multiple partners use condoms more frequently than people with a single partner alone. Our mathematical model revealed a positive relationship between the effective reproduction number and the proportion of people with multiple partners. Nevertheless, the association was reversed to be negative by employing a slightly greater value of the relative risk of condom use for people with multiple partners than that empirically estimated. Depending on the correlation between condom use and the existence of concurrency, association between the proportion of people with multiple partners and the reproduction number can be reversed, suggesting the sexually active population is not necessary a primary target population to encourage condom use (i.e., sexually less active individuals could equivalently be a target in some cases).

Moving Beyond Motive-based categories of Targeted Violence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weine, Stevan; Cohen, John; Brannegan, David

Today’s categories for responding to targeted violence are motive-based and tend to drive policies, practices, training, media coverage, and research. These categories are based on the assumption that there are significant differences between ideological and non-ideological actors and between domestic and international actors. We question the reliance on these categories and offer an alternative way to frame the response to multiple forms of targeted violence. We propose adopting a community-based multidisciplinary approach to assess risk and provide interventions that are focused on the pre-criminal space. We describe four capabilities that should be implemented locally by establishing and maintaining multidisciplinary responsemore » teams that combine community and law-enforcement components: (1) community members are educated, making them better able to identify and report patterns associated with elevated risk for violence; (2) community-based professionals are trained to assess the risks for violent behavior posed by individuals; (3) community-based professionals learn to implement strategies that directly intervene in causal factors for those individuals who are at elevated risk; and (4) community-based professionals learn to monitor and assess an individual’s risk for violent behaviors on an ongoing basis. Community-based multidisciplinary response teams have the potential to identify and help persons in the pre-criminal space and to reduce barriers that have traditionally impeded community/law-enforcement collaboration.« less

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

PubMed

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Projected drought risk in 1.5°C and 2°C warmer climates

NASA Astrophysics Data System (ADS)

Lehner, F.; Coats, S.; Stocker, T. F.; Pendergrass, A. G.; Sanderson, B. M.; Raible, C.; Smerdon, J. E.

2017-12-01

The large socioeconomic costs of droughts make them a crucial target for impact assessments of climate change scenarios. Using multiple drought metrics and a set of simulations with the Community Earth System Model (CESM) targeting 1.5°C and 2°C above preindustrial global mean temperatures, we investigate changes in aridity and the risk of consecutive drought years. The latter metric is motivated by recent droughts in California and the US Southwest in general, where consecutive years of moderate precipitation deficit can quickly lead to significant drought and elevated pressure on water resources. If warming is limited to 2°C, these simulations suggest little change in drought risk for the U.S. Southwest and Central Plains compared to present day, an interesting result that arises from a delicate balance between increases in evaporative demand and precipitation in CESM in that region. In the Mediterranean, central Europe, and a number of other regions across the globe, however, drought risk increases significantly for both 1.5°C and 2°C warming targets, and the additional 0.5°C of the 2°C climate leads to significantly higher drought risk. Our study suggests that limiting anthropogenic warming to 1.5°C rather than 2°C, as aspired to by the Paris Climate Agreement, may have benefits for future drought risk but that such benefits may be regional and in some cases highly uncertain. We will therefore also discuss the robustness of results across different drought metrics as well as the model uncertainties associated with drought projections for low warming targets.

Genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

PubMed Central

Scott, Robert A.; Freitag, Daniel F.; Li, Li; Chu, Audrey Y.; Surendran, Praveen; Young, Robin; Grarup, Niels; Stancáková, Alena; Chen, Yuning; V.Varga, Tibor; Yaghootkar, Hanieh; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Wessel, Jennifer; Wang, Shuai; Maruthur, Nisa; Michailidou, Kyriaki; Pirie, Ailith; van der Lee, Sven J.; Gillson, Christopher; Olama, Ali Amin Al; Amouyel, Philippe; Arriola, Larraitz; Arveiler, Dominique; Aviles-Olmos, Iciar; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Garcia, Sara Benlloch; Bis, Joshua C.; Blankenberg, Stefan; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Borecki, Ingrid B.; Bork-Jensen, Jette; Bowden, Sarah; Caldas, Carlos; Caslake, Muriel; Cupples, L. Adrienne; Cruchaga, Carlos; Czajkowski, Jacek; den Hoed, Marcel; Dunn, Janet A.; Earl, Helena M.; Ehret, Georg B.; Ferrannini, Ele; Ferrieres, Jean; Foltynie, Thomas; Ford, Ian; Forouhi, Nita G.; Gianfagna, Francesco; Gonzalez, Carlos; Grioni, Sara; Hiller, Louise; Jansson, Jan-Håkan; Jørgensen, Marit E.; Jukema, J. Wouter; Kaaks, Rudolf; Kee, Frank; Kerrison, Nicola D.; Key, Timothy J.; Kontto, Jukka; Kote-Jarai, Zsofia; Kraja, Aldi T.; Kuulasmaa, Kari; Kuusisto, Johanna; Linneberg, Allan; Liu, Chunyu; Marenne, Gaëlle; Mohlke, Karen L.; Morris, Andrew P.; Muir, Kenneth; Müller-Nurasyid, Martina; Munroe, Patricia B.; Navarro, Carmen; Nielsen, Sune F.; Nilsson, Peter M.; Nordestgaard, Børge G.; Packard, Chris J.; Palli, Domenico; Panico, Salvatore; Peloso, Gina M.; Perola, Markus; Peters, Annette; Poole, Christopher J.; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Salomaa, Veikko; Sánchez, María-José; Sattar, Naveed; Sharp, Stephen J.; Sims, Rebecca; Slimani, Nadia; Smith, Jennifer A.; Thompson, Deborah J.; Trompet, Stella; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Virtamo, Jarmo; Walker, Mark; Walter, Klaudia; Abraham, Jean E.; Amundadottir, Laufey T.; Aponte, Jennifer L.; Butterworth, Adam S.; Dupuis, Josée; Easton, Douglas F.; Eeles, Rosalind A.; Erdmann, Jeanette; Franks, Paul W.; Frayling, Timothy M.; Hansen, Torben; Howson, Joanna M. M.; Jørgensen, Torben; Kooner, Jaspal; Laakso, Markku; Langenberg, Claudia; McCarthy, Mark I.; Pankow, James S.; Pedersen, Oluf; Riboli, Elio; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schunkert, Heribert; Vollenweider, Peter; O'Rahilly, Stephen; Deloukas, Panos; Danesh, John; Goodarzi, Mark O.; Kathiresan, Sekar; Meigs, James B.; Ehm, Margaret G.; Wareham, Nicholas J.; Waterworth, Dawn M.

2016-01-01

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to inform development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in 6 genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing, and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr;rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and lower T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomised controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. PMID:27252175

Environmentally relevant mixing ratios in cumulative assessments: a study on the correlation of blood and brain concentrations of a mixture of pyrethroid insecticides to neurotoxicity in the rat

EPA Science Inventory

Human exposure to multiple pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to pyrethroids, it is important to understand their disposition and toxicity in target organs ...

Eroding gains in safe sex behavior, HIV/AIDS knowledge, and risk perceptions among royal Thai Navy conscripts after 28 years of the AIDS epidemic in Thailand.

PubMed

Yuntadilok, Nuntawun; Timmuang, Rattana; Timsard, Somkid; Guadamuz, Thomas E; Heylen, Elsa; Mandel, Jeffrey; Ekstrand, Maria L

2014-01-01

Despite extensive early prevention efforts, recent surveys suggest that sexual risk taking may again be on the rise in Thailand. The present cross-sectional study surveyed 3,299 recruits in the Thai Navy in 2010, to examine their rates and correlates of consistent condom use. Most participants were aged 21-22 years, unmarried, and had a secondary education. Almost half were employed in labor/agriculture. Only 17 % of sexually experienced recruits were consistent condom users, and 53 % reported multiple sex partners in the past 3 months. In multiple logistic regression, residence in the Northeast (AOR 1.47), age (AOR 1.43), being single (AOR 2.13), non-MSM status (AOR 1.41), voluntary testing (AOR 1.24), and condom use at first sex (AOR 4.29) were significantly associated with consistent condom use. These findings suggest gaps in Thailand's condom campaign targeting both sexually experienced and inexperienced youth. Interventions targeting naval recruits may benefit from including sex education in the training curriculum, building drillmasters' capacities to facilitate sex education/counseling, and creating a supportive environment with better access to condoms.

Laboratory analysis of risky driving at 0.05% and 0.08% blood alcohol concentration

PubMed Central

Van Dyke, Nicholas A.; Fillmore, Mark T.

2017-01-01

Background The public health costs associated with alcohol-related traffic crashes are a continuing problem for society. One harm reduction strategy has been to employ per se limits for blood alcohol concentrations (BACs) at which drivers can legally operate motor vehicles. This limit is currently 0.08% in all 50 US states. Recently, the National Transportation Safety Board proposed lowering the legal limit to 0.05 % (NTSB, 2013). While research has well-validated the ability of alcohol to impair driving performance and heighten crash-risk at these BACs, relatively little is known about the degree to which alcohol might increase drivers’ risk-taking. Methods Risk-taking was examined in 20 healthy adults who were each tested in a driving simulator following placebo and two doses of alcohol calculated to yield peak BACs of 0.08% and 0.05%, the respective current and proposed BAC limits. The drive test emphasized risk-taking by placing participants in a multiple-lane, high-traffic environment. The primary measure was how close drivers maneuvered relative to other vehicles on the road (i.e., time-to-collision, TTC). Results Alcohol increased risk-taking by decreasing drivers’ TTC at the 0.08% target BAC relative to placebo. Moreover, risk-taking at the 0.05% target was less than risk-taking at 0.08% target BAC. Conclusions These findings provide evidence that reducing the legal BAC limit in the USA to 0.05% would decrease risk-taking among drivers. A clearer understanding of the dose-response relationship between various aspects of driving behaviors, such as drivers’ accepted level of risk while driving, is an important step to improving traffic safety. PMID:28412303

Evaluating robustness in rank-based risk assessments of freshwater ecosystems

USGS Publications Warehouse

Mattson, K.M.; Angermeier, Paul

2007-01-01

Conservation planning aims to protect biodiversity by sustainng the natural physical, chemical, and biological processes within representative ecosystems. Often data to measure these components are inadequate or unavailable. The impact of human activities on ecosystem processes complicates integrity assessments and might alter ecosystem organization at multiple spatial scales. Freshwater conservation targets, such as populations and communities, are influenced by both intrinsic aquatic properties and the surrounding landscape, and locally collected data might not accurately reflect potential impacts. We suggest that changes in five major biotic drivers—energy sources, physical habitat, flow regime, water quality, and biotic interactions—might be used as surrogates to inform conservation planners of the ecological integrity of freshwater ecosystems. Threats to freshwater systems might be evaluated based on their impact to these drivers to provide an overview of potential risk to conservation targets. We developed a risk-based protocol, the Ecological Risk Index (ERI), to identify watersheds with least/most risk to conservation targets. Our protocol combines risk-based components, specifically the frequency and severity of human-induced stressors, with biotic drivers and mappable land- and water-use data to provide a summary of relative risk to watersheds. We illustrate application of our protocol with a case study of the upper Tennessee River basin, USA. Differences in risk patterns among the major drainages in the basin reflect dominant land uses, such as mining and agriculture. A principal components analysis showed that localized, moderately severe threats accounted for most of the threat composition differences among our watersheds. We also found that the relative importance of threats is sensitive to the spatial grain of the analysis. Our case study demonstrates that the ERI is useful for evaluating the frequency and severity of ecosystemwide risk, which can inform local and regional conservation planning.

Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

PubMed Central

Gamella-Pozuelo, Luis; Fuentes-Calvo, Isabel; Gómez-Marcos, Manuel A.; Recio-Rodriguez, José I.; Agudo-Conde, Cristina; Fernández-Martín, José L.; Cannata-Andía, Jorge B.; López-Novoa, José M.; García-Ortiz, Luis; Martínez-Salgado, Carlos

2015-01-01

Abstract The search for biomarkers of hypertension and diabetes-induced damage to multiple target organs is a priority. We analyzed the correlation between plasma cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular remodeling and organ fibrosis, and a wide range of parameters currently used to diagnose morphological and functional progressive injury in left ventricle, arteries, and kidneys of diabetic and hypertensive patients, in order to validate plasma levels of CT-1 as clinical biomarker. This is an observational study with 93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls in which we assessed the following parameters: plasma CT-1, basal glycaemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes), peripheral vascular disease (by pulse wave velocity—PWV, carotid intima-media thickness—C-IMT, and ankle-brachial index—ABI), and renal impairment (by microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine concentrations, and glomerular filtration rate). Hypertensive or diabetic patients have higher plasma CT-1 than control patients. CT-1 positively correlates with basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple linear regression analysis confirmed that CT-1 was associated with arterial injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage duration product. Increases in plasma CT-1 are strongly related to the intensity of several parameters associated to target organ damage supporting further investigation of its diagnostic capacity as single biomarker of cardiovascular injury and risk and, possibly, of subclinical renal damage. PMID:26222851

IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM).

PubMed

Krönke, J; Kuchenbauer, F; Kull, M; Teleanu, V; Bullinger, L; Bunjes, D; Greiner, A; Kolmus, S; Köpff, S; Schreder, M; Mügge, L-O; Straka, C; Engelhardt, M; Döhner, H; Einsele, H; Bassermann, F; Bargou, R; Knop, S; Langer, C

2017-06-01

Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial. We found that IKZF1 mRNA expression levels are significantly associated with progression-free survival (PFS). Patients in the lowest quartile (Q1) of IKZF1 expression had a superior PFS compared with patients in the remaining quartiles (Q2-Q4; 3-year PFS of 86 vs 51%, P=0.01). This translated into a significant better overall survival (100 vs 74%, P=0.03). Subgroup analysis revealed a significant impact of IKZF1, IKZF3 and BSG expression levels on PFS in cytogenetically defined standard-risk but not high-risk patients. Our data suggest a prognostic role of IKZF1, IKZF3 and BSG expression levels in lenalidomide-treated multiple myeloma.

Avoiding hypoglycaemia: a new target of care for elderly diabetic patients.

PubMed

Wong, C W

2015-10-01

Optimising glycaemic control to prevent diabetes-associated complications has received much attention. The associated risk of iatrogenic hypoglycaemia, however, is inevitable and can have a significant impact on health. The prevalence of iatrogenic hypoglycaemia tends to increase with advancing age. Elderly people are intrinsically prone to hypoglycaemia. Ageing attenuates the glucose counter-regulatory and symptomatic response to hypoglycaemia, particularly in the presence of a longer duration of diabetes. Multiple co-morbidities and polypharmacy correlated with advancing age also increase the hypoglycaemic risk. In addition to the acute adverse effects of hypoglycaemia, such as fall with injury, cardiovascular events and mortality, a hypoglycaemic episode can have long-term consequences. Repeated episodes may have a significant psychological impact and are also a risk factor for dementia. Because of the heterogeneous health status of the elderly, not all will benefit from optimal glycaemic control. Setting an individual glycaemic target and formulating a management plan that takes account of the patient's circumstances combined with balancing the benefit and risk of diabetes intervention to avoid hypoglycaemia is a more practical approach to the management of elderly diabetic patients.

Preventing Paraffin-Related Injury

PubMed Central

C. Schwebel, David; Swart, Dehran

2009-01-01

Abstract: Paraffin (called kerosene in North America and other parts of the world) is the most commonly used fuel in ‎non-electrified dwellings worldwide. It is especially popular in Africa and South Asia. Although paraffin ‎offers many advantages-especially its comparatively low cost to produce-it poses two major risks of ‎injury. First, paraffin poisoning is common, either through ingestion or through inhalation of smoke and ‎fumes. Second, paraffin is highly flammable, and poses fire risk through multiple causes. This commentary ‎discusses strategies to prevent paraffin-related injury. Prevention of paraffin-related injury must be through ‎multiple strategies, and should include policy-oriented change, changes to the safety of home environments, ‎and behavioral changes targeting how individuals store and use paraffin and paraffin appliances. We review ‎successful prevention strategies in each of these domains and discuss appropriate research and community ‎initiatives that should be implemented to improve paraffin safety among at-risk populations. PMID:21483184

Predictors of new-onset depressive disorders - Results from the longitudinal Finnish Health 2011 Study.

PubMed

Markkula, Niina; Marola, Niko; Nieminen, Tarja; Koskinen, Seppo; Saarni, Samuli I; Härkänen, Tommi; Suvisaari, Jaana

2017-01-15

Identifying risk factors for depression is important for understanding etiological mechanisms and targeting preventive efforts. No prior studies have compared risk factors of dysthymia and major depressive disorder (MDD) in a longitudinal setting. Predictors of new-onset MDD and dysthymia were examined in a longitudinal general population study (Health 2000 and 2011 Surveys, BRIF8901). 4057 persons free of depressive disorders at baseline were followed up for 11 years. DSM-IV MDD and dysthymia were diagnosed with the Composite International Diagnostic Interview. 126 persons (4.4%, 95%CI 3.6-5.2) were diagnosed with MDD or dysthymia at follow-up. Predictors of new-onset depressive disorders were younger age (adjusted OR 0.97, 95%CI 0.95-0.99 per year), female gender (aOR 1.46, 95%CI 1.01-2.12), multiple childhood adversities (aOR 1.76, 95%CI 1.10-2.83), low trust dimension of social capital (aOR 0.58, 95%CI 0.36-0.96 for high trust), baseline anxiety disorder (aOR 2.75, 95%CI 1.36-5.56), and baseline depressive symptoms (aOR 1.65, 95%CI 1.04-2.61 for moderate and aOR 2.49, 95%CI 1.20-5.17 for severe symptoms). Risk factors for MDD were younger age, female gender, anxiety disorder and depressive symptoms, whereas younger age, multiple childhood adversities, low trust, and having 1-2 somatic diseases predicted dysthymia. We only had one follow-up point at eleven years, and did not collect information on the subjects' health during the follow-up period. Persons with subclinical depressive symptoms, anxiety disorders, low trust, and multiple childhood adversities have a higher risk of depressive disorders. Predictors of MDD and dysthymia appear to differ. This information can be used to target preventive efforts and guide social policies. Copyright © 2016 Elsevier B.V. All rights reserved.

Patterns of women's aggression against partners and others: broadening our understanding of violence.

PubMed

Rivera, Echo A; Kubiak, Sheryl P; Bybee, Deborah

2014-12-01

Research on women's aggression typically focuses on relational aggression. However, the study of violence must include multiple forms of violence such as aggression against partners and non-partner others, while also considering victimization experiences by partners and non-partners. The focus of this study is the multiple experiences of violence (perpetration and victimization) of women who are incarcerated. Incarcerated women are likely to experience higher rates of both than women in community settings, but most will be released in a brief period of time. Using a random sample (N = 580) we conducted cluster analyses to identify five patterns of women's aggression. Clusters varied depending on the target/s of aggression (i.e., partner and/or others), and type of aggression (i.e., physical and/or intimidation). Multinomial logistic regression was performed to determine the relationship between women's membership in a perpetration cluster and their victimization. Victimization history was related to an increased risk of perpetrating aggression, and varied depending on the target and type of aggression. Our findings provide support that research and interventions addressing women's use of aggression must also address their victimization history. Furthermore, results indicate that for some women, aggression towards partners and others is related. Future research should investigate multiple forms of aggression.

Assessment of risky sexual behavior and practice among Aksum University students, Shire Campus, Shire Town, Tigray, Ethiopia, 2017.

PubMed

Kebede, Awoke; Molla, Bogale; Gerensea, Hadgu

2018-01-31

Having sex at early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs and unprotected sexual behaviors are the common characteristics of risky sexual behavior which increases risk of individuals to sexuality and reproductive health problems. Risky sexual behavior is the most common problem in adolescents and young adults which may expose individuals for permanent social, economical, psychological and physical problem. So that this study focus on assessment of risk sexual behavior using institution based cross-sectional study design on 287 randomly selected subjects among Aksum University students. Almost 60% students reported to have ever had sexual activity. Of which 86 (83.5%) and 112 (64.4%) reported having inconsistent condom use and multiple sexual partners respectively. Even though more than half of first sexual intercourse (61.5%) starts due to their desire but still peer pressure and alcohol have significant effect. Similarly the study indicated that a significant segment of students have risk sexual behaviors which increase individuals' risk of acquiring HIV/AIDS. Unless appropriate age and institutional targeted interventions exist, certain behaviors can place the university students at greater risk of HIV infection and sexually transmitted disease.

Are female orphans at risk for early marriage, early sexual debut, and teen pregnancy? Evidence from sub-Saharan Africa.

PubMed

Palermo, Tia; Peterman, Amber

2009-06-01

Female orphans are widely cited as being at risk for early marriage, early childbearing, and risky sexual behavior; however, to date no studies have examined these linkages using population-level data across multiple countries. This study draws from recent Demographic and Health Surveys from ten sub-Saharan African countries to examine the relationship between orphanhood status and measures of early marriage, early sexual debut, and teen pregnancy among adolescent girls aged 15 to 17. Results indicate that, overall, little association is found between orphanhood and early marriage or teen pregnancy, whereas evidence from seven countries supports associations between orphanhood and early sexual debut. Findings are sensitive to the use of multivariate models, type of orphan, and country setting. Orphanhood status alone may not be a sufficient targeting mechanism for addressing these outcomes in many countries; a broader, multidimensional targeting scheme including orphan type, schooling, and poverty measures would be more robust in identifying and aiding young women at risk.

Neuroblastoma: clinical and biological approach to risk stratification and treatment.

PubMed

Tolbert, Vanessa P; Matthay, Katherine K

2018-05-01

Neuroblastoma is the most common extra-cranial solid tumor of childhood and the most common in the first year of life. It is a unique malignancy in that infants often present with either localized or metastatic disease that can spontaneously regress without intervention while older children can succumb to the disease after months to years of arduous therapy. Given this wide range of outcomes, the International Neuroblastoma Risk Group was created to stratify patients based on presenting characteristics and tumor biology in order to guide intensity of treatment strategies. The goal has been to decrease therapy for low-risk patients to avoid long-term complications while augmenting and targeting therapies for high-risk patients to improve overall survival. The international risk stratification depends on age, stage, histology, MYCN gene amplification status, tumor cell ploidy and segmental chromosomal abnormalities. Treatment for asymptomatic low-risk patients with an estimated survival of > 98% is often observation or surgical resection alone, whereas intermediate-risk patients with an estimated survival of > 90% require moderate doses of response-adjusted chemotherapy along with resection. High-risk patients undergo multiple cycles of combination chemotherapy before surgery, followed by consolidation with myeloablative autologous hematopoietic stem cell transplantation and local radiation and finally immunotherapy with differentiation therapy as maintenance phase. With this approach, outcome for patients with neuroblastoma has improved, as the field continues to expand efforts in more targeted therapies for high-risk patients.

Ecosystem Risk Assessment Using the Comprehensive Assessment of Risk to Ecosystems (CARE) Tool

NASA Astrophysics Data System (ADS)

Battista, W.; Fujita, R.; Karr, K.

2016-12-01

Effective Ecosystem Based Management requires a localized understanding of the health and functioning of a given system as well as of the various factors that may threaten the ongoing ability of the system to support the provision of valued services. Several risk assessment models are available that can provide a scientific basis for understanding these factors and for guiding management action, but these models focus mainly on single species and evaluate only the impacts of fishing in detail. We have developed a new ecosystem risk assessment model - the Comprehensive Assessment of Risk to Ecosystems (CARE) - that allows analysts to consider the cumulative impact of multiple threats, interactions among multiple threats that may result in synergistic or antagonistic impacts, and the impacts of a suite of threats on whole-ecosystem productivity and functioning, as well as on specific ecosystem services. The CARE model was designed to be completed in as little as two hours, and uses local and expert knowledge where data are lacking. The CARE tool can be used to evaluate risks facing a single site; to compare multiple sites for the suitability or necessity of different management options; or to evaluate the effects of a proposed management action aimed at reducing one or more risks. This analysis can help users identify which threats are the most important at a given site, and therefore where limited management resources should be targeted. CARE can be applied to virtually any system, and can be modified as knowledge is gained or to better match different site characteristics. CARE builds on previous ecosystem risk assessment tools to provide a comprehensive assessment of fishing and non-fishing threats that can be used to inform environmental management decisions across a broad range of systems.

Ecosystem Risk Assessment Using the Comprehensive Assessment of Risk to Ecosystems (CARE) Tool

NASA Astrophysics Data System (ADS)

Battista, W.; Fujita, R.; Karr, K.

2016-02-01

Effective Ecosystem Based Management requires a localized understanding of the health and functioning of a given system as well as of the various factors that may threaten the ongoing ability of the system to support the provision of valued services. Several risk assessment models are available that can provide a scientific basis for understanding these factors and for guiding management action, but these models focus mainly on single species and evaluate only the impacts of fishing in detail. We have developed a new ecosystem risk assessment model - the Comprehensive Assessment of Risk to Ecosystems (CARE) - that allows analysts to consider the cumulative impact of multiple threats, interactions among multiple threats that may result in synergistic or antagonistic impacts, and the impacts of a suite of threats on whole-ecosystem productivity and functioning, as well as on specific ecosystem services. The CARE model was designed to be completed in as little as two hours, and uses local and expert knowledge where data are lacking. The CARE tool can be used to evaluate risks facing a single site; to compare multiple sites for the suitability or necessity of different management options; or to evaluate the effects of a proposed management action aimed at reducing one or more risks. This analysis can help users identify which threats are the most important at a given site, and therefore where limited management resources should be targeted. CARE can be applied to virtually any system, and can be modified as knowledge is gained or to better match different site characteristics. CARE builds on previous ecosystem risk assessment tools to provide a comprehensive assessment of fishing and non-fishing threats that can be used to inform environmental management decisions across a broad range of systems.

Future directions of multiple behavior change research.

PubMed

Geller, Karly; Lippke, Sonia; Nigg, Claudio R

2017-02-01

Non-communicable diseases (i.e., chronic diseases including cardiovascular disease, cancer, chronic respiratory disease, diabetes and obesity) result in 36 million deaths each year. Individuals' habitual participation in a single health-risk behaviors substantially contribute to morbidity and mortality (e.g., tobacco use, daily fast food intake, etc.); however, more concerning is the impact of typically co-occurring or clustering of multiple health-risk behaviors. This burden can be minimized through successful cessation of health-risk behaviors and adoption of healthy behaviors; namely healthy lifestyle adoption or multiple health behavior change (MHBC). MHBC is a developing field and future research recommendations are provided to advance MHBC research. A valid measure of MHBC (i.e., lifestyle) is warranted to provide the needed basis for MHBC investigations and evaluations. MHBC is thought to occur through shared co-variation of underlying motivating mechanisms, but how these relationships influence behavior remains unclear. A better understanding of the relationship between behaviors and the related motivating mechanisms (and potential cross-relationship of influences) is needed. Future research should also aim to improve lifestyles through understanding how to change multiple health behaviors. Finally, MHBC research should target the development of sustainable interventions which result in lasting effects (e.g., capacity, systems, policy and environmental changes), with dissemination considered during development. Focusing MHBC research in these areas will increase our understanding and maximize the impact on the health of populations.

Suboptimal management of cardiovascular risk factors in coronary heart disease patients in primary care occurs particularly in women.

PubMed

Driscoll, A; Beauchamp, A; Lyubomirsky, G; Demos, L; McNeil, J; Tonkin, A

2011-10-01

Patients with established coronary heart disease (CHD) are at the highest risk of further events. Despite proven therapies, secondary prevention is often suboptimal. General practitioners (GPs) are in an ideal position to improve secondary prevention. To contrast management of cardiovascular risk factors in patients with established CHD in primary care to those in clinical guidelines and according to gender. GPs throughout Australia were approached to participate in a programme incorporating a disease management software (mdCare) program. Participating practitioners (1258 GPs) recruited individual patients whose cardiovascular risk factor levels were measured. The mdCare programme included 12,509 patients (58% male) diagnosed with CHD. Their mean age was 71.7years (intra-quartile range 66-78) for men and 74years (intra-quartile range 68-80) for women. Low-density-lipoprotein cholesterol was above target levels in 69% (2032) of women compared with 58% (2487) in men (P < 0.0001). There was also a higher proportion of women with total cholesterol above target levels (76%, 3592) compared with men (57%, 3787) (P < 0.0001). In patients who were prescribed lipid-lowering medication, 53% (2504) of men and 72% (2285) of women continued to have a total cholesterol higher than recommended target levels (P < 0.0001). Overall, over half (52%, 6538) had at least five cardiovascular risk factors (55% (2914) in women and 50% (3624) in men, P < 0.0001). This study found less intensive management of cardiovascular risk factors in CHD patients, particularly among women, despite equivalent cardiovascular risk. This study has shown that these patients have multiple risk factors where gender also plays a role. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Overview of the Special Issue: A Multi-Model Framework to Achieve Consistent Evaluation of Climate Change Impacts in the United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waldhoff, Stephanie T.; Martinich, Jeremy; Sarofim, Marcus

2015-07-01

The Climate Change Impacts and Risk Analysis (CIRA) modeling exercise is a unique contribution to the scientific literature on climate change impacts, economic damages, and risk analysis that brings together multiple, national-scale models of impacts and damages in an integrated and consistent fashion to estimate climate change impacts, damages, and the benefits of greenhouse gas (GHG) mitigation actions in the United States. The CIRA project uses three consistent socioeconomic, emissions, and climate scenarios across all models to estimate the benefits of GHG mitigation policies: a Business As Usual (BAU) and two policy scenarios with radiative forcing (RF) stabilization targets ofmore » 4.5 W/m2 and 3.7 W/m2 in 2100. CIRA was also designed to specifically examine the sensitivity of results to uncertainties around climate sensitivity and differences in model structure. The goals of CIRA project are to 1) build a multi-model framework to produce estimates of multiple risks and impacts in the U.S., 2) determine to what degree risks and damages across sectors may be lowered from a BAU to policy scenarios, 3) evaluate key sources of uncertainty along the causal chain, and 4) provide information for multiple audiences and clearly communicate the risks and damages of climate change and the potential benefits of mitigation. This paper describes the motivations, goals, and design of the CIRA modeling exercise and introduces the subsequent papers in this special issue.« less

Everyday stress response targets in the science of behavior change.

PubMed

Smyth, Joshua M; Sliwinski, Martin J; Zawadzki, Matthew J; Scott, Stacey B; Conroy, David E; Lanza, Stephanie T; Marcusson-Clavertz, David; Kim, Jinhyuk; Stawski, Robert S; Stoney, Catherine M; Buxton, Orfeu M; Sciamanna, Christopher N; Green, Paige M; Almeida, David M

2018-02-01

Stress is an established risk factor for negative health outcomes, and responses to everyday stress can interfere with health behaviors such as exercise and sleep. In accordance with the Science of Behavior Change (SOBC) program, we apply an experimental medicine approach to identifying stress response targets, developing stress response assays, intervening upon these targets, and testing intervention effectiveness. We evaluate an ecologically valid, within-person approach to measuring the deleterious effects of everyday stress on physical activity and sleep patterns, examining multiple stress response components (i.e., stress reactivity, stress recovery, and stress pile-up) as indexed by two key response indicators (negative affect and perseverative cognition). Our everyday stress response assay thus measures multiple malleable stress response targets that putatively shape daily health behaviors (physical activity and sleep). We hypothesize that larger reactivity, incomplete recovery, and more frequent stress responses (pile-up) will negatively impact health behavior enactment in daily life. We will identify stress-related reactivity, recovery, and response in the indicators using coordinated analyses across multiple naturalistic studies. These results are the basis for developing a new stress assay and replicating the initial findings in a new sample. This approach will advance our understanding of how specific aspects of everyday stress responses influence health behaviors, and can be used to develop and test an innovative ambulatory intervention for stress reduction in daily life to enhance health behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Community-Engaged Modeling of Geographic and Demographic Patterns of Multiple Public Health Risk Factors

PubMed Central

Basra, Komal; Fabian, M. Patricia; Holberger, Raymond R.; French, Robert

2017-01-01

Many health risk factors are intervention targets within communities, but information regarding high-risk subpopulations is rarely available at a geographic resolution that is relevant for community-scale interventions. Researchers and community partners in New Bedford, Massachusetts (USA) collaboratively identified high-priority behaviors and health outcomes of interest available in the Behavioral Risk Factor Surveillance System (BRFSS). We developed multivariable regression models from the BRFSS explaining variability in exercise, fruit and vegetable consumption, body mass index, and diabetes prevalence as a function of demographic and behavioral characteristics, and linked these models with population microdata developed using spatial microsimulation to characterize high-risk populations and locations. Individuals with lower income and educational attainment had lower rates of multiple health-promoting behaviors (e.g., fruit and vegetable consumption and exercise) and higher rates of self-reported diabetes. Our models in combination with the simulated population microdata identified census tracts with an elevated percentage of high-risk subpopulations, information community partners can use to prioritize funding and intervention programs. Multi-stressor modeling using data from public databases and microsimulation methods for characterizing high-resolution spatial patterns of population attributes, coupled with strong community partner engagement, can provide significant insight for intervention. Our methodology is transferrable to other communities. PMID:28684710

Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer.

PubMed

Kurian, Allison W; Ward, Kevin C; Hamilton, Ann S; Deapen, Dennis M; Abrahamse, Paul; Bondarenko, Irina; Li, Yun; Hawley, Sarah T; Morrow, Monica; Jagsi, Reshma; Katz, Steven J

2018-05-10

Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice. To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories. Type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines. Among 5026 patients (mean [SD] age, 59.9 [10.7]), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%;in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 (BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%). Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.

Opportunities for Cancer Prevention During Midlife

PubMed Central

Holman, Dawn M.; Grossman, Melissa; Henley, S. Jane; Peipins, Lucy A.; Tison, Laura; White, Mary C.

2015-01-01

This paper provides highlights from a CDC-hosted meeting on opportunities for cancer prevention during midlife (roughly ages 45–64 years). Positive changes during this phase of life have the potential to prevent cancer incidence later in life, making this phase an opportune time for targeted prevention efforts to facilitate healthy aging and increased longevity. Risk and protective factors discussed during the meeting included exposure to radiation from medical imaging procedures, circadian disruption, chemical exposures, dietary factors, alcohol consumption, obesity, physical activity, diabetes, and the human microbiome. Although many of these factors are well recognized as being related to cancer incidence, others are not as widely recognized or have emerged as growing areas of research. Meeting participants discussed promising strategies for cancer prevention targeting this age group. Just as there are multiple determinants of cancer risk, there are likely multiple solutions. Changes to social and physical environments may facilitate healthy behaviors and minimize harmful exposures. Information shared during the meeting about health disparities in the U.S. highlighted the need to go beyond traditional approaches to cancer prevention to truly reach vulnerable populations. Partnerships are also a key component to prevention efforts; community-based and nonprofit organizations, the healthcare system, research institutions, state health departments, and federal agencies were all noted as important partners in prevention efforts. Coordinated, multi-disciplinary efforts across multiple chronic diseases may provide opportunities for synergistic effects. Further, leveraging key partnerships and existing communication channels can maximize success and facilitate timely translation of research findings into public health practice. PMID:24512934

From Recess to Lockdown: Targeting Adult and Child School-Based Practices and Behaviors That Impact Black Male Entry into the School to Prison Pipeline

ERIC Educational Resources Information Center

Chase, Lance Montieth

2012-01-01

Prior studies establish that Black males follow a disproportionate trajectory from school to prison when compared to other groups. This same research has documented that multiple risk factors operating within schools may contribute to this phenomenon, commonly known as the "school to prison pipeline." The specific focus of the present…

[Urban ecological risk assessment: a review].

PubMed

Wang, Mei-E; Chen, Wei-Ping; Peng, Chi

2014-03-01

With the development of urbanization and the degradation of urban living environment, urban ecological risks caused by urbanization have attracted more and more attentions. Based on urban ecology principles and ecological risk assessment frameworks, contents of urban ecological risk assessment were reviewed in terms of driven forces, risk resources, risk receptors, endpoints and integrated approaches for risk assessment. It was suggested that types and degrees of urban economical and social activities were the driven forces for urban ecological risks. Ecological functional components at different levels in urban ecosystems as well as the urban system as a whole were the risk receptors. Assessment endpoints involved in changes of urban ecological structures, processes, functional components and the integrity of characteristic and function. Social-ecological models should be the major approaches for urban ecological risk assessment. Trends for urban ecological risk assessment study should focus on setting a definite protection target and criteria corresponding to assessment endpoints, establishing a multiple-parameter assessment system and integrative assessment approaches.

MS Sunshine Study: Sun Exposure But Not Vitamin D Is Associated with Multiple Sclerosis Risk in Blacks and Hispanics.

PubMed

Langer-Gould, Annette; Lucas, Robyn; Xiang, Anny H; Chen, Lie H; Wu, Jun; Gonzalez, Edlin; Haraszti, Samantha; Smith, Jessica B; Quach, Hong; Barcellos, Lisa F

2018-02-27

Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31-0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48-0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42-1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics.

Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

PubMed Central

Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

2016-01-01

The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.

PubMed

Boldescu, Veaceslav; Behnam, Mira A M; Vasilakis, Nikos; Klein, Christian D

2017-08-01

Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis. Numerous compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For other compounds, broad-spectrum activity can be anticipated because of their mode of action and molecular targets.

Examining the Relationship Between Pain Catastrophizing and Suicide Risk in Patients with Rheumatic Disease: the Mediating Role of Depression, Perceived Social Support, and Perceived Burdensomeness.

PubMed

Shim, Eun -Jung; Song, Yeong Wook; Park, Seung-Hee; Lee, Kwang-Min; Go, Dong Jin; Hahm, Bong-Jin

2017-08-01

Little research has examined the role of pain catastrophizing (PC) in predicting suicide among patients with rheumatic disease or the mechanisms through which it works. This study examines whether depression, perceived social support (PSS), and perceived burdensomeness (PB) mediate the relationship between PC and suicide risk. It also examines the relative importance of sociodemographic, clinical, and psychological factors in predicting suicide risk. Three hundred sixty patients from a rheumatology clinic in Korea completed measures of pain catastrophizing, social support, depression, and perceived burdensomeness. In hierarchical multiple regression analysis, the PC magnification, PB, physical disability, and PSS were significantly related to suicide risk. Results of the serial multiple mediation analysis indicated that the total indirect effect of PC magnification on suicide risk was significant while the direct effect was not. Four specific indirect effects of PC magnification were found to be statistically significant. First of all, PC magnification was associated with suicide risk through PB and through depression and PB. PC magnification was also associated with suicide risk through depression and PSS. Lastly, PC magnification was associated with suicide risk through depression, PSS, and PB. The identified pathways through which PC affects suicide risk suggest the importance of depression, PSS, and PB. Evaluation and intervention targeted at physical disability and the psychological factors of PC magnification, depression, PSS, and PB may be integrated into the management of suicide risk in patients with rheumatic disease.

Prediction of breast cancer risk based on profiling with common genetic variants.

PubMed

Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; Dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Figueroa, Jonine; Chanock, Stephen J; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M; Hunter, David J; Lindstrom, Sara; Tamimi, Rulla M; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J; Doody, Michele M; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G; Milne, Roger L; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Koppert, Linetta B; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Eccles, Diana M; Tapper, William J; Rafiq, Sajjad; John, Esther M; Whittemore, Alice S; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E; Yao, Song; Zheng, Wei; Halverson, Sandra L; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; Simard, Jacques; Hall, Per; Easton, Douglas F; Garcia-Closas, Montserrat

2015-05-01

Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © The Author 2015. Published by Oxford University Press.

Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

PubMed Central

Pharoah, Paul D. P.; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Figueroa, Jonine; Chanock, Stephen J.; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Pankratz, Vernon S.; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M.; Hunter, David J.; Lindstrom, Sara; Tamimi, Rulla M.; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M.; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J.; Doody, Michele M.; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Koppert, Linetta B.; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Eccles, Diana M.; Tapper, William J.; Rafiq, Sajjad; John, Esther M.; Whittemore, Alice S.; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E.; Yao, Song; Zheng, Wei; Halverson, Sandra L.; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Simard, Jacques; Hall, Per; Easton, Douglas F.; Garcia-Closas, Montserrat

2015-01-01

Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. PMID:25855707

Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication–Adolescent Supplement Study

PubMed Central

Carliner, Hannah; Keyes, Katherine M.; McLaughlin, Katie A.; Meyers, Jacquelyn L.; Dunn, Erin C.; Martins, Silvia S.

2016-01-01

Objective Although potentially traumatic events (PTEs) are established risk factors for substance use disorders among adults, little is known about associations with drug use during adolescence, an important developmental stage for drug use prevention. We examined whether childhood PTEs were associated with illicit drug use among a representative sample of US adolescents. Method Data were drawn from the National Comorbidity Survey Replication–Adolescent Supplement (NCS-A), which included adolescents aged 13-18 years (N=9,956). Weighted logistic regression models estimated risk ratios for lifetime use of marijuana, cocaine, nonmedical prescription drugs, other drugs, and multiple drugs. Results Exposure to any PTE prior to age 11 was reported by 36% of the sample and was associated with higher risk for use of marijuana (risk ratio [RR] = 1.50), cocaine (RR = 2.78), prescription drugs (RR=1.80), other drugs (RR=1.90), and multiple drugs (RR=1.74). A positive monotonic relationship was observed between number of PTEs and marijuana, other drug, and multiple drug use. Interpersonal violence was associated with all drug use outcomes. Accidents and unspecified events were associated with higher risk for marijuana, cocaine, and prescription drug use. Conclusion Potentially traumatic events in childhood are associated with risk for illicit drug use among US adolescents. These findings add to the literature by illustrating a potentially modifiable health behavior that may be a target for intervention; and that adolescents with a trauma history are a high-risk group for illicit drug use and may benefit from trauma-focused prevention efforts that specifically address traumatic memories and coping strategies for dealing with stressful life events. PMID:27453084

Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication-Adolescent Supplement Study.

PubMed

Carliner, Hannah; Keyes, Katherine M; McLaughlin, Katie A; Meyers, Jacquelyn L; Dunn, Erin C; Martins, Silvia S

2016-08-01

Although potentially traumatic events (PTEs) are established risk factors for substance use disorders among adults, little is known about associations with drug use during adolescence, an important developmental stage for drug use prevention. We examined whether childhood PTEs were associated with illicit drug use among a representative sample of US adolescents. Data were drawn from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A), which included adolescents aged 13 to 18 years (N = 9,956). Weighted logistic regression models estimated risk ratios for lifetime use of marijuana, cocaine, nonmedical prescription drugs, other drugs, and multiple drugs. Exposure to any PTE before age 11 years was reported by 36% of the sample and was associated with higher risk for use of marijuana (risk ratio [RR] = 1.50), cocaine (RR = 2.78), prescription drugs (RR = 1.80), other drugs (RR = 1.90), and multiple drugs (RR = 1.74). A positive monotonic relationship was observed between number of PTEs and marijuana, other drug, and multiple drug use. Interpersonal violence was associated with all drug use outcomes. Accidents and unspecified events were associated with higher risk for marijuana, cocaine, and prescription drug use. Potentially traumatic events in childhood are associated with risk for illicit drug use among US adolescents. These findings add to the literature by illustrating a potentially modifiable health behavior that may be a target for intervention. The results also highlight that adolescents with a trauma history are a high-risk group for illicit drug use and may benefit from trauma-focused prevention efforts that specifically address traumatic memories and coping strategies for dealing with stressful life events. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Environmental equity: Reducing risk for all communities. Volume 2. Supporting document

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1992-06-01

In targeting its protection efforts to reduce the most serious risks, the Agency has begun to examine how the patterns of environmental problems converge on different places, how the people who live in those places are affected, and how environmental programs should be refined to address identified differences. A community surrounded by Multiple sources of air pollution, ringed by waste treatment facilities and landfills, and whose residences contain lead-based paint clearly faces higher than average potential environmental risks. It is in this context that concerns have been raised about the relative risk burden borne by low-income and racial minority communities.more » Examination of these differences in risk burden and how government agencies respond is known as environmental equity. Although there are many types of equity, this report focuses on racial and socioeconomic equity.« less

Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

PubMed

Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

2015-09-01

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

Alternative research funding to improve clinical outcomes: model of prediction and prevention of sudden cardiac death.

PubMed

Myerburg, Robert J; Ullmann, Steven G

2015-04-01

Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death risk as a base case, the complex epidemiology of sudden cardiac death risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of sudden cardiac death risk, but the concept is applicable to other areas of the medical enterprise. © 2015 American Heart Association, Inc.

Cognitive processing speed is related to fall frequency in older adults with multiple sclerosis.

PubMed

Sosnoff, Jacob J; Balantrapu, Swathi; Pilutti, Lara A; Sandroff, Brian M; Morrison, Steven; Motl, Robert W

2013-08-01

To examine mobility, balance, fall risk, and cognition in older adults with multiple sclerosis (MS) as a function of fall frequency. Retrospective, cross-sectional design. University research laboratory. Community-dwelling persons with MS (N=27) aged between 50 and 75 years were divided into 2 groups-single-time (n=11) and recurrent (n=16; >2 falls/12 mo) fallers-on the basis of fall history. Not applicable. Mobility was assessed using a variety of measures including Multiple Sclerosis Walking Scale-12, walking speed (Timed 25-Foot Walk test), endurance (6-Minute Walk test), and functional mobility (Timed Up and Go test). Balance was assessed with the Berg Balance Scale, posturography, and self-reported balance confidence. Fall risk was assessed with the Physiological Profile Assessment. Cognitive processing speed was quantified with the Symbol Digit Modalities Test and the Paced Auditory Serial Addition Test. Recurrent fallers had slower cognitive processing speed than single-time fallers (P ≤.01). There was no difference in mobility, balance, or fall risk between recurrent and single-time fallers (P>.05). Results indicated that cognitive processing speed is associated with fall frequency and may have implications for fall prevention strategies targeting recurrent fallers with MS. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Parents with mental health problems and their children in a German population based sample: Results of the BELLA study.

PubMed

Plass-Christl, Angela; Haller, Anne-Catherine; Otto, Christiane; Barkmann, Claus; Wiegand-Grefe, Silke; Hölling, Heike; Schulte-Markwort, Michael; Ravens-Sieberer, Ulrike; Klasen, Fionna

2017-01-01

Mental health problems (MHP) of parents are associated with an increased risk of psychological and developmental difficulties in their children. This study aims at analyzing population-based data of parents with MHP and their children and the effects of associated risk factors in order to further targeted preventive and therapeutic interventions. The BELLA study is the mental health module of the German National Health Interview and Examination Survey among Children and Adolescents. MHP in parents and in their children as well as associated risk factors were examined in a sample of N = 1158 parents with children aged 11 to 17 years. Parental MHP were identified in 18.6% of the sample. Risk factors associated with parental MHP were low SES, parental unemployment, stressful life events, parental daily strain, parental chronic disease, and child MHP. A rate of 19.1% of the children of parents with MHP reported MHP themselves, the corresponding rate among children of parents without MHP was 7.7%. In multiple regression analyses the risk for children of parents with MHP to report MHP themselves was almost two times higher than the risk of children of parents without MHP. Other significant associations with child MHP included gender, the parents' age, and stressful life events. Parental MHP constitute a significant risk for the mental health of their children. Targeted screening methods and preventive interventions are needed.

Empirically Based Strategies for Preventing Juvenile Delinquency.

PubMed

Pardini, Dustin

2016-04-01

Juvenile crime is a serious public health problem that results in significant emotional and financial costs for victims and society. Using etiologic models as a guide, multiple interventions have been developed to target risk factors thought to perpetuate the emergence and persistence of delinquent behavior. Evidence suggests that the most effective interventions tend to have well-defined treatment protocols, focus on therapeutic approaches as opposed to external control techniques, and use multimodal cognitive-behavioral treatment strategies. Moving forward, there is a need to develop effective policies and procedures that promote the widespread adoption of evidence-based delinquency prevention practices across multiple settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Future clinical challenges in multiple sclerosis: Relevance to sphingosine 1-phosphate receptor modulator therapy.

PubMed

Hohlfeld, Reinhard; Barkhof, Frederik; Polman, Chris

2011-02-22

The limitations of established therapies for multiple sclerosis (MS) are well-known and include the need for injections, treatment adherence and convenience issues, partial efficacy, and, in some cases, a risk of potentially life-threatening adverse events, such as progressive multifocal leukoencephalopathy. Recently, attention has focused on developing more effective therapies that are administered orally and target neurodegeneration as well as inflammation. In this review, we provide an outlook on the future clinical challenges for MS treatment and management, and focus specifically on the emerging sphingosine 1-phosphate receptor (S1PR) modulators. We highlight the importance of improving our understanding of the neurobiological basis of MS to develop well-tolerated targeted therapies and the need to include advanced MRI assessments that quantify neurodegeneration in interventional studies in MS. As more treatments become available, often with complex pharmacodynamic actions, objective assessment of benefit-to-risk profiles becomes increasingly important to ensure that patients receive appropriate care. Pharmacovigilance and immune monitoring will become important aspects of patient treatment and management in the future. With respect to S1PR modulation, we review the experimental agents that are in clinical development for MS and summarize the steps taken in postmarketing surveillance to ensure that fingolimod (FTY720) has a well-characterized safety profile.

20150325 - Application of High-Throughput In Vitro Assays for ...

EPA Pesticide Factsheets

Multiple drivers shape the types of human-health assessments performed on chemicals by U.S. EPA resulting in chemical assessments are “fit-for-purpose” ranging from prioritization for further testing to full risk assessments. Layered on top of the diverse assessment needs are the resource intensive nature of traditional toxicological studies used to test chemicals and the lack of toxicity information on many chemicals. To address these challenges, the Agency initiated the ToxCast program to screen thousands of chemicals across hundreds of high-throughput screening assays in concentrations-response format. One of the findings of the project has been that the majority of chemicals interact with multiple biological targets within a narrow concentration range and the extent of interactions increases rapidly near the concentration causing cytotoxicity. This means that application of high-throughput in vitro assays to chemical assessments will need to identify both the relative selectivity at chemicals interact with biological targets and the concentration at which these interactions perturb signaling pathways. The integrated analyses will be used to both define a point-of-departure for comparison with human exposure estimates and identify which chemicals may benefit from further studies in a mode-of-action or adverse outcome pathway framework. The application of new technologies in a risk-based, tiered manner provides flexibility in matching throughput and cos

Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation.

PubMed

Degelman, Michelle L; Herman, Katya M

2017-10-01

Despite being one of the most common neurological disorders globally, the cause(s) of multiple sclerosis (MS) remain unknown. Cigarette smoking has been studied with regards to both the development and progression of MS. The Bradford Hill criteria for causation can contribute to a more comprehensive evaluation of a potentially causal risk factor-disease outcome relationship. The objective of this systematic review and meta-analysis was to assess the relationship between smoking and both MS risk and MS progression, subsequently applying Hill's criteria to further evaluate the likelihood of causal associations. The Medline, EMBASE, CINAHL, PsycInfo, and Cochrane Library databases were searched for relevant studies up until July 28, 2015. A random-effects meta-analysis was conducted for three outcomes: MS risk, conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), and progression from relapsing-remitting multiple sclerosis (RRMS) to secondary-progressive multiple sclerosis (SPMS). Dose-response relationships and risk factor interactions, and discussions of mechanisms and analogous associations were noted. Hill's criteria were applied to assess causality of the relationships between smoking and each outcome. The effect of second-hand smoke exposure was also briefly reviewed. Smoking had a statistically significant association with both MS risk (conservative: OR/RR 1.54, 95% CI [1.46-1.63]) and SPMS risk (HR 1.80, 95% CI [1.04-3.10]), but the association with progression from CIS to CDMS was non-significant (HR 1.13, 95% CI [0.73-1.76]). Using Hill's criteria, there was strong evidence of a causal role of smoking in MS risk, but only moderate evidence of a causal association between smoking and MS progression. Heterogeneity in study designs and target populations, inconsistent results, and an overall scarcity of studies point to the need for more research on second-hand smoke exposure in relation to MS prior to conducting a detailed meta-analysis. This first review to supplement systematic review and meta-analytic methods with Hill's criteria to analyze the smoking-MS association provides evidence supporting the causal involvement of smoking in the development and progression of MS. Smoking prevention and cessation programs and policies should consider MS as an additional health risk when aiming to reduce smoking prevalence in the population. Copyright © 2017 Elsevier B.V. All rights reserved.

Endocannabinoid signalling and the deteriorating brain

PubMed Central

Di Marzo, Vincenzo; Stella, Nephi; Zimmer, Andreas

2015-01-01

Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics. PMID:25524120

Realizing drug repositioning by adapting a recommendation system to handle the process.

PubMed

Ozsoy, Makbule Guclin; Özyer, Tansel; Polat, Faruk; Alhajj, Reda

2018-04-12

Drug repositioning is the process of identifying new targets for known drugs. It can be used to overcome problems associated with traditional drug discovery by adapting existing drugs to treat new discovered diseases. Thus, it may reduce associated risk, cost and time required to identify and verify new drugs. Nowadays, drug repositioning has received more attention from industry and academia. To tackle this problem, researchers have applied many different computational methods and have used various features of drugs and diseases. In this study, we contribute to the ongoing research efforts by combining multiple features, namely chemical structures, protein interactions and side-effects to predict new indications of target drugs. To achieve our target, we realize drug repositioning as a recommendation process and this leads to a new perspective in tackling the problem. The utilized recommendation method is based on Pareto dominance and collaborative filtering. It can also integrate multiple data-sources and multiple features. For the computation part, we applied several settings and we compared their performance. Evaluation results show that the proposed method can achieve more concentrated predictions with high precision, where nearly half of the predictions are true. Compared to other state of the art methods described in the literature, the proposed method is better at making right predictions by having higher precision. The reported results demonstrate the applicability and effectiveness of recommendation methods for drug repositioning.

“I Do Not Take My Medicine while Hiding” - A Longitudinal Qualitative Assessment of HIV Discordant Couples’ Beliefs in Discordance and ART as Prevention in Uganda

PubMed Central

King, Rachel; Kim, Jiho; Nanfuka, Mastula; Shafic, Murisho; Nyonyitono, Maureen; Galenda, Florence; Moore, David

2017-01-01

Background HIV negative members of serostatus discordant couples are at high risk for HIV acquisition, but few interventions are in place to target them in sub-Saharan Africa. Methods In this study, we interviewed 28 couples, 3 times over a period of one year to understand their perceptions and attitudes around discordance, their relationship dynamics, their HIV risk behaviour, their beliefs and attitudes about antiretroviral therapy (ART) and their views of the community perceptions of discordance and treatment for HIV. Results Findings revealed that at baseline there were multiple complex explanations and interpretations about discordance among discordant couples and their surrounding community. Shifts in beliefs and attitudes about discordance, HIV risk reduction and ART over time were enabled through re-testing negative members of discordant couples and repeat counselling but some beliefs remain solidly embedded in cultural imperatives of the importance of childbearing as well as culturally determined and enforced gender roles. Conclusions Interventions that aim to target discordant couples must embrace the complex and dynamic understandings of HIV diagnosis and treatment in context of fluid relationships, and changing beliefs about HIV risk and treatment. PMID:28081158

Visceral adiposity as a target for the management of the metabolic syndrome.

PubMed

Kishida, Ken; Funahashi, Tohru; Matsuzawa, Yuji; Shimomura, Iichiro

2012-05-01

Atherosclerosis, the underlying cause of atherosclerotic cardiovascular disease (ACVD), develops due not only to a single cardiovascular risk factor but to a variety of complex factors. The concept of the multiple cardiometabolic risk factor clustering syndrome has been proposed as a highly atherogenic state, independent of hypercholesterolemia and smoking. Body fat distribution, especially visceral fat accumulation, is a major correlate of a cluster of diabetogenic, atherogenic, prothrombotic, and proinflammatory metabolic abnormalities referred to as the metabolic syndrome, with dysfunctional adipocytes and dysregulated production of adipocytokines (hypoadiponectinemia). Medical research has focused on visceral adiposity as an important component of the syndrome in Japanese subjects with a mild degree of adiposity compared with Western subjects. For the prevention of ACVD at least in Japan, it might be practical to stratify subjects with multiple risk factors for atherosclerotic cardiovascular disease based on visceral fat accumulation. Visceral fat reduction through health promotion programs using risk factor-oriented approaches may be effective in reducing ACVD events, as well as producing improvement in risks and hypoadiponectinemia. This review article discusses visceral adiposity as a key player in the syndrome. Visceral fat reduction with life-style modification is a potentially useful strategy in the prevention of ACVD in patients with the metabolic syndrome.

Multiple risk-behavior profiles of smokers with serious mental illness and motivation for change.

PubMed

Prochaska, Judith J; Fromont, Sebastien C; Delucchi, Kevin; Young-Wolff, Kelly C; Benowitz, Neal L; Hall, Stephen; Bonas, Thomas; Hall, Sharon M

2014-12-01

Individuals with serious mental illness (SMI) are dying on average 25 years prematurely. The leading causes are chronic preventable diseases. In the context of a tobacco-treatment trial, this exploratory study examined the behavioral risk profiles of adults with SMI to identify broader interventional needs. Recruited from five acute inpatient psychiatry units, participants were 693 adult smokers (recruitment rate = 76%, 50% male, 45% Caucasian, age M = 39, 49% had income < $10,000) diagnosed with mood disorders (71%), substance-use disorders (63%), posttraumatic stress disorder (39%), psychotic disorders (25%), and attention deficit-hyperactivity disorder (25%). The Staging Health Risk Assessment, the primary measure used in this study, screened for risk status and readiness to change 11 health behaviors, referencing the period prior to acute hospitalization. Participants averaged 5.2 (SD = 2.1) risk behaviors, including smoking (100%), high-fat diet (68%), inadequate fruits/vegetables (67%), poor sleep (53%), physical inactivity (52%), and marijuana use (46%). The percent prepared to change ranged from 23% for tobacco and marijuana to 76% for depression management. Latent class analysis differentiated three risk groups: the global higher risk group included patients elevated on all risk behaviors; the global lower risk group was low on all risks; and a mood and metabolic risk group, characterized by inactivity, unhealthy diet, sleep problems, and poor stress and depression management. The global higher risk group (11% of sample) was younger, largely male, and had the greatest number of risk behaviors and mental health diagnoses; had the most severe psychopathologies, addiction-treatment histories, and nicotine dependence; and the lowest confidence for quitting smoking and commitment to abstinence. Most smokers with SMI engaged in multiple risks. Expanding targets to treat co-occurring risks and personalizing treatment to individuals' multibehavioral profiles may increase intervention relevance, interest, and impact on health.

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

PubMed Central

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

2016-01-01

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.

PubMed

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J; Li, Qiyuan; Delgado, Melissa K; Lee, Janet M; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Bandera, Elisa V; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Matthias W; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B M; Cook, Linda S; Cox, Angela; Cramer, Daniel W; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Engel, Christoph; Lee, Eunjung; Evans, D Gareth; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fridley, Brooke L; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G; Glasspool, Rosalind; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Goode, Ellen L; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Harrington, Patricia A; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Hulick, Peter J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y; Khan, Sofia; Kiemeney, Lambertus A; Kjaer, Susanne Kruger; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F A G; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R; Milne, Roger L; Montagna, Marco; Moysich, Kirsten B; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poole, Elizabeth M; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Sellers, Thomas A; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F; Sinilnikova, Olga M; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tung, Nadine; Tworoger, Shelley S; Vachon, Celine; van den Ouweland, Ans M W; van Doorn, Helena C; van Rensburg, Elizabeth J; Van't Veer, Laura J; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Wildiers, Hans; Winqvist, Robert; Wu, Anna H; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N; French, Juliet D; Couch, Fergus J; Freedman, Matthew L; Easton, Douglas F; Dunning, Alison M; Pharoah, Paul D; Edwards, Stacey L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Gayther, Simon A

2016-09-07

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

Identifying housing that poisons: a critical step in eliminating childhood lead poisoning.

PubMed

Reyes, Nimia L; Wong, Lee-Yang; MacRoy, Patrick M; Curtis, Gerald; Meyer, Pamela A; Evens, Anne; Brown, Mary Jean

2006-01-01

The purpose of our study was to develop a method to identify and prioritize "high-risk" buildings in Chicago that could be targeted for childhood lead poisoning prevention activities. We defined "high-risk" buildings as those where multiple children younger than 6 years with elevated blood lead levels (BLLs) had lived and where lead hazards were previously identified on environmental inspection. By linking 1997-2003 Chicago elevated blood lead surveillance, environmental inspection, and building footprint data, we found that 49,362 children younger than 6 years with elevated BLLs lived at 30,742 buildings. Of those, 67 were "high-risk" buildings and these were associated with 994 children with elevated BLLs. On average, 15 children with elevated BLLs had lived in each building (range: 10-53, median: 13). Almost two thirds (n = 43) of the high-risk buildings had two or more referrals for inspection to the same apartment or housing unit; of those, 40 percent (n = 17) failed to maintain lead-safe status after compliance. Linking blood lead surveillance, environmental inspection, and building footprint databases allowed us to identify individual high-risk buildings. This approach prioritizes lead hazard control efforts and may help health, housing, and environmental agencies in targeting limited resources to increase lead-safe housing for children.

The importance of the community context in the epidemiology of early adolescent substance use and delinquency in a rural sample.

PubMed

Chilenski, Sarah M; Greenberg, Mark T

2009-12-01

Considerable research has demonstrated that substance use and delinquency during early adolescence can have long-term negative health consequences. As the correlates of these behaviors cross levels and contexts, it is likely that a social ecological approach will provide insight to inform community prevention. This approach informs the present study, which focuses on developing a multiple-method measurement strategy to examine associations among community risks, resources, and rates of early adolescent substance use and delinquency in 28 rural and small town communities. Measures include five domains of community risk, four domains of community resources, and population rates of early adolescent substance use and delinquency. Results demonstrated that several measures of context were significantly associated with community rates of adolescent substance use and delinquency, and different risks and resources appear important for different outcomes. Multiple associations were curvilinear, and interactions may also be important. Findings suggest that it may be worthwhile to create and test new intervention strategies that target community factors in the pursuit of prevention.

Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity

PubMed Central

Raj, Prithvi; Rai, Ekta; Song, Ran; Khan, Shaheen; Wakeland, Benjamin E; Viswanathan, Kasthuribai; Arana, Carlos; Liang, Chaoying; Zhang, Bo; Dozmorov, Igor; Carr-Johnson, Ferdicia; Mitrovic, Mitja; Wiley, Graham B; Kelly, Jennifer A; Lauwerys, Bernard R; Olsen, Nancy J; Cotsapas, Chris; Garcia, Christine K; Wise, Carol A; Harley, John B; Nath, Swapan K; James, Judith A; Jacob, Chaim O; Tsao, Betty P; Pasare, Chandrashekhar; Karp, David R; Li, Quan Zhen; Gaffney, Patrick M; Wakeland, Edward K

2016-01-01

Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional variations are a new and potent facet of HLA polymorphism. Variations modifying the consensus binding motifs of IRF4 and CTCF in the XL9 regulatory complex modified the transcription of HLA-DRB1, HLA-DQA1 and HLA-DQB1 in a chromosome-specific manner, resulting in a 2.5-fold increase in the surface expression of HLA-DR and DQ molecules on dendritic cells with SLE risk genotypes, which increases to over 4-fold after stimulation. Similar analyses of fifteen other SLE risk loci identified 1206 functional variants tightly linked with disease-associated SNPs and demonstrated that common disease alleles contain multiple causal variants modulating multiple immune system genes. DOI: http://dx.doi.org/10.7554/eLife.12089.001 PMID:26880555

Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

PubMed Central

Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

2010-01-01

Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (p<0.001 and p=0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression. Conclusions These findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

PubMed Central

Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

2015-01-01

Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3. PMID:25644994

Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

NASA Astrophysics Data System (ADS)

Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

2015-02-01

Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.

Patterns of multiple health risk–behaviours in university students and their association with mental health: application of latent class analysis

PubMed Central

Kwan, M. Y.; Arbour-Nicitopoulos, K. P.; Duku, E.; Faulkner, G.

2016-01-01

Abstract Introduction: University and college campuses may be the last setting where it is possible to comprehensively address the health of a large proportion of the young adult population. It is important that health promoters understand the collective challenges students are facing, and to better understand the broader lifestyle behavioural patterning evident during this life stage. The purpose of this study was to examine the clustering of modifiable health-risk behaviours and to explore the relationship between these identified clusters and mental health outcomes among a large Canadian university sample. Methods: Undergraduate students (n = 837; mean age = 21 years) from the University of Toronto completed the National College Health Assessment survey. The survey consists of approximately 300 items, including assessments of student health status, mental health and health-risk behaviours. Latent class analysis was used to identify patterning based on eight salient health-risk behaviours (marijuana use, other illicit drug use, risky sex, smoking, binge drinking, poor diet, physical inactivity, and insufficient sleep). Results: A three-class model based on student behavioural patterns emerged: “typical,” “high-risk” and “moderately healthy.” Results also found high-risk students reporting significantly higher levels of stress than typical students (χ2(1671) = 7.26, p < .01). Conclusion: Students with the highest likelihood of engaging in multiple health-risk behaviours reported poorer mental health, particularly as it relates to stress. Although these findings should be interpreted with caution due to the 28% response rate, they do suggest that interventions targeting specific student groups with similar patterning of multiple health-risk behaviours may be needed. PMID:27556920

An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors.

PubMed

Gabb, Henry A; Blake, Catherine

2016-08-01

Simultaneous or sequential exposure to multiple environmental stressors can affect chemical toxicity. Cumulative risk assessments consider multiple stressors but it is impractical to test every chemical combination to which people are exposed. New methods are needed to prioritize chemical combinations based on their prevalence and possible health impacts. We introduce an informatics approach that uses publicly available data to identify chemicals that co-occur in consumer products, which account for a significant proportion of overall chemical load. Fifty-five asthma-associated and endocrine disrupting chemicals (target chemicals) were selected. A database of 38,975 distinct consumer products and 32,231 distinct ingredient names was created from online sources, and PubChem and the Unified Medical Language System were used to resolve synonymous ingredient names. Synonymous ingredient names are different names for the same chemical (e.g., vitamin E and tocopherol). Nearly one-third of the products (11,688 products, 30%) contained ≥ 1 target chemical and 5,229 products (13%) contained > 1. Of the 55 target chemicals, 31 (56%) appear in ≥ 1 product and 19 (35%) appear under more than one name. The most frequent three-way chemical combination (2-phenoxyethanol, methyl paraben, and ethyl paraben) appears in 1,059 products. Further work is needed to assess combined chemical exposures related to the use of multiple products. The informatics approach increased the number of products considered in a traditional analysis by two orders of magnitude, but missing/incomplete product labels can limit the effectiveness of this approach. Such an approach must resolve synonymy to ensure that chemicals of interest are not missed. Commonly occurring chemical combinations can be used to prioritize cumulative toxicology risk assessments. Gabb HA, Blake C. 2016. An informatics approach to evaluating combined chemical exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155-1165; http://dx.doi.org/10.1289/ehp.1510529.

Rapid mapping of schistosomiasis and other neglected tropical diseases in the context of integrated control programmes in Africa

PubMed Central

BROOKER, S.; KABATEREINE, N. B.; GYAPONG, J. O.; STOTHARD, J. R.; UTZINGER, J.

2009-01-01

SUMMARY There is growing interest and commitment to the control of schistosomiasis and other so-called neglected tropical diseases (NTDs). Resources for control are inevitably limited, necessitating assessment methods that can rapidly and accurately identify and map high-risk communities so that interventions can be targeted in a spatially-explicit and cost-effective manner. Here, we review progress made with (i) mapping schistosomiasis across Africa using available epidemiological data and more recently, climate-based risk prediction; (ii) the development and use of morbidity questionnaires for rapid identification of high-risk communities of urinary schistosomiasis; and (iii) innovative sampling-based approaches for intestinal schistosomiasis, using the lot quality assurance sampling technique. Experiences are also presented for the rapid mapping of other NTDs, including onchocerciasis, loiasis and lymphatic filariasis. Future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool. The lessons from the mapping of human helminth infections may also be relevant for the rapid mapping of malaria as its control efforts are intensified. PMID:19450373

Single-Isocenter Multiple-Target Stereotactic Radiosurgery: Risk of Compromised Coverage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roper, Justin, E-mail: justin.roper@emory.edu; Department of Biostatistics and Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, Georgia; Chanyavanich, Vorakarn

2015-11-01

Purpose: To determine the dosimetric effects of rotational errors on target coverage using volumetric modulated arc therapy (VMAT) for multitarget stereotactic radiosurgery (SRS). Methods and Materials: This retrospective study included 50 SRS cases, each with 2 intracranial planning target volumes (PTVs). Both PTVs were planned for simultaneous treatment to 21 Gy using a single-isocenter, noncoplanar VMAT SRS technique. Rotational errors of 0.5°, 1.0°, and 2.0° were simulated about all axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using multivariate analysis to determine how PTV coverage was relatedmore » to PTV volume, PTV separation, and rotational error. Results: At 0.5° rotational error, D95 values and V95 coverage rates were ≥95% in all cases. For rotational errors of 1.0°, 7% of targets had D95 and V95 values <95%. Coverage worsened substantially when the rotational error increased to 2.0°: D95 and V95 values were >95% for only 63% of the targets. Multivariate analysis showed that PTV volume and distance to isocenter were strong predictors of target coverage. Conclusions: The effects of rotational errors on target coverage were studied across a broad range of SRS cases. In general, the risk of compromised coverage increased with decreasing target volume, increasing rotational error and increasing distance between targets. Multivariate regression models from this study may be used to quantify the dosimetric effects of rotational errors on target coverage given patient-specific input parameters of PTV volume and distance to isocenter.« less

Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system.

PubMed

Salmen, A; Gold, R; Chan, A

2014-05-01

The therapeutic armamentarium for autoimmune diseases of the central nervous system, specifically multiple sclerosis and neuromyelitis optica, is steadily increasing, with a large spectrum of immunomodulatory and immunosuppressive agents targeting different mechanisms of the immune system. However, increasingly efficacious treatment options also entail higher potential for severe adverse drug reactions. Especially in cases failing first-line treatment, thorough evaluation of the risk-benefit profile of treatment alternatives is necessary. This argues for the need of algorithms to identify patients more likely to benefit from a specific treatment. Moreover, paradigms to stratify the risk for severe adverse drug reactions need to be established. In addition to clinical/paraclinical measures, biomarkers may aid in individualized risk-benefit assessment. A recent example is the routine testing for anti-John Cunningham virus antibodies in natalizumab-treated multiple sclerosis patients to assess the risk for the development of progressive multi-focal leucoencephalopathy. Refined algorithms for individualized risk assessment may also facilitate early initiation of induction treatment schemes in patient groups with high disease activity rather than classical escalation concepts. In this review, we will discuss approaches for individiualized risk-benefit assessment both for newly introduced agents as well as medications with established side-effect profiles. In addition to clinical parameters, we will also focus on biomarkers that may assist in patient selection. © 2013 British Society for Immunology.

Physical victimization, gender identity and suicide risk among transgender men and women.

PubMed

Barboza, Gia Elise; Dominguez, Silvia; Chance, Elena

2016-12-01

We investigated whether being attacked physically due to one's gender identity or expression was associated with suicide risk among trans men and women living in Virginia. The sample consisted of 350 transgender men and women who participated in the Virginia Transgender Health Initiative Survey (THIS). Multivariate multinomial logistic regression was used to explore the competing outcomes associated with suicidal risk. Thirty-seven percent of trans men and women experienced at least one physical attack since the age of 13. On average, individuals experienced 3.97 (SD = 2.86) physical attacks; among these about half were attributed to one's gender identity or expression (mean = 2.08, SD = 1.96). In the multivariate multinomial regression, compared to those with no risk, being physically attacked increased the odds of both attempting and contemplating suicide regardless of gender attribution. Nevertheless, the relative impact of physical victimization on suicidal behavior was higher among those who were targeted on the basis of their gender identity or expression. Finally, no significant association was found between multiple measures of institutional discrimination and suicide risk once discriminatory and non-discriminatory physical victimization was taken into account. Trans men and women experience high levels of physical abuse and face multiple forms of discrimination. They are also at an increased risk for suicidal tendencies. Interventions that help transindividuals cope with discrimination and physical victimization simultaneously may be more effective in saving lives.

Integrating human impacts and ecological integrity into a risk-based protocol for conservation planning

USGS Publications Warehouse

Mattson, K.M.; Angermeier, P.L.

2007-01-01

Conservation planning aims to protect biodiversity by sustainng the natural physical, chemical, and biological processes within representative ecosystems. Often data to measure these components are inadequate or unavailable. The impact of human activities on ecosystem processes complicates integrity assessments and might alter ecosystem organization at multiple spatial scales. Freshwater conservation targets, such as populations and communities, are influenced by both intrinsic aquatic properties and the surrounding landscape, and locally collected data might not accurately reflect potential impacts. We suggest that changes in five major biotic drivers-energy sources, physical habitat, flow regime, water quality, and biotic interactions-might be used as surrogates to inform conservation planners of the ecological integrity of freshwater ecosystems. Threats to freshwater systems might be evaluated based on their impact to these drivers to provide an overview of potential risk to conservation targets. We developed a risk-based protocol, the Ecological Risk Index (ERI), to identify watersheds with least/most risk to conservation targets. Our protocol combines risk-based components, specifically the frequency and severity of human-induced stressors, with biotic drivers and mappable land- and water-use data to provide a summary of relative risk to watersheds. We illustrate application of our protocol with a case study of the upper Tennessee River basin, USA. Differences in risk patterns among the major drainages in the basin reflect dominant land uses, such as mining and agriculture. A principal components analysis showed that localized, moderately severe threats accounted for most of the threat composition differences among our watersheds. We also found that the relative importance of threats is sensitive to the spatial grain of the analysis. Our case study demonstrates that the ERI is useful for evaluating the frequency and severity of ecosystemwide risk, which can inform local and regional conservation planning. ?? 2006 Springer Science+Business Media, Inc.

A Changing Landscape for Vitamin A Programs: Implications for Optimal Intervention Packages, Program Monitoring, and Safety.

PubMed

Klemm, Rolf D W; Palmer, Amanda C; Greig, Alison; Engle-Stone, Reina; Dalmiya, Nita

2016-06-01

Vitamin A deficiency (VAD) remains a widespread public health problem in the developing world, despite changes in under-5 mortality rates, morbidity patterns, and intervention options. This article considers the implications of a changing epidemiologic and programmatic landscape for vitamin A (VA) programs. We review progress to prevent VAD and its health consequences, assess gaps in VA status and intervention coverage data, and assess data needed to guide decisions regarding the optimal mix, targeting, and dose of VA interventions to maximize benefit and minimize risk. Vitamin A supplementation programs have contributed to the reduction in under-5 mortality rates, but alone, do not address the underlying problem of inadequate dietary VA intakes and VAD among preschool-aged children in the developing world. A combination of VA interventions (eg, supplementation, fortified foods, multiple micronutrient powders, and lipid-based nutrient supplements) will be required to achieve VA adequacy in most settings. Current efforts to measure the coverage of multiple VA interventions, as well as whether and how much VA children are receiving, are few and fragmented. Where intervention overlap exists, further effort is needed to monitor VA intakes, ensuring that targeted groups are consuming adequate amounts but not exceeding the tolerable upper intake level. Vitamin A status data will also be critical for navigating the changing landscape of VA programs. Data from these monitoring efforts will help to guide decisions on the optimal mix, targeting, and exposure to VA interventions to maximize public health benefit while minimizing any potential risk. © The Author(s) 2016.

Diagnostic and psychosocial differences in psychiatrically hospitalized military service members with single versus multiple suicide attempts.

PubMed

Kochanski-Ruscio, Kristen M; Carreno-Ponce, Jaime T; DeYoung, Kathryn; Grammer, Geoffrey; Ghahramanlou-Holloway, Marjan

2014-04-01

Individuals with multiple versus single suicide attempts present a more severe clinical picture and may be at greater risk for suicide. Yet group differences within military samples have been vastly understudied. The objective is to determine demographic, diagnostic, and psychosocial differences, based on suicide attempt status, among military inpatients admitted for suicide-related events. A retrospective chart review design was used with a total of 423 randomly selected medical records of psychiatric admissions to a military hospital from 2001 to 2006. Chi-square analyses indicated that individuals with multiple versus single suicide attempts were significantly more likely to have documented childhood sexual abuse (p =.025); problem substance use (p=.001); mood disorder diagnosis (p=.005); substance disorder diagnosis (p =.050); personality disorder not otherwise specified diagnosis (p =.018); and Axis II traits or diagnosis (p=.038) when compared to those with a single attempt history. Logistic regression analyses showed that males with multiple suicide attempts were more likely to have problem substance use (p=.005) and a mood disorder diagnosis (p =.002), while females with a multiple attempt history were more likely to have a history of childhood sexual (p =.027). Clinically meaningful differences among military inpatients with single versus multiple suicide attempts exist. Targeted Department of Defense suicide prevention and intervention efforts that address the unique needs of these two specific at-risk subgroups are additionally needed. Published by Elsevier Inc.

Communication strategies to address geohydrological risks: the POLARIS web initiative in Italy

NASA Astrophysics Data System (ADS)

Salvati, Paola; Pernice, Umberto; Bianchi, Cinzia; Marchesini, Ivan; Fiorucci, Federica; Guzzetti, Fausto

2016-06-01

Floods and landslides are common phenomena that cause serious damage and pose a severe threat to the population of Italy. The social and economic impact of floods and landslides in Italy is severe, and strategies to target the mitigation of the effects of these phenomena are needed. In the last few years, the scientific community has started to use web technology to communicate information on geohydrological hazards and the associated risks. However, the communication is often targeted at technical experts. In the attempt to communicate relevant information on geohydrological hazards with potential human consequences to a broader audience, we designed the POpoLazione A RISchio (POLARIS) website. POLARIS publishes accurate information on geohydrological risk to the population of Italy, including periodic reports on landslide and flood risk, analyses of specific damaging events and blog posts on landslide and flood events. By monitoring the access to POLARIS in the 21-month period between January 2014 and October 2015, we found that access increased during particularly damaging geohydrological events and immediately after the website was advertised by press releases. POLARIS demonstrates that the scientific community can implement suitable communication strategies that address different societal audiences, exploiting the role of mass media and social media. The strategies can help multiple audiences understand how risks can be reduced through appropriate measures and behaviours, contributing to increasing the resilience of the population to geohydrological risk.

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.

PubMed

Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W; Gretarsdottir, Solveig; Anderson, Christopher D; Chong, Michael; Adams, Hieab H H; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M; Benavente, Oscar R; Bevan, Steve; Boncoraglio, Giorgio B; Brown, Robert D; Butterworth, Adam S; Carrera, Caty; Carty, Cara L; Chasman, Daniel I; Chen, Wei-Min; Cole, John W; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I W; DeStefano, Anita L; den Hoed, Marcel; Duan, Qing; Engelter, Stefan T; Falcone, Guido J; Gottesman, Rebecca F; Grewal, Raji P; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B; Hassan, Ahamad; Havulinna, Aki S; Heckbert, Susan R; Holliday, Elizabeth G; Howard, George; Hsu, Fang-Chi; Hyacinth, Hyacinth I; Ikram, M Arfan; Ingelsson, Erik; Irvin, Marguerite R; Jian, Xueqiu; Jiménez-Conde, Jordi; Johnson, Julie A; Jukema, J Wouter; Kanai, Masahiro; Keene, Keith L; Kissela, Brett M; Kleindorfer, Dawn O; Kooperberg, Charles; Kubo, Michiaki; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lee, Jin-Moo; Lemmens, Robin; Leys, Didier; Lewis, Cathryn M; Lin, Wei-Yu; Lindgren, Arne G; Lorentzen, Erik; Magnusson, Patrik K; Maguire, Jane; Manichaikul, Ani; McArdle, Patrick F; Meschia, James F; Mitchell, Braxton D; Mosley, Thomas H; Nalls, Michael A; Ninomiya, Toshiharu; O'Donnell, Martin J; Psaty, Bruce M; Pulit, Sara L; Rannikmäe, Kristiina; Reiner, Alexander P; Rexrode, Kathryn M; Rice, Kenneth; Rich, Stephen S; Ridker, Paul M; Rost, Natalia S; Rothwell, Peter M; Rotter, Jerome I; Rundek, Tatjana; Sacco, Ralph L; Sakaue, Saori; Sale, Michele M; Salomaa, Veikko; Sapkota, Bishwa R; Schmidt, Reinhold; Schmidt, Carsten O; Schminke, Ulf; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L M; Tanislav, Christian; Tatlisumak, Turgut; Taylor, Kent D; Thijs, Vincent N S; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiedt, Steffen; Trompet, Stella; Tzourio, Christophe; van Duijn, Cornelia M; Walters, Matthew; Wareham, Nicholas J; Wassertheil-Smoller, Sylvia; Wilson, James G; Wiggins, Kerri L; Yang, Qiong; Yusuf, Salim; Bis, Joshua C; Pastinen, Tomi; Ruusalepp, Arno; Schadt, Eric E; Koplev, Simon; Björkegren, Johan L M; Codoni, Veronica; Civelek, Mete; Smith, Nicholas L; Trégouët, David A; Christophersen, Ingrid E; Roselli, Carolina; Lubitz, Steven A; Ellinor, Patrick T; Tai, E Shyong; Kooner, Jaspal S; Kato, Norihiro; He, Jiang; van der Harst, Pim; Elliott, Paul; Chambers, John C; Takeuchi, Fumihiko; Johnson, Andrew D; Sanghera, Dharambir K; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W T; Rolfs, Arndt; Hata, Jun; Woo, Daniel; Rosand, Jonathan; Pare, Guillaume; Hopewell, Jemma C; Saleheen, Danish; Stefansson, Kari; Worrall, Bradford B; Kittner, Steven J; Seshadri, Sudha; Fornage, Myriam; Markus, Hugh S; Howson, Joanna M M; Kamatani, Yoichiro; Debette, Stephanie; Dichgans, Martin; Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W; Gretarsdottir, Solveig; Anderson, Christopher D; Chong, Michael; Adams, Hieab H H; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M; Benavente, Oscar R; Bevan, Steve; Boncoraglio, Giorgio B; Brown, Robert D; Butterworth, Adam S; Carrera, Caty; Carty, Cara L; Chasman, Daniel I; Chen, Wei-Min; Cole, John W; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I W; DeStefano, Anita L; Hoed, Marcel den; Duan, Qing; Engelter, Stefan T; Falcone, Guido J; Gottesman, Rebecca F; Grewal, Raji P; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B; Hassan, Ahamad; Havulinna, Aki S; Heckbert, Susan R; Holliday, Elizabeth G; Howard, George; Hsu, Fang-Chi; Hyacinth, Hyacinth I; Ikram, M Arfan; Ingelsson, Erik; Irvin, Marguerite R; Jian, Xueqiu; Jiménez-Conde, Jordi; Johnson, Julie A; Jukema, J Wouter; Kanai, Masahiro; Keene, Keith L; Kissela, Brett M; Kleindorfer, Dawn O; Kooperberg, Charles; Kubo, Michiaki; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lee, Jin-Moo; Lemmens, Robin; Leys, Didier; Lewis, Cathryn M; Lin, Wei-Yu; Lindgren, Arne G; Lorentzen, Erik; Magnusson, Patrik K; Maguire, Jane; Manichaikul, Ani; McArdle, Patrick F; Meschia, James F; Mitchell, Braxton D; Mosley, Thomas H; Nalls, Michael A; Ninomiya, Toshiharu; O'Donnell, Martin J; Psaty, Bruce M; Pulit, Sara L; Rannikmäe, Kristiina; Reiner, Alexander P; Rexrode, Kathryn M; Rice, Kenneth; Rich, Stephen S; Ridker, Paul M; Rost, Natalia S; Rothwell, Peter M; Rotter, Jerome I; Rundek, Tatjana; Sacco, Ralph L; Sakaue, Saori; Sale, Michele M; Salomaa, Veikko; Sapkota, Bishwa R; Schmidt, Reinhold; Schmidt, Carsten O; Schminke, Ulf; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L M; Tanislav, Christian; Tatlisumak, Turgut; Taylor, Kent D; Thijs, Vincent N S; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiedt, Steffen; Trompet, Stella; Tzourio, Christophe; van Duijn, Cornelia M; Walters, Matthew; Wareham, Nicholas J; Wassertheil-Smoller, Sylvia; Wilson, James G; Wiggins, Kerri L; Yang, Qiong; Yusuf, Salim; Amin, Najaf; Aparicio, Hugo S; Arnett, Donna K; Attia, John; Beiser, Alexa S; Berr, Claudine; Buring, Julie E; Bustamante, Mariana; Caso, Valeria; Cheng, Yu-Ching; Choi, Seung Hoan; Chowhan, Ayesha; Cullell, Natalia; Dartigues, Jean-François; Delavaran, Hossein; Delgado, Pilar; Dörr, Marcus; Engström, Gunnar; Ford, Ian; Gurpreet, Wander S; Hamsten, Anders; Heitsch, Laura; Hozawa, Atsushi; Ibanez, Laura; Ilinca, Andreea; Ingelsson, Martin; Iwasaki, Motoki; Jackson, Rebecca D; Jood, Katarina; Jousilahti, Pekka; Kaffashian, Sara; Kalra, Lalit; Kamouchi, Masahiro; Kitazono, Takanari; Kjartansson, Olafur; Kloss, Manja; Koudstaal, Peter J; Krupinski, Jerzy; Labovitz, Daniel L; Laurie, Cathy C; Levi, Christopher R; Li, Linxin; Lind, Lars; Lindgren, Cecilia M; Lioutas, Vasileios; Liu, Yong Mei; Lopez, Oscar L; Makoto, Hirata; Martinez-Majander, Nicolas; Matsuda, Koichi; Minegishi, Naoko; Montaner, Joan; Morris, Andrew P; Muiño, Elena; Müller-Nurasyid, Martina; Norrving, Bo; Ogishima, Soichi; Parati, Eugenio A; Peddareddygari, Leema Reddy; Pedersen, Nancy L; Pera, Joanna; Perola, Markus; Pezzini, Alessandro; Pileggi, Silvana; Rabionet, Raquel; Riba-Llena, Iolanda; Ribasés, Marta; Romero, Jose R; Roquer, Jaume; Rudd, Anthony G; Sarin, Antti-Pekka; Sarju, Ralhan; Sarnowski, Chloe; Sasaki, Makoto; Satizabal, Claudia L; Satoh, Mamoru; Sattar, Naveed; Sawada, Norie; Sibolt, Gerli; Sigurdsson, Ásgeir; Smith, Albert; Sobue, Kenji; Soriano-Tárraga, Carolina; Stanne, Tara; Stine, O Colin; Stott, David J; Strauch, Konstantin; Takai, Takako; Tanaka, Hideo; Tanno, Kozo; Teumer, Alexander; Tomppo, Liisa; Torres-Aguila, Nuria P; Touze, Emmanuel; Tsugane, Shoichiro; Uitterlinden, Andre G; Valdimarsson, Einar M; van der Lee, Sven J; Völzke, Henry; Wakai, Kenji; Weir, David; Williams, Stephen R; Wolfe, Charles D A; Wong, Quenna; Xu, Huichun; Yamaji, Taiki; Sanghera, Dharambir K; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W T; Rolfs, Arndt; Hata, Jun; Woo, Daniel; Rosand, Jonathan; Pare, Guillaume; Hopewell, Jemma C; Saleheen, Danish; Stefansson, Kari; Worrall, Bradford B; Kittner, Steven J; Seshadri, Sudha; Fornage, Myriam; Markus, Hugh S; Howson, Joanna M M; Kamatani, Yoichiro; Debette, Stephanie; Dichgans, Martin

2018-04-01

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

PubMed Central

Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W.; Gretarsdottir, Solveig; Anderson, Christopher D.; Chong, Michael; Adams, Hieab H. H.; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M.; Benavente, Oscar R.; Bevan, Steve; Boncoraglio, Giorgio B.; Brown, Robert D.; Butterworth, Adam S.; Carrera, Caty; Carty, Cara L.; Chasman, Daniel I.; Chen, Wei-Min; Cole, John W.; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I. W.; DeStefano, Anita L.; den Hoed, Marcel; Duan, Qing; Engelter, Stefan T.; Falcone, Guido J.; Gottesman, Rebecca F.; Grewal, Raji P.; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B.; Hassan, Ahamad; Havulinna, Aki S.; Heckbert, Susan R.; Holliday, Elizabeth G.; Howard, George; Hsu, Fang-Chi; Hyacinth, Hyacinth I.; Ikram, M. Arfan; ingelsson, Erik; Irvin, Marguerite R.; Jian, Xueqiu; Jimenez-Conde, Jordi; Johnson, Julie A.; Jukema, J. Wouter; Kanai, Masahiro; Keene, Keith L.; Kissela, Brett M.; Kleindorfer, Dawn O.; Kooperberg, Charles; Kubo, Michiaki; Lange, Leslie A.; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lee, Jin-Moo; Lemmens, Robin; Leys, Didier; Lewis, Cathryn M.; Lin, Wei-Yu; Lindgren, Arne G.; Lorentzen, Erik; Magnusson, Patrik K.; Maguire, Jane; Manichaikul, Ani; McArdle, Patrick F.; Meschia, James F.; Mitchell, Braxton D.; Mosley, Thomas H.; Nalls, Michael A.; Ninomiya, Toshiharu; O’Donnell, Martin J.; Psaty, Bruce M.; Pulit, Sara L.; Rannikmäe, Kristiina; Reiner, Alexander P.; Rexrode, Kathryn M.; Rice, Kenneth; Rich, Stephen S.; Ridker, Paul M.; Rost, Natalia S.; Rothwell, Peter M.; Rotter, Jerome I.; Rundek, Tatjana; Sacco, Ralph L.; Sakaue, Saori; Sale, Michele M.; Salomaa, Veikko; Sapkota, Bishwa R.; Schmidt, Reinhold; Schmidt, Carsten O.; Schminke, Ulf; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L. M.; Tanislav, Christian; Tatlisumak, Turgut; Taylor, Kent D.; Thijs, Vincent N. S.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiedt, Steffen; Trompet, Stella; Tzourio, Christophe; van Duijn, Cornelia M.; Walters, Matthew; Wareham, Nicholas J.; Wassertheil-Smoller, Sylvia; Wilson, James G.; Wiggins, Kerri L.; Yang, Qiong; Yusuf, Salim; Bis, Joshua C.; Pastinen, Tomi; Ruusalepp, Arno; Schadt, Eric E.; Koplev, Simon; Björkegren, Johan L. M.; Codoni, Veronica; Civelek, Mete; Smith, Nicholas L.; Tregouet, David A.; Christophersen, Ingrid E.; Roselli, Carolina; Lubitz, Steven A.; Ellinor, Patrick T.; Tai, E. Shyong; Kooner, Jaspal S.; Kato, Norihiro; He, Jiang; van der Harst, Pim; Elliott, Paul; Chambers, John C.; Takeuchi, Fumihiko; Johnson, Andrew D.; Sanghera, Dharambir K.; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W. T.; Rolfs, Arndt; Hata, Jun; Woo, Daniel; Rosand, Jonathan; Pare, Guillaume; Hopewell, Jemma C.; Saleheen, Danish; Stefansson, Kari; Worrall, Bradford B.; Kittner, Steven J.; Seshadri, Sudha; Fornage, Myriam; Markus, Hugh S.; Howson, Joanna M. M.; Kamatani, Yoichiro; Debette, Stephanie; Dichgans, Martin

2018-01-01

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy. PMID:29531354

Does natalizumab treatment increase the risk of herpes simplex encephalitis in multiple sclerosis? Case and discussion.

PubMed

Sharma, Kanchan; Ballham, Samantha A; Inglis, Kirsty E A; Renowden, Shelley; Cottrell, David A

2013-10-01

This report presents the 4th documented case worldwide of herpes simplex encephalitis in multiple sclerosis (MS) patients treated with natalizumab and the first case in the UK. Natalizumab is licensed for relapsing remitting multiple sclerosis in patients with high disease activity despite treatment with interferon-beta and patients with rapidly evolving severe, multiple sclerosis. Natalizumab is a monoclonal antibody targeted against alpha-4 integrin. Its proposed mechanism is attenuation of the migration of immune cells into the central nervous system. Reactivation of the JC virus causing progressive multifocal leucoencephalopathy (PML) and its association with natalizumab is well documented. This case adds support to the suggestion that natalizumab also increases the reactivation risk of CNS herpes simplex infection. A 34 year old woman was admitted with a generalized tonic-clonic seizure, fever and confusion following her 40th infusion of natalizumab. MRI demonstrated increased signal in the medial temporal lobes and EEG showed focal sharp waves over the temporal lobe. CSF PCR later confirmed herpes simplex virus. The patient made an eventual excellent recovery following 21 days of intravenous acyclovir therapy followed by 14 days of oral treatment. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Screening tools to identify patients with complex health needs at risk of high use of health care services: A scoping review.

PubMed

Marcoux, Valérie; Chouinard, Maud-Christine; Diadiou, Fatoumata; Dufour, Isabelle; Hudon, Catherine

2017-01-01

Many people with chronic conditions have complex health needs often due to multiple chronic conditions, psychiatric comorbidities, psychosocial issues, or a combination of these factors. They are at high risk of frequent use of healthcare services. To offer these patients interventions adapted to their needs, it is crucial to be able to identify them early. The aim of this study was to find all existing screening tools that identify patients with complex health needs at risk of frequent use of healthcare services, and to highlight their principal characteristics. Our purpose was to find a short, valid screening tool to identify adult patients of all ages. A scoping review was performed on articles published between 1985 and July 2016, retrieved through a comprehensive search of the Scopus and CINAHL databases, following the methodological framework developed by Arksey and O'Malley (2005), and completed by Levac et al. (2010). Of the 3,818 articles identified, 30 were included, presenting 14 different screening tools. Seven tools were self-reported. Five targeted adult patients, and nine geriatric patients. Two tools were designed for specific populations. Four can be completed in 15 minutes or less. Most screening tools target elderly persons. The INTERMED self-assessment (IM-SA) targets adults of all ages and can be completed in less than 15 minutes. Future research could evaluate its usefulness as a screening tool for identifying patients with complex needs at risk of becoming high users of healthcare services.

A framework for spatial risk assessments: Potential impacts of nonindigenous invasive species on native species

USGS Publications Warehouse

Allen, Craig R.; Johnson, A.R.; Parris, L.

2006-01-01

Many populations of wild animals and plants are declining and face increasing threats from habitat fragmentation and loss as well as exposure to stressors ranging from toxicants to diseases to invasive nonindigenous species. We describe and demonstrate a spatially explicit ecological risk assessment that allows for the incorporation of a broad array of information that may influence the distribution of an invasive species, toxicants, or other stressors, and the incorporation of landscape variables that may influence the spread of a species or substances. The first step in our analyses is to develop species models and quantify spatial overlap between stressor and target organisms. Risk is assessed as the product of spatial overlap and a hazard index based on target species vulnerabilities to the stressor of interest. We illustrate our methods with an example in which the stressor is the ecologically destructive nonindigenous ant, Solenopsis invicta, and the targets are two declining vertebrate species in the state of South Carolina, USA. A risk approach that focuses on landscapes and that is explicitly spatial is of particular relevance as remaining undeveloped lands become increasingly uncommon and isolated and more important in the management and recovery of species and ecological systems. Effective ecosystem management includes the control of multiple stressors, including invasive species with large impacts, understanding where those impacts may be the most severe, and implementing management strategies to reduce impacts. Copyright ?? 2006 by the author(s).

The validation index: a new metric for validation of segmentation algorithms using two or more expert outlines with application to radiotherapy planning.

PubMed

Juneja, Prabhjot; Evans, Philp M; Harris, Emma J

2013-08-01

Validation is required to ensure automated segmentation algorithms are suitable for radiotherapy target definition. In the absence of true segmentation, algorithmic segmentation is validated against expert outlining of the region of interest. Multiple experts are used to overcome inter-expert variability. Several approaches have been studied in the literature, but the most appropriate approach to combine the information from multiple expert outlines, to give a single metric for validation, is unclear. None consider a metric that can be tailored to case-specific requirements in radiotherapy planning. Validation index (VI), a new validation metric which uses experts' level of agreement was developed. A control parameter was introduced for the validation of segmentations required for different radiotherapy scenarios: for targets close to organs-at-risk and for difficult to discern targets, where large variation between experts is expected. VI was evaluated using two simulated idealized cases and data from two clinical studies. VI was compared with the commonly used Dice similarity coefficient (DSCpair - wise) and found to be more sensitive than the DSCpair - wise to the changes in agreement between experts. VI was shown to be adaptable to specific radiotherapy planning scenarios.

Proteomic characterization of Withaferin A-targeted protein networks for the treatment of monoclonal myeloma gammopathies.

PubMed

Dom, Martin; Offner, Fritz; Vanden Berghe, Wim; Van Ostade, Xaveer

2018-05-15

Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM). By blocking the PSMB10 proteasome subunit, downregulation of ANXA4, potential association with HDAC6 and upregulation of HMOX1, WA puts a massive blockage on both proteotoxic and oxidative stress responses pathways, leaving cancer cells defenseless against WA induced stresses. These results indicate that WA mediated apoptosis is preceded by simultaneous targeting of cellular stress response pathways like proteasome degradation, autophagy and unfolded protein stress response and thus suggests that WA can be used as an effective treatment for MGUS and other closely related disorders. Multifunctional antitumor compounds are of great potential since they reduce the risk of multidrug resistance in chemotherapy. Unfortunately, characterization of all protein targets of a multifunctional compound is lacking. Therefore, we optimized an SILAC quantitative chemoproteomics workflow to identify the potential protein targets of Withaferin A (WA), a natural multifunctional compound with promising antitumor properties. To further understand the antitumor mechanisms of WA, we performed a differential protein expression analysis and combined the altered expression data with chemoproteome WA target data in the highly curated Ingenuity Pathway database. We provide a first global overview on how WA kills multiple myeloma cancer cells and serve as a starting point for further in depth experiments. Furthermore, the combined approach can be used for other types of cancer and/or other promising multifunctional compounds, thereby increasing the potential development of new antitumor therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Osteo-cise: Strong Bones for Life: Protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures

PubMed Central

2012-01-01

Background Osteoporosis affects over 220 million people worldwide, and currently there is no ‘cure’ for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition. Methods/design The Osteo-cise: Strong Bones for Life study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged ≥60 years will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month ‘research to practise’ translational phase. Participants will be randomly assigned to either the Osteo-cise intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed. Discussion The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture. Trial registration Australian New Zealand Clinical Trials Registry reference ACTRN12609000100291 PMID:22640372

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

PubMed Central

Ruderfer, Douglas M; Charney, Alexander W; Readhead, Ben; Kidd, Brian A; Kähler, Anna K; Kenny, Paul J; Keiser, Michael J; Moran, Jennifer L; Hultman, Christina M; Scott, Stuart A; Sullivan, Patrick F; Purcell, Shaun M; Dudley, Joel T; Sklar, Pamela

2016-01-01

Summary Background Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia. Methods We defined schizophrenia risk loci as genomic regions reaching genome-wide significance in the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study (GWAS) of 36 989 cases and 113 075 controls and loss of function variants observed only once among 5079 individuals in an exome-sequencing study of 2536 schizophrenia cases and 2543 controls (Swedish Schizophrenia Study). Using two large and orthogonally created databases, we collated drug targets into 167 gene sets targeted by pharmacologically similar drugs and examined enrichment of schizophrenia risk loci in these sets. We further linked the exome-sequenced data with a national drug registry (the Swedish Prescribed Drug Register) to assess the contribution of rare variants to treatment response, using clozapine prescription as a proxy for treatment resistance. Findings We combined results from testing rare and common variation and, after correction for multiple testing, two gene sets were associated with schizophrenia risk: agents against amoebiasis and other protozoal diseases (106 genes, p=0·00046, pcorrected =0·024) and antipsychotics (347 genes, p=0·00078, pcorrected=0·046). Further analysis pointed to antipsychotics as having independent enrichment after removing genes that overlapped these two target sets. We noted significant enrichment both in known targets of antipsychotics (70 genes, p=0·0078) and novel predicted targets (277 genes, p=0·019). Patients with treatment-resistant schizophrenia had an excess of rare disruptive variants in gene targets of antipsychotics (347 genes, p=0·0067) and in genes with evidence for a role in antipsychotic efficacy (91 genes, p=0·0029). Interpretation Our results support genetic overlap between schizophrenia pathogenesis and antipsychotic mechanism of action. This finding is consistent with treatment efficacy being polygenic and suggests that single-target therapeutics might be insufficient. We provide evidence of a role for rare functional variants in antipsychotic treatment response, pointing to a subset of patients where their genetic information could inform treatment. Finally, we present a novel framework for identifying treatments from genetic data and improving our understanding of therapeutic mechanism. PMID:26915512

The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression

PubMed Central

2011-01-01

Background Infection with high-risk human papillomaviruses (HPVs) such as HPV-16 is intimately associated with squamous cell carcinomas (SCCs) of the anogenital tract and a subset of oropharyngeal carcinomas. Such lesions, including pre-invasive precursors, frequently show multipolar mitoses and aneuploidy. The high-risk HPV-16-encoded E7 oncoprotein has been shown to rapidly induce centrosome abnormalities thereby causing the formation of supernumerary mitotic spindle poles and increasing the risk for chromosome missegregation. HPV-16 E7 has been found to rapidly induce centriole overduplication, in part, through the simultaneous formation of more than one daughter centriole at single maternal centrioles (centriole multiplication). The precise molecular mechanism that underlies HPV-16 E7-induced centriole multiplication, however, remains poorly understood. Findings Here, we show that human keratinocytes engineered to stably express the HPV-16 E7 oncoprotein exhibit aberrant Polo-like kinase 4 (PLK4) protein expression at maternal centrioles. Real-time quantitative reverse transcriptase (qRT-PCR) analysis of these cells revealed an increase of PLK4 mRNA levels compared to control cells. Importantly, the ability of the HPV-16 E7 oncoprotein to induce centriole multiplication was found to correlate with its ability to activate the PLK4 promoter and to up-regulate PLK4 mRNA. Conclusions These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. Our findings encourage further experiments to test transcriptional inhibitors or small molecules targeting PLK4 to prevent centriole abnormalities, mitotic infidelity and malignant progression in HPV-associated neoplasms and other tumors in which PLK4 regulation is disrupted. PMID:21609466

The genetics of celiac disease: A comprehensive review of clinical implications.

PubMed

Dieli-Crimi, Romina; Cénit, M Carmen; Núñez, Concepción

2015-11-01

Celiac disease (CD) is a complex immune-related disease with a very strong genetic component. Multiple genetic findings over the last decade have added to the already known MHC influence numerous genetic variants associated to CD susceptibility. Currently, it is well-established that 6 MHC and 39 non-MHC loci, including a higher number of independent genetic variants, are associated to disease risk. Moreover, additional regions have been recently implicated in the disease, which would increase the number of involved loci. Together, the firmly described genetic variants account for roughly 31% of CD heritability, being 25% explained by the MHC influence. These new variants represent markers of disease risk and turn the identification of the causal genes and the causal variants inside the associated loci, as well as their precise biological role on the disease, into a major challenge in CD research. Numerous studies have been developed with this aim showing the high impact of risk variants on gene expression. These studies also indicate a central role of CD4(+) T cells in CD pathogenesis and point to B cells as important players, which is in accordance with the key steps highlighted by the immunological models of pathogenesis. We comprehensively summarize the current knowledge about the genetic architecture of CD, characterized by multiple low-risk variants located within diverse loci which are most likely affecting genes with immune-related functions. These findings are leading to a better understanding of CD pathogenesis and helping in the design of new treatments. The repertoire of potential drug targets for CD has largely broadened last years, bringing us closer to get alternative or complementary treatments to the life-long gluten-free diet, the only effective treatment so far. Epigenetics and microbiota are emerging as potent factors modulating disease risk and putatively affecting disease manifestation, which are also being explored as therapeutic targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Families at risk of poor parenting: a model for service delivery, assessment, and intervention.

PubMed

Ayoub, C; Jacewitz, M M

1982-01-01

The At Risk Parent Child Program is a multidisciplinary network agency designed for the secondary prevention of poor parenting and the extremes of child abuse and neglect. This model system of service delivery emphasizes (1) the coordination of existing community resources to access a target population of families at risk of parenting problems, (2) the provision of multiple special services in a neutral location (ambulatory pediatric clinic), and (3) the importance of intensive individual contact with a clinical professional who serves as primary therapist, social advocate and service coordinator for client families. Identification and assessment of families is best done during prenatal and perinatal periods. Both formal and informal procedures for screening for risk factors are described, and a simple set of at risk criteria for use by hospital nursing staff is provided. Preventive intervention strategies include special medical, psychological, social and developmental services, offered in an inpatient; outpatient, or in-home setting. Matching family needs to modality and setting of treatment is a major program concern. All direct services to at risk families are supplied by professionals employed within existing local agencies (hospital, public health department, state guidance center, and medical school pediatric clinic). Multiple agency involvement allows a broad-based screening capacity which allows thousands of families routine access to program services. The administrative center of the network stands as an independent, community-funded core which coordinates and monitors direct clinical services, and provides local political advocacy for families at risk of parenting problems.

Potential Impact of miR-137 and Its Targets in Schizophrenia

PubMed Central

Wright, Carrie; Turner, Jessica A.; Calhoun, Vince D.; Perrone-Bizzozero, Nora

2013-01-01

The significant impact of microRNAs (miRNAs) on disease pathology is becoming increasingly evident. These small non-coding RNAs have the ability to post-transcriptionally silence the expression of thousands of genes. Therefore, dysregulation of even a single miRNA could confer a large polygenic effect. Schizophrenia is a genetically complex illness thought to involve multiple genes each contributing a small risk. Large genome-wide association studies identified miR-137, a miRNA shown to be involved in neuronal maturation, as one of the top risk genes. To assess the potential mechanism of impact of miR-137 in this disorder and identify its targets, we used a combination of literature searches, ingenuity pathway analysis (IPA), and freely accessible bioinformatics resources. Using TargetScan and the schizophrenia gene resource (SZGR) database, we found that in addition to CSMD1, C10orf26, CACNA1C, TCF4, and ZNF804A, five schizophrenia risk genes whose transcripts are also validated miR-137 targets, there are other schizophrenia-associated genes that may be targets of miR-137, including ERBB4, GABRA1, GRIN2A, GRM5, GSK3B, NRG2, and HTR2C. IPA analyses of all the potential targets identified several nervous system (NS) functions as the top canonical pathways including synaptic long-term potentiation, a process implicated in learning and memory mechanisms and recently shown to be altered in patients with schizophrenia. Among the subset of targets involved in NS development and function, the top scoring pathways were ephrin receptor signaling and axonal guidance, processes that are critical for proper circuitry formation and were shown to be disrupted in schizophrenia. These results suggest that miR-137 may indeed play a substantial role in the genetic etiology of schizophrenia by regulating networks involved in neural development and brain function. PMID:23637704

Multiplicity distributions of shower particles and target fragments in 84 Kr 36-emulsion interactions at 1 GeV per nucleon

NASA Astrophysics Data System (ADS)

Singh, M. K.; Soma, A. K.; Pathak, Ramji; Singh, V.

2014-03-01

This article focuses on multiplicity distributions of shower particles and target fragments for interaction of 84 Kr 36 with NIKFI BR-2 nuclear emulsion target at kinetic energy of 1 GeV per nucleon. Experimental multiplicity distributions of shower particles, grey particles, black particles and heavily ionization particles are well described by multi-component Erlang distribution of multi-source thermal model. We have observed a linear correlation in multiplicities for the above mentioned particles or fragments. Further experimental studies have shown a saturation phenomenon in shower particle multiplicity with the increase of target fragment multiplicity.

The Virtual Space Telescope: A New Class of Science Missions

NASA Technical Reports Server (NTRS)

Shah, Neerav; Calhoun, Philip

2016-01-01

Many science investigations proposed by GSFC require two spacecraft alignment across a long distance to form a virtual space telescope. Forming a Virtual Space telescope requires advances in Guidance, Navigation, and Control (GNC) enabling the distribution of monolithic telescopes across multiple space platforms. The capability to align multiple spacecraft to an intertial target is at a low maturity state and we present a roadmap to advance the system-level capability to be flight ready in preparation of various science applications. An engineering proof of concept, called the CANYVAL-X CubeSat MIssion is presented. CANYVAL-X's advancement will decrease risk for a potential starshade mission that would fly with WFIRST.

Parents with mental health problems and their children in a German population based sample: Results of the BELLA study

PubMed Central

Otto, Christiane; Barkmann, Claus; Wiegand-Grefe, Silke; Hölling, Heike; Schulte-Markwort, Michael; Ravens-Sieberer, Ulrike; Klasen, Fionna

2017-01-01

Background Mental health problems (MHP) of parents are associated with an increased risk of psychological and developmental difficulties in their children. This study aims at analyzing population-based data of parents with MHP and their children and the effects of associated risk factors in order to further targeted preventive and therapeutic interventions. Methods The BELLA study is the mental health module of the German National Health Interview and Examination Survey among Children and Adolescents. MHP in parents and in their children as well as associated risk factors were examined in a sample of N = 1158 parents with children aged 11 to 17 years. Results Parental MHP were identified in 18.6% of the sample. Risk factors associated with parental MHP were low SES, parental unemployment, stressful life events, parental daily strain, parental chronic disease, and child MHP. A rate of 19.1% of the children of parents with MHP reported MHP themselves, the corresponding rate among children of parents without MHP was 7.7%. In multiple regression analyses the risk for children of parents with MHP to report MHP themselves was almost two times higher than the risk of children of parents without MHP. Other significant associations with child MHP included gender, the parents’ age, and stressful life events. Conclusions Parental MHP constitute a significant risk for the mental health of their children. Targeted screening methods and preventive interventions are needed. PMID:28671981

Reducing stroke in women with risk factor management: blood pressure and cholesterol.

PubMed

Baghshomali, Sanam; Bushnell, Cheryl

2014-09-01

Stroke is a major cause of death and disability in adults worldwide. Prevention focused on modifiable risk factors, such as hypertension and hyperlipidemia, has shown them to be of significant importance in decreasing the risk of stroke. Multiple studies have brought to light the differences between men and women with regards to stroke and these risk factors. Women have a higher prevalence of stroke, mortality and disability and it has been shown that preventive and treatment options are not as comprehensive for women. Hence, it is of great necessity to evaluate and summarize the differences in gender and stroke risk factors in order to target disparities and optimize prevention, especially because women have a higher lifetime risk of stroke. The purpose of this review is to summarize sex differences in the prevalence of hypertension and hyperlipidemia. In addition, we will review the sex differences in stroke prevention effectiveness and adherence to blood pressure and cholesterol medications, and suggest future directions for research to reduce the burden of stroke in women.

The Availability and Utility of Services to Address Risk Factors for Recidivism among Justice-Involved Veterans

PubMed Central

Blonigen, Daniel M.; Rodriguez, Allison L.; Manfredi, Luisa; Britt, Jessica; Nevedal, Andrea; Finlay, Andrea K.; Rosenthal, Joel; Smelson, David; Timko, Christine

2016-01-01

The availability and utility of services to address recidivism risk factors among justice-involved veterans is unknown. We explored these issues through qualitative interviews with 63 Specialists from the Department of Veterans Affairs’ (VA) Veterans Justice Programs. To guide the interviews, we utilized the Risk-Need-Responsivity (RNR) model of offender rehabilitation. Specialists reported that justice-involved veterans generally have access to services to address most RNR-based risk factors (substance abuse; lack of positive school/work involvement; family/marital dysfunction; lack of prosocial activities/interests), but have less access to services targeting risk factors of antisocial tendencies and associates and empirically-based treatments for recidivism in VA. Peer-based services, motivational interviewing/cognitive-behavioral therapy, and Veterans Treatment Courts were perceived as useful to address multiple risk factors. These findings highlight potential gaps in provision of evidence-based care to address recidivism among justice-involved veterans, as well as promising policy-based solutions that may have widespread impact on reducing recidivism in this population. PMID:26924887

The role of the RAS pathway in iAMP21-ALL

PubMed Central

Ryan, S L; Matheson, E; Grossmann, V; Sinclair, P; Bashton, M; Schwab, C; Towers, W; Partington, M; Elliott, A; Minto, L; Richardson, S; Rahman, T; Keavney, B; Skinner, R; Bown, N; Haferlach, T; Vandenberghe, P; Haferlach, C; Santibanez-Koref, M; Moorman, A V; Kohlmann, A; Irving, J A E; Harrison, C J

2016-01-01

Intrachromosomal amplification of chromosome 21 (iAMP21) identifies a high-risk subtype of acute lymphoblastic leukaemia (ALL), requiring intensive treatment to reduce their relapse risk. Improved understanding of the genomic landscape of iAMP21-ALL will ascertain whether these patients may benefit from targeted therapy. We performed whole-exome sequencing of eight iAMP21-ALL samples. The mutation rate was dramatically disparate between cases (average 24.9, range 5–51) and a large number of novel variants were identified, including frequent mutation of the RAS/MEK/ERK pathway. Targeted sequencing of a larger cohort revealed that 60% (25/42) of diagnostic iAMP21-ALL samples harboured 42 distinct RAS pathway mutations. High sequencing coverage demonstrated heterogeneity in the form of multiple RAS pathway mutations within the same sample and diverse variant allele frequencies (VAFs) (2–52%), similar to other subtypes of ALL. Constitutive RAS pathway activation was observed in iAMP21 samples that harboured mutations in the predominant clone (⩾35% VAF). Viable iAMP21 cells from primary xenografts showed reduced viability in response to the MEK1/2 inhibitor, selumetinib, in vitro. As clonal (⩾35% VAF) mutations were detected in 26% (11/42) of iAMP21-ALL, this evidence of response to RAS pathway inhibitors may offer the possibility to introduce targeted therapy to improve therapeutic efficacy in these high-risk patients. PMID:27168466

Progress and Challenges toward the Development of Vaccines against Avian Infectious Bronchitis

PubMed Central

Bande, Faruku; Arshad, Siti Suri; Hair Bejo, Mohd; Moeini, Hassan; Omar, Abdul Rahman

2015-01-01

Avian infectious bronchitis (IB) is a widely distributed poultry disease that has huge economic impact on poultry industry. The continuous emergence of new IBV genotypes and lack of cross protection among different IBV genotypes have been an important challenge. Although live attenuated IB vaccines remarkably induce potent immune response, the potential risk of reversion to virulence, neutralization by the maternal antibodies, and recombination and mutation events are important concern on their usage. On the other hand, inactivated vaccines induce a weaker immune response and may require multiple dosing and/or the use of adjuvants that probably have potential safety risks and increased economic burdens. Consequently, alternative IB vaccines are widely sought. Recent advances in recombinant DNA technology have resulted in experimental IB vaccines that show promise in antibody and T-cells responses, comparable to live attenuated vaccines. Recombinant DNA vaccines have also been enhanced to target multiple serotypes and their efficacy has been improved using delivery vectors, nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB DNA vaccines are yet to be licensed, it is expected that these types of vaccines may hold sway as future vaccines for inducing a cross protection against multiple IBV serotypes. PMID:25954763

Forward-backward multiplicity correlations of target fragments in nucleus-emulsion collisions at a few hundred MeV/u

NASA Astrophysics Data System (ADS)

Zhang, Dong-Hai; Chen, Yan-Ling; Wang, Guo-Rong; Li, Wang-Dong; Wang, Qing; Yao, Ji-Jie; Zhou, Jian-Guo; Li, Rong; Li, Jun-Sheng; Li, Hui-Ling

2015-01-01

The forward-backward multiplicity and correlations of a target evaporated fragment (black track particle) and target recoiled proton (grey track particle) emitted from 150 A MeV 4He, 290 A MeV 12C, 400 A MeV 12C, 400 A MeV 20Ne and 500 A MeV 56Fe induced different types of nuclear emulsion target interactions are investigated. It is found that the forward and backward averaged multiplicity of a grey, black and heavily ionized track particle increases with the increase of the target size. The averaged multiplicity of a forward black track particle, backward black track particle, and backward grey track particle do not depend on the projectile size and energy, but the averaged multiplicity of a forward grey track particle increases with an increase of projectile size and energy. The backward grey track particle multiplicity distribution follows an exponential decay law and the decay constant decreases with an increase of target size. The backward-forward multiplicity correlations follow linear law which is independent of the projectile size and energy, and the saturation effect is observed in some heavy target data sets.

Targeting Extracellular Histones with Novel RNA Bio drugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

organ involved in MODS is the lung (referred to as acute respiratory distress syndrome or ARDS). Trauma, smoke inhalation, burns, radiation , severe...and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome (MODS/ARDS) and ALI that can be easily delivered in combat...MODS, the risk of death is 40%. The most common organ involved in MODS is the lungs (referred to as acute respiratory distress syndrome or ARDS

DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.

PubMed

Kular, Lara; Liu, Yun; Ruhrmann, Sabrina; Zheleznyakova, Galina; Marabita, Francesco; Gomez-Cabrero, David; James, Tojo; Ewing, Ewoud; Lindén, Magdalena; Górnikiewicz, Bartosz; Aeinehband, Shahin; Stridh, Pernilla; Link, Jenny; Andlauer, Till F M; Gasperi, Christiane; Wiendl, Heinz; Zipp, Frauke; Gold, Ralf; Tackenberg, Björn; Weber, Frank; Hemmer, Bernhard; Strauch, Konstantin; Heilmann-Heimbach, Stefanie; Rawal, Rajesh; Schminke, Ulf; Schmidt, Carsten O; Kacprowski, Tim; Franke, Andre; Laudes, Matthias; Dilthey, Alexander T; Celius, Elisabeth G; Søndergaard, Helle B; Tegnér, Jesper; Harbo, Hanne F; Oturai, Annette B; Olafsson, Sigurgeir; Eggertsson, Hannes P; Halldorsson, Bjarni V; Hjaltason, Haukur; Olafsson, Elias; Jonsdottir, Ingileif; Stefansson, Kari; Olsson, Tomas; Piehl, Fredrik; Ekström, Tomas J; Kockum, Ingrid; Feinberg, Andrew P; Jagodic, Maja

2018-06-19

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10 -8 , odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.

Considerations on long-term immuno-intervention in the treatment of multiple sclerosis: an expert opinion.

PubMed

Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L

2016-10-01

As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.

Therapeutic Decisions In Multiple Sclerosis: Moving Beyond Efficacy

PubMed Central

Brück, Wolfgang; Ralf, Gold; Lund, Brett T.; Celia, Oreja-Guevara; Prat, Alexandre; Spencer, Collin M.; Steinman, Lawrence; Mar, Tintoré; Vollmer, Timothy; Weber, Martin S.; Weiner, Leslie P.; Ziemssen, Tjalf; Zamvil, Scott S.

2014-01-01

Importance Several innovative disease-modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS) have been licensed recently, or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least one of four properties: (1) immune cell trafficking, (2) cell depletion, (3) immune cell function, or (4) cell replication. In contrast to β-interferons and glatiramer acetate, the first generation DMTs, several newer therapies are imbued with safety issues. In addition to efficacy, understanding the relationship between the mechanism of action (MOA) of the DMTs and their safety profile is essential for decision-making in patient care. Objective In this article, we relate safety issues of newer DMTs to their pharmacological characteristics, including molecular targets, MOA, chemical structure, and metabolism. Some newer DMTs also represent repurposing or modifications of previous treatments used in other diseases. Here, we describe how identification and understanding of adverse events (AEs) observed with these established drugs within the same class, provide clues regarding safety and toxicities of newer MS therapeutics. Conclusions and relevance While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients, and to ensure future therapies have the most advantageous risk-benefit profiles. Recognizing the individual classes of DMTs described here may be beneficial when considering use of such agents sequentially and possibly in combination. PMID:23921521

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

PubMed Central

Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

2015-01-01

Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

PubMed

Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

2016-03-01

To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients.

Randomized pilot trial of a cognitive-behavioral alcohol, self-harm, and HIV prevention program for teens in mental health treatment.

PubMed

Esposito-Smythers, Christianne; Hadley, Wendy; Curby, Timothy W; Brown, Larry K

2017-02-01

Adolescents with mental health conditions represent a high-risk group for substance use, deliberate self-harm (DSH), and risky sexual behavior. Mental health treatment does not uniformly decrease these risks. Effective prevention efforts are needed to offset the developmental trajectory from mental health problems to these behaviors. This study tested an adjunctive cognitive-behavioral family-based alcohol, DSH, and HIV prevention program (ASH-P) for adolescents in mental healthcare. A two group randomized design was used to compare ASH-P to an assessment only control (AO-C). Participants included 81 adolescents and a parent. Assessments were completed at pre-intervention as well as 1, 6, and 12-months post-enrollment, and included measures of family-based mechanisms and high-risk behaviors. ASH-P relative to AO-C was associated with greater improvements in most family process variables (perceptions of communication and parental disapproval of alcohol use and sexual behavior) as well as less DSH and greater refusal of sex to avoid a sexually transmitted infection. It also had a moderate (but non-significant) effect on odds of binge drinking. No differences were found in suicidal ideation, alcohol use, or sexual intercourse. ASH-P showed initial promise in preventing multiple high-risk behaviors. Further testing of prevention protocols that target multiple high-risk behaviors in clinical samples is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring the socio-ecological levels for prevention of sexual risk behaviours of the youth in uMgungundlovu District Municipality, KwaZulu-Natal

PubMed Central

2018-01-01

Background Prevention of youth sexual risk behaviour among the youth in uMgungundlovu District Municipality continues to be a primary challenge for public health and health promotion. Current prevention interventions are targeted at an individual level, whilst youth behaviour is influenced by many social and environmental factors. Aim The aim of the study was to explore the factors influencing sexual risk behaviours of the youth at different socio-ecological levels in uMgungundlovu District Municipality. Methods An explorative and descriptive qualitative study design was used, using in-depth interviews and focus group discussions for data collection. A framework analysis was used to develop themes derived from the socio-ecological theory. Results Four themes were identified that influence youth to engage in sexual risk behaviours: (1) individual factors, related to role modelling behaviour, gender and negative stereotypes towards females; (2) the microsystem in which youth function including the influence of family and peers; (3) the exo-system comprising the disadvantaged socio-economic status of the communities where the youth live; and (4) the macrosystem where negative social norms were reported to influence youth health outcomes. Conclusion Sexual risk behaviour among youth in uMgungundlovu is influenced by many factors at multiple social levels. Interventions directed at these multiple levels are needed urgently. PMID:29781679

The Effectiveness of an Educational Brochure as a Risk Minimization Activity to Communicate Important Rare Adverse Events to Health-Care Professionals.

PubMed

Bester, Nicolette; Di Vito-Smith, Michelle; McGarry, Theresa; Riffkin, Michael; Kaehler, Stefan; Pilot, Richard; Bwire, Robert

2016-02-01

Educational brochures are an important tool for communicating risk to health-care professionals. It is important to evaluate the impact of any risk minimization tool to understand the effectiveness of the strategy. The objective of this study was to assess the effectiveness (i.e., respondents' awareness and understanding of the communication) of a targeted educational brochure distributed to health-care professionals (HCPs) as a risk minimization strategy for the communication of new rare and important adverse events (AEs). A prospective, non-interventional, online survey was performed following distribution of a specifically designed brochure highlighting new and important adverse events to a targeted HCP population, consisting of known users of the target medicine, as represented by a commercial database. Predefined multiple-choice survey questions assessed overall HCP awareness of the brochure and understanding and retention of information in those HCPs who reported receiving the brochure. The educational brochure was sent to a total of 565 HCPs; 121 (21.4%) responded to the survey. The majority of respondents (95.0%) had previously prescribed or dispensed the target medicine. In all, 88 (72.7%) respondents said they had received the educational brochure, of whom 95.5% stated they had at least scanned the main points. More participants who had received the brochure (86.4% to 96.6%) answered the five individual survey questions correctly compared with those who did not (51.5% to 97.0%); this was significant for four out of five questions (P ≤ 0.005). Significantly more HCPs who received the brochure achieved the predefined pass rate (at least four of five questions answered correctly) compared with HCPs who did not receive the brochure (93.2% vs 57.6%, respectively; P = 0.000003). Distribution of targeted educational brochures may be an effective risk minimization strategy to raise HCP awareness of new rare and important AEs; educational brochures may also be an effective channel for sharing information on how these AEs can be best managed and on the importance and means of reporting AEs. Celgene Pty Ltd, Melbourne, Australia.

Chemoprevention of Oral Cancer by Topical Application of Black Raspberries on High At-Risk Mucosa

PubMed Central

Warner, Blake M.; Casto, Bruce C.; Knobloch, Thomas J.; Accurso, Brent T.; Weghorst, Christopher M.

2014-01-01

Objective To evaluate the preclinical efficacy of topical administration of freeze-dried black raspberries (BRBs) to inhibit the progression of premalignant oral lesions and modulate biomarkers of cancer development in high at-risk mucosa (HARM). Study Design Hamster cheek pouches (HCPs) were treated with carcinogen for six weeks to initiate a HARM microenvironment. Subsequently, right HCPs were topically administered a BRB suspension in short-term or long-term studies. After 12 weeks, SCC multiplicity, SCC incidence, and cell proliferation rates were evaluated. mRNA expression was measured in short-term treated pouches for selected oral cancer biomarkers. Results SCC multiplicity (−41.3%), tumor incidence (−37.1%), and proliferation rate (−6.9%) were reduced in HCPs receiving BRBs. Topical BRBs correlated with an increase in Rb1 expression in developing oral lesions. Conclusion Topical BRBs inhibit SCC development when targeted to HARM tissues. These results support the translational role of BRBs to prevent oral cancer development in humans. PMID:25457886

The Committed Intimate Partnerships of Incarcerated African-American Men: Implications for Sexual HIV Transmission Risk and Prevention Opportunities.

PubMed

Khan, Maria R; El-Bassel, Nabila; Golin, Carol E; Scheidell, Joy D; Adimora, Adaora A; Coatsworth, Ashley M; Hu, Hui; Judon-Monk, Selena; Medina, Katie P; Wohl, David A

2017-10-01

Incarceration is thought to influence HIV transmission by disrupting partnerships that provide support and protect against sex risk-taking. Current correctional facility-based family-strengthening programs focus on marital partnerships, a minority of inmates' partnerships. Research on the sex partnerships of incarcerated African-American men and the types of partnerships most likely to protect against HIV-related sex risk is limited. Improved understanding can inform expansion of correctional facility-based family-strengthening programs to a greater proportion of protective partnerships and HIV risk reduction programs to partnerships vulnerable to sex risk. Project DISRUPT is a cohort study of African-American men being released from prison in North Carolina who were in committed heterosexual partnerships at prison entry. Using baseline survey data (N = 189), we conducted latent class analysis (LCA) to identify subgroups of participants with distinct relationship profiles and measured associations between relationship characteristics and multiple partnerships of inmates and their partners in the six months before incarceration. LCA indicated a two-class solution, with relationships distinguished by satisfaction/stability (satisfied/stable class: 58.0%; dissatisfied/unstable class: 42.0%); each class had comparable relationship length and levels of marriage and cohabitation. Dissatisfied/unstable relationships were associated with multiple partnerships among participants (AOR 2.93, 95% CI 1.50, 5.72) and partners (AOR 4.95, 95% CI 1.68, 14.58). Satisfaction indicators-versus length, marriage, or cohabitation-were the strongest independent correlates of inmates' and partners' multiple partnerships. Pre-incarceration economic deprivation, mental disorder symptoms, substance use, and violence in relationships were associated with dissatisfaction/instability. Prison-based programs designed to maintain healthy partnerships, strengthen relationship skills, and reduce HIV risk-taking and violence in relationships are warranted and should be targeted to both marital and nonmarital partnerships. Programming also should address the poverty, mental illness, and substance use factors that threaten relationship satisfaction/stability and increase HIV risk.

p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

PubMed Central

Menon, Ramkumar; Papaconstantinou, John

2016-01-01

Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

New Insight Into the Biology, Risk Stratification, and Targeted Treatment of Myelodysplastic Syndromes.

PubMed

Haider, Mintallah; Duncavage, Eric J; Afaneh, Khalid F; Bejar, Rafael; List, Alan F

2017-01-01

In myelodysplastic syndromes (MDS), somatic mutations occur in five major categories: RNA splicing, DNA methylation, activated cell signaling, myeloid transcription factors, and chromatin modifiers. Although many MDS cases harbor more than one somatic mutation, in general, there is mutual exclusivity of mutated genes within a class. In addition to the prognostic significance of individual somatic mutations, more somatic mutations in MDS have been associated with poor prognosis. Prognostic assessment remains a critical component of the personalization of care for patient with MDS because treatment is highly risk adapted. Multiple methods for risk stratification are available with the revised International Prognostic Scoring System (IPSS-R), currently considered the gold standard. Increasing access to myeloid gene panels and greater evidence for the diagnostic and predictive value of somatic mutations will soon make sequencing part of the standard evaluation of patients with MDS. In the absence of formal guidelines for their prognostic use, well-validated mutations can still refine estimates of risk made with the IPSS-R. Not only are somatic gene mutations advantageous in understanding the biology of MDS and prognosis, they also offer potential as biomarkers and targets for the treatment of patients with MDS. Examples include deletion 5q, spliceosome complex gene mutations, and TP53 mutations.

An ecological model of intimate partner violence perpetration at different levels of severity.

PubMed

Smith Slep, Amy M; Foran, Heather M; Heyman, Richard E

2014-08-01

Intimate partner violence (IPV) is a significant public health concern. This study proposed and tested an ecological model of both general and clinically significant (i.e., injurious or fear-evoking) IPV perpetration (IPVPerp). Risk and promotive factors from multiple ecological levels of influence (i.e., individual, family, workplace, community) were hypothesized to be important in the prediction of IPVPerp. Although clinically significant IPVPerp and general IPVPerp were hypothesized to relate, specific risks for clinically significant IPVPerp were hypothesized. U.S. Air Force active duty members and civilian spouses (N = 34,861 men; 24,331 women) from 82 sites worldwide completed the 2006 Community Assessment, an anonymous online survey assessing IPVPerp along with a variety of potential risk and promotive factors. Final structural equation models for men and women, cross-validated in holdout samples, clearly supported the relevance of an ecological approach to IPVPerp. Factors from all 4 levels were associated with both general IPVPerp and clinically significant IPVPerp, with relatively distal community and workplace factors operating via more proximal individual and family level variables (e.g., relationship satisfaction). The results suggest a variety of both established and novel potential targets for indirectly targeting general and clinically significant IPVPerp by improving risk profiles at the individual, family, workplace, and community levels.

Mapping multiple components of malaria risk for improved targeting of elimination interventions.

PubMed

Cohen, Justin M; Le Menach, Arnaud; Pothin, Emilie; Eisele, Thomas P; Gething, Peter W; Eckhoff, Philip A; Moonen, Bruno; Schapira, Allan; Smith, David L

2017-11-13

There is a long history of considering the constituent components of malaria risk and the malaria transmission cycle via the use of mathematical models, yet strategic planning in endemic countries tends not to take full advantage of available disease intelligence to tailor interventions. National malaria programmes typically make operational decisions about where to implement vector control and surveillance activities based upon simple categorizations of annual parasite incidence. With technological advances, an enormous opportunity exists to better target specific malaria interventions to the places where they will have greatest impact by mapping and evaluating metrics related to a variety of risk components, each of which describes a different facet of the transmission cycle. Here, these components and their implications for operational decision-making are reviewed. For each component, related mappable malaria metrics are also described which may be measured and evaluated by malaria programmes seeking to better understand the determinants of malaria risk. Implementing tailored programmes based on knowledge of the heterogeneous distribution of the drivers of malaria transmission rather than only consideration of traditional metrics such as case incidence has the potential to result in substantial improvements in decision-making. As programmes improve their ability to prioritize their available tools to the places where evidence suggests they will be most effective, elimination aspirations may become increasingly feasible.

Assessment of the potential health risks associated with the aluminium, arsenic, cadmium and lead content in selected fruits and vegetables grown in Jamaica.

PubMed

Antoine, Johann M R; Fung, Leslie A Hoo; Grant, Charles N

2017-01-01

Thirteen Jamaican-grown food crops - ackee ( Blighia sapida ), banana ( Musa acuminate ), cabbage ( Brassica oleracea ), carrot ( Daucus carota ), cassava ( Manihot esculenta ), coco ( Xanthosoma sagittifolium ), dasheen ( Colocasia esculenta ), Irish potato ( Solanum tuberosum ), pumpkin ( Cucurbita pepo ), sweet pepper ( Capsicum annuum ), sweet potato ( Ipomoea batatas ), tomato ( Solanum lycopersicum ) and turnip ( Brassica rapa ) - were analysed for aluminium, arsenic, cadmium and lead by atomic absorption spectrophotometry and instrumental neutron activation analysis. The fresh weight mean concentrations in these food crops (4.25-93.12 mg/kg for aluminium; 0.001-0.104 mg/kg for arsenic; 0.015-0.420 mg/kg for cadmium; 0.003-0.100 mg/kg for lead) were used to calculate the estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI) and target cancer risk (TCR) for arsenic, associated with dietary exposure to these potentially toxic elements. Each food type had a THQ and HI < 1 indicating no undue non-carcinogenic risk from exposure to a single or multiple potentially toxic elements from the same food. The TCR for arsenic in these foods were all below 1 × 10 -4 , the upper limit used for acceptable cancer risk. There is no significant health risk to the consumer associated with the consumption of these Jamaican-grown food crops.

Predicted outcomes of vaccinating wildlife to reduce human risk of Lyme disease.

PubMed

Tsao, Kimberly; Fish, Durland; Galvani, Alison P

2012-07-01

Vaccination efforts for Lyme disease prevention in humans have focused on wildlife reservoirs to target the causative agent, Borrelia burgdorferi, for elimination in vector ticks. Multiple host species are involved in the transmission and maintenance of the bacterium, but not all host species can be vaccinated effectively. To evaluate vaccinating a subset of hosts in the context of host-tick interactions, we constructed and evaluated a dynamic model of B. burgdorferi transmission in mice. Our analyses indicate that on average, a mouse-targeted vaccine is expected to proportionally reduce infection prevalence among ticks by 56%. However, relative to mouse vaccination, human risk of exposure is dominated by the number of tick bites received per person, the proportion of tick blood meals taken from the highly reservoir-competent white-footed mouse relative to other hosts, and the average number of tick bites per mouse. Variation in these factors reduces the predictability of vaccination outcomes. Additionally, contributions of nonmouse hosts to pathogen maintenance preclude elimination of B. burgdorferi through mouse vaccination alone. Our findings indicate that to increase the impact of wildlife vaccination, reducing tick populations by acaricide application, in addition to targeting additional reservoir-competent host species, should be employed.

Assessing, mapping and validating site-specific ecotoxicological risk for pesticide mixtures: a case study for small scale hot spots in aquatic and terrestrial environments.

PubMed

Vaj, Claudia; Barmaz, Stefania; Sørensen, Peter Borgen; Spurgeon, David; Vighi, Marco

2011-11-01

Mixture toxicity is a real world problem and as such requires risk assessment solutions that can be applied within different geographic regions, across different spatial scales and in situations where the quantity of data available for the assessment varies. Moreover, the need for site specific procedures for assessing ecotoxicological risk for non-target species in non-target ecosystems also has to be recognised. The work presented in the paper addresses the real world effects of pesticide mixtures on natural communities. Initially, the location of risk hotspots is theoretically estimated through exposure modelling and the use of available toxicity data to predict potential community effects. The concept of Concentration Addition (CA) is applied to describe responses resulting from exposure of multiple pesticides The developed and refined exposure models are georeferenced (GIS-based) and include environmental and physico-chemical parameters, and site specific information on pesticide usage and land use. As a test of the risk assessment framework, the procedures have been applied on a suitable study areas, notably the River Meolo basin (Northern Italy), a catchment characterised by intensive agriculture, as well as comparative area for some assessments. Within the studied areas, the risks for individual chemicals and complex mixtures have been assessed on aquatic and terrestrial aboveground and belowground communities. Results from ecological surveys have been used to validate these risk assessment model predictions. Value and limitation of the approaches are described and the possibilities for larger scale applications in risk assessment are also discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Measuring health-related problem solving among African Americans with multiple chronic conditions: application of Rasch analysis.

PubMed

Fitzpatrick, Stephanie L; Hill-Briggs, Felicia

2015-10-01

Identification of patients with poor chronic disease self-management skills can facilitate treatment planning, determine effectiveness of interventions, and reduce disease complications. This paper describes the use of a Rasch model, the Rating Scale Model, to examine psychometric properties of the 50-item Health Problem-Solving Scale (HPSS) among 320 African American patients with high risk for cardiovascular disease. Items on the positive/effective HPSS subscales targeted patients at low, moderate, and high levels of positive/effective problem solving, whereas items on the negative/ineffective problem solving subscales mostly targeted those at moderate or high levels of ineffective problem solving. Validity was examined by correlating factor scores on the measure with clinical and behavioral measures. Items on the HPSS show promise in the ability to assess health-related problem solving among high risk patients. However, further revisions of the scale are needed to increase its usability and validity with large, diverse patient populations in the future.

HIV and Childhood Sexual Violence: Implications for Sexual Risk Behaviors and HIV Testing in Tanzania.

PubMed

Chiang, Laura F; Chen, Jieru; Gladden, Matthew R; Mercy, James A; Kwesigabo, Gideon; Mrisho, Fatma; Dahlberg, Linda L; Nyunt, Myo Zin; Brookmeyer, Kate A; Vagi, Kevin

2015-10-01

Prior research has established an association between sexual violence and HIV. Exposure to sexual violence during childhood can profoundly impact brain architecture and stress regulatory response. As a result, individuals who have experienced such trauma may engage in sexual risk-taking behavior and could benefit from targeted interventions. In 2009, nationally representative data were collected on violence against children in Tanzania from 13-24 year old respondents (n=3,739). Analyses show that females aged 19-24 (n=579) who experienced childhood sexual violence, were more likely to report no/infrequent condom use in the past 12 months (AOR=3.0, CI [1.5, 6.1], p=0.0017) and multiple sex partners in the past 12 months (AOR=2.3, CI [1.0, 5.1], p=0.0491), but no more likely to know where to get HIV testing or to have ever been tested. Victims of childhood sexual violence could benefit from targeted interventions to mitigate impacts of violence and prevent HIV.

Communicative participation restrictions in multiple sclerosis: associated variables and correlation with social functioning.

PubMed

Yorkston, Kathryn M; Baylor, Carolyn; Amtmann, Dagmar

2014-01-01

Individuals with multiple sclerosis (MS) are at risk for communication problems that may restrict their ability to take participation in important life roles such as maintenance of relationships, work, or household management. The aim of this project is to examine selected demographic and symptom-related variables that may contribute to participation restrictions. This examination is intended to aid clinicians in predicting who might be at risk for such restrictions and what variables may be targeted in interventions. Community-dwelling adults with MS (n=216) completed a survey either online or using paper forms. The survey included the 46-item version of the Communicative Participation Item Bank, demographics (age, sex, living situation, employment status, education, and time since onset of diagnosis of MS), and self-reported symptom-related variables (physical activity, emotional problems, fatigue, pain, speech severity, and cognitive/communication skills). In order to identify predictors of restrictions in communicative participation, these variables were entered into a backwards stepwise multiple linear regression analysis. Five variables (cognitive/communication skills, speech severity, speech usage, physical activity, and education) were statistically significant predictors of communication participation. In order to examine the relationship of communicative participation and social role variables, bivariate Spearman correlations were conducted. Results suggest only a fair to moderate relationship between communicative participation and measures of social roles. Communicative participation is a complex construct associated with a number of self-reported variables. Clinicians should be alert to risk factors for reduced communicative participation including reduced cognitive and speech skills, lower levels of speech usage, limitations in physical activities and higher levels of education. The reader will be able to: (a) describe the factors that may restrict participation in individuals with multiple sclerosis; (b) list measures of social functioning that may be pertinent in adults with multiple sclerosis; (c) discuss factors that can be used to predict communicative participation in multiple sclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

YOUNG ADULT DATING RELATIONSHIPS AND THE MANAGEMENT OF SEXUAL RISK

PubMed Central

Manning, Wendy D.; Giordano, Peggy C.; Longmore, Monica A.; Flanigan, Christine M.

2012-01-01

Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize ‘risk management’ as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV. PMID:23805015

YOUNG ADULT DATING RELATIONSHIPS AND THE MANAGEMENT OF SEXUAL RISK.

PubMed

Manning, Wendy D; Giordano, Peggy C; Longmore, Monica A; Flanigan, Christine M

2012-04-01

Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize 'risk management' as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV.

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

PubMed

Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

2017-04-01

Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

Endotoxemia Following Multiple Trauma: Risk Factors and Prognostic Implications.

PubMed

Charbonney, Emmanuel; Tsang, Jennifer Y; Li, Yangmei; Klein, David; Duque, Patricia; Romaschin, Alexander; Marshall, John C

2016-02-01

To evaluate the prevalence and time course of systemic endotoxemia following severe multiple trauma, to define its risk factors, and to explore the correlation between post-trauma endotoxemia and organ dysfunction. Prospective single-center cohort study. Emergency department and ICU of adult tertiary care level I trauma center. Forty-eight severely injured (Injury Severity Score ≥ 16) patients, admitted to ICU within 24 hours of injury. None. Endotoxemia was not evident on initial presentation, but developed subsequently in 75% of patients, even in the absence of Gram-negative infection. Nonsurviving patients had higher endotoxin levels than survivors on day 1 (endotoxemia, 0.48 vs 0.28; p = 0.048). Shock at admission, or surgery within the first 48 hours after trauma, was associated with higher endotoxin levels and predicted subsequent maximal endotoxemia, after adjusting for other significant covariates. Maximal endotoxemia levels were higher in patients who developed organ dysfunction, reflected in a cumulative Multiple Organ Dysfunction Score greater than 25, and patients with an intermediate endotoxemia level (≥ 0.4) had more cardiovascular dysfunction. It is the first study to detect increasing levels of endotoxemia following multiple trauma. Shock and early surgery predict the development of endotoxemia; endotoxemia is particularly associated with cardiovascular dysfunction. However, Gram-negative infections are uncommon in these patients, suggesting that the gastrointestinal tract is the dominant reservoir of endotoxin. Endotoxin may be an appropriate therapeutic target in patients who have sustained severe multiple trauma.

Relationship between risk factor control and vascular events in the SAMMPRIS trial.

PubMed

Turan, Tanya N; Nizam, Azhar; Lynn, Michael J; Egan, Brent M; Le, Ngoc-Anh; Lopes-Virella, Maria F; Hermayer, Kathie L; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I

2017-01-24

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non-high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4-0.8). Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. NCT00576693. © 2016 American Academy of Neurology.

Screening tools to identify patients with complex health needs at risk of high use of health care services: A scoping review

PubMed Central

Chouinard, Maud-Christine; Diadiou, Fatoumata; Dufour, Isabelle

2017-01-01

Background Many people with chronic conditions have complex health needs often due to multiple chronic conditions, psychiatric comorbidities, psychosocial issues, or a combination of these factors. They are at high risk of frequent use of healthcare services. To offer these patients interventions adapted to their needs, it is crucial to be able to identify them early. Objective The aim of this study was to find all existing screening tools that identify patients with complex health needs at risk of frequent use of healthcare services, and to highlight their principal characteristics. Our purpose was to find a short, valid screening tool to identify adult patients of all ages. Methods A scoping review was performed on articles published between 1985 and July 2016, retrieved through a comprehensive search of the Scopus and CINAHL databases, following the methodological framework developed by Arksey and O’Malley (2005), and completed by Levac et al. (2010). Results Of the 3,818 articles identified, 30 were included, presenting 14 different screening tools. Seven tools were self-reported. Five targeted adult patients, and nine geriatric patients. Two tools were designed for specific populations. Four can be completed in 15 minutes or less. Most screening tools target elderly persons. The INTERMED self-assessment (IM-SA) targets adults of all ages and can be completed in less than 15 minutes. Conclusion Future research could evaluate its usefulness as a screening tool for identifying patients with complex needs at risk of becoming high users of healthcare services. PMID:29190658

Developing a multi-pollutant conceptual framework for the selection and targeting of interventions in water industry catchment management schemes.

PubMed

Bloodworth, J W; Holman, I P; Burgess, P J; Gillman, S; Frogbrook, Z; Brown, P

2015-09-15

In recent years water companies have started to adopt catchment management to reduce diffuse pollution in drinking water supply areas. The heterogeneity of catchments and the range of pollutants that must be removed to meet the EU Drinking Water Directive (98/83/EC) limits make it difficult to prioritise areas of a catchment for intervention. Thus conceptual frameworks are required that can disaggregate the components of pollutant risk and help water companies make decisions about where to target interventions in their catchments to maximum effect. This paper demonstrates the concept of generalising pollutants in the same framework by reviewing key pollutant processes within a source-mobilisation-delivery context. From this, criteria are developed (with input from water industry professionals involved in catchment management) which highlights the need for a new water industry specific conceptual framework. The new CaRPoW (Catchment Risk to Potable Water) framework uses the Source-Mobilisation-Delivery concept as modular components of risk that work at two scales, source and mobilisation at the field scale and delivery at the catchment scale. Disaggregating pollutant processes permits the main components of risk to be ascertained so that appropriate interventions can be selected. The generic structure also allows for the outputs from different pollutants to be compared so that potential multiple benefits can be identified. CaRPow provides a transferable framework that can be used by water companies to cost-effectively target interventions under current conditions or under scenarios of land use or climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Incorporating multiple secondary targets into learning trials for individuals with autism spectrum disorder.

PubMed

Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany; Kisamore, April N

2017-07-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary target was presented in the consequence of each trial, and (d) no additional targets were presented trials. The participants acquired the majority of secondary targets. Presenting one or multiple secondary targets per trial, regardless of the location of these secondary targets, increased the efficiency of instruction in comparison to a condition with no secondary target. © 2017 Society for the Experimental Analysis of Behavior.

Food-chain contamination evaluations in ecological risk assessments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linder, G.

Food-chain models have become increasingly important within the ecological risk assessment process. This is the case particularly when acute effects are not readily apparent, or the contaminants of concern are not readily detoxified, have a high likelihood for partitioning into lipids, or have specific target organs or tissues that may increase their significance in evaluating their potential adverse effects. An overview of food-chain models -- conceptual, theoretical, and empirical -- will be considered through a series of papers that will focus on their application within the ecological risk assessment process. Whether a food-chain evaluation is being developed to address relativelymore » simple questions related to chronic effects of toxicants on target populations, or whether a more complex food-web model is being developed to address questions related to multiple-trophic level transfers of toxicants, the elements within the food chain contamination evaluation can be generalized to address the mechanisms of toxicant accumulation in individual organisms. This can then be incorporated into more elaborate models that consider these organismal-level processes within the context of a species life-history or community-level responses that may be associated with long-term exposures.« less

Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework

PubMed Central

Huang, Bin; Pendley, Jennifer Shroff; Delamater, Alan; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis

2015-01-01

Objectives This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). Methods This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. Results Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. Conclusions Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood. PMID:26152400

Strength and cardiometabolic risk in young adults: The mediator role of aerobic fitness and waist circumference.

PubMed

Díez-Fernández, A; Martínez-Vizcaíno, V; Torres-Costoso, A; Cañete García-Prieto, J; Franquelo-Morales, P; Sánchez-López, M

2018-07-01

The aim of this study was to analyze the mediation role of cardiorespiratory fitness and waist circumference in the association between muscular strength and cardiometabolic risk. A cross-sectional study involved first-year college students (n = 370) from a Spanish public university was performed. We measured weight, height, waist circumference, blood pressure, biochemical variables, maximum handgrip strength assessment, and cardiorespiratory fitness. We calculated handgrip dynamometry/weight and a previously validated cardiometabolic risk index. Analysis of covariance models was conducted to test differences in cardiometabolic risk values across muscular strength, cardiorespiratory fitness, and waist circumference categories, controlling for confounders. Hayes' PROCESS macro was used for the multiple mediation analysis. The relationship between muscular strength and cardiometabolic risk did not remain significant (c' = 1.76 [1.4]; P > .05) in a multiple serial bootstrapped mediation model including cardiorespiratory fitness and waist circumference as mediators when controlling for age and sex. According to the indirect effect, the significant paths in the model mediating this relationship between muscular strength and cardiometabolic risk index were as follows: muscular strength → waist circumference → cardiometabolic risk index (-4.899; 95% CI: -6.690; -3.450) and muscular strength → cardiorespiratory fitness → waist circumference → cardiometabolic risk index (-0.720; 95% CI: -1.316; -0.360). Both cardiorespiratory fitness and waist circumference mediate the association between muscular strength and cardiometabolic risk in young adults. Thus, our results place cardiorespiratory fitness and waist circumference as the main targets of physical activity programmes aimed at preventing cardiometabolic diseases. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Written content indicators of problematic approach behavior toward political officials.

PubMed

Schoeneman, Katherine A; Scalora, Mario J; Darrow, Charles D; McLawsen, Julia E; Chang, Grace H; Zimmerman, William J

2011-01-01

Those charged with assessing and managing threatening communications must utilize risk factors that are behavioral, operational, and reasonably attainable during investigations. This project examined 326 written correspondence cases of an inappropriate, disruptive, or threatening nature that targeted political officials, with the specific goal of identifying written content indicators of problematic approach behavior. Results revealed that subjects who engaged in problematic approach activity toward their targets had more criminal history, past threat assessment activity, familiarity with firearms, past substance use, and indicators of serious mental illness. Approachers were more likely to engage in multiple contact methods, target dispersion, more overall contacts, and prior contact with their target. Numerous content themes were associated with future problematic approach, including longer handwritten correspondence, referencing specific events, making demands, mentioning stressors, focus on personal themes, feeling their rights were violated, and expressing an intention to approach. Harassing, insulting, and threatening language was not related to approach behavior. The implications of these findings are wide-ranging for the practice of threat assessment. Copyright © 2011 John Wiley & Sons, Ltd.

Use of the Impella 2.5 for prophylactic circulatory support during elective high-risk percutaneous coronary intervention.

PubMed

Alasnag, Mirvat A; Gardi, Delair O; Elder, Mahir; Kannam, Hari; Ali, Farhan; Petrina, Mircea; Kheterpal, Vipin; Hout, Mariah S; Schreiber, Theodore L

2011-01-01

Patients undergoing percutaneous coronary intervention (PCI) who are at high risk for cardiovascular collapse during the procedure may benefit from prophylactic circulatory support. The objective was to evaluate the safety and feasibility of prophylactic use of the Impella 2.5 during high-risk PCI. We used the Impella 2.5 for partial circulatory support during 60 consecutive elective high-risk PCI cases over 20 months. All patients either were deemed inoperable by the cardiac surgeons or were offered bypass surgery but declined. The patients had multiple risk factors including hypertension (95%), diabetes (52%), chronic pulmonary disease (23%), prior myocardial infarction (62%) and prior bypass surgery (18%). Forty-five percent presented with acute coronary syndrome. The mean left ventricular ejection fraction was 23%±15%. Nearly all patients had multivessel disease (93%), and 60% had left main disease. The average SYNTAX score was 30±9. Despite lesion complexity and high-risk factors, we achieved an angiographic success rate of 96%. Left main lesions were treated in 55% of the patients, and 83% of patients had multiple lesions treated. There was one procedural death. At 30 days postintervention, mortality was 5%, and rates of myocardial infarction, stroke, target vessel revascularization and urgent bypass surgery were 0%. The single-center experience reported here demonstrates that use of the Impella 2.5 during high-risk PCI in the "real world" - outside the controlled environment of a clinical trial - is safe and feasible. Copyright © 2011 Elsevier Inc. All rights reserved.

Examining perceptual and conceptual set biases in multiple-target visual search.

PubMed

Biggs, Adam T; Adamo, Stephen H; Dowd, Emma Wu; Mitroff, Stephen R

2015-04-01

Visual search is a common practice conducted countless times every day, and one important aspect of visual search is that multiple targets can appear in a single search array. For example, an X-ray image of airport luggage could contain both a water bottle and a gun. Searchers are more likely to miss additional targets after locating a first target in multiple-target searches, which presents a potential problem: If airport security officers were to find a water bottle, would they then be more likely to miss a gun? One hypothetical cause of multiple-target search errors is that searchers become biased to detect additional targets that are similar to a found target, and therefore become less likely to find additional targets that are dissimilar to the first target. This particular hypothesis has received theoretical, but little empirical, support. In the present study, we tested the bounds of this idea by utilizing "big data" obtained from the mobile application Airport Scanner. Multiple-target search errors were substantially reduced when the two targets were identical, suggesting that the first-found target did indeed create biases during subsequent search. Further analyses delineated the nature of the biases, revealing both a perceptual set bias (i.e., a bias to find additional targets with features similar to those of the first-found target) and a conceptual set bias (i.e., a bias to find additional targets with a conceptual relationship to the first-found target). These biases are discussed in terms of the implications for visual-search theories and applications for professional visual searchers.

Rendezvous Integration Complexities of NASA Human Flight Vehicles

NASA Technical Reports Server (NTRS)

Brazzel, Jack P.; Goodman, John L.

2009-01-01

Propellant-optimal trajectories, relative sensors and navigation, and docking/capture mechanisms are rendezvous disciplines that receive much attention in the technical literature. However, other areas must be considered. These include absolute navigation, maneuver targeting, attitude control, power generation, software development and verification, redundancy management, thermal control, avionics integration, robotics, communications, lighting, human factors, crew timeline, procedure development, orbital debris risk mitigation, structures, plume impingement, logistics, and in some cases extravehicular activity. While current and future spaceflight programs will introduce new technologies and operations concepts, the complexity of integrating multiple systems on multiple spacecraft will remain. The systems integration task may become more difficult as increasingly complex software is used to meet current and future automation, autonomy, and robotic operation requirements.

Attention-Deficit/Hyperactivity Disorder and Risk of Substance Use Disorder: Developmental Considerations, Potential Pathways, and Opportunities for Research

PubMed Central

Molina, Brooke S.G.; Pelham, William E.

2014-01-01

Many opportunities to explain ADHD-related risk of substance use/disorder (SUD) remain available for study. We detail these opportunities by considering characteristics of children with ADHD and factors affecting their outcomes side-by-side with overlapping variables in the developmental literature on SUD etiology. Although serious conduct problems are a known contributor to ADHD-related risk of SUD, few studies have considered their emergence developmentally and in relation to other candidate mediators and moderators that could also explain risk and be intervention targets. Common ADHD-related impairments, such as school difficulties, are in need of research. Heterogeneous social impairments have the potential for predisposing, and buffering, influences. Research on neurocognitive domains should move beyond standard executive function batteries to measure deficits in the interface between cognitive control, reward, and motivation. Ultimately, maximizing prediction will depend, as it has in the SUD literature, on simultaneous consideration of multiple risk factors. PMID:24437435

Multiple Health Behaviors: Patterns and Correlates of Diet and Exercise in a Hispanic College Sample

PubMed Central

Hu, Dixie; Taylor, Thom; Blow, Julie; Cooper, Theodore V.

2011-01-01

Obesity rates are alarming in various ethnocultural groups, particularly in Hispanics. With Hispanics being the fastest growing group to enter college, the aims of the current study were to examine patterns and correlates of exercise and dietary behaviors in Hispanic college students. Data were collected from 693 Hispanic undergraduates who enrolled online and received course extra credit for participation. Individuals completed questionnaires assessing constructs of the transtheoretical model for three health behaviors (exercise, dietary fat, and fruit/vegetable stages of change) along with demographic, psychosocial, and acculturation measures. Less than 1% of students had 0 obesity-relevant risks, while 68% indicated 2 or more risks. Only 2% of the sample met fruit and vegetable guidelines. Lower income was associated with greater obesity-relevant risks, while stress coping ability was associated with fewer such risks. Findings indicate specific obesity risk behaviors in Hispanic college students and suggest demographic and psychosocial targets for prevention and intervention according to stage of change. PMID:22051363

A comparison of email versus letter threat contacts toward members of the United States Congress.

PubMed

Schoeneman-Morris, Katherine A; Scalora, Mario J; Chang, Grace H; Zimmerman, William J; Garner, Yancey

2007-09-01

To better understand inappropriate correspondence sent to public officials, 301 letter cases and 99 email cases were randomly selected from the United States Capitol Police investigative case files and compared. Results indicate that letter writers were significantly more likely than emailers to exhibit indicators of serious mental illness (SMI), engage in target dispersion, use multiple methods of contact, and make a problematic approach toward their target. Emailers were significantly more likely than letter writers to focus on government concerns, use obscene language, and display disorganization in their writing. Also, letter writers tended to be significantly older, have more criminal history, and write longer communications. A multivariate model found that disorganization, SMI symptoms, problematic physical approach, and target dispersion significantly differentiated between the correspondence groups. The group differences illuminated by this study reveal that letter writers are engaging in behavior that is higher risk for problematic approach than are emailers.

Modifiable risk factors in periodontitis: at the intersection of aging and disease.

PubMed

Reynolds, Mark A

2014-02-01

Chronic inflammation is a prominent feature of aging and of common age-related diseases, including atherosclerosis, cancer and periodontitis. This volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases. Oral bacterial communities and viral infections, particularly with cytomegalovirus and other herpesviruses, elicit distinct immune responses and are central in the initiation of periodontal diseases. Risk of disease is dynamic and changes in response to complex interactions of genetic, environmental and stochastic factors over the lifespan. Many modifiable risk factors, such as smoking and excess caloric intake, contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms (e.g. epigenetic modifications). Periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors, such as tobacco smoking, psychological stress and depression, alcohol consumption, obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ASCCP Colposcopy Standards: Risk-Based Colposcopy Practice.

PubMed

Wentzensen, Nicolas; Schiffman, Mark; Silver, Michelle I; Khan, Michelle J; Perkins, Rebecca B; Smith, Katie M; Gage, Julia C; Gold, Michael A; Conageski, Christine; Einstein, Mark H; Mayeaux, Edward J; Waxman, Alan G; Huh, Warner K; Massad, L Stewart

2017-10-01

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. This article describes the rationale, evidence, and recommendations related to risk-based colposcopy practice. Women referred to colposcopy have a wide range of underlying precancer risk, which can be estimated by referral screening tests including cytology and human papillomavirus testing, in conjunction with the colposcopic impression. Multiple targeted biopsies, at least 2 and up to 4, are recommended to improve detection of prevalent precancers. At the lowest end of the risk spectrum, untargeted biopsies are not recommended, and women with a completely normal colposcopic impression can be observed. At the highest end of the risk spectrum, immediate treatment is an alternative to biopsy confirmation. Assessing the risk of cervical precancer at the colposcopy visit allows for modification of colposcopy procedures consistent with a woman's risk. Implementation of these recommendations is expected to lead to improved detection of cervical precancers at colposcopy, while providing more reassurance of negative colposcopy results.

Fixed combination of repaglinide and metformin in the management of type 2 diabetes

PubMed Central

Moses, Robert

2009-01-01

Treatment to target fasting blood glucose (FBG), postprandial glucose (PPG) and HbA1c are essential in the management of type 2 diabetes to reduce the risk of vascular complications. Early combination therapy with oral agents is increasingly being seen as important to achieve this. Repaglinide, a rapid-acting insulin secretagogue, targets PPG, and metformin, an insulin sensitizer, targets FBG. Because of their complementary modes of action these therapies are frequently given as combination therapy in separate tablets. To overcome the issues with adherence to multiple tablets, repaglinide and metformin are now available in a fixed-dose combination (FDC). Repaglinide/metformin FDC is bioequivalent to each tablet given separately, suggesting that the efficacy and safety profile is similar. There is no effect of food on repaglinide when in the FDC. Repaglinide/metformin FDC is as effective in reducing HbA1c and FBG whether given twice or three times daily, with a similar safety profile. Repaglinide/metformin FDC twice daily is as effective in reducing HbA1c and FBG as rosiglitazone/metformin FDC with a similar safety profile, but unlike the rosiglitazone/metformin FDC, repaglinide/metformin FDC improves the lipid profile. Repaglinide/metformin FDC represents a new option in the pursuit of achieving glucose targets and reducing vascular risk in type 2 diabetes, with the advantage of improving adherence. PMID:21437123

Fixed combination of repaglinide and metformin in the management of type 2 diabetes.

PubMed

Moses, Robert

2009-06-24

Treatment to target fasting blood glucose (FBG), postprandial glucose (PPG) and HbA(1c) are essential in the management of type 2 diabetes to reduce the risk of vascular complications. Early combination therapy with oral agents is increasingly being seen as important to achieve this. Repaglinide, a rapid-acting insulin secretagogue, targets PPG, and metformin, an insulin sensitizer, targets FBG. Because of their complementary modes of action these therapies are frequently given as combination therapy in separate tablets. To overcome the issues with adherence to multiple tablets, repaglinide and metformin are now available in a fixed-dose combination (FDC). Repaglinide/metformin FDC is bioequivalent to each tablet given separately, suggesting that the efficacy and safety profile is similar. There is no effect of food on repaglinide when in the FDC. Repaglinide/metformin FDC is as effective in reducing HbA(1c) and FBG whether given twice or three times daily, with a similar safety profile. Repaglinide/metformin FDC twice daily is as effective in reducing HbA(1c) and FBG as rosiglitazone/metformin FDC with a similar safety profile, but unlike the rosiglitazone/metformin FDC, repaglinide/metformin FDC improves the lipid profile. Repaglinide/metformin FDC represents a new option in the pursuit of achieving glucose targets and reducing vascular risk in type 2 diabetes, with the advantage of improving adherence.

Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

PubMed

Landry, Susan H; Smith, Karen E; Swank, Paul R

2006-07-01

Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

Matrix multiplication operations with data pre-conditioning in a high performance computing architecture

DOEpatents

Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A

2013-11-05

Mechanisms for performing matrix multiplication operations with data pre-conditioning in a high performance computing architecture are provided. A vector load operation is performed to load a first vector operand of the matrix multiplication operation to a first target vector register. A load and splat operation is performed to load an element of a second vector operand and replicating the element to each of a plurality of elements of a second target vector register. A multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the matrix multiplication operation. The partial product of the matrix multiplication operation is accumulated with other partial products of the matrix multiplication operation.

Sexual activity, substance use, and HIV/STD knowledge among detained male adolescents with multiple versus first admissions.

PubMed

Harwell, T S; Trino, R; Rudy, B; Yorkman, S; Gollub, E L

1999-05-01

Incarcerated and detained youth are at high risk for sexually transmitted diseases (STD), including human immunodeficiency virus (HIV). To compare the level of sexual activity and substance use-related risk and knowledge regarding HIV/STD among male adolescents with multiple (YMA) versus first admissions (YFA) to a detention facility as a basis for the development of specific intervention strategies. Sexual and substance use histories, HIV/STD knowledge, and perceived risk were collected through structured interviews of a consecutive sample of detained youth. Human immunodeficiency virus antibody seroprevalence was determined using a blind study of discarded blood. Overall, these youth (N = 486) reported high levels of noninjection drug use, sexual risk activities, and knowledge regarding HIV/STD prevention. Furthermore, most of these youth reported that their risk for HIV infection was low (68%). Eighty-one percent of all youth reported recent (past 6 months) vaginal sex, and 14% reported insertive anal sex. Controlling for age, YMA were more likely to initiate sex at age 13 or younger (OR 1.38; 95% CI, 1.11-1.70), to report eight or more lifetime sex partners (OR 1.36; 95% CI, 1.13-1.63), and to have ever exchanged drugs or money for sex (OR 1.54; 95% CI, 1.08-2.19). However, these youth were less likely to report condom use with their last sex partner (OR 0.74; 95% CI, 0.60-0.93). More than one third (34%) of all youth felt that consistent use of condoms would not provide a high level of protection against HIV. Youth with multiple versus first admissions are at higher risk of HIV/STD infections through their lifetime and recent sexual activities. Interventions targeted to this population will need to address the barriers to and facilitators of condom use, strategies to promote positive attitudes toward condoms, and strategies to reduce the high level of alcohol and substance use.

The Role of Herbs and Spices in Cancer Prevention

PubMed Central

Kaefer, Christine M.; Milner, John A.

2009-01-01

Historically herbs and spices have enjoyed a rich tradition of use for their flavor-enhancement characteristics and for their medicinal properties. The rising prevalence of chronic diseases world-wide and the corresponding rise in health care costs is propelling interest among researchers and the public for these food related items for multiple health benefits, including a reduction in cancer risk and modification of tumor behavior. A growing body of epidemiological and preclinical evidence points to culinary herbs and spices as minor dietary constituents with multiple anticancer characteristics. This review focuses on the anti-microbial, antioxidant, and anti-tumorigenic properties of herbs and spices, their ability to influence carcinogen bioactivation, and likely anticancer contributions. While culinary herbs and spices present intriguing possibilities for health promotion, more complete information is needed about the actual exposures to dietary components that are needed to bring about a response and the molecular target(s) for specific herbs and spices. Only after this information is obtained will it be possible to define appropriate intervention strategies to achieve maximum benefits from herbs and spices without eliciting ill-consequences. PMID:18499033

Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

PubMed Central

Passos, Giordani Rodrigues Dos; Sato, Douglas Kazutoshi; Becker, Jefferson; Fujihara, Kazuo

2016-01-01

Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders. PMID:26941483

An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors

PubMed Central

Gabb, Henry A.; Blake, Catherine

2016-01-01

Background: Simultaneous or sequential exposure to multiple environmental stressors can affect chemical toxicity. Cumulative risk assessments consider multiple stressors but it is impractical to test every chemical combination to which people are exposed. New methods are needed to prioritize chemical combinations based on their prevalence and possible health impacts. Objectives: We introduce an informatics approach that uses publicly available data to identify chemicals that co-occur in consumer products, which account for a significant proportion of overall chemical load. Methods: Fifty-five asthma-associated and endocrine disrupting chemicals (target chemicals) were selected. A database of 38,975 distinct consumer products and 32,231 distinct ingredient names was created from online sources, and PubChem and the Unified Medical Language System were used to resolve synonymous ingredient names. Synonymous ingredient names are different names for the same chemical (e.g., vitamin E and tocopherol). Results: Nearly one-third of the products (11,688 products, 30%) contained ≥ 1 target chemical and 5,229 products (13%) contained > 1. Of the 55 target chemicals, 31 (56%) appear in ≥ 1 product and 19 (35%) appear under more than one name. The most frequent three-way chemical combination (2-phenoxyethanol, methyl paraben, and ethyl paraben) appears in 1,059 products. Further work is needed to assess combined chemical exposures related to the use of multiple products. Conclusions: The informatics approach increased the number of products considered in a traditional analysis by two orders of magnitude, but missing/incomplete product labels can limit the effectiveness of this approach. Such an approach must resolve synonymy to ensure that chemicals of interest are not missed. Commonly occurring chemical combinations can be used to prioritize cumulative toxicology risk assessments. Citation: Gabb HA, Blake C. 2016. An informatics approach to evaluating combined chemical exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155–1165; http://dx.doi.org/10.1289/ehp.1510529 PMID:26955064

Multiple and concurrent sexual partnerships among men who have sex with men in Viet Nam: results from a National Internet-based Cross-sectional Survey.

PubMed

García, M C; Duong, Q L; Meyer, S B; Ward, P R

2016-03-01

Men who have sex with men (MSM) are one of the largest HIV risk groups in Viet Nam and have been understudied. Sexual concurrency and multiple sex partnerships may contribute to high HIV incidence among MSM in Viet Nam. Limited information is available on concurrency and multiple sexual partnerships among MSM in Viet Nam or on the extent to which this population engages in concurrent and multiple unprotected anal intercourse. Data are from a self-administered Internet-based survey of Vietnamese MSM aged 18 years or older, having sex with male partner(s) in the last 12 months and recruited from social networking MSM-specific websites in Viet Nam. Multiple partnerships and concurrency were measured using the UNAIDS-recommended sexual partner matrix, a key component in the questionnaire. Concurrent and multiple sexual partnerships were analyzed at the individual level. Logistic regression analyses were conducted to assess the demographic characteristics and behaviors associated with multiple sexual partnerships. A total of 1695 MSM reported on multiple sexual partnerships; 69.5% indicated multiple sexual partnerships in the last 6 months. A total of 257 MSM reported on concurrent sexual partnerships, with 51.0% reporting penetrative sex with concurrent partners in the last 6 months. Respondents were more likely to engage in multiple sexual partnerships if they were no longer a student, consumed alcohol before and/or during sex, used the Internet to meet casual sex partners and had never participated in a behavioral HIV intervention. Multiple sexual partnerships in the previous 6 months were common among MSM surveyed, as was sexual concurrency. High levels of multiple and concurrent sexual partnerships may be catalyzing the transmission of HIV among MSM in Viet Nam. Given the high prevalence of this high-risk sexual behavior, our findings underscore the urgent need for targeted prevention efforts, focusing on the reduction of multiple and concurrent sexual partners among this key population. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Next-Generation Sequencing Strategy for Evaluating the Most Common Genetic Abnormalities in Multiple Myeloma.

PubMed

Jiménez, Cristina; Jara-Acevedo, María; Corchete, Luis A; Castillo, David; Ordóñez, Gonzalo R; Sarasquete, María E; Puig, Noemí; Martínez-López, Joaquín; Prieto-Conde, María I; García-Álvarez, María; Chillón, María C; Balanzategui, Ana; Alcoceba, Miguel; Oriol, Albert; Rosiñol, Laura; Palomera, Luis; Teruel, Ana I; Lahuerta, Juan J; Bladé, Joan; Mateos, María V; Orfão, Alberto; San Miguel, Jesús F; González, Marcos; Gutiérrez, Norma C; García-Sanz, Ramón

2017-01-01

Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions. Forty-eight newly diagnosed myeloma patients were tested with the panel, which included IGH and six genes that are recurrently mutated in myeloma: NRAS, KRAS, HRAS, TP53, MYC, and BRAF. We identified 14 of 17 IGH translocations previously detected by FISH and three confirmed translocations not detected by FISH, with the additional advantage of breakpoint identification, which can be used as a target for evaluating minimal residual disease. IgH subclass and V(D)J rearrangements were identified in 77% and 65% of patients, respectively. Mutation analysis revealed the presence of missense protein-coding alterations in at least one of the evaluating genes in 16 of 48 patients (33%). This method may represent a time- and cost-effective diagnostic method for the molecular characterization of multiple myeloma. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Avalanche multiplication and impact ionization in amorphous selenium photoconductive target

NASA Astrophysics Data System (ADS)

Park, Wug-Dong; Tanioka, Kenkichi

2014-03-01

The avalanche multiplication factor and the hole ionization coefficient in the amorphous selenium (a-Se) high-gain avalanche rushing amorphous photoconductor (HARP) target depend on the electric field. The phenomenon of avalanche multiplication and impact ionization in the 0.4-µm-thick a-Se HARP target is investigated. The hot carrier energy in the 0.4-µm-thick a-Se HARP target increases linearly as the target voltage increases. The energy relaxation length of hot carriers in the a-Se photoconductor of the 0.4-µm-thick HARP target saturates as the electric field increases. The average energy Eav of a hot carrier and the energy relaxation length λE in the a-Se photoconductor of the 0.4-µm-thick HARP target at 1 × 108 V/m were 0.25 eV and 2.5 nm, respectively. In addition, the hole ionization coefficient β and the avalanche multiplication factor M are derived as a function of the electric field, the average energy of a hot carrier, and the impact ionization energy. The experimental hole ionization coefficient β and the avalanche multiplication factor M in the 0.4-µm-thick a-Se HARP target agree with the theoretical results.

Identifying Drug-Target Interactions with Decision Templates.

PubMed

Yan, Xiao-Ying; Zhang, Shao-Wu

2018-01-01

During the development process of new drugs, identification of the drug-target interactions wins primary concerns. However, the chemical or biological experiments bear the limitation in coverage as well as the huge cost of both time and money. Based on drug similarity and target similarity, chemogenomic methods can be able to predict potential drug-target interactions (DTIs) on a large scale and have no luxurious need about target structures or ligand entries. In order to reflect the cases that the drugs having variant structures interact with common targets and the targets having dissimilar sequences interact with same drugs. In addition, though several other similarity metrics have been developed to predict DTIs, the combination of multiple similarity metrics (especially heterogeneous similarities) is too naïve to sufficiently explore the multiple similarities. In this paper, based on Gene Ontology and pathway annotation, we introduce two novel target similarity metrics to address above issues. More importantly, we propose a more effective strategy via decision template to integrate multiple classifiers designed with multiple similarity metrics. In the scenarios that predict existing targets for new drugs and predict approved drugs for new protein targets, the results on the DTI benchmark datasets show that our target similarity metrics are able to enhance the predictive accuracies in two scenarios. And the elaborate fusion strategy of multiple classifiers has better predictive power than the naïve combination of multiple similarity metrics. Compared with other two state-of-the-art approaches on the four popular benchmark datasets of binary drug-target interactions, our method achieves the best results in terms of AUC and AUPR for predicting available targets for new drugs (S2), and predicting approved drugs for new protein targets (S3).These results demonstrate that our method can effectively predict the drug-target interactions. The software package can freely available at https://github.com/NwpuSY/DT_all.git for academic users. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A unique role of endogenous visual-spatial attention in rapid processing of multiple targets

PubMed Central

Guzman, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru

2012-01-01

Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions). We report that endogenous attention uniquely contributes to processing of multiple targets. For speeded visual discrimination, response times are faster for multiple redundant targets than for single targets due to probability summation and/or signal integration. This redundancy gain was unaffected when attention was exogenously diverted from the targets, but was completely eliminated when attention was endogenously diverted. This was not due to weaker manipulation of exogenous attention because our exogenous and endogenous cues similarly affected overall response times. Thus, whereas exogenous attention is superior for processing single targets, endogenous attention plays a unique role in allocating resources crucial for rapid concurrent processing of multiple targets. PMID:21517209

Dynamic optimization of ISR sensors using a risk-based reward function applied to ground and space surveillance scenarios

NASA Astrophysics Data System (ADS)

DeSena, J. T.; Martin, S. R.; Clarke, J. C.; Dutrow, D. A.; Newman, A. J.

2012-06-01

As the number and diversity of sensing assets available for intelligence, surveillance and reconnaissance (ISR) operations continues to expand, the limited ability of human operators to effectively manage, control and exploit the ISR ensemble is exceeded, leading to reduced operational effectiveness. Automated support both in the processing of voluminous sensor data and sensor asset control can relieve the burden of human operators to support operation of larger ISR ensembles. In dynamic environments it is essential to react quickly to current information to avoid stale, sub-optimal plans. Our approach is to apply the principles of feedback control to ISR operations, "closing the loop" from the sensor collections through automated processing to ISR asset control. Previous work by the authors demonstrated non-myopic multiple platform trajectory control using a receding horizon controller in a closed feedback loop with a multiple hypothesis tracker applied to multi-target search and track simulation scenarios in the ground and space domains. This paper presents extensions in both size and scope of the previous work, demonstrating closed-loop control, involving both platform routing and sensor pointing, of a multisensor, multi-platform ISR ensemble tasked with providing situational awareness and performing search, track and classification of multiple moving ground targets in irregular warfare scenarios. The closed-loop ISR system is fullyrealized using distributed, asynchronous components that communicate over a network. The closed-loop ISR system has been exercised via a networked simulation test bed against a scenario in the Afghanistan theater implemented using high-fidelity terrain and imagery data. In addition, the system has been applied to space surveillance scenarios requiring tracking of space objects where current deliberative, manually intensive processes for managing sensor assets are insufficiently responsive. Simulation experiment results are presented. The algorithm to jointly optimize sensor schedules against search, track, and classify is based on recent work by Papageorgiou and Raykin on risk-based sensor management. It uses a risk-based objective function and attempts to minimize and balance the risks of misclassifying and losing track on an object. It supports the requirement to generate tasking for metric and feature data concurrently and synergistically, and account for both tracking accuracy and object characterization, jointly, in computing reward and cost for optimizing tasking decisions.

Does age of onset of risk behaviors mediate the relationship between child abuse and neglect and outcomes in middle adulthood?

PubMed

Horan, Jacqueline M; Widom, Cathy Spatz

2015-03-01

Child maltreatment has been linked with a number of risk behaviors that are associated with long-lasting maladaptive outcomes across multiple domains of functioning. This study examines whether the ages of onset of four risk behaviors-sexual intercourse, alcohol use, drug use, and criminal behavior-mediate the relationship between child maltreatment and outcomes in middle adulthood among a sample of court-documented victims of child abuse/neglect and matched controls (N = 1,196; 51.7% female; 66.2% White, 32.6% Black). Adult outcomes included employment status, welfare receipt, internalizing symptoms of anxiety and depressive symptoms, substance use problems, and criminal arrests. The results indicated gender differences in these relationships. For females, age of onset of sexual intercourse mediated the relationship between child abuse/neglect and both internalizing symptoms and substance use problems in middle adulthood. For males, age at first criminal arrest mediated the relationship between child abuse/neglect and extensive involvement in the justice system in middle adulthood. Age of onset of alcohol use and drug use did not mediate the relationship between child abuse/neglect and middle adult outcomes. This study expands current knowledge by identifying associations between early initiation of risk behavior in one domain and later, continuing problems in different domains. Thus, early initiation of specific risk behaviors may have more wide-ranging negative consequences than are typically considered during intervention or treatment and strategies may need to target multiple domains of functioning.

Does Age of Onset of Risk Behaviors Mediate the Relationship between Child Abuse and Neglect and Outcomes in Middle Adulthood?

PubMed Central

Horan, Jacqueline M.; Widom, Cathy Spatz

2014-01-01

Child maltreatment has been linked with a number of risk behaviors that are associated with long-lasting maladaptive outcomes across multiple domains of functioning. This study examines whether the ages of onset of four risk behaviors—sexual intercourse, alcohol use, drug use, and criminal behavior—mediate the relationship between child maltreatment and outcomes in middle adulthood among a sample of court-documented victims of child abuse/neglect and matched controls (N = 1,196; 51.7% female; 66.2% White, 32.6% Black). Adult outcomes included employment status, welfare receipt, internalizing symptoms of anxiety and depressive symptoms, substance use problems, and criminal arrests. The results indicated gender differences in these relationships. For females, age of onset of sexual intercourse mediated the relationship between child abuse/neglect and both internalizing symptoms and substance use problems in middle adulthood. For males, age at first criminal arrest mediated the relationship between child abuse/neglect and extensive involvement in the justice system in middle adulthood. Age of onset of alcohol use and drug use did not mediate the relationship between child abuse/neglect and middle adult outcomes. This study expands current knowledge by identifying associations between early initiation of risk behavior in one domain and later, continuing problems in different domains. Thus, early initiation of specific risk behaviors may have more wide-ranging negative consequences than are typically considered during intervention or treatment and strategies may need to target multiple domains of functioning. PMID:25104419

Community narratives about women and HIV risk in 21 high-burden communities in Zambia and South Africa.

PubMed

Viljoen, Lario; Ndubani, Rhoda; Bond, Virginia; Seeley, Janet; Reynolds, Lindsey; Hoddinott, Graeme

2017-01-01

Public health researchers repeatedly represent women as a group vulnerable to ill health. This has been particularly true in the field of HIV research, where women are disproportionately affected by HIV in terms of disease burden and the social effects of the epidemic. Although women have been the focus of many prevention and treatment programs, structural barriers to implementation of these targeted programs persist. In this article we explore how high HIV-burden communities in South Africa and Zambia engage with the concepts of "woman" and "HIV risk". The data are drawn from participatory storytelling activities completed with 604 participants across 78 group discussions between December 2012 and May 2013. During discussions we found that participants made use of the core archetypal caricatures of "goodness," "badness," and "vulnerability" when describing women's HIV risk. Community members shifted between these categories in their characterizations of women, as they acknowledged the multiple roles women play, internalized different stories about women, and sometimes shifted register in the same stories. Findings suggest that health implementers, in consultation with community members, should consider the multiple positions women occupy and how this impacts the wider community's understandings of women and "risk". This approach of taking on board community understandings of the complexity of HIV risk can inform the design and implementation of HIV prevention and care programs by rendering programs more focused and in-line with community needs.

Sensor Compromise Detection in Multiple-Target Tracking Systems

PubMed Central

Doucette, Emily A.; Curtis, Jess W.

2018-01-01

Tracking multiple targets using a single estimator is a problem that is commonly approached within a trusted framework. There are many weaknesses that an adversary can exploit if it gains control over the sensors. Because the number of targets that the estimator has to track is not known with anticipation, an adversary could cause a loss of information or a degradation in the tracking precision. Other concerns include the introduction of false targets, which would result in a waste of computational and material resources, depending on the application. In this work, we study the problem of detecting compromised or faulty sensors in a multiple-target tracker, starting with the single-sensor case and then considering the multiple-sensor scenario. We propose an algorithm to detect a variety of attacks in the multiple-sensor case, via the application of finite set statistics (FISST), one-class classifiers and hypothesis testing using nonparametric techniques. PMID:29466314

Multiple shell fusion targets

DOEpatents

Lindl, J.D.; Bangerter, R.O.

1975-10-31

Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

Impact of functional and structural social relationships on two year depression outcomes: A multivariate analysis.

PubMed

Davidson, Sandra K; Dowrick, Christopher F; Gunn, Jane M

2016-03-15

High rates of persistent depression highlight the need to identify the risk factors associated with poor depression outcomes and to provide targeted interventions to people at high risk. Although social relationships have been implicated in depression course, interventions targeting social relationships have been disappointing. Possibly, interventions have targeted the wrong elements of relationships. Alternatively, the statistical association between relationships and depression course is not causal, but due to shared variance with other factors. We investigated whether elements of social relationships predict major depressive episode (MDE) when multiple relevant variables are considered. Data is from a longitudinal study of primary care patients with depressive symptoms. 494 participants completed questionnaires at baseline and a depression measure (PHQ-9) two years later. Baseline measures included functional (i.e. quality) and structural (i.e. quantity) social relationships, depression, neuroticism, chronic illness, alcohol abuse, childhood abuse, partner violence and sociodemographic characteristics. Logistic regression with generalised estimating equations was used to estimate the association between social relationships and MDE. Both functional and structural social relationships predicted MDE in univariate analysis. Only functional social relationships remained significant in multivariate analysis (OR: 0.87; 95%CI: 0.79-0.97; p=0.01). Other unique predictors of MDE were baseline depression severity, neuroticism, childhood sexual abuse and intimate partner violence. We did not assess how a person's position in their depression trajectory influenced the association between social relationships and depression. Interventions targeting relationship quality may be part of a personalised treatment plan for people at high risk due of persistent depression due to poor social relationships. Copyright © 2015 Elsevier B.V. All rights reserved.

Safety Lead Optimization and Candidate Identification: Integrating New Technologies into Decision-Making.

PubMed

Dambach, Donna M; Misner, Dinah; Brock, Mathew; Fullerton, Aaron; Proctor, William; Maher, Jonathan; Lee, Dong; Ford, Kevin; Diaz, Dolores

2016-04-18

Discovery toxicology focuses on the identification of the most promising drug candidates through the development and implementation of lead optimization strategies and hypothesis-driven investigation of issues that enable rational and informed decision-making. The major goals are to [a] identify and progress the drug candidate with the best overall drug safety profile for a therapeutic area, [b] remove the most toxic drugs from the portfolio prior to entry into humans to reduce clinical attrition due to toxicity, and [c] establish a well-characterized hazard and translational risk profile to enable clinical trial designs. This is accomplished through a framework that balances the multiple considerations to identify a drug candidate with the overall best drug characteristics and provides a cogent understanding of mechanisms of toxicity. The framework components include establishing a target candidate profile for each program that defines the qualities of a successful candidate based on the intended therapeutic area, including the risk tolerance for liabilities; evaluating potential liabilities that may result from engaging the therapeutic target (pharmacology-mediated or on-target) and that are chemical structure-mediated (off-target); and characterizing identified liabilities. Lead optimization and investigation relies upon the integrated use of a variety of technologies and models (in silico, in vitro, and in vivo) that have achieved a sufficient level of qualification or validation to provide confidence in their use. We describe the strategic applications of various nonclinical models (established and new) for a holistic and integrated risk assessment that is used for rational decision-making. While this review focuses on strategies for small molecules, the overall concepts, approaches, and technologies are generally applicable to biotherapeutics.

Developmental Patterns of Adolescent Marijuana and Alcohol Use and Their Joint Association with Sexual Risk Behavior and Outcomes in Young Adulthood.

PubMed

Green, Kerry M; Musci, Rashelle J; Matson, Pamela A; Johnson, Renee M; Reboussin, Beth A; Ialongo, Nicholas S

2017-02-01

Urban populations disproportionately experience poor sexual outcomes, including high rates of teenage pregnancy and sexually transmitted infections. However, the contribution of substance use across adolescence to poor sexual outcomes in young adulthood has not been investigated in depth, despite offering opportunities for more targeted prevention. This study aimed to estimate joint trajectories of adolescent alcohol and marijuana use to determine if they relate differently to four sexual outcomes: multiple sexual partners, sex without a condom, teenage pregnancy, and contraction of a sexually transmitted infection in young adulthood (by age 25). Data came from a longitudinal study of urban youth followed from age 6 to age 25, with annual assessments during adolescence and young adulthood (n = 608). The sample showed high levels of sexual risk, with young adults on average having sex without a condom once in the past month, 28.5% having multiple sexual partners in the past month, one quarter having contracted a sexually transmitted infection, and over 60% of the women being pregnant as a teenager and 36% of the men having gotten a partner pregnant. Applying longitudinal latent profile analysis to estimate joint trajectories of alcohol and marijuana use from grades 8-12, we identified four classes representing high dual use, moderate alcohol use, moderate alcohol use with increasing marijuana use, and non-use. Class membership differently predicted all four outcomes investigated with high dual users having the highest level of teenage pregnancy and the increasing marijuana trajectory having the highest risk of engaging with multiple sexual partners in the past month. Results suggest implications for both sexual risk and substance use prevention for urban youth.

Metabolic risk and television time in adolescent females.

PubMed

Machado-Rodrigues, Aristides M; Leite, Neiva; Coelho-e-Silva, Manuel J; Enes, Fernando; Fernandes, Rômulo; Mascarenhas, Luís P G; Boguszewski, Margaret C S; Malina, Robert M

2015-02-01

A sedentary lifestyle is increasingly implicated in a negative metabolic health profile among youth. The present study examined relationships between clustered metabolic risk factors and TV viewing in female adolescents. The sample comprised 262 girls 14-17 years. Height, weight, fasting glucose, insulin, HDL cholesterol, triglycerides, and blood pressure were measured. Body mass index (BMI) was calculated. TV viewing time and moderate-to-vigorous physical activity (MVPA) were estimated from a 3-day diary. Outcome variables were normalized and expressed as Z scores which were summed into a metabolic risk score. Multiple linear regression analysis was used. TV viewing was independently associated with increased prevalence of clustered metabolic risk in girls after adjustment for several confounders (i.e., chronological age, BMI, MVPA, and parental education). The final model also indicated that lower levels of MVPA, higher BMI, and lower mother education were associated with higher metabolic risk. Increased TV viewing had an adverse effect on metabolic health of adolescent girls. The findings highlight the potential importance of preventive actions to ameliorate metabolic risk in youth which target both sedentary and physically active behaviors.

Children of incarcerated parents: how a mentoring program can make a difference.

PubMed

Laakso, Janice; Nygaard, Julie

2012-01-01

In spite of the rapid increase in the U.S. prison population, with subsequent increase of parent-prisoners, there are few requirements that social systems serving children take note of a parent's incarceration. Thus the special needs of children of incarcerated parents are almost invisible. Given the multiple risks that these children experience, it is critical to recognize community programs that can help bridge the difficulties children face during their parents' incarceration. This article reports the outcome of a mentoring program specifically targeted to these children. The results show that although mentoring cannot address all of the issues facing these children, it can produce positive outcomes that may mitigate some of the risks associated with being a child of an incarcerated parent.

Posttraumatic Stress Disorder and Suicidal Behavior: Indirect Effects of Impaired Social Functioning.

PubMed

Dutton, Courtney E; Rojas, Sasha M; Badour, Christal L; Wanklyn, Sonya G; Feldner, Matthew T

2016-01-01

Social functioning is negatively impacted by the presence of PTSD, while increasing risk of suicidal behavior among individuals with PTSD. However, little research has examined the specific role of social functioning in the association between PTSD and suicidal behavior. Parallel multiple indirect effects analyses were performed to understand the unique indirect effects of four aspects of social functioning. Indirect effects of PTSD on suicidal ideation were significant through three pathways: interpersonal conflict, perceived family support, and interpersonal apprehension. Perceived family support was the only indirect pathway significantly associated with suicide attempt. Findings suggest that social functioning should be assessed and potentially targeted during treatment to help modify the risk for suicidal behavior among individuals with PTSD.

Hybrid foraging search: Searching for multiple instances of multiple types of target.

PubMed

Wolfe, Jeremy M; Aizenman, Avigael M; Boettcher, Sage E P; Cain, Matthew S

2016-02-01

This paper introduces the "hybrid foraging" paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8-64 target objects in memory. They viewed displays of 60-105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25-33% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hybrid foraging search: Searching for multiple instances of multiple types of target

PubMed Central

Wolfe, Jeremy M.; Aizenman, Avigael M.; Boettcher, Sage E.P.; Cain, Matthew S.

2016-01-01

This paper introduces the “hybrid foraging” paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8–64 targets objects in memory. They viewed displays of 60–105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25–33% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search. PMID:26731644

Building uncertainty into cost-effectiveness rankings: portfolio risk-return tradeoffs and implications for decision rules.

PubMed

O'Brien, B J; Sculpher, M J

2000-05-01

Current principles of cost-effectiveness analysis emphasize the rank ordering of programs by expected economic return (eg, quality-adjusted life-years gained per dollar expended). This criterion ignores the variance associated with the cost-effectiveness of a program, yet variance is a common measure of risk when financial investment options are appraised. Variation in health care program return is likely to be a criterion of program selection for health care managers with fixed budgets and outcome performance targets. Characterizing health care resource allocation as a risky investment problem, we show how concepts of portfolio analysis from financial economics can be adopted as a conceptual framework for presenting cost-effectiveness data from multiple programs as mean-variance data. Two specific propositions emerge: (1) the current convention of ranking programs by expected return is a special case of the portfolio selection problem in which the decision maker is assumed to be indifferent to risk, and (2) for risk-averse decision makers, the degree of joint risk or covariation in cost-effectiveness between programs will create incentives to diversify an investment portfolio. The conventional normative assumption of risk neutrality for social-level public investment decisions does not apply to a large number of health care resource allocation decisions in which health care managers seek to maximize returns subject to budget constraints and performance targets. Portfolio theory offers a useful framework for studying mean-variance tradeoffs in cost-effectiveness and offers some positive predictions (and explanations) of actual decision making in the health care sector.

Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial

PubMed Central

Grimm, Richard; Malik, Mobin; Yunis, Carla; Sutradhar, Santosh; Kursun, Attila

2010-01-01

TOGETHER investigated whether targeting multiple cardiovascular (CV) risk factors using single-pill amlodipine/atorvastatin (AML/ATO) and therapeutic lifestyle changes (TLC) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease (CVD) risk compared with blood pressure intervention only using amlodipine (AML) + TLC. TOGETHER was a 6-week, randomized, double-blind, double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes. Participants were randomized to either AML/ATO (5 to 10/20 mg) + TLC or AML (5 to 10 mg) + TLC. The primary end point was the difference in proportion of participants attaining both BP (<140/90 mm Hg) and low-density lipoprotein cholesterol (LDL-C) (<100 mg/dL) goals at week 6. At week 6, 67.8% of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6% with AML + TLC (RD [A–B]: 58.2; 95% CI [48.1 to 68.4] P < 0.001; OR: 19.0; 95% CI 9.1 to 39.6; P < 0.001). Significant reductions from baseline in LDL-C, total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed. Treatment with AML/ATO was well tolerated. In conclusion, a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population. PMID:20479948

Relationship between risk factor control and vascular events in the SAMMPRIS trial

PubMed Central

Nizam, Azhar; Lynn, Michael J.; Egan, Brent M.; Le, Ngoc-Anh; Lopes-Virella, Maria F.; Hermayer, Kathie L.; Harrell, Jamie; Derdeyn, Colin P.; Fiorella, David; Janis, L. Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I.

2017-01-01

Objective: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Methods: Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Results: Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non–high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4–0.8). Conclusions: Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. ClinicalTrials.gov identifier: NCT00576693. PMID:28003500

Maternal embryonic leucine zipper kinase is a novel target for proliferation-associated high-risk myeloma

PubMed Central

Bolomsky, Arnold; Heusschen, Roy; Schlangen, Karin; Stangelberger, Kathrin; Muller, Joséphine; Schreiner, Wolfgang; Zojer, Niklas; Caers, Jo; Ludwig, Heinz

2018-01-01

Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene expression profiling-defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified in order to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analyzed the activity of the MELK inhibitor OTSSP167 both in vitro and in vivo. MELK was found to be significantly overexpressed in the proliferative subgroup of myeloma. This finding translated into poor overall survival in patients with high vs. low MELK expression. Enrichment analysis of upregulated genes in myeloma cells of MELKhigh patients confirmed the strong implications in myeloma cell proliferation. Targeting MELK with OTSSP167 impaired the growth and survival of myeloma cells, thereby affecting central survival factors such as MCL-1 and IRF4. This activity was also observed in the 5TGM.1 murine model of myeloma. OTSSP167 reduced bone marrow infiltration and serum paraprotein levels in a dose-dependent manner. In addition, we revealed a strong link between MELK and other proliferation-associated high-risk genes (PLK-1, EZH2, FOXM1, DEPDC1) and MELK inhibition also impaired the expression of those genes. We therefore conclude that MELK is an essential component of a proliferative gene signature and that pharmacological inhibition of MELK represents an attractive novel approach to overcome the poor prognosis of high-risk patients with a proliferative expression pattern. PMID:29122991

Who Should Be Targeted for the Prevention of Birth Defects? A Latent Class Analysis Based on a Large, Population-Based, Cross-Sectional Study in Shaanxi Province, Western China.

PubMed

Zhu, Zhonghai; Cheng, Yue; Yang, Wenfang; Li, Danyang; Yang, Xue; Liu, Danli; Zhang, Min; Yan, Hong; Zeng, Lingxia

2016-01-01

The wide range and complex combinations of factors that cause birth defects impede the development of primary prevention strategies targeted at high-risk subpopulations. Latent class analysis (LCA) was conducted to identify mutually exclusive profiles of factors associated with birth defects among women between 15 and 49 years of age using data from a large, population-based, cross-sectional study conducted in Shaanxi Province, western China, between August and October, 2013. The odds ratios (ORs) and 95% confidence intervals (CIs) of associated factors and the latent profiles of indicators of birth defects and congenital heart defects were computed using a logistic regression model. Five discrete subpopulations of participants were identified as follows: No folic acid supplementation in the periconceptional period (reference class, 21.37%); low maternal education level + unhealthy lifestyle (class 2, 39.75%); low maternal education level + unhealthy lifestyle + disease (class 3, 23.71%); unhealthy maternal lifestyle + advanced age (class 4, 4.71%); and multi-risk factor exposure (class 5, 10.45%). Compared with the reference subgroup, the other subgroups consistently had a significantly increased risk of birth defects (ORs and 95% CIs: class 2, 1.75 and 1.21-2.54; class 3, 3.13 and 2.17-4.52; class 4, 5.02 and 3.20-7.88; and class 5, 12.25 and 8.61-17.42, respectively). For congenital heart defects, the ORs and 95% CIs were all higher, and the magnitude of OR differences ranged from 1.59 to 16.15. A comprehensive intervention strategy targeting maternal exposure to multiple risk factors is expected to show the strongest results in preventing birth defects.

A systematic review of risk and protective factors associated with family related violence in refugee families.

PubMed

Timshel, Isabelle; Montgomery, Edith; Dalgaard, Nina Thorup

2017-08-01

The current systematic review summarizes the evidence from studies examining the risk and protective factors associated with family related violence in refugee families. Data included 15 peer-reviewed qualitative and quantitative studies. In order to gain an overview of the identified risk and protective factors an ecological model was used to structure the findings. At the individual level, parental trauma experiences/mental illness, substance abuse and history of child abuse were found to be risk factors. Family level risk factors included parent-child interaction, family structure and family acculturation stress. At the societal level low socioeconomic status was identified as a risk factor. Cultural level risk factors included patriarchal beliefs. Positive parental coping strategies were a protective factor. An ecological analysis of the results suggests that family related violence in refugee families is a result of accumulating, multiple risk factors on the individual, familial, societal and cultural level. The findings suggest that individual trauma and exile related stress do not only affect the individual but have consequences at a family level. Thus, interventions targeting family related violence should not only include the individual, but the family. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predicting Parent-Child Aggression Risk: Cognitive Factors and Their Interaction With Anger.

PubMed

Rodriguez, Christina M

2018-02-01

Several cognitive elements have previously been proposed to elevate risk for physical child abuse. To predict parent-child aggression risk, the current study evaluated the role of approval of parent-child aggression, perceptions of children as poorly behaved, and discipline attributions. Several dimensions of attributions specifically tied to parents' discipline practices were targeted. In addition, anger experienced during discipline episodes was considered a potential moderator of these cognitive processes. Using a largely multiple-indicator approach, a sample of 110 mothers reported on these cognitive and affective aspects that may occur when disciplining their children as well as responding to measures of parent-child aggression risk. Findings suggest that greater approval of parent-child aggression, negative perceptions of their child's behavior, and discipline attributions independently predicted parent-child aggression risk, with anger significantly interacting with mothers' perception of their child as more poorly behaved to exacerbate their parent-child aggression risk. Of the discipline attribution dimensions evaluated, mothers' sense of external locus of control and believing their child deserved their discipline were related to increase parent-child aggression risk. Future work is encouraged to comprehensively evaluate how cognitive and affective components contribute and interact to increase risk for parent-child aggression.

Suicidal Ideation and Its Recurrence in Boys and Men from Early Adolescence to Early Adulthood: An Event History Analysis

PubMed Central

Kerr, David C. R.; Owen, Lee. D.; Capaldi, Deborah M.

2008-01-01

Occurrence and recurrences of suicidal ideation (SI) were modeled among boys/men assessed annually from ages 12 to 29 years. Multiple-spell discrete-time event history analyses permitted (a) determination of whether risk for SI escalates with prior experiences of SI (Spell effects), (b) while accounting for changes in risk with time (Period effects), and (c) controlling for vulnerability factors. Self-reported SI (presence/absence in past week), depressive symptoms, alcohol/substance use, and antisocial behavior, and official arrest records were collected annually from 205 boys recruited on the basis of community risk for delinquency. Parents’ self-reported psychopathology and SES were collected in childhood. Period effects supported decreasing risk for SI over time. Spell and time-varying, 1-year lagged substance use and depressive symptoms independently predicted increased risk for SI. Models involving SI with intent were explored. Consistent with interpersonal psychological theory, risk for young men’s SI increases with past experience of SI, even with key propensities controlled; however, risk also decays over time. Targeting conditions that confer risk for SI is essential. Preventing and delaying SI occurrence and recurrence may represent independent mechanisms by which prevention efforts operate. PMID:18729614

Cancer risk perception and preventive behaviors among grilled meat vendors.

PubMed

Meerith, Penrawee; Harncharoen, Kitiphong; Srisuphanunt, Mayuna; Kaewboonchoo, Orawan

2012-06-01

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that cause cancers in humans. Exposure results from incomplete burning of organic materials. Grilled meat vendors are occupationally exposed to PAHs in smoke from continuously burning charcoal and meat, which may have chance to get cancer. Individual risk perception is a critical antecedent of preventive behavior However relatively little is known about the cancer risk perception and preventive behaviors among grilled meat vendors. The present study aimed to examine cancer risk perception and preventive behaviors and factors associated with preventive behaviors among grilled meat vendors in Bangkok, Thailand. A cross-sectional survey was used in the present study. The subjects consisted of 40 males and 82 females grilled meat vendors who conducted their jobs at Victory Monument, Bang Lumpoo, Pratunam, Jakkawat or Patumwan. They were interviewed regarding cancer risk perception and preventive behaviors. Multiple logistic regression analysis was used to analyze data. Average cancer risk perception score was 23.3 +/- 3.3 out of 32. About 79.5% of the subjects had high risk perception. The prevalence of good preventive behaviors was 86.1%. The three most frequent preventive behaviors among the subjects during grilling meat were using good quality charcoal (65.6%), ventilation fan (41.0%) and wearing long sleeves shirt (36.1%). Only 10.7% always used gloves. Multiple logistic regression analysis showed 2 factors were independently associated with preventive behaviors: educational level and risk perception. The subjects who had higher educational level or risk perception were more likely to develop better behaviors than those who had a lower educational level and perception (p < 0.05). In conclusion, the present study found that the educational background and cancer risk perception were associated with preventive behaviors among grilled meat vendors. To improve the preventive behaviors among grilled meat vendors, interventions focusing on cancer risk perceptions and considering educational background among target group are recommended.

Social Orientation: Problem Behavior and Motivations Toward Interpersonal Problem Solving Among High Risk Adolescents

PubMed Central

Kuperminc, Gabriel P.; Allen, Joseph P.

2006-01-01

A model of problematic adolescent behavior that expands current theories of social skill deficits in delinquent behavior to consider both social skills and orientation toward the use of adaptive skills was examined in an ethnically and socioeconomically diverse sample of 113 male and female adolescents. Adolescents were selected on the basis of moderate to serious risk for difficulties in social adaptation in order to focus on the population of youth most likely to be targeted by prevention efforts. Structural equation modeling was used to examine cross-sectional data using multiple informants (adolescents, peers, and parents) and multiple methods (performance test and self-report). Adolescent social orientation, as reflected in perceived problem solving effectiveness, identification with adult prosocial values, and self-efficacy expectations, exhibited a direct association to delinquent behavior and an indirect association to drug involvement mediated by demonstrated success in using problem solving skills. Results suggest that the utility of social skill theories of adolescent problem behaviors for informing preventive and remedial interventions can be enhanced by expanding them to consider adolescents’ orientation toward using the skills they may already possess. PMID:16929380

Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

PubMed

Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

2015-02-10

Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

Testing a multiple mediator model of the effect of childhood sexual abuse on adolescent sexual victimization.

PubMed

Bramsen, Rikke H; Lasgaard, Mathias; Koss, Mary P; Shevlin, Mark; Elklit, Ask; Banner, Jytte

2013-01-01

The present study modeled the direct relationship between child sexual abuse (CSA) and adolescent peer-to-peer sexual victimization (APSV) and the mediated effect via variables representing the number of sexual partners, sexual risk behavior, and signaling sexual boundaries. A cross-sectional study on the effect of CSA on APSV was conducted, utilizing a multiple mediator model. Mediated and direct effects in the model were estimated employing Mplus using bootstrapped percentile based confidence intervals to test for significance of mediated effects. The study employed 327 Danish female adolescents with a mean age of 14.9 years (SD = 0.5). The estimates from the mediational model indicated full mediation of the effect of CSA on APSV via number of sexual partners and sexual risk behavior. The current study suggests that the link between CSA and APSV was mediated by sexual behaviors specifically pertaining to situations of social peer interaction, rather than directly on prior experiences of sexual victimization. The present study identifies a modifiable target area for intervention to reduce adolescent sexual revictimization. © 2013 American Orthopsychiatric Association.

Peer and Teacher Effects on the Early Onset of Sexual Intercourse

PubMed Central

Brendgen, Mara; Wanner, Brigitte; Vitaro, Frank

2007-01-01

Objectives. We examined the links between peer rejection and verbal abuse by a teacher during childhood with the early onset of sexual intercourse and the mediating role of delinquent behavior and low self-esteem in this context. Methods. We assessed 312 students (159 girls) in northwestern Quebec annually from kindergarten through seventh grade. Peer identifications were used to assess peer rejection and verbal abuse by teachers from kindergarten through fourth grade. In seventh grade, self-reports were used to assess delinquent behavior, self-esteem, and having sexual intercourse. Multiple sources were used to assess control variables. Results. Multiple imputation-based linear and logistic regressions showed that peer rejection was indirectly associated with a higher risk of early intercourse by its link with lower self-esteem, but only for girls. Verbal abuse by teachers during childhood was directly associated with a higher risk of early sexual intercourse and indirectly by its link with delinquent behavior. Conclusions. The results underline the importance of both peers and teachers in healthy sexual development among youths, especially for girls, and emphasize the need for targeted health and sexual education programs. PMID:17901435

Eliciting a policy response for the rising epidemic of overweight-obesity in India.

PubMed

Khandelwal, S; Reddy, K S

2013-11-01

India is experiencing multiple transitions with respect to nutrition patterns, epidemiology and demography. Along with staggering childhood undernutrition, a rapid rise in chronic diseases and their risk factors including overweight-obesity (O-O), among all sections of society, is compounding India's health challenges. We present an overview of the O-O scenario (prevalence, determinants) and profile existing initiatives to address this modifiable risk factor in India. Urgent attention from all sectors, committed resources, policy support and targeted actions are warranted to combat the dual burden of malnutrition. The health systems should be reoriented and strengthened, in addition to enabling actions in other sectors, to address prevention and control of non-communicable diseases and associated risk factors like O-O. © 2013 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of the International Association for the Study of Obesity.

Modeling the Interplay of Multilevel Risk Factors for Future Academic and Behavior Problems: A Person-Centered Approach

PubMed Central

Lanza, Stephanie T.; Rhoades, Brittany L.; Nix, Robert L.; Greenberg, Mark T.

2010-01-01

This study identified profiles of 13 risk factors across child, family, school, and neighborhood domains in a diverse sample of children in kindergarten from 4 US locations (n = 750; 45% minority). It then examined the relation of those early risk profiles to externalizing problems, school failure, and low academic achievement in Grade 5. A person-centered approach, latent class analysis, revealed four unique risk profiles, which varied considerably across urban African American, urban white, and rural white children. Profiles characterized by several risks that cut across multiple domains conferred the highest risk for negative outcomes. Compared to a variable-centered approach, such as a cumulative risk index, these findings provide a more nuanced understanding of the early precursors to negative outcomes. For example, results suggested that urban children in single-parent homes that have few other risk factors (i.e., show at least average parenting warmth and consistency and report relatively low stress and high social support) are at quite low risk for externalizing problems, but at relatively high risk for poor grades and low academic achievement. These findings provide important information for refining and targeting preventive interventions to groups of children who share particular constellations of risk factors. PMID:20423544

Modeling the interplay of multilevel risk factors for future academic and behavior problems: a person-centered approach.

PubMed

Lanza, Stephanie T; Rhoades, Brittany L; Nix, Robert L; Greenberg, Mark T

2010-05-01

This study identified profiles of 13 risk factors across child, family, school, and neighborhood domains in a diverse sample of children in kindergarten from four US locations (n = 750; 45% minority). It then examined the relation of those early risk profiles to externalizing problems, school failure, and low academic achievement in Grade 5. A person-centered approach, latent class analysis, revealed four unique risk profiles, which varied considerably across urban African American, urban White, and rural White children. Profiles characterized by several risks that cut across multiple domains conferred the highest risk for negative outcomes. Compared to a variable-centered approach, such as a cumulative risk index, these findings provide a more nuanced understanding of the early precursors to negative outcomes. For example, results suggested that urban children in single-parent homes that have few other risk factors (i.e., show at least average parenting warmth and consistency and report relatively low stress and high social support) are at quite low risk for externalizing problems, but at relatively high risk for poor grades and low academic achievement. These findings provide important information for refining and targeting preventive interventions to groups of children who share particular constellations of risk factors.

The utility of multiple synthesized views in the recognition of unfamiliar faces.

PubMed

Jones, Scott P; Dwyer, Dominic M; Lewis, Michael B

2017-05-01

The ability to recognize an unfamiliar individual on the basis of prior exposure to a photograph is notoriously poor and prone to errors, but recognition accuracy is improved when multiple photographs are available. In applied situations, when only limited real images are available (e.g., from a mugshot or CCTV image), the generation of new images might provide a technological prosthesis for otherwise fallible human recognition. We report two experiments examining the effects of providing computer-generated additional views of a target face. In Experiment 1, provision of computer-generated views supported better target face recognition than exposure to the target image alone and equivalent performance to that for exposure of multiple photograph views. Experiment 2 replicated the advantage of providing generated views, but also indicated an advantage for multiple viewings of the single target photograph. These results strengthen the claim that identifying a target face can be improved by providing multiple synthesized views based on a single target image. In addition, our results suggest that the degree of advantage provided by synthesized views may be affected by the quality of synthesized material.

Relationship between Risk Factor Control and Compliance with a Lifestyle Modification Program in the Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis Trial.

PubMed

Turan, Tanya N; Al Kasab, Sami; Nizam, Azhar; Lynn, Michael J; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany F; Montgomery, Jean; Chimowitz, Marc I

2018-03-01

Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had  greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non-high-density lipoprotein, nonsmoking, and exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors. Published by Elsevier Inc.

Criticism of EFSA's scientific opinion on combinatorial effects of 'stacked' GM plants.

PubMed

Bøhn, Thomas

2018-01-01

Recent genetically modified plants tend to include both insect resistance and herbicide tolerance traits. Some of these 'stacked' GM plants have multiple Cry-toxins expressed as well as tolerance to several herbicides. This means that non-target organisms in the environment (biodiversity) will be co-exposed to multiple stressors simultaneously. A similar co-exposure may happen to consumers through chemical residues in the food chain. EFSA, the responsible unit for minimizing risk of harm in European food chains, has expressed its scientific interest in combinatorial effects. However, when new data showed how two Cry-toxins acted in combination (added toxicity), and that the same Cry-toxins showed combinatorial effects when co-exposed with Roundup (Bøhn et al., 2016), EFSA dismissed these new peer-reviewed results. In effect, EFSA claimed that combinatorial effects are not relevant for itself. EFSA was justifying this by referring to a policy question, and by making invalid assumptions, which could have been checked directly with the lead-author. With such approach, EFSA may miss the opportunity to improve its environmental and health risk assessment of toxins and pesticides in the food chain. Failure to follow its own published requests for combinatorial effects research, may also risk jeopardizing EFSA's scientific and public reputation. Copyright © 2017. Published by Elsevier Ltd.

Models and mosaics: investigating cross-cultural differences in risk perception and risk preference.

PubMed

Weber, E U; Hsee, C K

1999-12-01

In this article, we describe a multistudy project designed to explain observed cross-national differences in risk taking between respondents from the People's Republic of China and the United States. Using this example, we develop the following recommendations for cross-cultural investigations. First, like all psychological research, cross-cultural studies should be model based. Investigators should commit themselves to a model of the behavior under study that explicitly specifies possible causal constructs or variables hypothesized to influence the behavior, as well as the relationship between those variables, and allows for individual, group, or cultural differences in the value of these variables or in the relationship between them. This moves the focus from a simple demonstration of cross-national differences toward a prediction of the behavior, including its cross-national variation. Ideally, the causal construct hypothesized and shown to differ between cultures should be demonstrated to serve as a moderator or a mediator between culture and observed behavioral differences. Second, investigators should look for converging evidence for hypothesized cultural effects on behavior by looking at multiple dependent variables and using multiple methodological approaches. Thus, the data collection that will allow for the establishment of conclusive causal connections between a cultural variable and some target behavior can be compared with the creation of a mosaic.

Factors associated with falls in older patients with diffuse polyneuropathy.

PubMed

Richardson, James K

2002-11-01

To identify clinical factors associated with falls by older persons with polyneuropathy (PN). A cross-sectional study of 82 subjects aged 50 to 85 with clinical and electrodiagnostic evidence of PN. Electrodiagnostic and biomechanical research laboratories. Patients referred to the electrodiagnostic laboratory. History and physical examination, including semiquantitative methods of peripheral nerve function, and clinical balance testing. Falls were defined by retrospective self-report over a 2-year period. Forty (48.8%), 28 (34.1%), and 18 (22.0%) subjects reported a history of at least one fall, multiple falls, and injurious falls, respectively. Factors associated with single and multiple falls were similar, so only results for multiple and injurious falls are reported. Bivariate analysis showed that an increased body mass index (BMI) and more severe PN (as determined by the Michigan Diabetes Neuropathy Score) were associated with both fall categories. Men reporting falls also demonstrated a decreased unipedal stance time. Age, sex, nerve conduction study parameters, Romberg testing, medications, and comorbidities were not consistently associated with either fall category. Logistic regression demonstrated that multiple and injurious falls were associated with an increased BMI and more severe PN, controlling for age, sex, medications, and comorbidities (pseudo R2 = 0.458 and 0.484, respectively). Although previous work has demonstrated that all older persons with PN are at increased risk for falls, patients with increased BMI and more severe PN are at particularly high risk and should be targeted for intervention.

Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review.

PubMed

Mushtaq, Adeela; Kapoor, Vikas; Latif, Azka; Iftikhar, Ahmad; Zahid, Umar; McBride, Ali; Abraham, Ivo; Riaz, Irbaz Bin; Anwer, Faiz

2018-05-01

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM. Copyright © 2018 Elsevier B.V. All rights reserved.

Incidence and related clinical factors of falls among older Chinese veterans in military communities: a prospective study.

PubMed

Xu, Wei; Chen, Da-Wei; Jin, Yan-Bin; Dong, Zhen-Jun; Zhang, Wei-Jiang; Chen, Jin-Wen; Yang, Shu-Mei; Wang, Jian-Rong

2015-02-01

[Purpose] The aim of this study was to determine fall incidence and explore clinical factors of falls among older Chinese veterans in military communities. [Subjects and Methods] We carried out a 12-month prospective study among 13 military communities in Beijing, China. Fall events were obtained by self-report to military community liaisons and monthly telephone interviews by researchers. [Results] Among the final sample of 447 older veterans, 86 fell once, 25 fell twice or more, and 152 falls occurred altogether. The incidence of falls and fallers were 342/1,000 person-years and 249/1,000 person-years. In Cox regression models, independent clinical factors associated with falls were visual acuity (RR=0.47), stroke (RR=2.43), lumbar diseases (RR=1.73), sedatives (RR=1.80), fall history in the past 6 months (RR=2.77), multiple chronic diseases (RR=1.53), multiple medications (RR=1.34), and five-repetition sit-to-stand test score (RR=1.41). Hearing acuity was close to being statistically significant. [Conclusion] The incidences of falls and fallers among older Chinese veterans were lower than those of Hong Kong and western countries. The clinical risk factors of falls were poor senses, stroke, lumbar diseases, taking sedatives, fall history in the past 6 months, having multiple chronic diseases, taking multiple medications, and poor physical function. The preventive strategies targeting the above risk factors are very significant for reducing falls.

Incidence and related clinical factors of falls among older Chinese veterans in military communities: a prospective study

PubMed Central

Xu, Wei; Chen, Da-Wei; Jin, Yan-Bin; Dong, Zhen-Jun; Zhang, Wei-Jiang; Chen, Jin-Wen; Yang, Shu-Mei; Wang, Jian-Rong

2015-01-01

[Purpose] The aim of this study was to determine fall incidence and explore clinical factors of falls among older Chinese veterans in military communities. [Subjects and Methods] We carried out a 12-month prospective study among 13 military communities in Beijing, China. Fall events were obtained by self-report to military community liaisons and monthly telephone interviews by researchers. [Results] Among the final sample of 447 older veterans, 86 fell once, 25 fell twice or more, and 152 falls occurred altogether. The incidence of falls and fallers were 342/1,000 person-years and 249/1,000 person-years. In Cox regression models, independent clinical factors associated with falls were visual acuity (RR=0.47), stroke (RR=2.43), lumbar diseases (RR=1.73), sedatives (RR=1.80), fall history in the past 6 months (RR=2.77), multiple chronic diseases (RR=1.53), multiple medications (RR=1.34), and five-repetition sit-to-stand test score (RR=1.41). Hearing acuity was close to being statistically significant. [Conclusion] The incidences of falls and fallers among older Chinese veterans were lower than those of Hong Kong and western countries. The clinical risk factors of falls were poor senses, stroke, lumbar diseases, taking sedatives, fall history in the past 6 months, having multiple chronic diseases, taking multiple medications, and poor physical function. The preventive strategies targeting the above risk factors are very significant for reducing falls. PMID:25729162

The Impact of the Nursing Practice Environment on Missed Nursing Care.

PubMed

Hessels, Amanda J; Flynn, Linda; Cimiotti, Jeannie P; Cadmus, Edna; Gershon, Robyn R M

2015-12-01

Missed nursing care is an emerging problem negatively impacting patient outcomes. There are gaps in our knowledge of factors associated with missed nursing care. The aim of this study was to determine the relationship between the nursing practice environment and missed nursing care in acute care hospitals. This is a secondary analysis of cross sectional data from a survey of over 7.000 nurses from 70 hospitals on workplace and process of care. Ordinary least squares and multiple regression models were constructed to examine the relationship between the nursing practice environment and missed nursing care while controlling for characteristics of nurses and hospitals. Nurses missed delivering a significant amount of necessary patient care (10-27%). Inadequate staffing and inadequate resources were the practice environment factors most strongly associated with missed nursing care events. This multi-site study examined the risk and risk factors associated with missed nursing care. Improvements targeting modifiable risk factors may reduce the risk of missed nursing care.

Alcohol Use as a Determinant of HIV Risk Behaviors Among Recent Latino Immigrants in South Florida

PubMed Central

Rojas, Patria; Dillon, Frank R.; Cyrus, Elena; Ravelo, Gira J.; Malow, Robert M.; De La Rosa, Mario

2013-01-01

Information on the association between alcohol use and Latino sexual risk behavior prior to immigrating to the United States is scarce. Given this population's rapid growth, documenting the influence of alcohol use on Recent Latino Immigrants’ (RLI) sexual risk behaviors is essential. Data prior to immigration were retrospectively collected from 527 RLI ages 18-39. Quantity and frequency of alcohol use during the 90 days prior to immigration and pre-immigration sexual risk behaviors were measured. Structural equation modeling was used to examine the relationships. Males, single participants, and participants with higher incomes reported more alcohol use. Higher alcohol use was associated with lower condom use frequency, having sex under the influence, and more sexual partners among all participants. Results point to the importance of creating interventions targeting adult RLI men, given their likelihood to engage in alcohol consumption, sex under the influence of alcohol, and sex with multiple partners without condoms. PMID:23706771

Promoting Expressive Language in Young Children with or At-Risk for Autism Spectrum Disorder in a Preschool Classroom.

PubMed

Lane, Justin D; Shepley, Collin; Lieberman-Betz, Rebecca

2016-10-01

Young children with autism spectrum disorder (ASD) often demonstrate delays in expressive communication, impacting their ability to independently function in typical environments. Individuals with ASD who develop expressive language during early childhood experience better outcomes later in life; therefore, examination of naturalistic language interventions (NLIs) remain an important area of investigation. The current study used a multiple probe design across participants to examine the effects of a classroom-based NLI on various expressive language targets in three preschool-aged children demonstrating characteristics of ASD. Findings suggest the intervention had positive and maintained effects on trial-based use of language targets, as well as concomitant changes in commenting, requesting, and phrase complexity. Implications regarding implementation of NLIs within typical classroom play activities are discussed.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

PubMed

Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Mitochondrial abnormalities in Alzheimer’s disease: Possible targets for therapeutic intervention

PubMed Central

Silva, Diana F.; Selfridge, J. Eva; Lu, Jianghua; Lezi, E; Cardoso, Sandra M.; Swerdlow, Russell H.

2013-01-01

Mitochondria from persons with Alzheimer’s disease (AD) differ from those of age-matched, control subjects. Differences in mitochondrial morphology and function are well-documented, and are not brain-limited. Some of these differences are present during all stages of AD, and are even seen in individuals who are without AD symptoms and signs but who have an increased risk of developing AD. This chapter considers the status of mitochondria in AD subjects, the potential basis for AD subject mitochondrial perturbations, and the implications of these perturbations. Data from multiple lines of investigation, including epidemiologic, biochemical, molecular, and cytoplasmic hybrid studies are reviewed. The possibility that mitochondria could potentially constitute a reasonable AD therapeutic target is discussed, as are several potential mitochondrial medicine treatment strategies. PMID:22840745

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

PubMed Central

Zhong, Hong; Ma, Minjuan

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction. PMID:29484304

Structured Instruction With Modified Storybooks to Teach Morphosyntax and Vocabulary to Preschoolers Who are Deaf/Hard of Hearing.

PubMed

Richels, Corrin G; Schwartz, Kathryn S; Bobzien, Jonna L; Raver, Sharon A

2016-10-01

Children who are deaf/hard of hearing (D/HH) are at risk for diminished morphosyntactical and vocabulary development. The purpose of this study was to examine the effects of repeated reading combined with structured instruction. Targets were a morphosyntactical form and novel vocabulary words. Participants were 3 preschoolers who are D/HH who were receiving instruction with an oral approach. Data from a multiple baseline design indicated that all children acquired the targeted skills and demonstrated high levels of generalization of these skills to untrained context. Implications for teaching young children who are D/HH using repeated storybook reading are discussed. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acceptable Risk Analysis for Abrupt Environmental Pollution Accidents in Zhangjiakou City, China.

PubMed

Du, Xi; Zhang, Zhijiao; Dong, Lei; Liu, Jing; Borthwick, Alistair G L; Liu, Renzhi

2017-04-20

Abrupt environmental pollution accidents cause considerable damage worldwide to the ecological environment, human health, and property. The concept of acceptable risk aims to answer whether or not a given environmental pollution risk exceeds a societally determined criterion. This paper presents a case study on acceptable environmental pollution risk conducted through a questionnaire survey carried out between August and October 2014 in five representative districts and two counties of Zhangjiakou City, Hebei Province, China. Here, environmental risk primarily arises from accidental water pollution, accidental air pollution, and tailings dam failure. Based on 870 valid questionnaires, demographic and regional differences in public attitudes towards abrupt environmental pollution risks were analyzed, and risk acceptance impact factors determined. The results showed females, people between 21-40 years of age, people with higher levels of education, public servants, and people with higher income had lower risk tolerance. People with lower perceived risk, low-level risk knowledge, high-level familiarity and satisfaction with environmental management, and without experience of environmental accidents had higher risk tolerance. Multiple logistic regression analysis indicated that public satisfaction with environmental management was the most significant factor in risk acceptance, followed by perceived risk of abrupt air pollution, occupation, perceived risk of tailings dam failure, and sex. These findings should be helpful to local decision-makers concerned with environmental risk management (e.g., selecting target groups for effective risk communication) in the context of abrupt environmental accidents.

Preventing delirium in dementia: Managing risk factors.

PubMed

Ford, Andrew H

2016-10-01

Delirium is a common, disabling medical condition that is associated with numerous adverse outcomes. A number of inter-related factors, including pre-existing cognitive impairment, usually contribute to the development of delirium in a particular susceptible individual. Non-pharmacological approaches to prevention typically target multiple risk factors in a systematic manner (multicomponent interventions). There is generally good evidence that multicomponent interventions reduce the incidence of delirium in hospital populations but there are limited data in people with dementia and those living in the community. It is likely that there is a differential effect of specific interventions in those with cognitive impairment (e.g. people with dementia may respond better to simpler, more pragmatic interventions rather than complex procedures) but this cannot be determined from the existing data. Targeted interventions focussed on hydration, medication rationalization and sleep promotion may also be effective in reducing the incidence of delirium, as well as the active involvement of family members in the care of the elderly hospitalized patient. Hospitalization itself is a potential risk factor for delirium and promising data are emerging of the benefits of home-based care as an alternative to hospitalization but this is restricted to specific sub-populations of patients and is reliant on these services being available. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Influenza vaccination coverage among US children from 2004/2005 to 2015/2016.

PubMed

Tian, Changwei; Wang, Hua; Wang, Wenming; Luo, Xiaoming

2018-05-15

Quantify the influenza vaccine coverage is essential to identify emerging concerns and to immunization programs for targeting interventions. Data from National Health Interview Survey were used to estimate receipt of at least one dose of influenza vaccination among children 6 months to 17 years of age. Influenza vaccination coverage increased from 16.70% during 2004/2005 to 49.43% during 2015/2016 (3.18% per year, P < 0.001); however, the coverage increased slightly after 2010/2011. Children at high risk of influenza complications had higher influenza vaccination coverage than non at-risk children. Boys and girls had similar coverage each year. While the coverage increased from 2004/2005 to 2015/2016 for all age groups, the coverage decreased with age each year (-0.64 to -1.58% per age group). There was a higher and rapid increase of coverage in Northeast than Midwest, South and West. American Indian or Alaskan Native and Asian showed higher coverage than other race groups (White, Black/African American, Multiple race). Multivariable analysis showed that high-risk status and region had the greatest associations with levels of vaccine coverage. Although the influenza vaccination coverage among children had increased remarkably since 2004/2005, establishing more effective immunization programs are warranted to achieve the Healthy People 2020 target.

Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework.

PubMed

Rohan, Jennifer M; Huang, Bin; Pendley, Jennifer Shroff; Delamater, Alan; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis

2015-10-01

This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effectiveness of a CD-ROM Nutrient Analysis Program on Self-Monitoring Behavior of Active Duty Military Personnel Receiving Nutrition Counseling for Weight Loss.

DTIC Science & Technology

1999-12-01

classified as "obese" with resulting elevated risk for co- morbid conditions (2). However, only one study is published regarding use of computer...described as one of the single most important predictors of successful weight loss in multiple studies (4,5,6,7,8); however, it consistently remains a...Considering this study as well as previously published studies , the authors propose a target of self-monitoring all foods eaten on at least 75% of

Dynamic conservation of forest genetic resources in 33 European countries.

PubMed

Lefèvre, François; Koskela, Jarkko; Hubert, Jason; Kraigher, Hojka; Longauer, Roman; Olrik, Ditte C; Schüler, Silvio; Bozzano, Michele; Alizoti, Paraskevi; Bakys, Remigijus; Baldwin, Cathleen; Ballian, Dalibor; Black-Samuelsson, Sanna; Bednarova, Dagmar; Bordács, Sándor; Collin, Eric; de Cuyper, Bart; de Vries, Sven M G; Eysteinsson, Thröstur; Frýdl, Josef; Haverkamp, Michaela; Ivankovic, Mladen; Konrad, Heino; Koziol, Czesław; Maaten, Tiit; Notivol Paino, Eduardo; Oztürk, Hikmet; Pandeva, Ivanova Denitsa; Parnuta, Gheorghe; Pilipovič, Andrej; Postolache, Dragos; Ryan, Cathal; Steffenrem, Arne; Varela, Maria Carolina; Vessella, Federico; Volosyanchuk, Roman T; Westergren, Marjana; Wolter, Frank; Yrjänä, Leena; Zariŋa, Inga

2013-04-01

Dynamic conservation of forest genetic resources (FGR) means maintaining the genetic diversity of trees within an evolutionary process and allowing generation turnover in the forest. We assessed the network of forests areas managed for the dynamic conservation of FGR (conservation units) across Europe (33 countries). On the basis of information available in the European Information System on FGR (EUFGIS Portal), species distribution maps, and environmental stratification of the continent, we developed ecogeographic indicators, a marginality index, and demographic indicators to assess and monitor forest conservation efforts. The pan-European network has 1967 conservation units, 2737 populations of target trees, and 86 species of target trees. We detected a poor coincidence between FGR conservation and other biodiversity conservation objectives within this network. We identified 2 complementary strategies: a species-oriented strategy in which national conservation networks are specifically designed for key target species and a site-oriented strategy in which multiple-target units include so-called secondary species conserved within a few sites. The network is highly unbalanced in terms of species representation, and 7 key target species are conserved in 60% of the conservation units. We performed specific gap analyses for 11 tree species, including assessment of ecogeographic, demographic, and genetic criteria. For each species, we identified gaps, particularly in the marginal parts of their distribution range, and found multiple redundant conservation units in other areas. The Mediterranean forests and to a lesser extent the boreal forests are underrepresented. Monitoring the conservation efficiency of each unit remains challenging; however, <2% of the conserved populations seem to be at risk of extinction. On the basis of our results, we recommend combining species-oriented and site-oriented strategies. © 2012 Society for Conservation Biology.

Effectiveness of treat-to-target strategy for LDL-cholesterol control in type 2 diabetes: post-hoc analysis of data from the MIND.IT study.

PubMed

Ardigò, Diego; Vaccaro, Olga; Cavalot, Franco; Rivellese, Albarosa Angela; Franzini, Laura; Miccoli, Roberto; Patti, Lidia; Boemi, Massimo; Trovati, Mariella; Zavaroni, Ivana

2014-04-01

The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study. MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach. Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p < 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction <0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p < 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target. The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

Intimate Partner Violence, Relationship Power Inequity and the Role of Sexual and Social Risk Factors in the Production of Violence among Young Women Who Have Multiple Sexual Partners in a Peri-Urban Setting in South Africa

PubMed Central

Zembe, Yanga Z.; Townsend, Loraine; Thorson, Anna; Silberschmidt, Margrethe; Ekstrom, Anna Mia

2015-01-01

Introduction This paper aims to assess the extent and correlates of intimate partner violence (IPV), explore relationship power inequity and the role of sexual and social risk factors in the production of violence among young women aged 16–24 reporting more than one partner in the past three months in a peri-urban setting in the Western Cape, South Africa. Recent estimates suggest that every six hours a woman is killed by an intimate partner in South Africa, making IPV a leading public health problem in the country. While there is mounting evidence that levels of IPV are high in peri-urban settings in South Africa, not much is known about how it manifests among women who engage in concomitantly high HIV risk behaviours such as multiple sexual partnering, transactional sex and age mixing. We know even less about how such women negotiate power and control if exposed to violence in such sexual networks. Methods Two hundred and fifty nine women with multiple sexual partners, residing in a predominantly Black peri-urban community in the Western Cape, South Africa, were recruited into a bio-behavioural survey using Respondent Driven Sampling (RDS). After the survey, focus group discussions and individual interviews were conducted among young women and men to understand the underlying factors informing their risk behaviours and experiences of violence. Findings 86% of the young women experienced IPV in the past 12 months. Sexual IPV was significantly correlated with sex with a man who was 5 years or older than the index female partner (OR 1.7, 95% CI 1.0–3.2) and transactional sex with most recent casual partner (OR 2.1, 95% CI 1.1–3.8). Predictably, women experienced high levels of relationship power inequity. However, they also identified areas in their controlling relationships where they shared decision making power. Discussion Levels of IPV among young women with multiple sexual partners were much higher than what is reported among women in the general population and shown to be associated with sexual risk taking. Interventions targeting IPV need to address sexual risk taking as it heightens vulnerability to violence. PMID:26599394

Personalizing guidelines for diabetes management: twilight or dawn of the expert?

PubMed

Paschou, Stavroula A; Leslie, Richard David

2013-07-10

This opinion article on the management of type 2 diabetes considers the old and new format of guidelines and critical changes in the character of such guidelines. We highlight limitations of the guidelines and make recommendations for how treatment can be more personalised. Published guidelines for the management of adult-onset non-insulin requiring diabetes have adopted a formulaic approach to patient management that can be overseen centrally and delivered by personnel with limited training. Recently, guidelines have taken a patient-centered, multiple risk-factor approach. Importantly, local funding issues are considered, but drive the final action and not the decision-making process. The nature of the disease can be determined by laboratory tests, including screening for diabetes-associated autoantibodies. The strategy remains step-up, with intensification of drug or insulin dose. As with past guidelines, there is an assumption that in each patient with type 2 diabetes, metformin is used initially, but targets and therapies then veer in different directions to create a matrix of options based on the features and responses of each individual. Factors to consider include: (A)ge, (B)ody weight, (C)omplications and co-morbidities, Diabetes (D)uration and (E)xpense, but also patient preference and patient response. Guidelines for the management of type 2 diabetes have important limitations and a patient-centered, multiple target, multiple therapy approach is proposed.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

In Silico Enhancing M. tuberculosis Protein Interaction Networks in STRING To Predict Drug-Resistance Pathways and Pharmacological Risks.

PubMed

Mei, Suyu

2018-05-04

Bacterial protein-protein interaction (PPI) networks are significant to reveal the machinery of signal transduction and drug resistance within bacterial cells. The database STRING has collected a large number of bacterial pathogen PPI networks, but most of the data are of low quality without being experimentally or computationally validated, thus restricting its further biomedical applications. We exploit the experimental data via four solutions to enhance the quality of M. tuberculosis H37Rv (MTB) PPI networks in STRING. Computational results show that the experimental data derived jointly by two-hybrid and copurification approaches are the most reliable to train an L 2 -regularized logistic regression model for MTB PPI network validation. On the basis of the validated MTB PPI networks, we further study the three problems via breadth-first graph search algorithm: (1) discovery of MTB drug-resistance pathways through searching for the paths between known drug-target genes and drug-resistance genes, (2) choosing potential cotarget genes via searching for the critical genes located on multiple pathways, and (3) choosing essential drug-target genes via analysis of network degree distribution. In addition, we further combine the validated MTB PPI networks with human PPI networks to analyze the potential pharmacological risks of known and candidate drug-target genes from the point of view of system pharmacology. The evidence from protein structure alignment demonstrates that the drugs that act on MTB target genes could also adversely act on human signaling pathways.

Influence of educational status and other variables on HIV risk perception among military personnel: A large cohort finding

PubMed Central

Essien, E. James; Ogungbade, Gbadebo O.; Ward, Doriel; Ekong, Ernest; Ross, Michael W.; Meshack, Angela; Holmes, Laurens

2007-01-01

HIV risk perception remains an effective determinant of HIV transmission. Although higher educational attainment has been associated with increased HIV risk perception, this predictor remains to be assessed among Nigerian military personnel (NMP). In a prospective cohort of 2,213 NMP, the effect of education and other factors on HIV risk perception were assessed at baseline using chi square statistic and unconditional logistic regression. There was an inverse correlation between higher educational attainment and HIV risk perception in the univarible model, prevalence odds ratio (POR), 0.64, 95% confidence interval (CI) = 0.52–0.79. This association persisted after adjustment for relevant covariates in the multivariable model (POR, 0.70, 95% CI=0.56–0.88). Likewise, there was a direct correlation between use of alcohol and marijuana and HIV risk perception (p <0.05). In contrast, casual sex and gender were not statistically significantly associated with HIV risk perception, P >0.05. This study is indicative of an inverse correlation between educational attainment and HIV risk perception, as well as a direct correlation between alcohol and marijuana and HIV risk perception among NMP. Therefore HIV prevention interventions targeted at NMP need to include multiple factors that may impact on risk perception regardless of educational status of the participants. PMID:18062392

Forward-backward emission of target evaporated fragments in high energy nucleus-nucleus collisions

NASA Astrophysics Data System (ADS)

Zhang, Zhi; Ma, Tian-Li; Zhang, Dong-Hai

2015-10-01

The multiplicity distribution, multiplicity moment, scaled variance, entropy and reduced entropy of target evaporated fragments emitted in forward and backward hemispheres in 12 A GeV 4He, 3.7 A GeV 16O, 60 A GeV 16O, 1.7 A GeV 84Kr and 10.7 A GeV 197Au -induced emulsion heavy target (AgBr) interactions are investigated. It is found that the multiplicity distribution of target evaporated fragments emitted in both forward and backward hemispheres can be fitted by a Gaussian distribution. The multiplicity moments of target evaporated particles emitted in the forward and backward hemispheres increase with the order of the moment q, and the second-order multiplicity moment is energy independent over the entire energy range for all the interactions in the forward and backward hemisphere. The scaled variance, a direct measure of multiplicity fluctuations, is close to one for all the interactions, which indicate a correlation among the produced particles. The entropy of target evaporated fragments emitted in both forward and backward hemispheres are the same within experimental errors. Supported by National Science Foundation of China (11075100), Natural Science Foundation of Shanxi Province (2011011001-2) and the Shanxi Provincial Foundation for Returned Overseas Chinese Scholars, (2011-058)

Cumulative effects of mothers' risk and promotive factors on daughters' disruptive behavior.

PubMed

van der Molen, Elsa; Hipwell, Alison E; Vermeiren, Robert; Loeber, Rolf

2012-07-01

Little is known about the ways in which the accumulation of maternal factors increases or reduces risk for girls' disruptive behavior during preadolescence. In the current study, maternal risk and promotive factors and the severity of girls' disruptive behavior were assessed annually among girls' ages 7-12 in an urban community sample (N = 2043). Maternal risk and promotive factors were operative at different time points in girls' development. Maternal warmth explained variance in girls' disruptive behavior, even after controlling for maternal risk factors and relevant child and neighborhood factors. In addition, findings supported the cumulative hypothesis that the number of risk factors increased the chance on girls' disruptive behavior disorder (DBD), while the number of promotive factors decreased this probability. Daughters of mothers with a history of Conduct Disorder (CD) were exposed to more risk factors and fewer promotive factors compared to daughters of mothers without prior CD. The identification of malleable maternal factors that can serve as targets for intervention has important implications for intergenerational intervention. Cumulative effects show that the focus of prevention efforts should not be on single factors, but on multiple factors associated with girls' disruptive behavior.

Cumulative Effects of Mothers’ Risk and Promotive Factors on Daughters’ Disruptive Behavior

PubMed Central

Hipwell, Alison E.; Vermeiren, Robert; Loeber, Rolf

2012-01-01

Little is known about the ways in which the accumulation of maternal factors increases or reduces risk for girls’ disruptive behavior during preadolescence. In the current study, maternal risk and promotive factors and the severity of girls’ disruptive behavior were assessed annually among girls’ ages 7–12 in an urban community sample (N=2043). Maternal risk and promotive factors were operative at different time points in girls’ development. Maternal warmth explained variance in girls’ disruptive behavior, even after controlling for maternal risk factors and relevant child and neighborhood factors. In addition, findings supported the cumulative hypothesis that the number of risk factors increased the chance on girls’ disruptive behavior disorder (DBD), while the number of promotive factors decreased this probability. Daughters of mothers with a history of Conduct Disorder (CD) were exposed to more risk factors and fewer promotive factors compared to daughters of mothers without prior CD. The identification of malleable maternal factors that can serve as targets for intervention has important implications for intergenerational intervention. Cumulative effects show that the focus of prevention efforts should not be on single factors, but on multiple factors associated with girls’ disruptive behavior. PMID:22127641

Pre-migration trauma and HIV-risk behavior.

PubMed

Steel, Jennifer; Herlitz, Claes; Matthews, Jesse; Snyder, Wendy; Mazzaferro, Kathryn; Baum, Andy; Theorell, Töres

2003-03-01

This study examined the relationship between pre-migration trauma and HIV-risk behavior in refugees from sub-Saharan Africa. The sample comprised 122 persons who had emigrated from sub-Saharan Africa and were currently residing in Sweden. Qualitative methods including individual interviews, focus groups, and interviews with key informants addressed questions regarding trauma experience and HIV-risk behavior. A history of pre-migration trauma was found to be associated with HIV-risk behavior. According to the participants, symptoms associated with post-traumatic stress disorder, depression, adjustment disorder, and substance use mediated the relationship between pre-migration trauma and sexual risk behavior. In contrast, a minority of the participants who reported pre-migration trauma but not psychological sequelae, or experienced post-traumatic growth, reported safer sexual practices. It appears that for some individuals, pre-migration trauma resulted in psychiatric sequelae, which may increase an individual's risk to be infected with HIV. Interventions targeted at individuals at increased risk (i.e. pre-migration trauma with unresolved psychiatric symptomatology) may facilitate the prevention of HIV and other sexually transmitted diseases in this population. Integration of multiple psychosocial and health issues is recommended for comprehensive treatment and prevention programs.

76 FR 34953 - Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... Corporation Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program... Corporation (FCIC), operating through the Risk Management Agency (RMA), announces its intent to award... same time as funding availability for similar but separate program, the Risk Management Education and...

Spatially explicit risk approach for multi-hazard assessment and management in marine environment: The case study of the Adriatic Sea.

PubMed

Furlan, Elisa; Torresan, Silvia; Critto, Andrea; Marcomini, Antonio

2018-03-15

In the last few decades the health of marine ecosystems has been progressively endangered by the anthropogenic presence. Natural and human-made pressures, as well as climate change effects, are posing increasing threats on marine areas, triggering alteration of biological, chemical and physical processes. Planning of marine areas has become a challenge for decision makers involved in the design of sustainable management options. In order to address threats posed by climate drivers in combination with local to regional anthropogenic pressures affecting marine ecosystems and activities, a multi-hazard assessment methodology was developed and applied to the Adriatic Sea for the reference scenario 2000-2015. Through a four-stages process based on the consecutive analysis of hazard, exposure, vulnerability and risk the methodology allows a semi-quantitative evaluation of the relative risk from anthropogenic and natural sources to multiple endpoints, thus supporting the identification and ranking of areas and targets more likely to be at risk. Resulting output showed that the higher relative hazard scores are linked to exogenic pressures (e.g. sea surface temperature variation) while the lower ones resulted from endogenic and more localized stressors (e.g. abrasion, nutrient input). Relatively very high scores were observed for vulnerability over the whole case study for almost all the considered pressures, showing seagrasses meadows, maërl and coral beds as the most susceptible targets. The approach outlined in this study provides planners and decision makers a quick-screening tool to evaluate progress towards attaining a good environmental status and to identify marine areas where management actions and adaptation strategies would be best targeted. Moreover, by focusing on risks induced by land-based drivers, resulting output can support the design of infrastructures for reducing pressures on the sea, contributing to improve the land-sea interface management. Copyright © 2017 Elsevier B.V. All rights reserved.

Global Natural Disaster Risk Hotspots: Transition to a Regional Approach

NASA Astrophysics Data System (ADS)

Lerner-Lam, A.; Chen, R.; Dilley, M.

2005-12-01

The "Hotspots Project" is a collaborative study of the global distribution and occurrence of multiple natural hazards and the associated exposures of populations and their economic output. In this study we assess the global risks of two disaster-related outcomes: mortality and economic losses. We estimate risk levels by combining hazard exposure with historical vulnerability for two indicators of elements at risk-gridded population and Gross Domestic Product (GDP) per unit area - for six major natural hazards: earthquakes, volcanoes, landslides, floods, drought, and cyclones. By calculating relative risks for each grid cell rather than for countries as a whole, we are able to estimate risk levels at sub-national scales. These can then be used to estimate aggregate relative multiple hazard risk at regional and national scales. Mortality-related risks are assessed on a 2.5' x 2.5' latitude-longitude grid of global population (GPW Version 3). Economic risks are assessed at the same resolution for gridded GDP per unit area, using World Bank estimates of GDP based on purchasing power parity. Global hazard data were compiled from multiple sources. The project collaborated directly with UNDP and UNEP, the International Research Institute for Climate Prediction (IRI) at Columbia, and the Norwegian Geotechnical Institute (NGI) in the creation of data sets for several hazards for which global data sets did not previously exist. Drought, flood and volcano hazards are characterized in terms of event frequency, storms by frequency and severity, earthquakes by frequency and ground acceleration exceedance probability, and landslides by an index derived from probability of occurrence. The global analysis undertaken in this project is clearly limited by issues of scale as well as by the availability and quality of data. For some hazards, there exist only 15- to 25-year global records with relatively crude spatial information. Data on historical disaster losses, and particularly on economic losses, are also limited. On one hand the data are adequate for general identification of areas of the globe that are at relatively higher single- or multiple-hazard risk than other areas. On the other hand they are inadequate for understanding the absolute levels of risk posed by any specific hazard or combination of hazards. Nevertheless it is possible to assess in general terms the exposure and potential magnitude of losses to people and their assets in these areas. Such information, although not ideal, can still be very useful for informing a range of disaster prevention and preparedness measures, including prioritization of resources, targeting of more localized and detailed risk assessments, implementation of risk-based disaster management and emergency response strategies, and development of long-term plans for poverty reduction and economic development. In addition to summarizing the results of the Hotspots Project, we discuss data collection issues and suggest methodological approaches for making the transition to more detailed regional and national studies. Preliminary results for several regional case studies will be presented.

Incorporating Multiple Secondary Targets into Learning Trials for Individuals with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Nottingham, Casey L.; Vladescu, Jason C.; Kodak, Tiffany; Kisamore, April N.

2017-01-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary…

HIV Risk Behavior Among Methamphetamine Users Entering Substance Abuse Treatment in Cape Town, South Africa.

PubMed

Meade, Christina S; Lion, Ryan R; Cordero, Daniella M; Watt, Melissa H; Joska, John A; Gouse, Hetta; Burnhams, Warren

2016-10-01

South Africa is experiencing a growing methamphetamine problem, and there is concern that methamphetamine use may accelerate HIV transmission. There has been little research on the HIV prevention needs of methamphetamine users receiving substance abuse treatment in South Africa. This study assessed the prevalence and correlates of HIV risk behaviors among 269 methamphetamine users entering substance abuse treatment in two clinics in Cape Town. The prevalence of sexual risk behaviors was high among sexually active participants: 34 % multiple partners, 26 % unprotected intercourse with a casual partner, and 24 % sex trading for money/methamphetamine. The strongest predictor of all sexual risk behaviors was concurrent other drug use. Over half had not been HIV tested in the past year, and 25 % had never been tested, although attitudes toward HIV testing were overwhelmingly positive. This population of primarily heterosexual, non-injecting methamphetamine users is a high-risk group in need of targeted HIV prevention interventions. Substance abuse treatment is an ideal setting in which to reach methamphetamine users for HIV services.

Factors associated with escalation and problematic approaches toward public figures.

PubMed

Meloy, J Reid; James, David V; Mullen, Paul E; Pathé, Michele T; Farnham, Frank R; Preston, Lulu F; Darnley, Brian J

2011-01-01

Detailed comparison of factors associated with abnormal approach to the prominent and with escalation from communication to approach has not hitherto been undertaken. This partially reflects the failure of individual studies to adopt compatible terminologies. This study involves a careful dissection of six public figure studies, three involving U.S. politicians, two Hollywood celebrities, and one the British Royal Family. Common findings were unearthed across six headings. Approachers were significantly more likely to exhibit serious mental illness, engage in multiple means of communication, involve multiple contacts/targets, and to incorporate into their communication requests for help. They were significantly less likely to use threatening or antagonistic language in their communications, except in those cases involving security breaches. These results emphasize the importance of integrating mental health findings and preventive measures into risk management. Approach should not be regarded as a single behavioral category and has multiple motivations. Future studies should adopt standard terminology, preferably taken from the general stalking research. © 2010 American Academy of Forensic Sciences.

Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ying; Li, Zhaohui; Liu, Misha

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeledmore » single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.« less

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system

PubMed Central

Sowa, Steven W.; Gelderman, Grant; Leistra, Abigail N.; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A.; Romeo, Tony; Baldea, Michael

2017-01-01

Abstract Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. PMID:28126921

Risk and protective factors for recreational and hard drug use among Malaysian adolescents and young adults.

PubMed

Razali, Muzafar Mohd; Kliewer, Wendy

2015-11-01

This study investigated risk and protective factors for recreational and hard drug use in Malaysian adolescents and young adults. Participants (n = 859; M age = 17.24 years, SD = 2.75 years, range = 13-25 years; 59% male) were recruited from secondary schools, technical colleges, a juvenile detention center and a national training center in Malaysia. A version of the Communities That Care survey validated for use in Malaysia (Razali & Kliewer, 2015) was used to assess study constructs. One in 6 adolescents and 1 in 3 young adults reported lifetime recreational and hard drug use, with greater use reported by males across all drug categories. Structural equation modeling was used to determine the strongest risk and protective factors for recreational and hard drug use. The overall pattern of findings was similar for recreational and hard drug use. Shared risk factors for lifetime recreational and hard drug use included early initiation of antisocial behavior, peer antisocial behavior, and peer reinforcement for engaging in antisocial behavior; shared protective factors included religious practices and opportunities for prosocial school involvement. Multiple group analyses comparing adolescents and young adults indicated that patterns of risk and protective factors predicting drug use differed across these age groups. There were fewer significant predictors of either recreational or hard drug use for young adults relative to adolescents. Results suggest that interventions should target multiple microsystems (e.g., peer groups, family systems, school environments) and be tailored to the developmental stage of the individual. Copyright © 2015. Published by Elsevier Ltd.

A Profile of HIV Risk Factors in the Context of Sex Work Environments among Migrant Female Sex Workers in Beijing, China

PubMed Central

Yi, Huso; Mantell, Joanne E.; Wu, Rongrong; Lu, Zhao; Zeng, Jing; Wan, Yanhai

2010-01-01

Migrant female sex workers (FSWs) are one of the most at-risk populations for HIV in China. This study demonstrates how multiple risk factors are situated and vary by types of sex work environments in a sample of 348 migrant FSWs in Beijing. Participants reported high rates of clients' refusal to use condoms (76%), unsafe sex with both clients (32%), non-paid regular partners (e.g., boyfriend or husband) (76%), and a STI symptom (79%) last year. Only 22% of FSWs had been tested for HIV. Risk factors were compared by three types of sex work environments: (1) entertainment establishments, (2) personal services sectors, and (3) street-based venues, including roadside brothels. Street-based FSWs, compared to the other FSWs, were more likely to be older, married with children, migrate from rural areas, and be arrested by police, and less likely to be educated, have contact with prevention services, be knowledgeable about HIV, and be tested for HIV. The FSWs in entertainment establishments were more likely than street-based FSWs to have reported being physically, verbally, and/or sexually abused by clients. Multiple discriminant analysis distinguished a profile of two different groups of risk factors: (1) police arrest, lack of protection from violence, access to prevention and health care, and HIV knowledge, and (2) verbal and physical abuse and clients' refusal of condom use. In the massive internal migration in China, disadvantages in economic sectors drive women to become involved in sex work. HIV prevention strategies must target socio-structural factors embedded in sex work environments. PMID:20391235

Image-based tracking and sensor resource management for UAVs in an urban environment

NASA Astrophysics Data System (ADS)

Samant, Ashwin; Chang, K. C.

2010-04-01

Coordination and deployment of multiple unmanned air vehicles (UAVs) requires a lot of human resources in order to carry out a successful mission. The complexity of such a surveillance mission is significantly increased in the case of an urban environment where targets can easily escape from the UAV's field of view (FOV) due to intervening building and line-of-sight obstruction. In the proposed methodology, we focus on the control and coordination of multiple UAVs having gimbaled video sensor onboard for tracking multiple targets in an urban environment. We developed optimal path planning algorithms with emphasis on dynamic target prioritizations and persistent target updates. The command center is responsible for target prioritization and autonomous control of multiple UAVs, enabling a single operator to monitor and control a team of UAVs from a remote location. The results are obtained using extensive 3D simulations in Google Earth using Tangent plus Lyapunov vector field guidance for target tracking.

Targeting the SAVA (Substance Abuse, Violence, and AIDS) Syndemic Among Women and Girls: A Global Review of Epidemiology and Integrated Interventions.

PubMed

Gilbert, Louisa; Raj, Anita; Hien, Denise; Stockman, Jamila; Terlikbayeva, Assel; Wyatt, Gail

2015-06-01

Multiple pathways link gender-based violence (GBV) to HIV and other sexually transmitted infections among women and girls who use or inject drugs. The aim of this article is to synthesize global literature that examines associations among the synergistic epidemics of substance abuse, violence, and HIV/AIDS, known as the SAVA syndemic. It also aims to identify a continuum of multilevel integrated interventions that target key SAVA syndemic mechanisms. We conducted a selective search strategy, prioritizing use of meta-analytic epidemiological and intervention studies that address different aspects of the SAVA syndemic among women and girls who use drugs worldwide from 2000 to 2015 using PubMed, MEDLINE, and Google Scholar. Robust evidence from different countries suggests that GBV significantly increases the risk of HIV and other sexually transmitted infections among women and girls who use drugs. Multiple structural, biological, and behavioral mechanisms link GBV and HIV among women and girls. Emerging research has identified a continuum of brief and extended multilevel GBV prevention and treatment interventions that may be integrated into a continuum of HIV prevention, testing, and treatment interventions to target key SAVA syndemic mechanisms among women and girls who use drugs. There remain significant methodological and geographical gaps in epidemiological and intervention research on the SAVA syndemic, particularly in low- and middle-income countries. This global review underscores the need to advance a continuum of multilevel integrated interventions that target salient mechanisms of the SAVA syndemic, especially for adolescent girls, young women, and transgender women who use drugs.

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

PubMed

Mathew, Geetha; Unnikrishnan, M K

2015-10-01

Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

Applications of amorphous track models in radiation biology

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Nikjoo, H.; Goodhead, D. T.; Wilson, J. W. (Principal Investigator)

1999-01-01

The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion's path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

Hybrid value foraging: How the value of targets shapes human foraging behavior.

PubMed

Wolfe, Jeremy M; Cain, Matthew S; Alaoui-Soce, Abla

2018-04-01

In hybrid foraging, observers search visual displays for multiple instances of multiple target types. In previous hybrid foraging experiments, although there were multiple types of target, all instances of all targets had the same value. Under such conditions, behavior was well described by the marginal value theorem (MVT). Foragers left the current "patch" for the next patch when the instantaneous rate of collection dropped below their average rate of collection. An observer's specific target selections were shaped by previous target selections. Observers were biased toward picking another instance of the same target. In the present work, observers forage for instances of four target types whose value and prevalence can vary. If value is kept constant and prevalence manipulated, participants consistently show a preference for the most common targets. Patch-leaving behavior follows MVT. When value is manipulated, observers favor more valuable targets, though individual foraging strategies become more diverse, with some observers favoring the most valuable target types very strongly, sometimes moving to the next patch without collecting any of the less valuable targets.

The Control of Single-color and Multiple-color Visual Search by Attentional Templates in Working Memory and in Long-term Memory.

PubMed

Grubert, Anna; Carlisle, Nancy B; Eimer, Martin

2016-12-01

The question whether target selection in visual search can be effectively controlled by simultaneous attentional templates for multiple features is still under dispute. We investigated whether multiple-color attentional guidance is possible when target colors remain constant and can thus be represented in long-term memory but not when they change frequently and have to be held in working memory. Participants searched for one, two, or three possible target colors that were specified by cue displays at the start of each trial. In constant-color blocks, the same colors remained task-relevant throughout. In variable-color blocks, target colors changed between trials. The contralateral delay activity (CDA) to cue displays increased in amplitude as a function of color memory load in variable-color blocks, which indicates that cued target colors were held in working memory. In constant-color blocks, the CDA was much smaller, suggesting that color representations were primarily stored in long-term memory. N2pc components to targets were measured as a marker of attentional target selection. Target N2pcs were attenuated and delayed during multiple-color search, demonstrating less efficient attentional deployment to color-defined target objects relative to single-color search. Importantly, these costs were the same in constant-color and variable-color blocks. These results demonstrate that attentional guidance by multiple-feature as compared with single-feature templates is less efficient both when target features remain constant and can be represented in long-term memory and when they change across trials and therefore have to be maintained in working memory.

Forward-Backward Emission of Target Evaporated Fragments at High Energy Nucleus-Nucleus Collisions

NASA Astrophysics Data System (ADS)

Zhang, Zhi; Ma, Tian-Li; Zhang, Dong-Hai

The multiplicity distribution, multiplicity moments, scaled variance and entropy of target evaporated fragment emitted in forward and backward hemispheres in relativistic heavy ions induced emulsion heavy targets (AgBr) interactions are investigated. It is found that the multiplicity distribution can be fitted by the Gaussian distribution, and the fitting parameters are different between two hemispheres for all the interactions. The multiplicity moment increases with the order of the moment q, and second-order multiplicity moment is energy independent over the entire energy for all the interactions. The scaled variance is close to one for all the interactions. The entropy in forward hemisphere is greater than that in backward hemisphere for all the interactions.

Associations of Sexual Victimization, Depression, and Sexual Assertiveness with Unprotected Sex: A Test of the Multifaceted Model of HIV Risk Across Gender

PubMed Central

Morokoff, Patricia J.; Redding, Colleen A.; Harlow, Lisa L.; Cho, Sookhyun; Rossi, Joseph S.; Meier, Kathryn S.; Mayer, Kenneth H.; Koblin, Beryl; Brown-Peterside, Pamela

2014-01-01

This study examined whether the Multifaceted Model of HIV Risk (MMOHR) would predict unprotected sex based on predictors including gender, childhood sexual abuse (CSA), sexual victimization (SV), depression, and sexual assertiveness for condom use. A community-based sample of 473 heterosexually active men and women, aged 18–46 years completed survey measures of model variables. Gender predicted several variables significantly. A separate model for women demonstrated excellent fit, while the model for men demonstrated reasonable fit. Multiple sample model testing supported the use of MMOHR in both men and women, while simultaneously highlighting areas of gender difference. Prevention interventions should focus on sexual assertiveness, especially for CSA and SV survivors, as well as targeting depression, especially among men. PMID:25018617

Condom Use With a Casual Partner: What Distinguishes College Students' Use When Intoxicated?

PubMed Central

Abbey, Antonia; Parkhill, Michele R.; Buck, Philip O.; Saenz, Christopher

2015-01-01

Determining alcohol's precise role in sexual risk taking has proven to be an elusive goal. Past research has produced mixed results, depending on characteristics of individuals, their partners, and the situation, as well as how the link between alcohol consumption and sexual behavior was assessed. In this study, cross-sectional predictors of the frequency of condom use were examined for 298 heterosexual college students at a large urban university. In hierarchical multiple regression analyses that controlled for frequency of condom use when sober, alcohol expectancies regarding sexual risk taking and self-efficacy regarding condom use when intoxicated were significant predictors of frequency of condom use when intoxicated. These findings highlight the importance of targeting beliefs about alcohol's disinhibiting effects in STD- and HIV-prevention programs. PMID:17385957

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

PubMed

Hernández, Glenn; Cavalcanti, Alexandre Biasi; Ospina-Tascón, Gustavo; Zampieri, Fernando Godinho; Dubin, Arnaldo; Hurtado, F Javier; Friedman, Gilberto; Castro, Ricardo; Alegría, Leyla; Cecconi, Maurizio; Teboul, Jean-Louis; Bakker, Jan

2018-04-23

Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

Focusing of light energy inside a scattering medium by controlling the time-gated multiple light scattering

NASA Astrophysics Data System (ADS)

Jeong, Seungwon; Lee, Ye-Ryoung; Choi, Wonjun; Kang, Sungsam; Hong, Jin Hee; Park, Jin-Sung; Lim, Yong-Sik; Park, Hong-Gyu; Choi, Wonshik

2018-05-01

The efficient delivery of light energy is a prerequisite for the non-invasive imaging and stimulating of target objects embedded deep within a scattering medium. However, the injected waves experience random diffusion by multiple light scattering, and only a small fraction reaches the target object. Here, we present a method to counteract wave diffusion and to focus multiple-scattered waves at the deeply embedded target. To realize this, we experimentally inject light into the reflection eigenchannels of a specific flight time to preferably enhance the intensity of those multiple-scattered waves that have interacted with the target object. For targets that are too deep to be visible by optical imaging, we demonstrate a more than tenfold enhancement in light energy delivery in comparison with ordinary wave diffusion cases. This work will lay a foundation to enhance the working depth of imaging, sensing and light stimulation.

Methodological and Design Considerations in Evaluating the Impact of Prevention Programs on Violence and Related Health Outcomes.

PubMed

Massetti, Greta M; Simon, Thomas R; Smith, Deborah Gorman

2016-10-01

Drawing on research that has identified specific predictors and trajectories of risk for violence and related negative outcomes, a multitude of small- and large-scale preventive interventions for specific risk behaviors have been developed, implemented, and evaluated. One of the principal challenges of these approaches is that a number of separate problem-specific programs targeting different risk areas have emerged. However, as many negative health behaviors such as substance abuse and violence share a multitude of risk factors, many programs target identical risk factors. There are opportunities to understand whether evidence-based programs can be leveraged for potential effects across a spectrum of outcomes and over time. Some recent work has documented longitudinal effects of evidence-based interventions on generalized outcomes. This work has potential for advancing our understanding of the effectiveness of promising and evidence-based prevention strategies. However, conducting longitudinal follow-up of established interventions presents a number of methodological and design challenges. To answer some of these questions, the Centers for Disease Control and Prevention convened a panel of multidisciplinary experts to discuss opportunities to take advantage of evaluations of early prevention programs and evaluating multiple long-term outcomes. This special section of the journal Prevention Science includes a series of papers that begin to address the relevant considerations for conducting longitudinal follow-up evaluation research. This collection of papers is intended to inform our understanding of the challenges and strategies for conducting longitudinal follow-up evaluation research that could be used to drive future research endeavors.

Food safety practices among Norwegian consumers.

PubMed

Røssvoll, Elin Halbach; Lavik, Randi; Ueland, Øydis; Jacobsen, Eivind; Hagtvedt, Therese; Langsrud, Solveig

2013-11-01

An informed consumer can compensate for several potential food safety violations or contaminations that may occur earlier in the food production chain. However, a consumer can also destroy the work of others in the chain by poor food handling practices, e.g., by storing chilled ready-to-eat foods at abusive temperatures. To target risk-reducing strategies, consumer groups with high-risk behavior should be identified. The aim of this study was to identify demographic characteristics associated with high-risk food handling practices among Norwegian consumers. More than 2,000 randomly selected Norwegian consumers were surveyed, and the results were analyzed with a risk-based grading system, awarding demerit points for self-reported food safety violations. The violations were categorized into groups, and an ordinary multiple linear regression analysis was run on the summarized demerit score for each group and for the entire survey group as a whole. Young and elderly men were identified as the least informed consumer groups with the most unsafe practices regarding food safety. Single persons reported poorer practices than those in a relationship. People with higher education reported poorer practices than those with lower or no education, and those living in the capital of Norway (Oslo) reported following more unsafe food practices than people living elsewhere in Norway. Men reported poorer food safety practices than women in all categories with two exceptions: parboiling raw vegetables before consumption and knowledge of refrigerator temperature. These findings suggest that risk-reducing measures should target men, and a strategy is needed to change their behavior and attitudes.

Bridging a translational gap: using machine learning to improve the prediction of PTSD.

PubMed

Karstoft, Karen-Inge; Galatzer-Levy, Isaac R; Statnikov, Alexander; Li, Zhiguo; Shalev, Arieh Y

2015-03-16

Predicting Posttraumatic Stress Disorder (PTSD) is a pre-requisite for targeted prevention. Current research has identified group-level risk-indicators, many of which (e.g., head trauma, receiving opiates) concern but a subset of survivors. Identifying interchangeable sets of risk indicators may increase the efficiency of early risk assessment. The study goal is to use supervised machine learning (ML) to uncover interchangeable, maximally predictive combinations of early risk indicators. Data variables (features) reflecting event characteristics, emergency department (ED) records and early symptoms were collected in 957 trauma survivors within ten days of ED admission, and used to predict PTSD symptom trajectories during the following fifteen months. A Target Information Equivalence Algorithm (TIE*) identified all minimal sets of features (Markov Boundaries; MBs) that maximized the prediction of a non-remitting PTSD symptom trajectory when integrated in a support vector machine (SVM). The predictive accuracy of each set of predictors was evaluated in a repeated 10-fold cross-validation and expressed as average area under the Receiver Operating Characteristics curve (AUC) for all validation trials. The average number of MBs per cross validation was 800. MBs' mean AUC was 0.75 (95% range: 0.67-0.80). The average number of features per MB was 18 (range: 12-32) with 13 features present in over 75% of the sets. Our findings support the hypothesized existence of multiple and interchangeable sets of risk indicators that equally and exhaustively predict non-remitting PTSD. ML's ability to increase prediction versatility is a promising step towards developing algorithmic, knowledge-based, personalized prediction of post-traumatic psychopathology.

Multiple-target tracking implementation in the ebCMOS camera system: the LUSIPHER prototype

NASA Astrophysics Data System (ADS)

Doan, Quang Tuyen; Barbier, Remi; Dominjon, Agnes; Cajgfinger, Thomas; Guerin, Cyrille

2012-06-01

The domain of the low light imaging systems progresses very fast, thanks to detection and electronic multiplication technology evolution, such as the emCCD (electron multiplying CCD) or the ebCMOS (electron bombarded CMOS). We present an ebCMOS camera system that is able to track every 2 ms more than 2000 targets with a mean number of photons per target lower than two. The point light sources (targets) are spots generated by a microlens array (Shack-Hartmann) used in adaptive optics. The Multiple-Target-Tracking designed and implemented on a rugged workstation is described. The results and the performances of the system on the identification and tracking are presented and discussed.

Labeled RFS-Based Track-Before-Detect for Multiple Maneuvering Targets in the Infrared Focal Plane Array.

PubMed

Li, Miao; Li, Jun; Zhou, Yiyu

2015-12-08

The problem of jointly detecting and tracking multiple targets from the raw observations of an infrared focal plane array is a challenging task, especially for the case with uncertain target dynamics. In this paper a multi-model labeled multi-Bernoulli (MM-LMB) track-before-detect method is proposed within the labeled random finite sets (RFS) framework. The proposed track-before-detect method consists of two parts-MM-LMB filter and MM-LMB smoother. For the MM-LMB filter, original LMB filter is applied to track-before-detect based on target and measurement models, and is integrated with the interacting multiple models (IMM) approach to accommodate the uncertainty of target dynamics. For the MM-LMB smoother, taking advantage of the track labels and posterior model transition probability, the single-model single-target smoother is extended to a multi-model multi-target smoother. A Sequential Monte Carlo approach is also presented to implement the proposed method. Simulation results show the proposed method can effectively achieve tracking continuity for multiple maneuvering targets. In addition, compared with the forward filtering alone, our method is more robust due to its combination of forward filtering and backward smoothing.

Labeled RFS-Based Track-Before-Detect for Multiple Maneuvering Targets in the Infrared Focal Plane Array

PubMed Central

Li, Miao; Li, Jun; Zhou, Yiyu

2015-01-01

The problem of jointly detecting and tracking multiple targets from the raw observations of an infrared focal plane array is a challenging task, especially for the case with uncertain target dynamics. In this paper a multi-model labeled multi-Bernoulli (MM-LMB) track-before-detect method is proposed within the labeled random finite sets (RFS) framework. The proposed track-before-detect method consists of two parts—MM-LMB filter and MM-LMB smoother. For the MM-LMB filter, original LMB filter is applied to track-before-detect based on target and measurement models, and is integrated with the interacting multiple models (IMM) approach to accommodate the uncertainty of target dynamics. For the MM-LMB smoother, taking advantage of the track labels and posterior model transition probability, the single-model single-target smoother is extended to a multi-model multi-target smoother. A Sequential Monte Carlo approach is also presented to implement the proposed method. Simulation results show the proposed method can effectively achieve tracking continuity for multiple maneuvering targets. In addition, compared with the forward filtering alone, our method is more robust due to its combination of forward filtering and backward smoothing. PMID:26670234

A 24-Week Multi-Modality Exercise Program Improves Executive Control in Older Adults with a Self-Reported Cognitive Complaint: Evidence from the Antisaccade Task.

PubMed

Heath, Matthew; Shellington, Erin; Titheridge, Sam; Gill, Dawn P; Petrella, Robert J

2017-01-01

Exercise programs involving aerobic and resistance training (i.e., multiple-modality) have shown promise in improving cognition and executive control in older adults at risk, or experiencing, cognitive decline. It is, however, unclear whether cognitive training within a multiple-modality program elicits an additive benefit to executive/cognitive processes. This is an important question to resolve in order to identify optimal training programs that delay, or ameliorate, executive deficits in persons at risk for further cognitive decline. In the present study, individuals with a self-reported cognitive complaint (SCC) participated in a 24-week multiple-modality (i.e., the M2 group) exercise intervention program. In addition, a separate group of individuals with a SCC completed the same aerobic and resistance training as the M2 group but also completed a cognitive-based stepping task (i.e., multiple-modality, mind-motor intervention: M4 group). Notably, pre- and post-intervention executive control was examined via the antisaccade task (i.e., eye movement mirror-symmetrical to a target). Antisaccades are an ideal tool for the study of individuals with subtle executive deficits because of its hands- and language-free nature and because the task's neural mechanisms are linked to neuropathology in cognitive decline (i.e., prefrontal cortex). Results showed that M2 and M4 group antisaccade reaction times reliably decreased from pre- to post-intervention and the magnitude of the decrease was consistent across groups. Thus, multi-modality exercise training improved executive performance in persons with a SCC independent of mind-motor training. Accordingly, we propose that multiple-modality training provides a sufficient intervention to improve executive control in persons with a SCC.

THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET

PubMed Central

Schmidt-Erfurth, Ursula; van Lookeren Campagne, Menno; Henry, Erin C.; Brittain, Christopher

2017-01-01

Purpose: Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Methods: Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA. Results: Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials. Conclusion: The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets. PMID:27902638

graph-GPA: A graphical model for prioritizing GWAS results and investigating pleiotropic architecture.

PubMed

Chung, Dongjun; Kim, Hang J; Zhao, Hongyu

2017-02-01

Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. However, identification of risk variants associated with complex diseases remains challenging as they are often affected by many genetic variants with small or moderate effects. There has been accumulating evidence suggesting that different complex traits share common risk basis, namely pleiotropy. Recently, several statistical methods have been developed to improve statistical power to identify risk variants for complex traits through a joint analysis of multiple GWAS datasets by leveraging pleiotropy. While these methods were shown to improve statistical power for association mapping compared to separate analyses, they are still limited in the number of phenotypes that can be integrated. In order to address this challenge, in this paper, we propose a novel statistical framework, graph-GPA, to integrate a large number of GWAS datasets for multiple phenotypes using a hidden Markov random field approach. Application of graph-GPA to a joint analysis of GWAS datasets for 12 phenotypes shows that graph-GPA improves statistical power to identify risk variants compared to statistical methods based on smaller number of GWAS datasets. In addition, graph-GPA also promotes better understanding of genetic mechanisms shared among phenotypes, which can potentially be useful for the development of improved diagnosis and therapeutics. The R implementation of graph-GPA is currently available at https://dongjunchung.github.io/GGPA/.

Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

PubMed

Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

2017-10-17

Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

Obesity prevention in pediatrics: A pilot pediatric resident curriculum intervention on nutrition and obesity education and counseling.

PubMed

Gonzalez, Jose L; Gilmer, Loise

2006-09-01

Obesity is a highly burdensome public health issue associated with premature death, multiple comorbid disabilities and staggering healthcare costs. Between 1980-2000, the prevalence of obesity among children and adolescents nearly tripled. Obesity subjects youth to social stigmatization and discrimination. These economic and personal burdens mandate targeted prevention and detection educational programs for all individuals at risk. The most cost-effective method of approaching this obesity epidemic is through education of health professionals. As part of an "Obesity Prevention in Pediatrics" curriculum, postgraduate-year (PGY)-2 residents first observed and then participated in the dietary evaluation and counseling of pediatric patients and their families. Attitudinal questionnaires, multiple-choice knowledge examinations and a pre-established checklist of desired skills and behaviors provided evaluation of the curriculum's effect on the participants' ability and willingness to manage actually obese or at-risk pediatric patients and their families. Attitudinal survey and knowledge test scores from control PGY-3 residents generally confirmed that their knowledge and counseling skills on obesity prevention and management were well below expectation. Following participation in the curriculum, study residents' knowledge tended to improve, as did their level of comfort in counseling obese and at-risk children, adolescents and their parents. Implementation of an "Obesity Prevention in Pediatrics" curriculum appears to improve participants' knowledge base as well as their skills and level of personal comfort in the recognition, evaluation and management, including counseling, of both obese and at-risk pediatric patients and their families.

A Study of Multiplicities in Hadronic Interactions (in Spanish)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Estrada Tristan, Nora Patricia; /San Luis Potosi U.

Using data from the SELEX (Fermilab E781) experiment obtained with a minimum-bias trigger, we study multiplicity and angular distributions of secondary particles produced in interactions in the experimental targets. We observe interactions of {Sigma}{sup -}, proton, {pi}{sup -}, and {pi}{sup +}, at beam momenta between 250 GeV/c and 650 GeV/c, in copper, polyethylene, graphite, and beryllium targets. We show that the multiplicity and angular distributions for meson and baryon beams at the same momentum are identical. We also show that the mean multiplicity increases with beam momentum, and presents only small variations with the target material.

Epidemiology of cervical cancer with special focus on India.

PubMed

Sreedevi, Aswathy; Javed, Reshma; Dinesh, Avani

2015-01-01

Cervical cancer is on the declining trend in India according to the population-based registries; yet it continues to be a major public health problem for women in India. Multifactorial causation, potential for prevention, and the sheer threat it poses make cervical cancer an important disease for in-depth studies, as has been attempted by this paper. This paper attempts to review the available knowledge regarding the epidemiology and pattern of cervical cancer; types of HPV (human papilloma virus) prevalent among cervical cancer patients and among women in general, high-risk groups such as commercial sex workers, and HIV (human immunodeficiency virus)-positive women; and the role of the national program on cancer in control efforts. The peak age of incidence of cervical cancer is 55-59 years, and a considerable proportion of women report in the late stages of disease. Specific types of oncogenic HPV-16, 18 have been identified in patients with cervical cancer. Other epidemiological risk factors are early age at marriage, multiple sexual partners, multiple pregnancies, poor genital hygiene, malnutrition, use of oral contraceptives, and lack of awareness. A multipronged approach is necessary which can target areas of high prevalence identified by registries with a combination of behavior change communication exercises and routine early screening with VIA. Sensitizing the people of the area, including menfolk, is necessary to increase uptake levels. Vaccination against types 16 and 18 can also be undertaken after taking into confidence all stakeholders, including the parents of adolescent girls. Preventing and treating cervical cancer and reducing the burden are possible by targeting resources to the areas with high prevalence.

Development, Application, and Implementation of RAMCAP to Characterize Nuclear Power Plant Risk From Terrorism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaertner, John P.; Teagarden, Grant A.

2006-07-01

In response to increased interest in risk-informed decision making regarding terrorism, EPRI and ERIN Engineering were selected by U.S. DHS and ASME to develop and demonstrate the RAMCAP method for nuclear power plant (NPP) risk assessment. The objective is to characterize plant-specific NPP risk for risk management opportunities and to provide consistent information for DHS decision making. This paper is an update of this project presented at the American Nuclear Society (ANS) International Topical Meeting on Probabilistic Safety Analysis (PSA05) in September, 2005. The method uses a characterization of risk as a function of Consequence, Vulnerability, and Threat. For eachmore » site, worst case scenarios are developed for each of sixteen benchmark threats. Nuclear RAMCAP hypothesizes that the intent of the perpetrator is to cause offsite radiological consequences. Specific targets are the reactor core, the spent fuel pool, and nuclear spent fuel in a dry storage facility (ISFSI). Results for each scenario are presented as conditional risk for financial loss, early fatalities and early injuries. Expected consequences for each scenario are quantified, while vulnerability is estimated on a relative likelihood scale. Insights for other societal risks are provided. Although threat frequencies are not provided, target attractiveness and threat deterrence are estimated. To assure efficiency, completeness, and consistency; results are documented using standard RAMCAP Evaluator software. Trial applications were successfully performed at four plant sites. Implementation at all other U.S. commercial sites is underway, supported by the Nuclear Sector Coordinating Council (NSCC). Insights from RAMCAP results at 23 U.S. plants completed to date have been compiled and presented to the NSCC. Results are site-specific. Physical security barriers, an armed security force, preparedness for design-basis threats, rugged design against natural hazards, multiple barriers between fuel and environment, accident mitigation capability, severe accident management procedures, and offsite emergency plans are risk-beneficial against all threat types. (authors)« less

A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.

PubMed

Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S

2017-03-31

The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.

Stress and Multiple Substance Use Behaviors Among Hispanic Adolescents.

PubMed

Cardoso, Jodi Berger; Goldbach, Jeremy T; Cervantes, Richard C; Swank, Paul

2016-02-01

Hispanic adolescents reported a higher annual prevalence of use of nearly all major drugs compared to non-Hispanic White and African American adolescents. Cultural or minority stressors, such as those related to the acculturation process, discrimination, immigration, poverty, and community violence, have been implicated in these outcomes. Unfortunately, few studies have examined how these stressors may have a differential or additive effect when considered simultaneously. The current study examined the relation between stress and multiple substance use behaviors in a sample of Hispanic adolescents (n = 1036), age 11-19 years old. Latent class analysis identified subgroups of Hispanic adolescents based on combinations of substance use behaviors. General linear models were used to examine mean differences by class among the eight domains of stress. Fit statistics revealed a six-class structure: no substance use risk, predominately alcohol use, low polysubstance use, high polysubstance use, illicit drug use, and predominately marijuana use. Differences in stress across the six classes were identified for four of the eight domains: family economic, acculturation gap, community and gang, and family and drug stress. The effect sizes revealed the largest mean differences in stress between the no substance use group and the two polysubstance use groups and between the no risk group and alcohol use group. The findings from this study support the use of interventions that target stress to affect multiple substance use behaviors in Hispanic adolescents.

[Incidence of fall related injury in people aged 50 and above and risk factors in 8 provinces in China: a cross-sectional study].

PubMed

Guo, Y F; Ma, W J; Zhang, Q J; Yu, M; Xiao, Y Z; Guo, X L; Zhu, Y L; Liu, F; Ruan, Y; Sun, S Y; Huang, Z Z; Zheng, Y; Wu, F

2018-03-10

Objective: To estimate the incidence and distribution characteristics of fall related injury in people aged ≥50 years in 8 provinces in China and related physiological, psychological and social risk factors. Methods: Cross-sectional data were collected from adults aged ≥50 years participating in the World Health Organization (WHO) study on global ageing and adult health (SAGE) round 1 in China. Two-level hierarchical logistic model was used to identify the related factors for fall-related injury. All the models were stratified by living area (urban/rural). Results: Estimated incidence of fall related injury (road traffic injury was not included) was 3.2 %. Ageing and multiple chronic conditions ( OR =2.55, 95 %CI : 1.41-4.64) was significantly associated with the incidence of fall related injury in urban area. In rural area, depression ( OR =4.33, 95 % CI : 2.52-7.42) and multiple chronic conditions ( OR =2.46, 95 %CI : 1.37-4.41) were associated with the incidence of fall related injury. Conclusions: This study estimated the incidence of fall related injury in adults aged ≥50 years in 8 provinces in China. A significant association between multiple chronic conditions and fall related injury were found in both urban and rural residents. Targeted measures should be taken for the prevention and control of chronic diseases in elderly population.

Child Maltreatment Among Singletons and Multiple Births in Japan: A Population-Based Study.

PubMed

Yokoyama, Yoshie; Oda, Terumi; Nagai, Noriyo; Sugimoto, Masako; Mizukami, Kenji

2015-12-01

The occurrence of multiple births has been recognized as a risk factor for child maltreatment. However, few population-based studies have examined the relationship between multiple births and child maltreatment. This study aimed to evaluate the degree of risk of child maltreatment among singletons and multiple births in Japan and to identify factors associated with increased risk. Using population-based data, we analyzed the database of records on child maltreatment and medical checkups for infants aged 1.5 years filed at Nishinomiya City Public Health Center between April 2007 and March 2011. To protect personal information, the data were transferred to anonymized electronic files for analysis. After adjusting by logistic regression for each associated factor and gestation number, multiples themselves were not associated with the risk of child maltreatment. However, compared with singletons, multiples had a significantly higher rate of risk factors for child maltreatment, including low birth weight and neural abnormality. Moreover, compared with mothers of singleton, mothers of twins had a significantly higher rate of poor health, which is a risk factor of child maltreatment. Multiples were not associated with the risk of child maltreatment. However, compared with singletons, multiples and their mothers had a significantly higher rate of risk factors of child maltreatment.

The impact of attachment and depression symptoms on multiple risk behaviors in post-war adolescents in northern Uganda.

PubMed

Okello, J; Nakimuli-Mpungu, E; Klasen, F; Voss, C; Musisi, S; Broekaert, E; Derluyn, I

2015-07-15

We have previously shown that depression symptoms are associated with multiple risk behaviors and that parental attachments are protective against depression symptoms in post-war adolescents. Accumulating literature indicates that low levels of attachment may sensitize individuals to increased multiple risk behaviors when depression symptoms exist. This investigation examined the interactive effects of attachment and depression symptoms on multiple risk behavior. We conducted hierarchical logistic regression analyses to examine the impact of attachment and depression symptoms on multiple risk behavior in our post-war sample of 551 adolescents in Gulu district. Analyses revealed interactive effects for only maternal attachment-by-depression interaction. Interestingly, high levels of maternal attachment exacerbated the relationship between depression symptoms and multiple risk behaviors while low levels of maternal attachment attenuated this relationship. It is possible that this analysis could be biased by a common underlying factor that influences self-reporting and therefore is correlated with each of self-reported attachment security, depressive symptoms, and multiple risk behaviors. These findings suggest that maternal attachment serves as a protective factor at low levels while serving as an additional risk factor at high levels. Findings support and expand current knowledge about the roles that attachment and depression symptoms play in the development of multiple risk behaviors and suggest a more complex etiology for post-war adolescents. Copyright © 2015 Elsevier B.V. All rights reserved.

Sex Differences in Proximal Control of the Knee Joint

PubMed Central

Mendiguchia, Jurdan; Ford, Kevin R.; Quatman, Carmen E.; Alentorn-Geli, Eduard; Hewett, Timothy E.

2014-01-01

Following the onset of maturation, female athletes have a significantly higher risk for anterior cruciate ligament (ACL) injury compared with male athletes. While multiple sex differences in lower-extremity neuromuscular control and biomechanics have been identified as potential risk factors for ACL injury in females, the majority of these studies have focused specifically on the knee joint. However, increasing evidence in the literature indicates that lumbopelvic (core) control may have a large effect on knee-joint control and injury risk. This review examines the published evidence on the contributions of the trunk and hip to knee-joint control. Specifically, the sex differences in potential proximal controllers of the knee as risk factors for ACL injury are identified and discussed. Sex differences in trunk and hip biomechanics have been identified in all planes of motion (sagittal, coronal and transverse). Essentially, female athletes show greater lateral trunk displacement, altered trunk and hip flexion angles, greater ranges of trunk motion, and increased hip adduction and internal rotation during sport manoeuvres, compared with their male counterparts. These differences may increase the risk of ACL injury among female athletes. Prevention programmes targeted towards trunk and hip neuromuscular control may decrease the risk for ACL injuries. PMID:21688868

Clustering of four major lifestyle risk factors among Korean adults with metabolic syndrome.

PubMed

Ha, Shin; Choi, Hui Ran; Lee, Yo Han

2017-01-01

The purpose of this study was to investigate the clustering pattern of four major lifestyle risk factors-smoking, heavy drinking, poor diet, and physical inactivity-among people with metabolic syndrome in South Korea. There were 2,469 adults with metabolic syndrome aged 30 years or older available with the 5th Korean National Health and Nutrition Examination Survey dataset. We calculated the ratio of the observed to expected (O/E) prevalence for the 16 different combinations and the prevalence odds ratios (POR) of four lifestyle risk factors. The four lifestyle risk factors tended to cluster in specific multiple combinations. Smoking and heavy drinking was clustered (POR: 1.86 for male, 4.46 for female), heavy drinking and poor diet were clustered (POR: 1.38 for male, 1.74 for female), and smoking and physical inactivity were also clustered (POR: 1.48 for male). Those who were male, younger, low-educated and living alone were much more likely to have a higher number of lifestyle risk factors. Some helpful implications can be drawn from the knowledge on clustering pattern of lifestyle risk factors for more effective intervention program targeting metabolic syndrome.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Daniel Steven; Efroymson, Rebecca Ann; Hargrove, William Walter

A multiple stressor risk assessment was conducted at Yuma Proving Ground, Arizona, as a demonstration of the Military Ecological Risk Assessment Framework. The focus was a testing program at Cibola Range, which involved an Apache Longbow helicopter firing Hellfire missiles at moving targets, M60- A1 tanks. This paper describes the ecological risk assessment for the missile launch and detonation. The primary stressor associated with this activity was sound. Other minor stressors included the detonation impact, shrapnel, and fire. Exposure to desert mule deer (Odocoileus hemionus crooki) was quantified using the Army sound contour program BNOISE2, as well as distances frommore » the explosion to deer. Few effects data were available from related studies. Exposure-response models for the characterization of effects consisted of human "disturbance" and hearing damage thresholds in units of C-weighted decibels (sound exposure level) and a distance-based No Observed Adverse Effects Level for moose and cannonfire. The risk characterization used a weight-of-evidence approach and concluded that risk to mule deer behavior from the missile firing was likely for a negligible number of deer, but that no risk to mule deer abundance and reproduction is expected.« less

The influence of the perceived consequences of refusing to share injection equipment among injection drug users: Balancing competing risks

PubMed Central

Wagner, Karla D.; Lankenau, Stephen E.; Palinkas, Lawrence A.; Richardson, Jean L.; Chou, Chih-Ping; Unger, Jennifer B.

2011-01-01

Injection drug users (IDUs) are at risk for HIV and other bloodborne pathogens through receptive syringe sharing (RSS) and receptive paraphernalia sharing (RPS). Research into the influence of the perceived risk of HIV infection on injection risk behavior has yielded mixed findings. One explanation may be that consequences other than HIV infection are considered when IDUs are faced with decisions about whether or not to share equipment. We investigated the perceived consequences of refusing to share injection equipment among 187 IDUs recruited from a large syringe exchange program in Los Angeles, California, assessed their influence on RSS and RPS, and evaluated gender differences. Two sub-scales of perceived consequences were identified: structural/external consequences and social/internal consequences. In multiple linear regression, the perceived social/internal consequences of refusing to share were associated with both RSS and RPS, after controlling for other psychosocial constructs and demographic variables. Few statistically significant gender differences emerged. Assessing the consequences of refusing to share injection equipment may help explain persistent injection risk behavior, and may provide promising targets for comprehensive intervention efforts designed to address both individual and structural risk factors. PMID:21498004

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

PubMed Central

Kendler, Kenneth S.; Hitzemann, Robert J.

2012-01-01

A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data. PMID:21910077

Connecting Eating Pathology with Risk for Engaging in Suicidal Behavior: The Mediating Role of Experiential Avoidance.

PubMed

Skinner, Kayla D; Rojas, Sasha M; Veilleux, Jennifer C

2017-02-01

Individuals with eating pathology, particularly those with diagnosed eating disorders, are at high risk for suicide. It is less clear whether undiagnosed eating pathology and subsyndromal eating disorders carry the same risk and, if so, what mechanisms may explain why higher levels of eating pathology yield greater risk for engaging in suicidal behaviors. The indirect relationship between disordered eating and risk for suicidal behaviors via facets of experiential avoidance was tested using a multiple-mediator model. The model was tested using bootstrapping estimates of indirect effects in a sample of 218 noncollege student adults (Mage = 32.33, 66.1% women) with a history of suicidal attempt and/or history of nonsuicidal self-injury (NSSI). Results revealed that disordered eating indirectly predicted risk for suicidal behaviors, distress aversion (i.e., negative attitudes or dislike of distress), and procrastination (i.e., delaying engagement with distressing activities). Results suggest that targeting experiential avoidance and helping those who have a history of engaging in suicidal behaviors and/or NSSI develop regulation strategies to use during times of distress may be of utmost importance for treatment and prevention of eating pathology. © 2016 The American Association of Suicidology.

A novel approach for evaluating the risk of health care failure modes.

PubMed

Chang, Dong Shang; Chung, Jenq Hann; Sun, Kuo Lung; Yang, Fu Chiang

2012-12-01

Failure mode and effects analysis (FMEA) can be employed to reduce medical errors by identifying the risk ranking of the health care failure modes and taking priority action for safety improvement. The purpose of this paper is to propose a novel approach of data analysis. The approach is to integrate FMEA and a mathematical tool-Data envelopment analysis (DEA) with "slack-based measure" (SBM), in the field of data analysis. The risk indexes (severity, occurrence, and detection) of FMEA are viewed as multiple inputs of DEA. The practicality and usefulness of the proposed approach is illustrated by one case of health care. Being a systematic approach for improving the service quality of health care, the approach can offer quantitative corrective information of risk indexes that thereafter reduce failure possibility. For safety improvement, these new targets of the risk indexes could be used for management by objectives. But FMEA cannot provide quantitative corrective information of risk indexes. The novel approach can surely overcome this chief shortcoming of FMEA. After combining DEA SBM model with FMEA, the two goals-increase of patient safety, medical cost reduction-can be together achieved.

Memory for found targets interferes with subsequent performance in multiple-target visual search.

PubMed

Cain, Matthew S; Mitroff, Stephen R

2013-10-01

Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Interventions for age-related diseases: Shifting the paradigm.

PubMed

Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra; Lopez-Contreras, Andres; Henriques, Catarina M; Selman, Colin; Ferreiro, Elisabete; Gonos, Efstathios S; Trejo, José Luis; Misra, Juhi; Rasmussen, Lene Juel; Xapelli, Sara; Ellam, Timothy; Bellantuono, Ilaria

2016-12-01

Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The role of helical tomotherapy in the treatment of bone plasmacytoma.

PubMed

Chargari, Cyrus; Hijal, Tarek; Bouscary, Didier; Caussa, Lucas; Dendale, Remi; Zefkili, Sofia; Fourquet, Alain; Kirova, Youlia M

2012-01-01

We evaluated the early clinical outcome of patients with solitary bone plasmacytoma (SP) or a solitary lesion of multiple myeloma (MM) treated with helical tomotherapy (HT) compared with 3D conformal radiotherapy (3D-CRT), in terms of target coverage and exposure of critical organs. Ten patients with SP and 3 patients with a solitary lesion of MM underwent radiation therapy (RT) delivered by HT, to a dose of 40 Gy in 20 fractions. Treatment planning was then performed with 3D-CRT and the dosimetric parameters of both techniques were compared. Patients were also assessed for response to treatment and acute toxicities. With a median follow-up of 13 months, 78% of patients with pain before RT had resolution of their symptoms. Coverage of target lesion was adequate with both techniques in 12 of 13 patients. Target coverage was significantly lower for HT (V(95%) = 98.55% vs. 97.15%; p = 0.04, for 3D-CRT and HT, respectively). Target overdoses were also lower with HT (V(105%) = 2.01% vs. 0.19%; p= 0.16), although nonsignificant. Finally, there were no significant differences in organs-at-risk irradiation between both techniques. The early treatment tolerance was excellent, with no toxicity higher than grade I. RT of SP and MM with a solitary lesion can be safely delivered with HT, with no major acute side effects and good symptomatic control. Finally, HT provides a dosimetry similar to that of 3D-CRT in terms of organs-at-risk sparing and target volume coverage. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Deflection by kinetic impact: Sensitivity to asteroid properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruck Syal, Megan; Michael Owen, J.; Miller, Paul L.

Impacting an asteroid with a spacecraft traveling at high speed delivers an impulsive change in velocity to the body. In certain circumstances, this strategy could be used to deflect a hazardous asteroid, moving its orbital path off of an Earth-impacting course. However, the efficacy of momentum delivery to asteroids by hypervelocity impact is sensitive to both the impact conditions (particularly velocity) and specific characteristics of the target asteroid. We numerically model asteroid response to kinetic impactors under a wide range of initial conditions, using an Adaptive Smoothed Particle Hydrodynamics code. Impact velocities spanning 1–30 km/s were investigated, yielding, for amore » particular set of assumptions about the modeled target material, a power-law dependence consistent with a velocity-scaling exponent of μ = 0.44. Target characteristics including equation of state, strength model, porosity, rotational state, and shape were varied, and corresponding changes in asteroid response were documented. Moreover, the kinetic-impact momentum-multiplication factor, β, decreases with increasing asteroid cohesion and increasing porosity. Although increased porosity lowers β, larger porosities result in greater deflection velocities, as a consequence of reduced target masses for asteroids of fixed size. Porosity also lowers disruption risk for kinetic impacts near the threshold of disruption. Including fast (P = 2.5 h) and very fast (P = 100 s) rotation did not significantly alter β but did affect the risk of disruption by the impact event. Asteroid shape is found to influence the efficiency of momentum delivery, as local slope conditions can change the orientation of the crater ejecta momentum vector. Our results emphasize the need for asteroid characterization studies to bracket the range of target conditions expected at near-Earth asteroids while also highlighting some of the principal uncertainties associated with the kinetic-impact deflection strategy.« less

Deflection by kinetic impact: Sensitivity to asteroid properties

DOE PAGES

Bruck Syal, Megan; Michael Owen, J.; Miller, Paul L.

2016-05-01

Impacting an asteroid with a spacecraft traveling at high speed delivers an impulsive change in velocity to the body. In certain circumstances, this strategy could be used to deflect a hazardous asteroid, moving its orbital path off of an Earth-impacting course. However, the efficacy of momentum delivery to asteroids by hypervelocity impact is sensitive to both the impact conditions (particularly velocity) and specific characteristics of the target asteroid. We numerically model asteroid response to kinetic impactors under a wide range of initial conditions, using an Adaptive Smoothed Particle Hydrodynamics code. Impact velocities spanning 1–30 km/s were investigated, yielding, for amore » particular set of assumptions about the modeled target material, a power-law dependence consistent with a velocity-scaling exponent of μ = 0.44. Target characteristics including equation of state, strength model, porosity, rotational state, and shape were varied, and corresponding changes in asteroid response were documented. Moreover, the kinetic-impact momentum-multiplication factor, β, decreases with increasing asteroid cohesion and increasing porosity. Although increased porosity lowers β, larger porosities result in greater deflection velocities, as a consequence of reduced target masses for asteroids of fixed size. Porosity also lowers disruption risk for kinetic impacts near the threshold of disruption. Including fast (P = 2.5 h) and very fast (P = 100 s) rotation did not significantly alter β but did affect the risk of disruption by the impact event. Asteroid shape is found to influence the efficiency of momentum delivery, as local slope conditions can change the orientation of the crater ejecta momentum vector. Our results emphasize the need for asteroid characterization studies to bracket the range of target conditions expected at near-Earth asteroids while also highlighting some of the principal uncertainties associated with the kinetic-impact deflection strategy.« less

Estimating the lifetime risk of cancer associated with multiple CT scans.

PubMed

Ivanov, V K; Kashcheev, V V; Chekin, S Yu; Menyaylo, A N; Pryakhin, E A; Tsyb, A F; Mettler, F A

2014-12-01

Multiple CT scans are often done on the same patient resulting in an increased risk of cancer. Prior publications have estimated risks on a population basis and often using an effective dose. Simply adding up the risks from single scans does not correctly account for the survival function. A methodology for estimating personal radiation risks attributed to multiple CT imaging using organ doses is presented in this article. The estimated magnitude of the attributable risk fraction for the possible development of radiation-induced cancer indicates the necessity for strong clinical justification when ordering multiple CT scans.

Fuzzy Neural Network-Based Interacting Multiple Model for Multi-Node Target Tracking Algorithm

PubMed Central

Sun, Baoliang; Jiang, Chunlan; Li, Ming

2016-01-01

An interacting multiple model for multi-node target tracking algorithm was proposed based on a fuzzy neural network (FNN) to solve the multi-node target tracking problem of wireless sensor networks (WSNs). Measured error variance was adaptively adjusted during the multiple model interacting output stage using the difference between the theoretical and estimated values of the measured error covariance matrix. The FNN fusion system was established during multi-node fusion to integrate with the target state estimated data from different nodes and consequently obtain network target state estimation. The feasibility of the algorithm was verified based on a network of nine detection nodes. Experimental results indicated that the proposed algorithm could trace the maneuvering target effectively under sensor failure and unknown system measurement errors. The proposed algorithm exhibited great practicability in the multi-node target tracking of WSNs. PMID:27809271

Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein

PubMed Central

Curtin, François; Perron, Hervé; Kromminga, Arno; Porchet, Hervé; Lang, Alois B

2015-01-01

Monoclonal antibodies (mAbs) play an increasing important role in the therapeutic armamentarium against multiple sclerosis (MS), an inflammatory and degenerative disorder of the central nervous system. Most of the mAbs currently developed for MS are immunomodulators blocking the inflammatory immune process. In contrast with mAbs targeting immune function, GNbAC1, a humanized IgG4 mAb, targets the multiple sclerosis associated retrovirus envelope (MSRV-Env) protein, an upstream factor in the pathophysiology of MS. MSRV-Env protein is of endogenous retroviral origin, expressed in MS brain lesions, and it is pro-inflammatory and toxic to the remyelination process, by preventing the differentiation of oligodendrocyte precursor cells. We present the preclinical and early clinical development results of GNbAC1. The specificity of GNbAC1 for its endogenous retroviral target is described. Efficacy of different mAb versions of GNbAC1 were assessed in MSRV-Env induced experimental allergic encephalitis (EAE), an animal model of MS. Because the target MSRV-Env is not expressed in animals, no relevant animal model exists for a proper in vivo toxicological program. An off-target 2-week toxicity study in mice was thus performed, and it showed an absence of safety risk. Additional in vitro analyses showed an absence of complement or antibody-dependent cytotoxicity as well as a low level of cross-reactivity to human tissues. The first-in-man clinical study in 33 healthy subjects and a long-term clinical study in 10 MS patients showed that GNbAC1 is well tolerated in humans without induction of immunogenicity and that it induces a pharmacodynamic response on MSRV biomarkers. These initial results suggest that the mAb GNbAC1 could be a safe long-term treatment for patients with MS with a unique therapeutic mechanism of action. PMID:25427053

Diverse ways of perturbing the human arachidonic acid metabolic network to control inflammation.

PubMed

Meng, Hu; Liu, Ying; Lai, Luhua

2015-08-18

Inflammation and other common disorders including diabetes, cardiovascular disease, and cancer are often the result of several molecular abnormalities and are not likely to be resolved by a traditional single-target drug discovery approach. Though inflammation is a normal bodily reaction, uncontrolled and misdirected inflammation can cause inflammatory diseases such as rheumatoid arthritis and asthma. Nonsteroidal anti-inflammatory drugs including aspirin, ibuprofen, naproxen, or celecoxib are commonly used to relieve aches and pains, but often these drugs have undesirable and sometimes even fatal side effects. To facilitate safer and more effective anti-inflammatory drug discovery, a balanced treatment strategy should be developed at the biological network level. In this Account, we focus on our recent progress in modeling the inflammation-related arachidonic acid (AA) metabolic network and subsequent multiple drug design. We first constructed a mathematical model of inflammation based on experimental data and then applied the model to simulate the effects of commonly used anti-inflammatory drugs. Our results indicated that the model correctly reproduced the established bleeding and cardiovascular side effects. Multitarget optimal intervention (MTOI), a Monte Carlo simulated annealing based computational scheme, was then developed to identify key targets and optimal solutions for controlling inflammation. A number of optimal multitarget strategies were discovered that were both effective and safe and had minimal associated side effects. Experimental studies were performed to evaluate these multitarget control solutions further using different combinations of inhibitors to perturb the network. Consequently, simultaneous control of cyclooxygenase-1 and -2 and leukotriene A4 hydrolase, as well as 5-lipoxygenase and prostaglandin E2 synthase were found to be among the best solutions. A single compound that can bind multiple targets presents advantages including low risk of drug-drug interactions and robustness regarding concentration fluctuations. Thus, we developed strategies for multiple-target drug design and successfully discovered several series of multiple-target inhibitors. Optimal solutions for a disease network often involve mild but simultaneous interventions of multiple targets, which is in accord with the philosophy of traditional Chinese medicine (TCM). To this end, our AA network model can aptly explain TCM anti-inflammatory herbs and formulas at the molecular level. We also aimed to identify activators for several enzymes that appeared to have increased activity based on MTOI outcomes. Strategies were then developed to predict potential allosteric sites and to discover enzyme activators based on our hypothesis that combined treatment with the projected activators and inhibitors could balance different AA network pathways, control inflammation, and reduce associated adverse effects. Our work demonstrates that the integration of network modeling and drug discovery can provide novel solutions for disease control, which also calls for new developments in drug design concepts and methodologies. With the rapid accumulation of quantitative data and knowledge of the molecular networks of disease, we can expect an increase in the development and use of quantitative disease models to facilitate efficient and safe drug discovery.

Venous thromboembolism capture on electronic systems in obstetrics patients at St Thomas' Hospital

PubMed Central

Ahmad, Aminah Noor; Byrne, Megan Leyla; Imambaccus, Nazia; Hubert, Dawid; Gateley, Anna; Abdullahi Idle, Salwa; Lloyd, Jilly

2016-01-01

Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the UK. Therefore, timely VTE risk assessment is essential in all obstetrics patients. The Commissioning for Quality and Innovation (CQUIN) payment framework set a target for trusts to complete a VTE risk assessment within 24 hours of admission for 95% of patients. A combination of factors, including lack of integration between multiple IT systems, means that this CQUIN target is currently not being met for obstetric patients in the Hospital Birth Centre at Guys and St Thomas' NHS Trust. This project aims to increase staff awareness of this issue and educate them regarding the correct procedure for VTE assessment. Trialled methods included reminders at staff handovers, use of magnets on the patient whiteboard, posters and stickers displayed around the unit and a loyalty card scheme as incentive to complete assessments. Initial average completion rate was 20.7%, which increased to 67.5% after the first plan, do, study, act (PDSA) cycle with a slight drop to 65.7% after the second cycle. Completion rates increased to 92.3% on the last day of the third PDSA cycle. Although we did not reach the 95% target, we have raised awareness of the importance of recording VTE assessment on electronic systems, and hope we have created sustainable change. PMID:27933149

Sexual Behavior Among Young Carers in the Context of a Kenyan Empowerment Program Combining Cash-Transfer, Psychosocial Support, and Entrepreneurship.

PubMed

Goodman, Michael L; Selwyn, Beatrice J; Morgan, Robert O; Lloyd, Linda E; Mwongera, Moses; Gitari, Stanley; Keiser, Philip H

2016-01-01

This study examined associations between sexual initiation, unprotected sex, and having multiple sex partners in the past year with participation in a three-year empowerment program targeting orphan and vulnerable children (OVC). The Kenya-based program combines community-conditioned cash transfer, psychosocial empowerment, health education, and microenterprise development. Program participants (n = 1,060) were interviewed in a cross-sectional design. Analyses used gender-stratified hierarchical logit models to assess program participation and other potential predictors. Significant predictors of increased female sexual activity included less program exposure, higher age, younger age at most recent parental death, fewer years of schooling, higher food consumption, higher psychological resilience, and lower general self-efficacy. Significant predictors of increased male sexual activity included more program exposure, higher age, better food consumption, not having a living father, and literacy. Findings support a nuanced view of current cash transfer programs, where female sexual activity may be reduced through improved financial status but male sexual activity may increase. Targeting of OVC sexual risk behaviors would likely benefit from being tailored according to associations found in this study. Data suggest involving fathers in sexual education, targeting women who lost a parent at a younger age, and providing social support for female OVC may decrease risk of human immunodeficiency virus (HIV) transmission.

Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

PubMed

Miron, S D; Astărăstoae, V

2014-01-01

Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered.

Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

PubMed

Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

2014-07-01

The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acceptable Risk Analysis for Abrupt Environmental Pollution Accidents in Zhangjiakou City, China

PubMed Central

Du, Xi; Zhang, Zhijiao; Dong, Lei; Liu, Jing; Borthwick, Alistair G. L.; Liu, Renzhi

2017-01-01

Abrupt environmental pollution accidents cause considerable damage worldwide to the ecological environment, human health, and property. The concept of acceptable risk aims to answer whether or not a given environmental pollution risk exceeds a societally determined criterion. This paper presents a case study on acceptable environmental pollution risk conducted through a questionnaire survey carried out between August and October 2014 in five representative districts and two counties of Zhangjiakou City, Hebei Province, China. Here, environmental risk primarily arises from accidental water pollution, accidental air pollution, and tailings dam failure. Based on 870 valid questionnaires, demographic and regional differences in public attitudes towards abrupt environmental pollution risks were analyzed, and risk acceptance impact factors determined. The results showed females, people between 21–40 years of age, people with higher levels of education, public servants, and people with higher income had lower risk tolerance. People with lower perceived risk, low-level risk knowledge, high-level familiarity and satisfaction with environmental management, and without experience of environmental accidents had higher risk tolerance. Multiple logistic regression analysis indicated that public satisfaction with environmental management was the most significant factor in risk acceptance, followed by perceived risk of abrupt air pollution, occupation, perceived risk of tailings dam failure, and sex. These findings should be helpful to local decision-makers concerned with environmental risk management (e.g., selecting target groups for effective risk communication) in the context of abrupt environmental accidents. PMID:28425956

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system.

PubMed

Sowa, Steven W; Gelderman, Grant; Leistra, Abigail N; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A; Romeo, Tony; Baldea, Michael; Contreras, Lydia M

2017-02-28

Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cumulative Effects of Several Target Organ Damages in Risk Assessment in Hypertension.

PubMed

Harbaoui, Brahim; Courand, Pierre-Yves; Defforges, Alice; Khettab, Fouad; Milon, Hugues; Girerd, Nicolas; Lantelme, Pierre

2016-02-01

The prognostic value of screening multiple target organ damages (TODs) in hypertensive subjects has not been extensively studied. We estimated the prognostic value of considering 3 TODs in estimating the 10-year survival in hypertensive subjects. At baseline 1,848 out of a cohort of 1,963 hypertensive patients had a previous cardiovascular disease (CVD) or assessments of 3 TODs: Modification in Diet in Renal Disease (MDRD) <60ml/min or albuminuria >300mg/day, Sokolow index >3.5 mV, and advanced hypertensive retinopathy (grades 3 and 4 of Keith-Wagener-Barker classification). The cohort was divided into 5 groups: 0 TOD (N = 978), 1 TOD (N = 308), 2 TODs (N = 94), 3 TODs (N = 30), and previous CVD (N = 438). After 10 years of follow-up, we observed 418 deaths of which 254 from cardiovascular cause. The adjusted hazard ratios for the major cardiovascular risk factors showed a progressive risk associated with the number of TODs. For all-cause death, the hazard ratios [95% confidence intervals] vs. 0 TOD of the other 4 groups were 1.91 [1.39-2.63], 1.99 [1.28-3.10], 4.33 [2.42-7.72], and 3.09 [2.35-4.05], respectively. For cardiovascular death, the hazard ratios [95% confidence intervals] were of the same order of magnitude: 2.14 [1.38-3.32], 2.12 [1.15-3.89], 4.22 [1.83-9.72], and 4.24 [2.95-6.11], respectively. Our results indicate that hypertensive patients with several TODs had a worst outcome. Thus, it seems important to screen for multiple TODs in hypertension; especially check for severe hypertensive retinopathy in patients with left ventricular hypertrophy (LVH) and renal damage. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of high-intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: A phase 2 randomized controlled trial.

PubMed

Adams, Scott C; DeLorey, Darren S; Davenport, Margie H; Stickland, Michael K; Fairey, Adrian S; North, Scott; Szczotka, Alexander; Courneya, Kerry S

2017-10-15

Testicular cancer survivors (TCS) have an increased risk of treatment-related cardiovascular disease (CVD), which may limit their overall survival. We evaluated the effects of high-intensity aerobic interval training (HIIT) on traditional and novel CVD risk factors and surrogate markers of mortality in a population-based sample of TCS. This phase 2 trial (ClinicalTrials.gov identifier NCT02459132) randomly assigned 63 TCS to usual care (UC) or 12 weeks of supervised HIIT (ie, alternating periods of vigorous-intensity and light-intensity aerobic exercise). The primary outcome was peak aerobic fitness (VO 2peak ) assessed via a treadmill-based maximal cardiorespiratory exercise test. Secondary endpoints included CVD risk (eg, Framingham Risk Score), arterial health, parasympathetic nervous system function, and blood-based biomarkers. Postintervention VO 2peak data were obtained for 61 participants (97%). HIIT participants attended 99% of the exercise sessions and achieved 98% of the target exercise intensity. Analysis of covariance demonstrated that HIIT was superior to UC for improving VO 2peak (adjusted between-group mean difference, 3.7 mL O 2 /kg/min; 95% confidence interval, 2.4-5.1 [P<.001]) and multiple secondary outcomes including CVD risk (P = .011), arterial thickness (P<.001), arterial stiffness (P<.001), postexercise parasympathetic reactivation (P = .001), inflammation (P = .045), and low-density lipoprotein (P = .014). Overall, HIIT reduced the prevalence of modifiable CVD risk factors by 20% compared with UC. This randomized trial provides the first evidence that HIIT improves cardiorespiratory fitness, multiple pathways of CVD risk, and surrogate markers of mortality in TCS. These findings have important implications for the management of TCS. Further research concerning the long-term effects of HIIT on CVD morbidity and mortality in TCS is warranted. Cancer 2017;123:4057-65. © 2017 American Cancer Society. © 2017 American Cancer Society.

Effect of child marriage on girls' school dropout in Nepal: Analysis of data from the Multiple Indicator Cluster Survey 2014

PubMed Central

Sekine, Kazutaka; Hodgkin, Marian Ellen

2017-01-01

School dropout and child marriage are interrelated outcomes that have an enormous impact on adolescent girls. However, the literature reveals gaps in the empirical evidence on the link between child marriage and the dropout of girls from school. This study identifies the ‘tipping point’ school grades in Nepal when the risk of dropout due to marriage is highest, measures the effect of child marriage on girls’ school dropout rates, and assesses associated risk factors. Weighted percentages were calculated to examine the grades at highest risk and the distribution of reasons for discontinuing school. Using the Nepal Multiple Indicator Cluster Survey (MICS) 2014 data, we estimated the effect of marriage on school attendance and dropout among girls aged 15–17 by constructing logistic regression models. A multivariate logistic regression model was used to assess risk factors of school dropout due to child marriage. It was found that early marriage is the most common reason given for leaving school. Overall, the risk of school dropout due to marriage heightens after girls complete the fifth or sixth grade. The risk of girls’ dropping out peaks in the seventh and eighth grades and remains noteworthy in the ninth and tenth grades. Married girls in Nepal are 10 times more likely to drop out than their unmarried peers. Little or no education of the household head, belonging to the Kirat religion, and membership of a traditionally disadvantaged social class each elevate the risk of school dropout due to early marriage. The findings underscore the need to delay girl’s marriage so as to reduce girls’ school dropout in Nepal. School-based programmes aimed at preventing child marriage should target girls from the fifth grade because they are at increased risk of dropping out, as well as prioritizing girls from disadvantaged groups. PMID:28727793

Effect of child marriage on girls' school dropout in Nepal: Analysis of data from the Multiple Indicator Cluster Survey 2014.

PubMed

Sekine, Kazutaka; Hodgkin, Marian Ellen

2017-01-01

School dropout and child marriage are interrelated outcomes that have an enormous impact on adolescent girls. However, the literature reveals gaps in the empirical evidence on the link between child marriage and the dropout of girls from school. This study identifies the 'tipping point' school grades in Nepal when the risk of dropout due to marriage is highest, measures the effect of child marriage on girls' school dropout rates, and assesses associated risk factors. Weighted percentages were calculated to examine the grades at highest risk and the distribution of reasons for discontinuing school. Using the Nepal Multiple Indicator Cluster Survey (MICS) 2014 data, we estimated the effect of marriage on school attendance and dropout among girls aged 15-17 by constructing logistic regression models. A multivariate logistic regression model was used to assess risk factors of school dropout due to child marriage. It was found that early marriage is the most common reason given for leaving school. Overall, the risk of school dropout due to marriage heightens after girls complete the fifth or sixth grade. The risk of girls' dropping out peaks in the seventh and eighth grades and remains noteworthy in the ninth and tenth grades. Married girls in Nepal are 10 times more likely to drop out than their unmarried peers. Little or no education of the household head, belonging to the Kirat religion, and membership of a traditionally disadvantaged social class each elevate the risk of school dropout due to early marriage. The findings underscore the need to delay girl's marriage so as to reduce girls' school dropout in Nepal. School-based programmes aimed at preventing child marriage should target girls from the fifth grade because they are at increased risk of dropping out, as well as prioritizing girls from disadvantaged groups.

Multiple targets detection method in detection of UWB through-wall radar

NASA Astrophysics Data System (ADS)

Yang, Xiuwei; Yang, Chuanfa; Zhao, Xingwen; Tian, Xianzhong

2017-11-01

In this paper, the problems and difficulties encountered in the detection of multiple moving targets by UWB radar are analyzed. The experimental environment and the penetrating radar system are established. An adaptive threshold method based on local area is proposed to effectively filter out clutter interference The objective of the moving target is analyzed, and the false target is further filtered out by extracting the target feature. Based on the correlation between the targets, the target matching algorithm is proposed to improve the detection accuracy. Finally, the effectiveness of the above method is verified by practical experiment.

Characteristics of compound multiplicity in 84Kr36 with various light and heavy targets at 1 GeV per nucleon

NASA Astrophysics Data System (ADS)

Chouhan, N. S.; Singh, M. K.; Singh, V.; Pathak, R.

2013-12-01

Interactions of 84Kr36 having kinetic energy around 1 GeV per nucleon with NIKFI BR-2 nuclear emulsion detector's target reveal some of the important features of compound multiplicity. Present article shows that width of compound multiplicity distributions and value of mean compound multiplicity have linear relationship with mass number of the projectile colliding system.

Qualitative differences in the guidance of attention during single-color and multiple-color visual search: behavioral and electrophysiological evidence.

PubMed

Grubert, Anna; Eimer, Martin

2013-10-01

To find out whether attentional target selection can be effectively guided by top-down task sets for multiple colors, we measured behavioral and ERP markers of attentional target selection in an experiment where participants had to identify color-defined target digits that were accompanied by a single gray distractor object in the opposite visual field. In the One Color task, target color was constant. In the Two Color task, targets could have one of two equally likely colors. Color-guided target selection was less efficient during multiple-color relative to single-color search, and this was reflected by slower response times and delayed N2pc components. Nontarget-color items that were presented in half of all trials captured attention and gained access to working memory when participants searched for two colors, but were excluded from attentional processing in the One Color task. Results demonstrate qualitative differences in the guidance of attentional target selection between single-color and multiple-color visual search. They suggest that top-down attentional control can be applied much more effectively when it is based on a single feature-specific attentional template. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Quantum partial search for uneven distribution of multiple target items

NASA Astrophysics Data System (ADS)

Zhang, Kun; Korepin, Vladimir

2018-06-01

Quantum partial search algorithm is an approximate search. It aims to find a target block (which has the target items). It runs a little faster than full Grover search. In this paper, we consider quantum partial search algorithm for multiple target items unevenly distributed in a database (target blocks have different number of target items). The algorithm we describe can locate one of the target blocks. Efficiency of the algorithm is measured by number of queries to the oracle. We optimize the algorithm in order to improve efficiency. By perturbation method, we find that the algorithm runs the fastest when target items are evenly distributed in database.

Investigation of the Feasibility of an Intervention to Manage Fall Risk in Wheeled Mobility Device Users with Multiple Sclerosis.

PubMed

Rice, Laura A; Isaacs, Zadok; Ousley, Cherita; Sosnoff, Jacob

2018-01-01

Falls are a common concern for wheeled mobility device users with multiple sclerosis (MS); however, no evidence-based fall prevention programs have been developed to meet the specific needs of the population. We examine the preliminary feasibility of a fall management intervention in wheeled mobility device users with MS. Study participants were exposed to an intervention program targeting risk factors for falls, including transfer skills and seated postural control. The feasibility of the program was evaluated by assessing participant perspectives, cost, recruitment rates, study adherence, participant retention, safety, and the ability to collect primary and secondary outcomes, including fall frequency, concerns about falling, transfer quality, and seated postural control. 16 wheeled mobility device users completed the program, which was found to be feasible and was positively evaluated by participants. No adverse events were experienced. After exposure to the intervention, fall frequency significantly decreased (P < .001) and transfer quality (P = .001) and seated postural control (P = .002) significantly improved. No significant differences were found regarding concerns about falling (P = .728). This study examined the feasibility of an intervention program to manage fall risk in wheeled mobility device users with MS. The program was found to be feasible, and preliminary results showed the intervention to be effective in decreasing fall frequency. Additional testing is needed to further examine the efficacy and long-term impact of the intervention.

Microtubule-Targeting Therapy for Prostate Cancer

DTIC Science & Technology

2007-02-01

that were done to achieve the above specific goals. 1. Biological effects of ribozyme -carrying adenoviruses that target stathmin mRNA in human...prostate cancer cells: A ribozyme is a small RNA molecule that acts stoichiometrically to cleave multiple target RNA molecules [1]. This unique ability...of a ribozyme to degrade multiple target RNA molecules is a more efficient approach for down regulating genes that are expressed at very high levels

Development of assessment tools to measure organizational support for employee health.

PubMed

Golaszewski, Thomas; Barr, Donald; Pronk, Nico

2003-01-01

To develop systems that measure and effect organizational support for employee health. Multiple studies and developmental projects were reviewed that show the process of instrument development, metric quality testing, utilization within intervention studies, and prediction modeling efforts. Demographic patterns indicate high support levels and relationships of subsections to various employee health risks. Successes with the initial version have given rise to 2 additional evaluation tools. The availability of these systems illustrates how ecological models can be practically applied. Such efforts contribute to the paradigm shift in worksite health promotion that focuses on the organization as the target of intervention.

The Multiple Carbohydrate Binding Specificities of Helicobacter pylori

NASA Astrophysics Data System (ADS)

Teneberg, Susann

Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of peptic ulcer disease and gastric cancer. Adhesion of microbes to the target tissue is an important determinant for successful initiation, establishment and maintenance of infection, and a variety of different candidate carbohydrate receptors for H. pylori have been identified. Here the different the binding specifities, and their potential role in adhesion to human gastric epithelium are described. Finally, recent findings on the roles of sialic acid binding SabA adhesin in interactions with human neutrophils and erythrocytes are discussed.

The Role of Allergen Exposure and Avoidance in Asthma

PubMed Central

Baxi, Sachin N.; Phipatanakul, Wanda

2010-01-01

Allergy testing and avoidance of allergens plays an important role in asthma control. Increased allergen exposure, in genetically susceptible individuals, can lead to allergic sensitization. Continued allergen exposure can increase the risk of asthma and other allergic diseases. In a patient with persistent asthma, identification of indoor and outdoor allergens and subsequent avoidance can improve symptoms. Often times, a patient will have multiple allergies and the avoidance plan should target all positive allergens. Several studies have shown that successful allergen remediation includes a comprehensive approach including education, cleaning, physical barriers and maintaining these practices. PMID:20568555

Increasing adolescents' depth of understanding of cross-curriculum words: an intervention study.

PubMed

Spencer, Sarah; Clegg, Judy; Lowe, Hilary; Stackhouse, Joy

2017-09-01

There is some evidence that vocabulary intervention is effective for children, although further research is needed to confirm the impact of intervention within contexts of social disadvantage. Very little is known about the effectiveness of interventions to increase adolescent knowledge of cross-curriculum words. To evaluate the effectiveness of an intervention programme designed to develop adolescents' knowledge of cross-curriculum words. Participants were 35 adolescents aged between 12 and 14 years who were at risk of educational underachievement with low scores on a range of assessments. Participants received a 10-week intervention programme in small groups, targeting 10 cross-curriculum words (e.g., 'summarize'). This was evaluated using a bespoke outcome measure (the Word Knowledge Profile). The study involved an AABA design, with a repeated baseline, delayed intervention cohort and blind assessment. Intervention included both semantic and phonological information about the target words and involved the adolescents using the words in multiple contexts. Results were promising and participants' knowledge of the targeted words significantly increased following intervention. Progress was demonstrated on the Word Knowledge Profile on the item requiring participants to define the word (for the summer intervention group only). This increase in depth of knowledge was seen on taught words but not on matched non-taught words. Cross-curriculum words are not consistently understood by adolescents at risk of low educational attainment within a low socio-economic context. A 10-week intervention programme resulted in some increases to the depth of knowledge of targeted cross-curriculum words. © 2017 Royal College of Speech and Language Therapists.

Identification of Treatment Targets in a Genetic Mouse Model of Voluntary Methamphetamine Drinking.

PubMed

Phillips, T J; Mootz, J R K; Reed, C

2016-01-01

Methamphetamine has powerful stimulant and euphoric effects that are experienced as rewarding and encourage use. Methamphetamine addiction is associated with debilitating illnesses, destroyed relationships, child neglect, violence, and crime; but after many years of research, broadly effective medications have not been identified. Individual differences that may impact not only risk for developing a methamphetamine use disorder but also affect treatment response have not been fully considered. Human studies have identified candidate genes that may be relevant, but lack of control over drug history, the common use or coabuse of multiple addictive drugs, and restrictions on the types of data that can be collected in humans are barriers to progress. To overcome some of these issues, a genetic animal model comprised of lines of mice selectively bred for high and low voluntary methamphetamine intake was developed to identify risk and protective alleles for methamphetamine consumption, and identify therapeutic targets. The mu opioid receptor gene was supported as a target for genes within a top-ranked transcription factor network associated with level of methamphetamine intake. In addition, mice that consume high levels of methamphetamine were found to possess a nonfunctional form of the trace amine-associated receptor 1 (TAAR1). The Taar1 gene is within a mouse chromosome 10 quantitative trait locus for methamphetamine consumption, and TAAR1 function determines sensitivity to aversive effects of methamphetamine that may curb intake. The genes, gene interaction partners, and protein products identified in this genetic mouse model represent treatment target candidates for methamphetamine addiction. © 2016 Elsevier Inc. All rights reserved.

The Effects of Sexual Partnerships and Relationship Characteristics on Three Sexual Risk Variables in Young Men Who Have Sex with Men

PubMed Central

Newcomb, Michael E.; Ryan, Daniel T.; Garofalo, Robert; Mustanski, Brian

2014-01-01

Young men who have sex with men (YMSM) in the United States are experiencing an alarming increase in HIV incidence. Recent evidence suggests that the majority of new HIV infections in YMSM occur in the context of serious relationships, which underscores the importance of examining predictors of sexual risk behavior in the context of sexual partnerships, including relationship type, sexual partner characteristics, and relationship dynamics. The current study aimed to evaluate relationship and sexual partnership influences on sexual risk behavior in YMSM, including differentiating between multiple sexual risk variables (i.e., any unprotected anal or vaginal intercourse, unprotected insertive anal or vaginal intercourse, and unprotected receptive anal intercourse). More serious/familiar partnerships were associated with more sexual risk across all three risk variables, while wanting a relationship to last was protective against risk across all three risk variables. Some variables were differentially linked to unprotected insertive sex (partner gender) or unprotected receptive sex (partner age, partner race, believing a partner was having sex with others, and partners repeated across waves). Sexual risk behavior in YMSM is inconsistent across sexual partnerships and appears to be determined in no small part by sexual partner characteristics, relationship dynamics, and sexual role (i.e., insertive or receptive partner). These influences are critical in understanding sexual risk in YMSM and provide important targets for intervention. PMID:24217953

Influence of educational status and other variables on human immunodeficiency virus risk perception among military personnel: a large cohort finding.

PubMed

Essien, E James; Ogungbade, Gbadebo O; Ward, Doriel; Ekong, Ernest; Ross, Michael W; Meshack, Angela; Holmes, Laurens

2007-11-01

Human immunodeficiency virus (HIV) risk perception remains an effective determinant of HIV transmission. Although higher educational attainment has been associated with increased HIV risk perception, this predictor remains to be assessed among Nigerian military personnel (NMP). In a prospective cohort of 2,213 NMP, the effects of education and other factors on HIV risk perception were assessed at baseline by using the X2 statistic and unconditional logistic regression. There was an inverse correlation between higher educational attainment and HIV risk perception in the univariate model (prevalence odds ratio, 0.64; 95% confidence interval, 0.52-0.79). This association persisted after adjustment for relevant covariates in the multivariate model (prevalence odds ratio, 0.70; 95% confidence interval, 0.56-0.88). Similarly, there was a direct correlation between use of alcohol and marijuana and HIV risk perception (p < 0.05). In contrast, casual sex and gender were not statistically significantly associated with HIV risk perception (p > 0.05). This study indicates an inverse correlation between educational attainment and HIV risk perception, as well as a direct correlation between alcohol and marijuana use and HIV risk perception, among NMP. Therefore, HIV prevention interventions targeted at NMP need to include multiple factors that may affect risk perception regardless of the educational status of the participants.

The effects of sexual partnership and relationship characteristics on three sexual risk variables in young men who have sex with men.

PubMed

Newcomb, Michael E; Ryan, Daniel T; Garofalo, Robert; Mustanski, Brian

2014-01-01

Young men who have sex with men (YMSM) in the United States are experiencing an alarming increase in HIV incidence. Recent evidence suggests that the majority of new HIV infections in YMSM occur in the context of serious relationships, which underscores the importance of examining predictors of sexual risk behavior in the context of sexual partnerships, including relationship type, sexual partner characteristics, and relationship dynamics. The current study aimed to evaluate relationship and sexual partnership influences on sexual risk behavior in YMSM, including differentiating between multiple sexual risk variables (i.e., any unprotected anal or vaginal intercourse, unprotected insertive anal or vaginal intercourse, and unprotected receptive anal intercourse). More serious/familiar partnerships were associated with more sexual risk across all three risk variables, while wanting a relationship to last was protective against risk across all three risk variables. Some variables were differentially linked to unprotected insertive sex (partner gender) or unprotected receptive sex (partner age, partner race, believing a partner was having sex with others, and partners repeated across waves). Sexual risk behavior in YMSM is inconsistent across sexual partnerships and appears to be determined in no small part by sexual partner characteristics, relationship dynamics, and sexual role (i.e., insertive or receptive partner). These influences are critical in understanding sexual risk in YMSM and provide important targets for intervention.

Modifiable risk factors of hypertension: A hospital-based case-control study from Kerala, India.

PubMed

Pilakkadavath, Zarin; Shaffi, Muhammed

2016-01-01

Hypertension is a major cause of cardiovascular morbidity and mortality in Kerala. Excess dietary salt, low dietary potassium, overweight and obesity, physical inactivity, excess alcohol, smoking, socioeconomic status, psychosocial stressors, and diabetes are considered as modifiable risk factors for hypertension. To estimate and compare the distribution of modifiable risk factors among hypertensive (cases) and nonhypertensive (controls) patients and to estimate the effect relationship of risk factors. Age- and sex-matched case-control study was conducted in a tertiary care hospital in Kerala using a pretested interviewer-administered structured questionnaire based on the WHO STEPS instrument for chronic disease risk factor surveillance. Bivariate and multiple logistic regression analyses were done. A total of 296 subjects were included in the study. The mean age of study sample was 50.13 years. All modifiable risk factors studied vis-ΰ-vis obesity, lack of physical activity, inadequate fruits and vegetable intake, diabetes, smoking, and alcohol use were significantly different in proportion among cases and controls. Obesity, lack of physical activity, smoking, and diabetes were found to be significant risk factors for hypertension after adjusting for other risk factors. Hypertension is strongly driven by a set of modifiable risk factors. Massive public awareness campaign targeting risk factors is essential in controlling hypertension in Kerala, especially focusing on physical exercise and control of diabetes, obesity, and on quitting smoking.

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies.

PubMed

McKay, Fiona C; Gatt, Prudence N; Fewings, Nicole; Parnell, Grant P; Schibeci, Stephen D; Basuki, Monica A I; Powell, Joseph E; Goldinger, Anita; Fabis-Pedrini, Marzena J; Kermode, Allan G; Burke, Therese; Vucic, Steve; Stewart, Graeme J; Booth, David R

2016-02-01

Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p<0.028 for TBX21) and demonstrate longitudinal stability (p<10(-4)) and high heritability (h(2)=0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Role of Adiposity-Driven Inflammation in Depressive Morbidity

PubMed Central

Capuron, Lucile; Lasselin, Julie; Castanon, Nathalie

2017-01-01

Depression and metabolic disorders, including overweight and obesity, appear tightly interrelated. The prevalence of these conditions is concurrently growing worldwide, and both depression and overweight/obesity represent substantial risk factors for multiple medical complications. Moreover, there is now multiple evidence for a bidirectional relationship between depression and increased adiposity, with overweight/obesity being associated with an increased prevalence of depression, and in turn, depression augmenting the risk of weight gain and obesity. Although the reasons for this intricate link between depression and increased adiposity remain unclear, converging clinical and preclinical evidence points to a critical role for inflammatory processes and related alterations of brain functions. In support of this notion, increased adiposity leads to a chronic low-grade activation of inflammatory processes, which have been shown elsewhere to have a potent role in the pathophysiology of depression. It is therefore highly possible that adiposity-driven inflammation contributes to the development of depressive disorders and their growing prevalence worldwide. This review will present recent evidence in support of this hypothesis and will discuss the underlying mechanisms and potential therapeutic targets. Altogether, findings presented here should help to better understand the mechanisms linking adiposity to depression and facilitate the identification of new preventive and/or therapeutic strategies. PMID:27402495

Matrix multiplication operations using pair-wise load and splat operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eichenberger, Alexandre E.; Gschwind, Michael K.; Gunnels, John A.

Mechanisms for performing a matrix multiplication operation are provided. A vector load operation is performed to load a first vector operand of the matrix multiplication operation to a first target vector register. A pair-wise load and splat operation is performed to load a pair of scalar values of a second vector operand and replicate the pair of scalar values within a second target vector register. An operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the matrix multiplication operation. The partial product is accumulatedmore » with other partial products and a resulting accumulated partial product is stored. This operation may be repeated for a second pair of scalar values of the second vector operand.« less

Patterns of HIV Risks and Related Factors among People Who Inject Drugs in Kermanshah, Iran: A Latent Class Analysis.

PubMed

Sharifi, Hamid; Mirzazadeh, Ali; Noroozi, Alireza; Marshall, Brandon D L; Farhoudian, Ali; Higgs, Peter; Vameghi, Meroe; Mohhamadi Shahboulaghi, Farahnaz; Qorbani, Mostafa; Massah, Omid; Armoon, Bahram; Noroozi, Mehdi

2017-01-01

The objective of this study was to explore patterns of drug use and sexual risk behaviors among people who inject drugs (PWID) in Iran. We surveyed 500 PWID in Kermanshah concerning demographic characteristics, sexual risk behaviors, and drug-related risk behaviors in the month prior to study. We used latent class analysis (LCA) to establish a baseline model of risk profiles and to identify the optimal number of latent classes, and we used ordinal regression to identify factors associated with class membership. Three classes of multiple HIV risk were identified. The probability of membership in the high-risk class was 0.33, compared to 0.26 and 0.40 for the low- and moderate-risk classes, respectively. Compared to members in the lowest-risk class (reference group), the highest-risk class members had higher odds of being homeless (OR = 4.5, CI: 1.44-8.22; p = 0.001) in the past 12 months. Members of the high-risk class had lower odds of regularly visiting a needle and syringe exchange program as compared to the lowest-risk class members (AOR = 0.42, CI: 0.2-0.81; p = 0.01). Findings show the sexual and drug-related HIV risk clusters among PWID in Iran, and emphasize the importance of developing targeted prevention and harm reduction programs for all domains of risk behaviors, both sexual and drug use related.

War-related trauma exposure and multiple risk behaviors among school-going adolescents in Northern Uganda: the mediating role of depression symptoms.

PubMed

Okello, James; Nakimuli-Mpungu, Etheldreda; Musisi, Seggane; Broekaert, Eric; Derluyn, Ilse

2013-11-01

The relationship between war-related trauma exposure, depressive symptoms and multiple risk behaviors among adolescents is less clear in sub-Saharan Africa. We analyzed data collected from a sample of school-going adolescents four years postwar. Participants completed interviews assessing various risk behaviors defined by the Youth Self Report (YSR) and a sexual risk behavior survey, and were screened for post-traumatic stress, anxiety and depression symptoms based on the Impact of Events Scale Revised (IESR) and Hopkins Symptom Checklist for Adolescents (HSCL-37A) respectively. Multivariate logistic regression was used to assess factors independently associated with multiple risk behaviors. The logistic regression model of Baron and Kenny (1986) was used to evaluate the mediating role of depression in the relationship between stressful war events and multiple risk behaviors. Of 551 participants, 139 (25%) reported multiple (three or more) risk behaviors in the past year. In the multivariate analyses, depression symptoms remained uniquely associated with multiple risk behavior after adjusting for potential confounders including socio-demographic characteristics, war-related trauma exposure variables, anxiety and post-traumatic stress symptoms. In mediation analysis, depression symptoms mediated the associations between stressful war events and multiple risk behaviors. The psychometric properties of the questionnaires used in this study are not well established in war affected African samples thus ethno cultural variation may decrease the validity of our measures. Adolescents with depression may be at a greater risk of increased engagement in multiple risk behaviors. Culturally sensitive and integrated interventions to treat and prevent depression among adolescents in post-conflict settings are urgently needed. © 2013 Elsevier B.V. All rights reserved.

Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

ERIC Educational Resources Information Center

Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

2010-01-01

The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene.

PubMed

Silvestri, Valentina; Zelli, Veronica; Valentini, Virginia; Rizzolo, Piera; Navazio, Anna Sara; Coppa, Anna; Agata, Simona; Oliani, Cristina; Barana, Daniela; Castrignanò, Tiziana; Viel, Alessandra; Russo, Antonio; Tibiletti, Maria Grazia; Zanna, Ines; Masala, Giovanna; Cortesi, Laura; Manoukian, Siranoush; Azzollini, Jacopo; Peissel, Bernard; Bonanni, Bernardo; Peterlongo, Paolo; Radice, Paolo; Palli, Domenico; Giannini, Giuseppe; Chillemi, Giovanni; Montagna, Marco; Ottini, Laura

2017-01-01

Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutation-negative MBC cases. Germ-line DNA of 1 male and 2 female BRCA1/2 mutation-negative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high-risk, BRCA1/2 mutation-negative MBC cases from an Italian multicenter study of MBC. A case-control series of 433 BRCA1/2 mutation-negative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study. WES in the family identified the partner and localizer of BRCA2 (PALB2) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the N-acetyltransferase 1 (NAT1) c.97C>T nonsense mutation carried by the proband's maternal aunt. Targeted PALB2 sequencing detected the c.1984A>T nonsense mutation in 1 of the 48 BRCA1/2 mutation-negative MBC cases. NAT1 c.97C>T was not found in the case-control series. These results add strength to the evidence showing that PALB2 is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutation-negative families with multiple MBC and FBC cases. Cancer 2017;123:210-218. © 2016 American Cancer Society. © 2016 American Cancer Society.

Selecting at-risk populations for sexually transmitted disease/HIV intervention studies.

PubMed

Wu, Zunyou; Rotheram-Borus, Mary Jane; Detels, Roger; Li, Li; Guan, Jihui; Liang, Guojun; Yap, Lorraine

2007-12-01

This paper describes one option to select populations for randomized, controlled trials (RCT). We used a popular opinion leader intervention in Fuzhou, China, to: (1) identify population selection criteria; (2) systematically examine the suitability of potential target populations and settings; (3) briefly evaluate risk and stability in the population; and (4) evaluate regional and organizational support among administrators and government officials. After comparing migrant villagers, truck drivers, factory workers, construction workers, and market employees in five regions of China, market employees in Fuzhou were identified as the optimal target population. Markets were the optimal sites for several reasons: (1) the population demonstrated a sufficient base rate of sexually transmitted diseases; (2) the population was stable over time; (3) a sufficient number of sites of manageable sizes were available; (4) stable networks existed; (5) local gatekeepers/stakeholders supported the intervention; (6) there was organizational capacity in the local health department to mount the intervention; (7) the demographic profile was similar across potential sites; and (8) the sites were sufficiently distanced to minimize contamination. Evaluating intervention efficacy in an RCT requires a time-consuming and rigorous process that systematically and routinely documents selection criteria, evaluates multiple populations, sites, and organizations for their appropriateness.

Cranial Stereotactic Radiosurgery: Current Status of the Initial Paradigm Shifter

PubMed Central

Sheehan, Jason P.; Yen, Chun-Po; Lee, Cheng-Chia; Loeffler, Jay S.

2014-01-01

The concept of stereotactic radiosurgery (SRS) was first described by Lars Leksell in 1951. It was proposed as a noninvasive alternative to open neurosurgical approaches to manage a variety of conditions. In the following decades, SRS emerged as a unique discipline involving a collegial partnership among neurosurgeons, radiation oncologists, and medical physicists. SRS relies on the precisely guided delivery of high-dose ionizing radiation to an intracranial target. The focused convergence of multiple beams yields a potent therapeutic effect on the target and a steep dose fall-off to surrounding structures, thereby minimizing the risk of collateral damage. SRS is typically administered in a single session but can be given in as many as five sessions or fractions. By providing an ablative effect noninvasively, SRS has altered the treatment paradigms for benign and malignant intracranial tumors, functional disorders, and vascular malformations. Literature on extensive intracranial radiosurgery has unequivocally demonstrated the favorable benefit-to-risk profile that SRS affords for appropriately selected patients. In a departure from conventional radiotherapeutic strategies, radiosurgical principles have recently been extended to extracranial indications such as lung, spine, and liver tumors. The paradigm shift resulting from radiosurgery continues to alter the landscape of related fields. PMID:25113762

Blood pressure, hypertension, RAAS blockade, and drug therapy in diabetic kidney disease.

PubMed

Yamout, Hala; Lazich, Ivana; Bakris, George L

2014-05-01

Type 2 diabetes is the most common cause of CKD and ESRD in the United States and the Western world. Hypertension is prevalent in this cohort, and control of blood pressure is perhaps the most important risk factor to reduce CKD progression. The most recent blood pressure target recommended by the Kidney Disease: Improving Global Outcomes and Kidney Disease Outcomes Quality Initiative guideline committees is less than 140/90 mmHg for all patients with CKD. There is some evidence for those with 1 g or more of albuminuria, albeit weak, to support a blood pressure target of less than 130/80 mmHg. Multiple studies demonstrate that renin-angiotensin-aldosterone system (RAAS) blockers are important in reducing cardiovascular risk and progression of CKD in those with advanced proteinuric nephropathy. However, there is no evidence that they prevent nephropathy or that reduction in microalbuminuria alone is associated with slowed nephropathy progression. The purpose of this article is to review the major studies that have evaluated cardiovascular and kidney endpoints in patients with diabetes and the role of RAAS blockers in the treatment of this disease. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cardiac surgery-associated acute kidney injury.

PubMed

Vives, Marc; Wijeysundera, Duminda; Marczin, Nandor; Monedero, Pablo; Rao, Vivek

2014-05-01

Acute kidney injury develops in up to 30% of patients who undergo cardiac surgery, with up to 3% of patients requiring dialysis. The requirement for dialysis after cardiac surgery is associated with an increased risk of infection, prolonged stay in critical care units and long-term need for dialysis. The development of acute kidney injury is independently associated with substantial short- and long-term morbidity and mortality. Its pathogenesis involves multiple pathways. Haemodynamic, inflammatory, metabolic and nephrotoxic factors are involved and overlap each other leading to kidney injury. Clinical studies have identified predictors for cardiac surgery-associated acute kidney injury that can be used effectively to determine the risk for acute kidney injury in patients undergoing cardiac surgery. High-risk patients can be targeted for renal protective strategies. Nonetheless, there is little compelling evidence from randomized trials supporting specific interventions to protect or prevent acute kidney injury in cardiac surgery patients. Several strategies have shown some promise, including less invasive procedures in those at greatest risk, natriuretic peptide, fenoldopam, preoperative hydration, preoperative optimization of anaemia and postoperative early use of renal replacement therapy. The efficacy of larger-scale trials remains to be confirmed.

Using Integrated Earth and Social Science Data for Disaster Risk Assessment

NASA Astrophysics Data System (ADS)

Downs, R. R.; Chen, R. S.; Yetman, G.

2016-12-01

Society faces many different risks from both natural and technological hazards. In some cases, disaster risk managers focus on only a few risks, e.g., in regions where a single hazard such as earthquakes dominate. More often, however, disaster risk managers deal with multiple hazards that pose diverse threats to life, infrastructure, and livelihoods. From the viewpoint of scientists, hazards are often studied based on traditional disciplines such as seismology, hydrology, climatology, and epidemiology. But from the viewpoint of disaster risk managers, data are needed on all hazards in a specific region and on the exposure and vulnerability of population, infrastructure, and economic resources and activity. Such managers also need to understand how hazards, exposures, and vulnerabilities may interact, and human and environmental systems respond, to hazard events, as in the case of the Fukushima nuclear disaster that followed from the Sendai earthquake and tsunami. In this regard, geospatial tools that enable visualization and analysis of both Earth and social science data can support the use case of disaster risk managers who need to quickly assess where specific hazard events occur relative to population and critical infrastructure. Such information can help them assess the potential severity of actual or predicted hazard events, identify population centers or key infrastructure at risk, and visualize hazard dynamics, e.g., earthquakes and their aftershocks or the paths of severe storms. This can then inform efforts to mitigate risks across multiple hazards, including reducing exposure and vulnerability, strengthening system resiliency, improving disaster response mechanisms, and targeting mitigation resources to the highest or most critical risks. We report here on initial efforts to develop hazard mapping tools that draw on open web services and support simple spatial queries about population exposure. The NASA Socioeconomic Data and Applications Center (SEDAC) Hazards Mapper, a web-based mapping tool, enables users to estimate population living in areas subject to flood or tornado warnings, near recent earthquakes, or around critical infrastructure. The HazPop mobile app, implemented for iOS devices, utilizes location services to support disaster risk managers working in field conditions.

The role of men's physical attractiveness in women's perceptions of sexual risk: danger or allure?

PubMed

Lennon, Carter A; Kenny, David A

2013-09-01

The rate of casual sexual encounters is increasing on college campuses. To decrease sexual risk behavior, information used to judge sexual risk in others needs to be identified. Women rated male targets on willingness to have unprotected sex with the target and likelihood that the target has a sexually transmitted infection. Physical attractiveness was the strongest predictor of ratings, accounting for all the target variance in willingness to have unprotected sex. However, risk factors reported by the target were inconsistent predictors of perceived sexual risk. Findings are discussed within the context of safer sex interventions for college students.

Young Thai women who use methamphetamine: Intersection of sexual partnerships, drug use, and social networks

PubMed Central

German, Danielle; Sherman, Susan A.; Latkin, Carl A.; Sirirojn, Bangorn; Thomson, Nick; Sutcliffe, Catherine G.; Aramrattana, Apinun; Celentano, David D.

2009-01-01

Background Given high rates of methamphetamine (MA) use among young people in Thailand and evidence of an association between MA and increased sexual risk behavior, we examined the association between women’s recent sexual partnerships, social network characteristics and drug and alcohol use. Methods Female participants (n=320) in an HIV behavioral trial among young (18–25 years) MA users in Chiang Mai completed a drug and sexual behavior survey and social network inventory. Multinomial regression analyses accounting for clustered data examined individual and network characteristics associated with recent sexual partnership category. We compared women with only one male partner in the past year (39%) to those with multiple male partners (37%) and those with only female partners (24%). Results Differences in levels of drug and alcohol use and social and sexual network characteristics were dependent on recent sexual partnership profiles. The multiple partner group reported an average of five male partners in the past year; 12% reported consistent condom use in the past 30 days. Compared to both groups, women with multiple male partners used MA more frequently, had larger non-sex networks with more MA users, were more likely to have an MA-using sex partner, and received less emotional support from their partners. Women with multiple male partners and only female partners reported more frequent alcohol use. Conclusions Policy and intervention efforts targeting drug use and sexual behavior among young Thai women are drastically needed and may benefit from consideration of the diversity within the population. These data point to the need for targeted prevention approaches that take into account the varying characteristics and social influences of these different groups of women. PMID:18191393

SU-F-T-349: Dosimetric Comparison of Three Different Simultaneous Integrated Boost Irradiation Techniques for Multiple Brain Metastases: Intensity-Modulatedradiotherapy, Hybrid Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, X; Sun, T; Yin, Y

Purpose: To study the dosimetric impact of intensity-modulated radiotherapy (IMRT), hybrid intensity-modulated radiotherapy (h-IMRT) and volumetric modulated arc therapy(VMAT) for whole-brain radiotherapy (WBRT) with simultaneous integrated boost in patients with multiple brain metastases. Methods: Ten patients with multiple brain metastases were included in this analysis. The prescribed dose was 45 Gy to the whole brain (PTVWBRT) and 55 Gy to individual brain metastases (PTVboost) delivered simultaneously in 25 fractions. Three treatment techniques were designed: the 7 equal spaced fields IMRT plan, hybrid IMRT plan and VMAT with two 358°arcs. In hybrid IMRT plan, two fields(90°and 270°) were planned to themore » whole brain. This was used as a base dose plan. Then 5 fields IMRT plan was optimized based on the two fields plan. The dose distribution in the target, the dose to the organs at risk and total MU in three techniques were compared. Results: For the target dose, conformity and homogeneity in PTV, no statistically differences were observed in the three techniques. For the maximum dose in bilateral lens and the mean dose in bilateral eyes, IMRT and h-IMRT plans showed the highest and lowest value respectively. No statistically significant differences were observed in the dose of optic nerve and brainstem. For the monitor units, IMRT and VMAT plans showed the highest and lowest value respectively. Conclusion: For WBRT with simultaneous integrated boost in patients with multiple brain metastases, hybrid IMRT could reduce the doses to lens and eyes. It is feasible for patients with brain metastases.« less

Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System.

PubMed

Sato, Masahiro; Miyoshi, Kazuchika; Nakamura, Shingo; Ohtsuka, Masato; Sakurai, Takayuki; Watanabe, Satoshi; Kawaguchi, Hiroaki; Tanimoto, Akihide

2017-12-04

The recent advancement in genome editing such a CRISPR/Cas9 system has enabled isolation of cells with knocked multiple alleles through a one-step transfection. Somatic cell nuclear transfer (SCNT) has been frequently employed as one of the efficient tools for the production of genetically modified (GM) animals. To use GM cells as SCNT donor, efficient isolation of transfectants with mutations at multiple target loci is often required. The methods for the isolation of such GM cells largely rely on the use of drug selection-based approach using selectable genes; however, it is often difficult to isolate cells with mutations at multiple target loci. In this study, we used a novel approach for the efficient isolation of porcine cells with at least two target loci mutations by one-step introduction of CRISPR/Cas9-related components. A single guide (sg) RNA targeted to GGTA1 gene, involved in the synthesis of cell-surface α-Gal epitope (known as xenogenic antigen), is always a prerequisite. When the transfected cells were reacted with toxin-labeled BS-I-B₄ isolectin for 2 h at 37 C to eliminate α-Gal epitope-expressing cells, the surviving clones lacked α-Gal epitope expression and were highly expected to exhibit induced mutations at another target loci. Analysis of these α-Gal epitope-negative surviving cells demonstrated a 100% occurrence of genome editing at target loci. SCNT using these cells as donors resulted in the production of cloned blastocysts with the genotype similar to that of the donor cells used. Thus, this novel system will be useful for SCNT-mediated acquisition of GM cloned piglets, in which multiple target loci may be mutated.

Successfully recruiting, surveying, and retaining college students: a description of methods for the Risk, Religiosity, and Emerging Adulthood Study.

PubMed

Berry, Devon M; Bass, Colleen P

2012-12-01

The selection of methods that purposefully reflect the norms of the target population increases the likelihood of effective recruitment, data collection, and retention. In the case of research among college students, researchers' appreciation of college student norms might be skewed by unappreciated generational and developmental differences. Our purpose in this article is to illustrate how attention to the generational and developmental characteristics of college students enhanced the methods of the Risk, Religiosity, and Emerging Adulthood study. We address the following challenges related to research with college students: recruitment, communication, data collection, and retention. Solutions incorporating Internet-based applications (e.g., Facebook) and sensitivity to the generational norms of participants (e.g., multiple means of communication) are described in detail. Copyright © 2012 Wiley Periodicals, Inc.

Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine

PubMed Central

Simeon, Vittorio; Todoerti, Katia; La Rocca, Francesco; Caivano, Antonella; Trino, Stefania; Lionetti, Marta; Agnelli, Luca; De Luca, Luciana; Laurenzana, Ilaria; Neri, Antonino; Musto, Pellegrino

2015-01-01

Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL). PMID:26263974

Condom use with a casual partner: what distinguishes college students' use when intoxicated?

PubMed

Abbey, Antonia; Parkhill, Michele R; Buck, Philip O; Saenz, Christopher

2007-03-01

Determining alcohol's precise role in sexual risk taking has proven to be an elusive goal. Past research has produced mixed results, depending on characteristics of individuals, their partners, and the situation, as well as how the link between alcohol consumption and sexual behavior was assessed. In this study, cross-sectional predictors of the frequency of condom use were examined for 298 heterosexual college students at a large urban university. In hierarchical multiple regression analyses that controlled for frequency of condom use when sober, alcohol expectancies regarding sexual risk taking and self-efficacy regarding condom use when intoxicated were significant predictors of frequency of condom use when intoxicated. These findings highlight the importance of targeting beliefs about alcohol's disinhibiting effects in STD- and HIV-prevention programs. (c) 2007 APA, all rights reserved.

Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine.

PubMed

Simeon, Vittorio; Todoerti, Katia; La Rocca, Francesco; Caivano, Antonella; Trino, Stefania; Lionetti, Marta; Agnelli, Luca; De Luca, Luciana; Laurenzana, Ilaria; Neri, Antonino; Musto, Pellegrino

2015-07-30

Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL).

Vitamin D and Heart Failure.

PubMed

Marshall Brinkley, D; Ali, Omair M; Zalawadiya, Sandip K; Wang, Thomas J

2017-10-01

Vitamin D is principally known for its role in calcium homeostasis, but preclinical studies implicate multiple pathways through which vitamin D may affect cardiovascular function and influence risk for heart failure. Many adults with cardiovascular disease have low vitamin D status, making it a potential therapeutic target. We review the rationale and potential role of vitamin D supplementation in the prevention and treatment of chronic heart failure. Substantial observational evidence has associated low vitamin D status with the risk of heart failure, ventricular remodeling, and clinical outcomes in heart failure, including mortality. However, trials assessing the influence of vitamin D supplementation on surrogate markers and clinical outcomes in heart failure have generally been small and inconclusive. There are insufficient data to recommend routine assessment or supplementation of vitamin D for the prevention or treatment of chronic heart failure. Prospective trials powered for clinical outcomes are warranted.

Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates

PubMed Central

Dostalek, Miroslav; Prueksaritanont, Thomayant; Kelley, Robert F.

2017-01-01

ABSTRACT Pharmacokinetic studies play an important role in all stages of drug discovery and development. Recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. Implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advancing multiple candidates toward clinical development. In this review, we describe tools that should be considered during drug discovery, and discuss approaches that could be included in the pharmacokinetic screening part of the lead candidate generation process to de-risk unexpected pharmacokinetic behaviors of Fc-based therapeutic proteins, with an emphasis on monoclonal antibodies. PMID:28463063

Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing.

PubMed

Ryland, Georgina L; Jones, Kate; Chin, Melody; Markham, John; Aydogan, Elle; Kankanige, Yamuna; Caruso, Marisa; Guinto, Jerick; Dickinson, Michael; Prince, H Miles; Yong, Kwee; Blombery, Piers

2018-05-14

Multiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre. A cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline. At least one mutation was found in 69 (80%) patients. Frequently mutated genes included TP53 (36%), KRAS (22.1%), NRAS (15.1%), FAM46C/DIS3 (8.1%) and TET2/FGFR3 (5.8%), including multiple mutations not previously described in myeloma. Importantly we observed TP53 mutations in the absence of a 17 p deletion in 8% of the cohort, highlighting the need for sequencing-based assessment in addition to cytogenetics to identify these high-risk patients. Multiple novel copy number changes and immunoglobulin heavy chain translocations are also discussed. Our results demonstrate that many clinically relevant genomic findings remain in multiple myeloma which have not yet been identified through large-scale sequencing efforts, and provide important mechanistic insights into plasma cell pathobiology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Factors related to suicidal ideation in stroke patients in South Korea.

PubMed

Park, Eun-Young; Kim, Jung-Hee

2016-01-01

Suicide rates in Korea have increased dramatically. Stroke is considered one of the most debilitating neurological disorders, resulting in physical impairment, disability, and death. The present study attempted to examine factors related to suicidal ideation in community-dwelling stroke patients. The Korea Welfare Panel Study was used to investigate the relationship between demographic and psychological variables and suicidal ideation among these individuals. Depression was assessed using the Center for Epidemiological Studies Depression Scale 11 (CES-D-11). Self-esteem was assessed using Rosenberg's Self-Esteem Scale. The prevalence of suicidal thought among stroke patients was estimated at 13.99%. Multiple logistic regression analysis indicated that both older age and depression were significant independent risk factors for suicidal ideation. High-priority health care plans can prevent suicide in stroke patients suffering from depression. Assessing risk for suicide and monitoring the high-risk group is integral to health care. Stroke patients with depression, particularly older patients, would be prime targets for suicide intervention programs.

Global Epidemiology of Plasmodium vivax

PubMed Central

Howes, Rosalind E.; Battle, Katherine E.; Mendis, Kamini N.; Smith, David L.; Cibulskis, Richard E.; Baird, J. Kevin; Hay, Simon I.

2016-01-01

Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum. Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded. PMID:27402513

The role of early maturation, perceived popularity, and rumors in the emergence of internalizing symptoms among adolescent girls.

PubMed

Reynolds, Bridget M; Juvonen, Jaana

2011-11-01

Despite the widely reported link between early pubertal timing and internalizing symptoms among girls, less is known about the peer reputation of earlier maturing girls. The current study assesses whether early maturation is associated with perceived popularity and/or rumors, and whether these reputational factors help account for earlier maturing girls' vulnerability to emotional distress. Drawing on three waves of data collected from an ethnically diverse sample of middle school girls (n = 912), hierarchical multiple regression analyses revealed that more advanced development at the start of middle school predicted peer- and teacher-reported popularity as well as increased risk of being targeted for rumors. Mediation analyses suggested that popularity among boys can put earlier developing girls at risk for rumors. Finally, rumors acted as a partial mechanism through which early maturation was associated with subsequent internalizing symptoms. Knowledge of the peer mechanisms putting earlier developing girls at risk for psychosocial maladjustment can inform intervention and prevention efforts aimed at improving adolescent well-being.

Does Context Matter? Examining PRISM as a Guiding Framework for Context-Specific Health Risk Information Seeking Among Young Adults.

PubMed

Willoughby, Jessica Fitts; Myrick, Jessica Gall

2016-06-01

Research indicates that when people seek health information, they typically look for information about a specific symptom, preventive measure, disease, or treatment. It is unclear, however, whether general or disease-specific theoretical models best predict how people search for health information. We surveyed undergraduates (N = 963) at a large public southeastern university to examine health information seeking in two incongruent health contexts (sexual health and cancer) to test whether a general model would hold for specific topics that differed in their immediate personal relevance for the target population. We found that the planned risk information seeking model was statistically a good fit for the data. Yet multiple predicted paths were not supported in either data set. Certain variables, such as attitudes, norms, and affect, appear to be strong predictors of intentions to seek information across health contexts. Implications for theory building, research methodology, and applied work in health-related risk information seeking are discussed.

[D.lgsl. 625/1994--Protection against carcinogenic agents: the obligation to educate].

PubMed

Fucci, P; Anselmi, E; Bracci, C; Comba, P

1997-01-01

According to act 626/1994, employers have the duty to inform and train workers and their representatives. The implementation of training activities requires the following points: planning the training program according to the needs of the target population, use of the methods aimed at promoting learning and the adoption of safe behaviour, setting-up of evaluation tools. The disciplines of risk perception and communication and adult training may provide useful contribution in this frame. At the light of the preliminary experiences in this field, the importance of the following items for workers, workers representatives and employers is emphasized: probabilistic causality models, role of cognitive and emotional factors in the learning process, definition of carcinogenic according to national and international organisation, meaning of TLV with respect to carcinogenic exposure, interaction between carcinogens in the case of multiple exposition, risk evaluation, preventive measures, transfer of carcinogen risk from workplace to domestic environment, due to lack of compliance with basic hygienic rules such proper use of work clothes.

Using agent-based modeling to study multiple risk factors and multiple health outcomes at multiple levels.

PubMed

Yang, Yong

2017-11-01

Most health studies focus on one health outcome and examine the influence of one or multiple risk factors. However, in reality, various pathways, interactions, and associations exist not only between risk factors and health outcomes but also among the risk factors and among health outcomes. The advance of system science methods, Big Data, and accumulated knowledge allows us to examine how multiple risk factors influence multiple health outcomes at multiple levels (termed a 3M study). Using the study of neighborhood environment and health as an example, I elaborate on the significance of 3M studies. 3M studies may lead to a significantly deeper understanding of the dynamic interactions among risk factors and outcomes and could help us design better interventions that may be of particular relevance for upstream interventions. Agent-based modeling (ABM) is a promising method in the 3M study, although its potentials are far from being fully explored. Future challenges include the gap of epidemiologic knowledge and evidence, lack of empirical data sources, and the technical challenges of ABM. © 2017 New York Academy of Sciences.

Global Conservation Priorities for Marine Turtles

PubMed Central

Wallace, Bryan P.; DiMatteo, Andrew D.; Bolten, Alan B.; Chaloupka, Milani Y.; Hutchinson, Brian J.; Abreu-Grobois, F. Alberto; Mortimer, Jeanne A.; Seminoff, Jeffrey A.; Amorocho, Diego; Bjorndal, Karen A.; Bourjea, Jérôme; Bowen, Brian W.; Briseño Dueñas, Raquel; Casale, Paolo; Choudhury, B. C.; Costa, Alice; Dutton, Peter H.; Fallabrino, Alejandro; Finkbeiner, Elena M.; Girard, Alexandre; Girondot, Marc; Hamann, Mark; Hurley, Brendan J.; López-Mendilaharsu, Milagros; Marcovaldi, Maria Angela; Musick, John A.; Nel, Ronel; Pilcher, Nicolas J.; Troëng, Sebastian; Witherington, Blair; Mast, Roderic B.

2011-01-01

Where conservation resources are limited and conservation targets are diverse, robust yet flexible priority-setting frameworks are vital. Priority-setting is especially important for geographically widespread species with distinct populations subject to multiple threats that operate on different spatial and temporal scales. Marine turtles are widely distributed and exhibit intra-specific variations in population sizes and trends, as well as reproduction and morphology. However, current global extinction risk assessment frameworks do not assess conservation status of spatially and biologically distinct marine turtle Regional Management Units (RMUs), and thus do not capture variations in population trends, impacts of threats, or necessary conservation actions across individual populations. To address this issue, we developed a new assessment framework that allowed us to evaluate, compare and organize marine turtle RMUs according to status and threats criteria. Because conservation priorities can vary widely (i.e. from avoiding imminent extinction to maintaining long-term monitoring efforts) we developed a “conservation priorities portfolio” system using categories of paired risk and threats scores for all RMUs (n = 58). We performed these assessments and rankings globally, by species, by ocean basin, and by recognized geopolitical bodies to identify patterns in risk, threats, and data gaps at different scales. This process resulted in characterization of risk and threats to all marine turtle RMUs, including identification of the world's 11 most endangered marine turtle RMUs based on highest risk and threats scores. This system also highlighted important gaps in available information that is crucial for accurate conservation assessments. Overall, this priority-setting framework can provide guidance for research and conservation priorities at multiple relevant scales, and should serve as a model for conservation status assessments and priority-setting for widespread, long-lived taxa. PMID:21969858

Risk factors for acute knee injury in female youth football.

PubMed

Hägglund, Martin; Waldén, Markus

2016-03-01

To prospectively evaluate risk factors for acute time-loss knee injury, in particular ACL injury, in female youth football players. Risk factors were studied in 4556 players aged 12-17 years from a randomised controlled trial during the 2009 season. Covariates were both intrinsic (body mass index, age, relative age effect, onset of menarche, previous acute knee injury or ACL injury, current knee complaints, and familial disposition of ACL injury) and extrinsic (no. of training sessions/week, no. of matches/week, match exposure ratio, match play with other teams, and artificial turf exposure). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from individual variable and multiple Cox regression analyses. Ninety-six acute knee injuries were recorded, 21 of them ACL injuries. Multiple Cox regression showed a fourfold higher ACL injury rate for players with familial disposition of ACL injury (HR 3.57; 95% CI 1.48-8.62). Significant predictor variables for acute knee injury were age >14 years (HR 1.97; 95% CI 1.30-2.97), knee complaints at the start of the season (HR 1.98; 95% CI 1.30-3.02), and familial disposition of ACL injury (HR 1.96; 95% CI 1.22-3.16). No differences in injury rates were seen when playing on artificial turf compared with natural grass. Female youth football players with a familial disposition of ACL injury had an increased risk of ACL injury and acute knee injury. Older players and those with knee complaints at pre-season were more at risk of acute knee injury. Although the predictive values were low, these factors could be used in athlete screening to target preventive interventions. II.

Evaluation of Parkinson Disease Risk Variants as Expression-QTLs

PubMed Central

Latourelle, Jeanne C.; Dumitriu, Alexandra; Hadzi, Tiffany C.; Beach, Thomas G.; Myers, Richard H.

2012-01-01

The recent Parkinson Disease GWAS Consortium meta-analysis and replication study reports association at several previously confirmed risk loci SNCA, MAPT, GAK/DGKQ, and HLA and identified a novel risk locus at RIT2. To further explore functional consequences of these associations, we investigated modification of gene expression in prefrontal cortex brain samples of pathologically confirmed PD cases (N = 26) and controls (N = 24) by 67 associated SNPs in these 5 loci. Association between the eSNPs and expression was evaluated using a 2-degrees of freedom test of both association and difference in association between cases and controls, adjusted for relevant covariates. SNPs at each of the 5 loci were tested for cis-acting effects on all probes within 250 kb of each locus. Trans-effects of the SNPs on the 39,122 probes passing all QC on the microarray were also examined. From the analysis of cis-acting SNP effects, several SNPs in the MAPT region show significant association to multiple nearby probes, including two strongly correlated probes targeting the gene LOC644246 and the duplicated genes LRRC37A and LRRC37A2, and a third uncorrelated probe targeting the gene DCAKD. Significant cis-associations were also observed between SNPs and two probes targeting genes in the HLA region on chromosome 6. Expanding the association study to examine trans effects revealed an additional 23 SNP-probe associations reaching statistical significance (p<2.8×10−8) including SNPs from the SNCA, MAPT and RIT2 regions. These findings provide additional context for the interpretation of PD associated SNPs identified in recent GWAS as well as potential insight into the mechanisms underlying the observed SNP associations. PMID:23071545

Five-Year Safety Data for More than 55,000 Subjects following Breast Implantation: Comparison of Rare Adverse Event Rates with Silicone Implants versus National Norms and Saline Implants.

PubMed

Singh, Navin; Picha, George J; Hardas, Bhushan; Schumacher, Andrew; Murphy, Diane K

2017-10-01

The U.S. Food and Drug Administration has required postapproval studies of silicone breast implants to evaluate the incidence of rare adverse events over 10 years after implantation. The Breast Implant Follow-Up Study is a large 10-year study (>1000 U.S. sites) evaluating long-term safety following primary augmentation, revision-augmentation, primary reconstruction, or revision-reconstruction with Natrelle round silicone breast implants compared with national norms and outcomes with saline implants. Targeted adverse events in subjects followed for 5 to 8 years included connective tissue diseases, neurologic diseases, cancer, and suicide. The safety population comprised 55,279 women (primary augmentation, n = 42,873; revision-augmentation, n = 6837; primary reconstruction, n = 4828; and revision-reconstruction, n = 741). No targeted adverse events occurred at significantly greater rates in silicone implant groups versus national norms across all indications. The standardized incidence rate (observed/national norm) for all indications combined was 1.4 for cervical/vulvar cancer, 0.8 for brain cancer, 0.3 for multiple sclerosis, and 0.1 for lupus/lupus-like syndrome. Silicone implants did not significantly increase the risk for any targeted adverse events compared with saline implants. The risk of death was similar with silicone versus saline implants across all indications. The suicide rate (10.6 events per 100,000 person-years) was not significantly higher than the national norm. No implant-related deaths occurred. Results from 5 to 8 years of follow-up for a large number of subjects confirmed the safety of Natrelle round silicone implants, with no increased risk of systemic disease or suicide versus national norms or saline implants. Therapeutic, II.

Targeting the SAVA (Substance Abuse, Violence and AIDS) Syndemic among Women and Girls: A Global Review of Epidemiology and Integrated Interventions

PubMed Central

Gilbert, Louisa; Raj, Anita; Hien, Denise; Stockman, Jamila; Terlikbayeva, Assel; Wyatt, Gail

2016-01-01

Objectives Multiple pathways link gender-based violence (GBV) to HIV and other sexually transmitted infections (STIs) among women and girls who use or inject drugs. The aim of this paper is to synthesize global literature that examines associations among the synergistic epidemics of substance abuse, violence and HIV/AIDS, known as the SAVA syndemic. It also aims to identify a continuum of multi-level integrated interventions that target key SAVA syndemic mechanisms. Methods We conducted a selective search strategy, prioritizing use of meta-analytic epidemiological and intervention studies that address different aspects of the SAVA syndemic among women and girls who use drugs worldwide from 2000–2015 using PubMed, MEDLINE, and Google Scholar. Results Robust evidence from different countries suggests that GBV significantly increases the risk of HIV and other STIs among women and girls who use drugs. Multiple structural, biological and behavioral mechanisms link GBV and HIV among women and girls. Emerging research has identified a continuum of brief and extended multi-level GBV prevention and treatment interventions that may be integrated into a continuum of HIV prevention, testing, and treatment interventions to target key SAVA syndemic mechanisms among women and girls who use drugs. Conclusion There remain significant methodological and geographical gaps in epidemiological and intervention research on the SAVA syndemic, particularly in low and middle-income countries. This global review underscores the need to advance a continuum of multi-level integrated interventions that target salient mechanisms of the SAVA syndemic, especially for adolescent girls, young women and transgender women who use drugs. PMID:25978478

The Next Generation of Targeted Molecules for the Treatment of Chronic Lymphocytic Leukemia.

PubMed

Jeyakumar, Deepa; O'Brien, Susan

2016-11-15

With the recent approval of several new targeted therapies for chronic lymphocytic leukemia (CLL), there are now multiple options for its treatment. Inhibitors of Bruton tyrosine kinase (with ibrutinib being the first-in-class US Food and Drug Administration-approved agent) and phosphoinositide 3-kinase (with idelalisib as the first-in-class approved agent) are promising because they are generally well tolerated and highly effective against this malignancy. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and subsequent infections) associated with chemoimmunotherapy. As a class of medications, B-cell receptor inhibitors have some unique side effects, including redistribution lymphocytosis. Toxicities associated specifically with ibrutinib include increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities: transaminitis, colitis, and pneumonitis. Targeted therapies recently approved for use in CLL include the novel anti-CD20 monoclonal antibodies obinutuzumab and ofatumumab, and the B-cell lymphoma 2 inhibitor venetoclax. This article describes the clinical data that led to approval of these B-cell receptor inhibitors for the treatment of CLL, and highlights newer agents in clinical development that target the same kinases as the currently available therapies.

Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer.

PubMed

Mitsui, Jun; Fukuda, Yoko; Azuma, Kyo; Tozaki, Hirokazu; Ishiura, Hiroyuki; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

2010-07-01

We have recently found that multiple rare variants of the glucocerebrosidase gene (GBA) confer a robust risk for Parkinson disease, supporting the 'common disease-multiple rare variants' hypothesis. To develop an efficient method of identifying rare variants in a large number of samples, we applied multiplexed resequencing using a next-generation sequencer to identification of rare variants of GBA. Sixteen sets of pooled DNAs from six pooled DNA samples were prepared. Each set of pooled DNAs was subjected to polymerase chain reaction to amplify the target gene (GBA) covering 6.5 kb, pooled into one tube with barcode indexing, and then subjected to extensive sequence analysis using the SOLiD System. Individual samples were also subjected to direct nucleotide sequence analysis. With the optimization of data processing, we were able to extract all the variants from 96 samples with acceptable rates of false-positive single-nucleotide variants.

Systemic Prenatal Insults Disrupt Telencephalon Development

PubMed Central

Robinson, Shenandoah

2006-01-01

Infants born prematurely are prone to chronic neurologic deficits including cerebral palsy (CP), epilepsy, cognitive delay, behavioral problems, and neurosensory impairments. In affected children, imaging and neuropathological findings demonstrate significant damage to white matter. The extent of cortical damage has been less obvious. Advances in the understanding of telencephalon development provide insights into how systemic intrauterine insults affect the developing white matter, subplate and cortex, and lead to multiple neurologic impairments. In addition to white matter oligodendrocytes and axons, other elements at risk for perinatal brain injury include subplate neurons, GABAergic neurons migrating through white matter and subplate, and afferents of maturing neurotransmitter systems. Common insults including hypoxia-ischemia and infection often affect the developing brain differently than the mature brain, and insults precipitate a cascade of damage to multiple neural lineages. Insights from development can identify potential targets for therapies to repair the damaged neonatal brain before it has matured. PMID:16061421

Teaching math skills to at-risk students using home-based peer tutoring.

PubMed

Mayfield, Kristin H; Vollmer, Timothy R

2007-01-01

Home-based peer tutoring was used to teach math skills to 4 girls with deficits in mathematics and histories of abuse or neglect. Girls living in the same home formed tutoring dyads, and each participant served as both the peer tutor and the tutee during the course of the study. At the initiation of the tutoring intervention, an expert tutor provided multiple 3-min tutoring sessions to the designated peer tutor on three or four mathematics skills. The peer tutor concurrently provided 3-min tutoring sessions on the same skills to the tutee using a multiple baseline design. Results showed that participants improved their performance on all target skills. Additional interventions were implemented for some skills to improve accuracy further. Maintenance tests were also administered after 3 to 5 months of no practice on the skills. Results showed that tutors and tutees maintained their accuracy on 7 of the 12 skills assessed.

Teaching Math Skills to At-risk Students Using Home-based Peer Tutoring

PubMed Central

Mayfield, Kristin H; Vollmer, Timothy R

2007-01-01

Home-based peer tutoring was used to teach math skills to 4 girls with deficits in mathematics and histories of abuse or neglect. Girls living in the same home formed tutoring dyads, and each participant served as both the peer tutor and the tutee during the course of the study. At the initiation of the tutoring intervention, an expert tutor provided multiple 3-min tutoring sessions to the designated peer tutor on three or four mathematics skills. The peer tutor concurrently provided 3-min tutoring sessions on the same skills to the tutee using a multiple baseline design. Results showed that participants improved their performance on all target skills. Additional interventions were implemented for some skills to improve accuracy further. Maintenance tests were also administered after 3 to 5 months of no practice on the skills. Results showed that tutors and tutees maintained their accuracy on 7 of the 12 skills assessed. PMID:17624064

Design of inventory pools in spare part support operation systems

NASA Astrophysics Data System (ADS)

Mo, Daniel Y.; Tseng, Mitchell M.; Cheung, Raymond K.

2014-06-01

The objective of a spare part support operation is to fulfill the part request order with different service contracts in the agreed response time. With this objective to achieve different service targets for multiple service contracts and the considerations of inventory investment, it is not only important to determine the inventory policy but also to design the structure of inventory pools and the order fulfilment strategies. In this research, we focused on two types of inventory pools: multiple inventory pool (MIP) and consolidated inventory pool (CIP). The idea of MIP is to maintain separated inventory pools based on the types of service contract, while CIP solely maintains a single inventory pool regardless of service contract. Our research aims to design the inventory pool analytically and propose reserve strategies to manage the order fulfilment risks in CIP. Mathematical models and simulation experiments would be applied for analysis and evaluation.

Reducing falls and improving mobility in multiple sclerosis.

PubMed

Sosnoff, Jacob J; Sung, JongHun

2015-06-01

Falls are common in persons with multiple sclerosis (MS), and are related to physical injury and reduce the quality of life. Mobility impairments are a significant risk factor for falls in persons with MS. Although there is evidence that mobility in persons with MS can be improved with rehabilitation, much less is known about fall prevention. This review focuses on fall prevention in persons with MS. Ten fall prevention interventions consisting of 524 participants with a wide range of disability were systematically identified. Nine of the 10 investigations report a reduction in falls and/or proportion of fallers following treatment. The vast majority observed an improvement in balance that co-occurred with the reduction in falls. Methodological limitations preclude any firm conclusions. Numerous gaps in the understanding of fall prevention in persons with MS are discussed. Well-designed randomized control trials targeting mobility and falls are warranted.

Molecular markers in bladder cancer: Novel research frontiers.

PubMed

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools combining standard clinical-pathological factors with molecular markers represents a major quest in managing this poorly predictable disease.

Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease.

PubMed

Chaudhury, Sultan; Patel, Tulsi; Barber, Imelda S; Guetta-Baranes, Tamar; Brookes, Keeley J; Chappell, Sally; Turton, James; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Hardy, John; Mann, David; Morgan, Kevin

2018-02-01

Sporadic early-onset Alzheimer's disease (sEOAD) exhibits the symptoms of late-onset Alzheimer's disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer's disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer's Project consortium, with association data from 17,008 late-onset Alzheimer's disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

The co-occurrence of AIDS and homelessness: results from the integration of administrative databases for AIDS surveillance and public shelter utilisation in Philadelphia.

PubMed

Culhane, D P; Gollub, E; Kuhn, R; Shpaner, M

2001-07-01

Administrative databases from the City of Philadelphia that track public shelter utilisation (n=44 337) and AIDS case reporting (n=7749) were merged to identify rates and risk factors for co-occurring homelessness and AIDS. Multiple decrement life tables analyses were conducted, and logistic regression analyses used to identify risk factors associated with AIDS among the homeless, and homelessness among people with AIDS. City of Philadelphia, Pennsylvania, USA. People admitted to public shelters had a three year rate of subsequent AIDS diagnosis of 1.8 per 100 person years; nine times the rate for the general population of Philadelphia. Logistic regression results show that substance abuse history (OR = 3.14), male gender (OR = 2.05), and a history of serious mental disorder (OR = 1.62) were significantly related to the risk for AIDS diagnosis among shelter users. Among people with AIDS, results show a three year rate of subsequent shelter admission of 6.9 per 100 person years, and a three year rate of prior shelter admission of 9%, three times the three year rate of shelter admission for the general population. Logistic regression results show that intravenous drug user history (OR = 3.14); no private insurance (OR = 2.93); black race (OR = 2.82); pulmonary or extra-pulmonary TB (OR = 1.43); and pneumocystis pneumonia (OR = 0.56) were all related to the risk for shelter admission. Homelessness prevention programmes should target people with HIV risk factors, and HIV prevention programmes should be targeted to homeless persons, as these populations have significant intersection. Reasons and implications for this intersection are discussed.

Multiple Risks, Emotion Regulation Skill, and Cortisol in Low-Income African American Youth: A Prospective Study

ERIC Educational Resources Information Center

Kliewer, Wendy; Reid-Quinones, Kathryn; Shields, Brian J.; Foutz, Lauren

2009-01-01

Associations between multiple risks, emotion regulation skill, and basal cortisol levels were examined in a community sample of 69 African American youth (mean age = 11.30 years; 49% male) living in an urban setting. Multiple risks were assessed at Time 1 and consisted of 10 demographic and psychosocial risk factors including parent, child, and…

Progress in the Visualization and Mining of Chemical and Target Spaces.

PubMed

Medina-Franco, José L; Aguayo-Ortiz, Rodrigo

2013-12-01

Chemogenomics is a growing field that aims to integrate the chemical and target spaces. As part of a multi-disciplinary effort to achieve this goal, computational methods initially developed to visualize the chemical space of compound collections and mine single-target structure-activity relationships, are being adapted to visualize and mine complex relationships in chemogenomics data sets. Similarly, the growing evidence that clinical effects are many times due to the interaction of single or multiple drugs with multiple targets, is encouraging the development of novel methodologies that are integrated in multi-target drug discovery endeavors. Herein we review advances in the development and application of approaches to generate visual representations of chemical space with particular emphasis on methods that aim to explore and uncover relationships between chemical and target spaces. Also, progress in the data mining of the structure-activity relationships of sets of compounds screened across multiple targets are discussed in light of the concept of activity landscape modeling. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

What role does transactional sex play in the HIV/STI and reproductive health risk behaviour among high-tier entertainment centre workers in China?

PubMed

Mantell, Joanne E; LeVasseur, Michael T; Sun, Xiaoming; Zhou, Jiangfang; Mao, Jingshu; Peng, Yanhui; Zhou, Feng; DiCarlo, Abby L; Kelvin, Elizabeth A

2015-01-01

China's rapid economic growth over the last three decades has led to increased population wealth and the proliferation of entertainment centres where people can conduct business, relax and meet new people. Little is known about the sexual risk behaviours of employees at high-tier entertainment centres. This paper addresses this gap in knowledge by comparing HIV risk perception and sexual and reproductive health behaviours among female and male employees at three high-tier entertainment centres in two cities in China, comparing those who report a history of transactional sex to those who do not. In both cities, participants who reported a history of transactional sex were more likely than those without a history of transactional sex to report multiple sexual partnerships, more lifetime sexual partners, a history of sexually transmitted infections (STIs), having anal sex and/or recent abortions, and were more likely to perceive themselves to be at risk for STIs/HIV. However, risk behaviour was also high among those with no history of transactional sex. These findings highlight the need for targeted sexual and reproductive health initiatives for employees in these work settings.

High-risk behaviour in young men attending sexually transmitted disease clinics in Pune, India

PubMed Central

BRAHME, R. G.; SAHAY, S.; MALHOTRA-KOHLI, R.; DIVEKAR, A. D.; GANGAKHEDKAR, R. R.; PARKHE, A. P.; KHARAT, M. P.; RISBUD, A. R.; BOLLINGER, R. C.; MEHENDALE, S. M.; PARANJAPE, R. S.

2012-01-01

The present study reports sexual risk factors associated with HIV infection among men attending two sexually transmitted disease (STD) clinics in Pune, India and compares these behaviours between young and older men. Between April 1998 and May 2000, 1,872 STD patients were screened for HIV infection. Data on demographics, medical history and sexual behaviour were collected at baseline. The overall HIV prevalence was 22.2%. HIV risk was associated with being divorced or widowed, less educated, living away from the family, having multiple sexual partners and initiation of sex at an early age. The risk behaviours in younger men were different to older men. Younger men were more likely to report early age of initiation of sex, having friends, acquaintances or commercial sex workers as their regular partners, having premarital sex and bisexual orientation. Young men were more educated and reported condom use more frequently compared with the older men. Similar high HIV prevalence among younger and older men highlights the need for focused targeted interventions aimed at adolescents and young men and also appropriate interventions for older men to reduce the risk of HIV and STD acquisition. PMID:15832886

What role does transactional sex play in the HIV/STI and reproductive health risk behaviour among high-tier entertainment centre workers in China?

PubMed Central

Mantell, Joanne E.; LeVasseur, Michael T.; Sun, Xiaoming; Zhou, Jiangfang; Mao, Jingshu; Peng, Yanhui; Zhou, Feng; DiCarlo, Abby L.; Kelvin, Elizabeth A.

2015-01-01

China’s rapid economic growth over the last three decades has led to increased population wealth and the proliferation of entertainment centres where people can conduct business, relax and meet new people. Little is known about the sexual risk behaviours of employees at high-tier entertainment centres. This paper addresses this gap in knowledge by comparing HIV risk perception and sexual and reproductive health behaviours among female and male employees at three high-tier entertainment centres in two cities in China, comparing those who report a history of transactional sex to those who do not. In both cities, participants who reported a history of transactional sex were more likely than those without a history of transactional sex to report multiple sexual partnerships, more lifetime sexual partners, a history of STIs, having anal sex and/or recent abortions, and were more likely to perceive themselves to be at risk for STIs/HIV. However, risk behaviour was also high among those with no history of transactional sex. These findings highlight the need for targeted sexual and reproductive health initiatives for employees in these work settings. PMID:26274897

Social Context and Problem Factors among Youth with Juvenile Justice Involvement Histories.

PubMed

Voisin, Dexter R; Sales, Jessica M; Hong, Jun Sung; Jackson, Jerrold M; Rose, Eve S; DiClemente, Ralph J

2017-01-01

Youth with juvenile justice histories often reside in poorly resourced communities and report high rates of depression, gang involved networks, and STI-sexual related risk behaviors, compared to their counterparts. The primary aim of this study was to examine the relationship between social context (ie, a combined index score comprised of living in public housing, being a recipient of free school lunch, and witnessing community violence) and risk factors that are disproportionately worse for juvenile justice youth such as depression, gang involved networks and STI sexual risk behaviors. Data were collected from a sample of detained youth ages 14 to 16 (N = 489). Questions assessed demographics, social context, depression, gang-involved networks, and STI risk behaviors. Multiple logistic regression models, controlling for age, gender, race, school enrollment, and family social support, indicated that participants who reported poorer social context had double the odds of reporting being depressed; three times higher odds of being in a gang; three times higher odds of personally knowing a gang member; and double the odds of having engaged in STI-risk behaviors. These results provide significant information that can help service providers target certain profiles of youth with juvenile justice histories for early intervention initiatives.

Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways.

PubMed

Shenk, Chad E; Griffin, Amanda M; O'Donnell, Kieran J

2015-11-01

Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: neuroendocrine, autonomic, affective, and emotion regulation. Female adolescents (N = 110; age range = 14-19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed 18 months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed.

Assessing patient risk of central line-associated bacteremia via machine learning.

PubMed

Beeler, Cole; Dbeibo, Lana; Kelley, Kristen; Thatcher, Levi; Webb, Douglas; Bah, Amadou; Monahan, Patrick; Fowler, Nicole R; Nicol, Spencer; Judy-Malcolm, Alisa; Azar, Jose

2018-04-13

Central line-associated bloodstream infections (CLABSIs) contribute to increased morbidity, length of hospital stay, and cost. Despite progress in understanding the risk factors, there remains a need to accurately predict the risk of CLABSIs and, in real time, prevent them from occurring. A predictive model was developed using retrospective data from a large academic healthcare system. Models were developed with machine learning via construction of random forests using validated input variables. Fifteen variables accounted for the most significant effect on CLABSI prediction based on a retrospective study of 70,218 unique patient encounters between January 1, 2013, and May 31, 2016. The area under the receiver operating characteristic curve for the best-performing model was 0.82 in production. This model has multiple applications for resource allocation for CLABSI prevention, including serving as a tool to target patients at highest risk for potentially cost-effective but otherwise time-limited interventions. Machine learning can be used to develop accurate models to predict the risk of CLABSI in real time prior to the development of infection. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

New Genes and New Insights from Old Genes: Update on Alzheimer Disease

PubMed Central

Ringman, John M.; Coppola, Giovanni

2013-01-01

Purpose of Review: This article discusses the current status of knowledge regarding the genetic basis of Alzheimer disease (AD) with a focus on clinically relevant aspects. Recent Findings: The genetic architecture of AD is complex, as it includes multiple susceptibility genes and likely nongenetic factors. Rare but highly penetrant autosomal dominant mutations explain a small minority of the cases but have allowed tremendous advances in understanding disease pathogenesis. The identification of a strong genetic risk factor, APOE, reshaped the field and introduced the notion of genetic risk for AD. More recently, large-scale genome-wide association studies are adding to the picture a number of common variants with very small effect sizes. Large-scale resequencing studies are expected to identify additional risk factors, including rare susceptibility variants and structural variation. Summary: Genetic assessment is currently of limited utility in clinical practice because of the low frequency (Mendelian mutations) or small effect size (common risk factors) of the currently known susceptibility genes. However, genetic studies are identifying with confidence a number of novel risk genes, and this will further our understanding of disease biology and possibly the identification of therapeutic targets. PMID:23558482

HIV Risk Perception and Risky Behavior Among People Who Inject Drugs in Kermanshah, Western Iran.

PubMed

Noroozi, Mehdi; Ahounbar, Elahe; Karimi, Salah Eddin; Ahmadi, Sina; Najafi, Mohammad; Bazrafshan, Ali; Shushtari, Zahra Jorjoran; Farhadi, Mohammad Hassan; Higgs, Peter; Rezaei, Fatemeh; Ghiasvand, Hesam; Sharhani, Asaad; Armoon, Bahram; Waye, Katherine

2017-08-01

Understanding and increasing awareness on individual risk for HIV infection as well as HIV risk perception's effects on different behavioral outcomes for people who inject drugs (PWID) is important for policymaking and planning purposes. The objectives of the present study were to determine whether HIV risk perception was associated with greater injection and sexual risk-taking behaviors among PWIDs. We surveyed 460 PWID in Kermanshah regarding their demographic characteristics, sexual risk behaviors, HIV risk perception, and drug-related risk behaviors in the month prior to the study. Three classes of HIV risk perception were identified using ordinal regression to determine factors associated with HIV risk perception. Study participants were categorized as follows: "low" (n = 100, 22%), "moderate" (n = 150, 32%), and "high" (n = 210, 46%) risk perception for becoming infected with HIV. The odds of categorizing as "high" risk for HIV was significantly greater in PWID that reported unprotected sex (adjusted odds ratio (AOR) 2.4, p value 0.02), receptive syringe sharing (AOR 1.8, p value 0.01), and multiple sex partners (AOR 1.4, p value 0.03). PWID who reported unprotected sex had 2.7 times the odds of "high" risk perception when compared to PWID with "low" risk perception. Findings show that PWID could rate their HIV risk with acceptable accuracy. Additionally, perceived HIV risk was associated with many risk factors for transmission of HIV, emphasizing the importance of developing targeted prevention and harm reduction programs for all domains of risk behaviors, both sexual and drug-related use.

Multiple products monitoring as a robust approach for peptide quantification.

PubMed

Baek, Je-Hyun; Kim, Hokeun; Shin, Byunghee; Yu, Myeong-Hee

2009-07-01

Quantification of target peptides and proteins is crucial for biomarker discovery. Approaches such as selected reaction monitoring (SRM) and multiple reaction monitoring (MRM) rely on liquid chromatography and mass spectrometric analysis of defined peptide product ions. These methods are not very widespread because the determination of quantifiable product ion using either SRM or MRM is a very time-consuming process. We developed a novel approach for quantifying target peptides without such an arduous process of ion selection. This method is based on monitoring multiple product ions (multiple products monitoring: MpM) from full-range MS2 spectra of a target precursor. The MpM method uses a scoring system that considers both the absolute intensities of product ions and the similarities between the query MS2 spectrum and the reference MS2 spectrum of the target peptide. Compared with conventional approaches, MpM greatly improves sensitivity and selectivity of peptide quantification using an ion-trap mass spectrometer.

Designing multiple ligands - medicinal chemistry strategies and challenges.

PubMed

Morphy, Richard; Rankovic, Zoran

2009-01-01

It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.

Multi-pixel high-resolution three-dimensional imaging radar

NASA Technical Reports Server (NTRS)

Cooper, Ken B. (Inventor); Dengler, Robert J. (Inventor); Siegel, Peter H. (Inventor); Chattopadhyay, Goutam (Inventor); Ward, John S. (Inventor); Juan, Nuria Llombart (Inventor); Bryllert, Tomas E. (Inventor); Mehdi, Imran (Inventor); Tarsala, Jan A. (Inventor)

2012-01-01

A three-dimensional imaging radar operating at high frequency e.g., 670 GHz radar using low phase-noise synthesizers and a fast chirper to generate a frequency-modulated continuous-wave (FMCW) waveform, is disclosed that operates with a multiplexed beam to obtain range information simultaneously on multiple pixels of a target. A source transmit beam may be divided by a hybrid coupler into multiple transmit beams multiplexed together and directed to be reflected off a target and return as a single receive beam which is demultiplexed and processed to reveal range information of separate pixels of the target associated with each transmit beam simultaneously. The multiple transmit beams may be developed with appropriate optics to be temporally and spatially differentiated before being directed to the target. Temporal differentiation corresponds to a different intermediate frequencies separating the range information of the multiple pixels. Collinear transmit beams having differentiated polarizations may also be implemented.

Complex matrix multiplication operations with data pre-conditioning in a high performance computing architecture

DOEpatents

Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A

2014-02-11

Mechanisms for performing a complex matrix multiplication operation are provided. A vector load operation is performed to load a first vector operand of the complex matrix multiplication operation to a first target vector register. The first vector operand comprises a real and imaginary part of a first complex vector value. A complex load and splat operation is performed to load a second complex vector value of a second vector operand and replicate the second complex vector value within a second target vector register. The second complex vector value has a real and imaginary part. A cross multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the complex matrix multiplication operation. The partial product is accumulated with other partial products and a resulting accumulated partial product is stored in a result vector register.

Pathways from childhood abuse to prospective revictimization: depression, sex to reduce negative affect, and forecasted sexual behavior.

PubMed

Miron, Lynsey R; Orcutt, Holly K

2014-11-01

Research suggests that adverse events in childhood, such as childhood physical, sexual, and emotional abuse, confer risk for later sexual assault. Psychological distress, coping strategies, and sexual behavior may help explain the path from childhood abuse to revictimization. The present study explored how the use of sex to regulate negative affect (SRNA) operates independently, and in combination with other psychosocial factors to increase college women's (N=541) risk of experiencing prospective adult sexual assault (ASA). Sequential multiple mediator models in Mplus were used to assess the effect of three different forms of childhood abuse on prospective ASA, both independently and while controlling for other forms of childhood abuse. The indirect effect of adolescent sexual assault (AdolSA), depressive symptoms, SRNA, and participants' response to a sex-related vignette was tested using bias-corrected bootstrapping. In the full path model, childhood emotional abuse and AdolSA predicted ASA, while childhood physical and sexual abuse were directly associated with AdolSA, but not ASA. Additionally, depressive symptoms and participants' estimate of their likely behavior in a sex-related vignette directly predicted prospective ASA. Results using bootstrapping revealed that a history of childhood abuse predicted prospective ASA via diverse direct and indirect paths, as well as through a similar multiple mediator path. Overall, findings suggest that a combination of affective, coping, and sexual expectancy factors contribute to risk for revictimization in adult survivors of childhood abuse. Future research directions and targets for risk-reduction programming are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pathways from Childhood Abuse to Prospective Revictimization: Depression, Sex to Reduce Negative Affect, and Forecasted Sexual Behavior

PubMed Central

Miron, Lynsey R.; Orcutt, Holly K.

2014-01-01

Research suggests that adverse events in childhood, such as childhood physical, sexual, and emotional abuse, confer risk for later sexual assault. Psychological distress, coping strategies, and sexual behavior may help explain the path from childhood abuse to revictimization. The present study explored how the use of sex to regulate negative affect (SRNA) operates independently, and in combination with other psychosocial factors to increase college women’s (N = 541) risk of experiencing prospective adult sexual assault (ASA). Sequential multiple mediator models in Mplus were used to assess the effect of three different forms of childhood abuse on prospective ASA, both independently and while controlling for other forms of childhood abuse. The indirect effect of adolescent sexual assault (AdolSA), depressive symptoms, SRNA, and participants’ response to a sex-related vignette was tested using bias-corrected bootstrapping. In the full path model, childhood emotional abuse and AdolSA predicted ASA, while childhood physical and sexual abuse were directly associated with AdolSA, but not ASA. Additionally, depressive symptoms and participants’ estimate of their likely behavior in a sex-related vignette directly predicted prospective ASA. Results using bootstrapping revealed that a history of childhood abuse predicted prospective ASA via diverse direct and indirect paths, as well as through a similar multiple mediator path. Overall, findings suggest that a combination of affective, coping, and sexual expectancy factors contribute to risk for revictimization in adult survivors of childhood abuse. Future research directions and targets for risk-reduction programming will be discussed. PMID:25455965

Risk factors and mediating pathways of loneliness and social support in community-dwelling older adults.

PubMed

Schnittger, Rebecca I B; Wherton, Joseph; Prendergast, David; Lawlor, Brian A

2012-01-01

To develop biopsychosocial models of loneliness and social support thereby identifying their key risk factors in an Irish sample of community-dwelling older adults. Additionally, to investigate indirect effects of social support on loneliness through mediating risk factors. A total of 579 participants (400 females; 179 males) were given a battery of biopsychosocial assessments with the primary measures being the De Jong Gierveld Loneliness Scale and the Lubben Social Network Scale along with a broad range of secondary measures. Bivariate correlation analyses identified items to be included in separate psychosocial, cognitive, biological and demographic multiple regression analyses. The resulting model items were then entered into further multiple regression analyses to obtain overall models. Following this, bootstrapping mediation analyses was conducted to examine indirect effects of social support on the subtypes (emotional and social) of loneliness. The overall model for (1) emotional loneliness included depression, neuroticism, perceived stress, living alone and accommodation type, (2) social loneliness included neuroticism, perceived stress, animal naming and number of grandchildren and (3) social support included extraversion, executive functioning (Trail Making Test B-time), history of falls, age and whether the participant drives or not. Social support influenced emotional loneliness predominantly through indirect means, while its effect on social loneliness was more direct. These results characterise the biopsychosocial risk factors of emotional loneliness, social loneliness and social support and identify key pathways by which social support influences emotional and social loneliness. These findings highlight issues with the potential for consideration in the development of targeted interventions.

Application of Intervention Mapping to develop a community-based health promotion pre-pregnancy intervention for adolescent girls in rural South Africa: Project Ntshembo (Hope).

PubMed

Draper, Catherine E; Micklesfield, Lisa K; Kahn, Kathleen; Tollman, Stephen M; Pettifor, John M; Dunger, David B; Norris, Shane A

2014-01-01

South Africa (SA) is undergoing multiple transitions with an increasing burden of non-communicable diseases and high levels of overweight and obesity in adolescent girls and women. Adolescence is key to addressing trans-generational risk and a window of opportunity to intervene and positively impact on individuals' health trajectories into adulthood. Using Intervention Mapping (IM), this paper describes the development of the Ntshembo intervention, which is intended to improve the health and well-being of adolescent girls in order to limit the inter-generational transfer of risk of metabolic disease, in particular diabetes risk. This paper describes the application of the first four steps of IM. Evidence is provided to support the selection of four key behavioural objectives: viz. to eat a healthy, balanced diet, increase physical activity, reduce sedentary behaviour, and promote reproductive health. Appropriate behaviour change techniques are suggested and a theoretical framework outlining components of relevant behaviour change theories is presented. It is proposed that the Ntshembo intervention will be community-based, including specialist adolescent community health workers who will deliver a complex intervention comprising of individual, peer, family and community mobilisation components. The Ntshembo intervention is novel, both in SA and globally, as it is: (1) based on strong evidence, extensive formative work and best practice from evaluated interventions; (2) combines theory with evidence to inform intervention components; (3) includes multiple domains of influence (community through to the individual); (4) focuses on an at-risk target group; and (5) embeds within existing and planned health service priorities in SA.

Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation.

PubMed

Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei

2016-11-01

Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions. Copyright © 2016 Elsevier Inc. All rights reserved.

Diversity-oriented synthesis yields novel multistage antimalarial inhibitors.

PubMed

Kato, Nobutaka; Comer, Eamon; Sakata-Kato, Tomoyo; Sharma, Arvind; Sharma, Manmohan; Maetani, Micah; Bastien, Jessica; Brancucci, Nicolas M; Bittker, Joshua A; Corey, Victoria; Clarke, David; Derbyshire, Emily R; Dornan, Gillian L; Duffy, Sandra; Eckley, Sean; Itoe, Maurice A; Koolen, Karin M J; Lewis, Timothy A; Lui, Ping S; Lukens, Amanda K; Lund, Emily; March, Sandra; Meibalan, Elamaran; Meier, Bennett C; McPhail, Jacob A; Mitasev, Branko; Moss, Eli L; Sayes, Morgane; Van Gessel, Yvonne; Wawer, Mathias J; Yoshinaga, Takashi; Zeeman, Anne-Marie; Avery, Vicky M; Bhatia, Sangeeta N; Burke, John E; Catteruccia, Flaminia; Clardy, Jon C; Clemons, Paul A; Dechering, Koen J; Duvall, Jeremy R; Foley, Michael A; Gusovsky, Fabian; Kocken, Clemens H M; Marti, Matthias; Morningstar, Marshall L; Munoz, Benito; Neafsey, Daniel E; Sharma, Amit; Winzeler, Elizabeth A; Wirth, Dyann F; Scherer, Christina A; Schreiber, Stuart L

2016-10-20

Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.

The 150 most important questions in cancer research and clinical oncology series: Questions 25-30 : Edited by Chinese Journal of Cancer.

PubMed

2017-05-04

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questions are presented as followed. Question 25: Does imprinting of immune responses to infections early in life predict future risk of childhood and adult cancers? Question 26: How to induce homogeneous tumor antigen expression in a heterogeneous tumor mass to enhance the efficacy of cancer immunotherapy? Question 27: Could we enhance the therapeutic effects of immunotherapy by targeting multiple tumor antigens simultaneously or sequentially? Question 28: Can immuno-targeting to cytokines halt cancer metastasis? Question 29: How can we dynamically and less-invasively monitor the activity of CD8 + T killer cells at tumor sites and draining lymph nodes? Question 30: How can the immune system destroy the niches for cancer initiation?

Androgen Receptor Gene Polymorphisms and Alterations in Prostate Cancer: Of Humanized Mice and Men

PubMed Central

Robins, Diane M.

2011-01-01

Germline polymorphisms and somatic mutations of the androgen receptor (AR) have been intensely investigated in prostate cancer but even with genomic approaches their impact remains controversial. To assess the functional significance of AR genetic variation, we converted the mouse gene to the human sequence by germline recombination and engineered alleles to query the role of a polymorphic glutamine (Q) tract implicated in cancer risk. In a prostate cancer model, AR Q tract length influences progression and castration response. Mutation profiling in mice provides direct evidence that somatic AR variants are selected by therapy, a finding validated in human metastases from distinct treatment groups. Mutant ARs exploit multiple mechanisms to resist hormone ablation, including alterations in ligand specificity, target gene selectivity, chaperone interaction and nuclear localization. Regardless of their frequency, these variants permute normal function to reveal novel means to target wild type AR and its key interacting partners. PMID:21689727

[Type 2 diabetes mellitus and cardiovascular risk factors: is comprehensive treatment required?].

PubMed

Nadal, Josep Franch; Gutiérrez, Pedro Conthe

2013-09-01

Diabetes mellitus, especially type 2, is a metabolic disease involving the coexistence of several cardiovascular risk factors. Affected patients are therefore at high cardiovascular risk (2-3 times higher than that of men in the general population and 2-6 times higher than that of women). Cardiovascular disease is the main cause of death in the diabetic population, followed by cancer. Cardiovascular risk cannot be compared between diabetic patients and persons who have already shown one or more manifestations of cardiovascular disease (such as myocardial infarction). Single risk factors should be evaluated in combination with other risk factors and a person's cardiovascular risk should be individually assessed. Cardiovascular risk assessment in patients with diabetes through current calculations methods is complex because their ability to predict risk in individuals is very low. Studies such as that by Steno have demonstrated the validity of a comprehensive strategy to control all the risk factors present in persons with type 2 diabetes mellitus, which can reduce the development of micro- and macrovascular complications and mortality by almost 50%. The present article reviews each of the classical cardiovascular risk factors (hypertension, dyslipidemia, smoking, obesity, sedentariness) in relation to diabetes, as well as their recommended targets and the benefits of their control. In view of the above, a comprehensive approach is recommended to control the multiple risk factors that can coexist in persons with type 2 diabetes mellitus. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Health Risks of an Inactive Lifestyle - Multiple Languages

MedlinePlus

... Are Here: Home → Multiple Languages → All Health Topics → Health Risks of an Inactive Lifestyle URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Health Risks of an Inactive Lifestyle - Multiple Languages To use the sharing features on ...

Analyzing the Role of MicroRNAs in Schizophrenia in the Context of Common Genetic Risk Variants.

PubMed

Hauberg, Mads Engel; Roussos, Panos; Grove, Jakob; Børglum, Anders Dupont; Mattheisen, Manuel

2016-04-01

The recent implication of 108 genomic loci in schizophrenia marked a great advancement in our understanding of the disease. Against the background of its polygenic nature there is a necessity to identify how schizophrenia risk genes interplay. As regulators of gene expression, microRNAs (miRNAs) have repeatedly been implicated in schizophrenia etiology. It is therefore of interest to establish their role in the regulation of schizophrenia risk genes in disease-relevant biological processes. To examine the role of miRNAs in schizophrenia in the context of disease-associated genetic variation. The basis of this study was summary statistics from the largest schizophrenia genome-wide association study meta-analysis to date (83 550 individuals in a meta-analysis of 52 genome-wide association studies) completed in 2014 along with publicly available data for predicted miRNA targets. We examined whether schizophrenia risk genes were more likely to be regulated by miRNA. Further, we used gene set analyses to identify miRNAs that are regulators of schizophrenia risk genes. Results from association tests for miRNA targetomes and related analyses. In line with previous studies, we found that similar to other complex traits, schizophrenia risk genes were more likely to be regulated by miRNAs (P < 2 × 10-16). Further, the gene set analyses revealed several miRNAs regulating schizophrenia risk genes, with the strongest enrichment for targets of miR-9-5p (P = .0056 for enrichment among the top 1% most-associated single-nucleotide polymorphisms, corrected for multiple testing). It is further of note that MIR9-2 is located in a genomic region showing strong evidence for association with schizophrenia (P = 7.1 × 10-8). The second and third strongest gene set signals were seen for the targets of miR-485-5p and miR-137, respectively. This study provides evidence for a role of miR-9-5p in the etiology of schizophrenia. Its implication is of particular interest as the functions of this neurodevelopmental miRNA tie in with established disease biology: it has a regulatory loop with the fragile X mental retardation homologue FXR1 and regulates dopamine D2 receptor density.

Combining clinical and angiographic variables for estimating risk of target lesion revascularization after drug eluting stent placement.

PubMed

Stolker, Joshua M; Cohen, David J; Kennedy, Kevin F; Pencina, Michael J; Arnold, Suzanne V; Kleiman, Neal S; Spertus, John A

Drug-eluting stents (DES) reduce restenosis but require prolonged antiplatelet therapy, when compared with bare metal stents. Ideally, the patient should be involved in this risk:benefit assessment prior to selecting DES, to maximize the benefits and cost-effectiveness of care, and to improve medication adherence. However, accurate estimation of restenosis risk may require angiographic factors identified at cardiac catheterization. In a large PCI registry, we used logistic regression to identify clinical and angiographic predictors of clinically-driven target lesion revascularization (TLR) over the first year after stent placement. Discrimination c-statistic and integrated discrimination improvement (IDI) were used to calculate the incremental utility of angiographic variables when added to clinical predictors. Of 8501 PCI patients, TLR occurred in 4.5%. After adjusting for DES use, clinical TLR predictors were younger age, female sex, diabetes, prior PCI, and prior bypass surgery (model c-statistic 0.630). Angiographic predictors were vein graft PCI, in-stent restenosis lesion, longer stent length, and smaller stent diameter (c-statistic 0.650). After adding angiographic factors to the clinical model, c-statistic improved to 0.680 and the average separation in TLR risk among patients with and without TLR improved by 1% (IDI=0.010, 95% CI 0.009-0.014), primarily driven by those experiencing TLR (from 5.9% to 6.9% absolute risk). Among unselected PCI patients, the incidence of clinically-indicated TLR is <5% at 1-year, and standard clinical variables only moderately discriminate who will and will not experience TLR. Angiographic variables significantly improve TLR risk assessment, suggesting that stent selection may be best performed after coronary anatomy has been delineated. Although several recent studies have challenged traditional expectations regarding the duration of dual antiplatelet therapy, current guidelines recommend at least 6 to 12months of treatment after implantation of a drug eluting stent, with a shorter course for bare metal stents. Stent selection ideally should involve input from the patient receiving these stents, but multiple studies have suggested that angiographic factors - obtained after the patient has received sedation during the diagnostic catheterization - are important predictors of repeat revascularization. In this analysis from a large registry of patients receiving coronary stents, angiographic characteristics were found to significantly improve risk assessment for target lesion revascularization, when added to clinical variables alone. Copyright © 2016 Elsevier Inc. All rights reserved.

Incomplete Multisource Transfer Learning.

PubMed

Ding, Zhengming; Shao, Ming; Fu, Yun

2018-02-01

Transfer learning is generally exploited to adapt well-established source knowledge for learning tasks in weakly labeled or unlabeled target domain. Nowadays, it is common to see multiple sources available for knowledge transfer, each of which, however, may not include complete classes information of the target domain. Naively merging multiple sources together would lead to inferior results due to the large divergence among multiple sources. In this paper, we attempt to utilize incomplete multiple sources for effective knowledge transfer to facilitate the learning task in target domain. To this end, we propose an incomplete multisource transfer learning through two directional knowledge transfer, i.e., cross-domain transfer from each source to target, and cross-source transfer. In particular, in cross-domain direction, we deploy latent low-rank transfer learning guided by iterative structure learning to transfer knowledge from each single source to target domain. This practice reinforces to compensate for any missing data in each source by the complete target data. While in cross-source direction, unsupervised manifold regularizer and effective multisource alignment are explored to jointly compensate for missing data from one portion of source to another. In this way, both marginal and conditional distribution discrepancy in two directions would be mitigated. Experimental results on standard cross-domain benchmarks and synthetic data sets demonstrate the effectiveness of our proposed model in knowledge transfer from incomplete multiple sources.

Multiple target laser ablation system

DOEpatents

Mashburn, Douglas N.

1996-01-01

A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film.

Combatting Inherent Vulnerabilities of CFAR Algorithms and a New Robust CFAR Design

DTIC Science & Technology

1993-09-01

elements of any automatic radar system. Unfortunately, CFAR systems are inherently vulnerable to degradation caused by large clutter edges, multiple ...edges, multiple targets, and electronic countermeasures (ECM) environments. 20 Distribution, Availability of Abstract 21 Abstract Security...inherently vulnerable to degradation caused by large clutter edges, multiple targets and jamming environments. This thesis presents eight popular and studied

Environmental health risk assessment and management for global climate change

NASA Astrophysics Data System (ADS)

Carter, P.

2014-12-01

This environmental health risk assessment and management approach for atmospheric greenhouse gas (GHG) pollution is based almost entirely on IPCC AR5 (2014) content, but the IPCC does not make recommendations. Large climate model uncertainties may be large environmental health risks. In accordance with environmental health risk management, we use the standard (IPCC-endorsed) formula of risk as the product of magnitude times probability, with an extremely high standard of precaution. Atmospheric GHG pollution, causing global warming, climate change and ocean acidification, is increasing as fast as ever. Time is of the essence to inform and make recommendations to governments and the public. While the 2ºC target is the only formally agreed-upon policy limit, for the most vulnerable nations, a 1.5ºC limit is being considered by the UNFCCC Secretariat. The Climate Action Network International (2014), representing civil society, recommends that the 1.5ºC limit be kept open and that emissions decline from 2015. James Hansen et al (2013) have argued that 1ºC is the danger limit. Taking into account committed global warming, its millennial duration, multiple large sources of amplifying climate feedbacks and multiple adverse impacts of global warming and climate change on crops, and population health impacts, all the IPCC AR5 scenarios carry extreme environmental health risks to large human populations and to the future of humanity as a whole. Our risk consideration finds that 2ºC carries high risks of many catastrophic impacts, that 1.5ºC carries high risks of many disastrous impacts, and that 1ºC is the danger limit. IPCC AR4 (2007) showed that emissions must be reversed by 2015 for a 2ºC warming limit. For the IPCC AR5 only the best-case scenario RCP2.6, is projected to stay under 2ºC by 2100 but the upper range is just above 2ºC. It calls for emissions to decline by 2020. We recommend that for catastrophic environmental health risk aversion, emissions decline from 2015 (CAN International 2014), and if policy makers are limited to the IPCC AR5 we recommend RCP2.6, with emissions declining by 2020.

Harassment, stalking, threats and attacks targeting New Zealand politicians: A mental health issue.

PubMed

Every-Palmer, Susanna; Barry-Walsh, Justin; Pathé, Michele

2015-07-01

Due to the nature of their work, politicians are at greater risk of stalking, harassment and attack than the general population. The small, but significantly elevated risk of violence to politicians is predominantly due not to organised terrorism or politically motivated extremists but to fixated individuals with untreated serious mental disorders, usually psychosis. Our objective was to ascertain the frequency, nature and effects of unwanted harassment of politicians in New Zealand and the possible role of mental illness in this harassment. New Zealand Members of Parliament were surveyed, with an 84% response rate (n = 102). Quantitative and qualitative data were collected on Parliamentarians' experiences of harassment and stalking. Eighty-seven percent of politicians reported unwanted harassment ranging from disturbing communications to physical violence, with most experiencing harassment in multiple modalities and on multiple occasions. Cyberstalking and other forms of online harassment were common, and politicians felt they (and their families) had become more exposed as a result of the Internet. Half of MPs had been personally approached by their harassers, 48% had been directly threatened and 15% had been attacked. Some of these incidents were serious, involving weapons such as guns, Molotov cocktails and blunt instruments. One in three politicians had been targeted at their homes. Respondents believed the majority of those responsible for the harassment exhibited signs of mental illness. The harassment of politicians in New Zealand is common and concerning. Many of those responsible were thought to be mentally ill by their victims. This harassment has significant psychosocial costs for both the victim and the perpetrator and represents an opportunity for mental health intervention. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Harassment, stalking, threats and attacks targeting New Zealand politicians: A mental health issue

PubMed Central

Every-Palmer, Susanna; Barry-Walsh, Justin; Pathé, Michele

2015-01-01

Objective: Due to the nature of their work, politicians are at greater risk of stalking, harassment and attack than the general population. The small, but significantly elevated risk of violence to politicians is predominantly due not to organised terrorism or politically motivated extremists but to fixated individuals with untreated serious mental disorders, usually psychosis. Our objective was to ascertain the frequency, nature and effects of unwanted harassment of politicians in New Zealand and the possible role of mental illness in this harassment. Methods: New Zealand Members of Parliament were surveyed, with an 84% response rate (n = 102). Quantitative and qualitative data were collected on Parliamentarians’ experiences of harassment and stalking. Results: Eighty-seven percent of politicians reported unwanted harassment ranging from disturbing communications to physical violence, with most experiencing harassment in multiple modalities and on multiple occasions. Cyberstalking and other forms of online harassment were common, and politicians felt they (and their families) had become more exposed as a result of the Internet. Half of MPs had been personally approached by their harassers, 48% had been directly threatened and 15% had been attacked. Some of these incidents were serious, involving weapons such as guns, Molotov cocktails and blunt instruments. One in three politicians had been targeted at their homes. Respondents believed the majority of those responsible for the harassment exhibited signs of mental illness. Conclusion: The harassment of politicians in New Zealand is common and concerning. Many of those responsible were thought to be mentally ill by their victims. This harassment has significant psychosocial costs for both the victim and the perpetrator and represents an opportunity for mental health intervention. PMID:25954019

SU-E-T-300: Spatial Variations of Multiple Off-Axial Targets for a Single Isocenter SRS Treatment Plan in ExacTrac 6D Robotic Couch System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, S; Tseng, T

2014-06-01

Purpose: To evaluate the spatial variations of multiple off-axial targets for a single isocenter stereotactic radiosurgery (SRS) treatment plan in ExacTrac 6D robotic couch system (BrainLab AG). Methods: Five metallic ball bearing (BB) markers were placed sparsely in 3D off-axial locations (non-coplanar) inside a skull phantom as the representatives of multiple targets mimicking multiple brain metastases. The locations of the BB markers were carefully chosen to minimize overlapping of each other in a port imaging detector plane. The skull phantom was immobilized by a frameless mask and CT scanned with a BrainLab Head and Neck Localizer using a GE Optimamore » MDCT scanner. The CT images were exported to iPlan software (BrainLab AG) and a multiple target PTV was drawn by combining all the contours of the BBs. The margin of the MLC opening was selected as 3 mm expansion outward. Two coplanar arc beams were placed to generate a single isocenter SRS plan to treat the PTV. The arc beams were delivered using Novalis Tx system with portal imaging acquisition mode per 10% temporal resolution. The locations of the BBs were visualized and analyzed with respect to the MLC aperture in the treatment plan similar to the Winston-Lutz test. Results: All the BBs were clearly identified inside the MLC openings. The positional errors for the BBs were overall less than 1 mm along the rotational path of the two arcs. Conclusion: This study verified that the spatial deviations of multiple off-axial targets for a single isocenter SRS treatment plan is within sub-millimeter range in ExacTrac 6D robotic couch system. Accompanied with the Winston-Lutz test, this test will quality-assure the spatial accuracies of the isocenter as well as the positions of multiple off-axial targets for the SRS treatment using a single isocenter multiple target treatment plan.« less

Simultaneous detection of multiple DNA targets by integrating dual-color graphene quantum dot nanoprobes and carbon nanotubes.

PubMed

Qian, Zhaosheng; Shan, Xiaoyue; Chai, Lujing; Chen, Jianrong; Feng, Hui

2014-12-01

Simultaneous detection of multiple DNA targets was achieved based on a biocompatible graphene quantum dots (GQDs) and carbon nanotubes (CNTs) platform through spontaneous assembly between dual-color GQD-based probes and CNTs and subsequently self-recognition between DNA probes and targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Activating Situation Schemas: The Effects of Multiple Thematic Roles on Related Verbs in a Continuous Priming Paradigm

ERIC Educational Resources Information Center

Herlofsky, Stacey M.; Edmonds, Lisa A.

2013-01-01

Extensive evidence has shown that presentation of a word (target) following a related word (prime) results in faster reaction times compared to unrelated words. Two primes preceding a target have been used to examine the effects of multiple influences on a target. Several studies have observed greater, or additive, priming effects of multiple…

Assessment of the Casualty Risk of Multiple Meteorological Hazards in China

PubMed Central

Xu, Wei; Zhuo, Li; Zheng, Jing; Ge, Yi; Gu, Zhihui; Tian, Yugang

2016-01-01

A study of the frequency, intensity, and risk of extreme climatic events or natural hazards is important for assessing the impacts of climate change. Many models have been developed to assess the risk of multiple hazards, however, most of the existing approaches can only model the relative levels of risk. This paper reports the development of a method for the quantitative assessment of the risk of multiple hazards based on information diffusion. This method was used to assess the risks of loss of human lives from 11 types of meteorological hazards in China at the prefectural and provincial levels. Risk curves of multiple hazards were obtained for each province and the risks of 10-year, 20-year, 50-year, and 100-year return periods were mapped. The results show that the provinces (municipalities, autonomous regions) in southeastern China are at higher risk of multiple meteorological hazards as a result of their geographical location and topography. The results of this study can be used as references for the management of meteorological disasters in China. The model can be used to quantitatively calculate the risks of casualty, direct economic losses, building collapse, and agricultural losses for any hazards at different spatial scales. PMID:26901210

Assessment of the Casualty Risk of Multiple Meteorological Hazards in China.

PubMed

Xu, Wei; Zhuo, Li; Zheng, Jing; Ge, Yi; Gu, Zhihui; Tian, Yugang

2016-02-17

A study of the frequency, intensity, and risk of extreme climatic events or natural hazards is important for assessing the impacts of climate change. Many models have been developed to assess the risk of multiple hazards, however, most of the existing approaches can only model the relative levels of risk. This paper reports the development of a method for the quantitative assessment of the risk of multiple hazards based on information diffusion. This method was used to assess the risks of loss of human lives from 11 types of meteorological hazards in China at the prefectural and provincial levels. Risk curves of multiple hazards were obtained for each province and the risks of 10-year, 20-year, 50-year, and 100-year return periods were mapped. The results show that the provinces (municipalities, autonomous regions) in southeastern China are at higher risk of multiple meteorological hazards as a result of their geographical location and topography. The results of this study can be used as references for the management of meteorological disasters in China. The model can be used to quantitatively calculate the risks of casualty, direct economic losses, building collapse, and agricultural losses for any hazards at different spatial scales.

Interventions in the commercial sex industry during the rise in syphilis rates among men who have sex with men (MSM).

PubMed

Taylor, Melanie; Montoya, Jorge A; Cantrell, Russell; Mitchell, Samuel J; Williams, Mark; Jordahl, Lori; Freeman, Millicent; Brown, James; Broussard, Dawn; Roland, Eric

2005-10-01

Describe sexually transmitted disease/human immunodeficiency virus prevention interventions targeting men who have sex with men (MSM) in commercial sex venues (CSV). Compilation of descriptive and evaluation data from the CDC 8-city MSM Syphilis Response on interventions conducted in bathhouses/sex clubs, circuit parties, the Internet, male sex workers, and the adult film industry. Interventions in the commercial sex industry (CSI) often involved multiple collaborative efforts between public health departments (PHD), community-based organizations (CBO), and CSV owners and managers. Education and condoms were provided at multiple venues, including circuit parties, bathhouses, and sex clubs. CBO staff reported one-on-one street and CSV outreach to engage MSM at risk. Evaluation data demonstrate that MSM exposed to media campaigns were more aware of syphilis and more likely to have been tested for syphilis than MSM who did not see the campaigns. PHD and CBO are using multiple means of reaching MSM in the CSI. Evaluations are needed to determine which of these efforts decreases syphilis transmission.

Multiple Service System Involvement and Later Offending Behavior: Implications for Prevention and Early Intervention.

PubMed

Bright, Charlotte Lyn; Jonson-Reid, Melissa

2015-07-01

We investigated patterns of childhood and adolescent experiences that correspond to later justice system entry, including persistence into adulthood, and explored whether timing of potential supports to the child or onset of family poverty, according to developmental periods and gender, would distinguish among latent classes. We constructed a database containing records for 8587 youths from a Midwestern metropolitan region, born between 1982 and 1991, with outcomes. We used data from multiple publicly funded systems (child welfare, income maintenance, juvenile and criminal justice, mental health, Medicaid, vital statistics). We applied a latent class analysis and interpreted a 7-class model. Classes with higher rates of offending persisting into adulthood were characterized by involvement with multiple publicly funded systems in childhood and adolescence, with the exception of 1 less-urban, predominantly female class that had similarly high system involvement coupled with lower rates of offending. Poverty and maltreatment appear to play a critical role in offending trajectories. Identifying risk factors that cluster together may help program and intervention staff best target those most in need of more intensive intervention.

Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

PubMed

Birmann, Brenda M; Andreotti, Gabriella; De Roos, Anneclaire J; Camp, Nicola J; Chiu, Brian C H; Spinelli, John J; Becker, Nikolaus; Benhaim-Luzon, Véronique; Bhatti, Parveen; Boffetta, Paolo; Brennan, Paul; Brown, Elizabeth E; Cocco, Pierluigi; Costas, Laura; Cozen, Wendy; de Sanjosé, Silvia; Foretová, Lenka; Giles, Graham G; Maynadié, Marc; Moysich, Kirsten; Nieters, Alexandra; Staines, Anthony; Tricot, Guido; Weisenburger, Dennis; Zhang, Yawei; Baris, Dalsu; Purdue, Mark P

2017-06-01

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m 2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design ( P = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( P trend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m 2 ; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( P interaction <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25-<30 kg/m 2 ) or obese (30+ kg/m 2 ) in both younger and usual adulthood (vs. individuals consistently <25 kg/m 2 ), but not for those overweight or obese at only one time period. Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood. Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Multiple-collision analysis of characteristic X-rays from low-energy Ar 2+ travelling in solid targets

NASA Astrophysics Data System (ADS)

Cipolla, Sam J.; Mildebrath, Mark E.

1983-12-01

The density of atoms in a solid target fosters a multiple-collision mechanism that leads to the production of an equilibrium fraction of L-shell vacancies in an incident heavy ion. It is then possiblein a subsequent ion-atom collision in the solid for an L-vacancy to be transferred to the K-shell of a target atom via rotational coupling of the 2p π-2p σ molecular orbitals formed in the ion-atom quasimolecule. The vacancy-transfer cross section and the equilibrium fraction and lifetime of the vacancies can be found by using an appropriate multiple-collision analysis of the characteristic target and projectile X-rays. Results will be presented for 160-380 keV Ar 2+ incident of targets of Mg, Al, and Si.

Age-related changes in gait adaptability in response to unpredictable obstacles and stepping targets.

PubMed

Caetano, Maria Joana D; Lord, Stephen R; Schoene, Daniel; Pelicioni, Paulo H S; Sturnieks, Daina L; Menant, Jasmine C

2016-05-01

A large proportion of falls in older people occur when walking. Limitations in gait adaptability might contribute to tripping; a frequently reported cause of falls in this group. To evaluate age-related changes in gait adaptability in response to obstacles or stepping targets presented at short notice, i.e.: approximately two steps ahead. Fifty older adults (aged 74±7 years; 34 females) and 21 young adults (aged 26±4 years; 12 females) completed 3 usual gait speed (baseline) trials. They then completed the following randomly presented gait adaptability trials: obstacle avoidance, short stepping target, long stepping target and no target/obstacle (3 trials of each). Compared with the young, the older adults slowed significantly in no target/obstacle trials compared with the baseline trials. They took more steps and spent more time in double support while approaching the obstacle and stepping targets, demonstrated poorer stepping accuracy and made more stepping errors (failed to hit the stepping targets/avoid the obstacle). The older adults also reduced velocity of the two preceding steps and shortened the previous step in the long stepping target condition and in the obstacle avoidance condition. Compared with their younger counterparts, the older adults exhibited a more conservative adaptation strategy characterised by slow, short and multiple steps with longer time in double support. Even so, they demonstrated poorer stepping accuracy and made more stepping errors. This reduced gait adaptability may place older adults at increased risk of falling when negotiating unexpected hazards. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

PubMed Central

Cohan, Stanley

2016-01-01

Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

MO-FG-CAMPUS-TeP1-04: Pseudo-In-Vivo Dose Verification of a New Mono-Isocentric Technique for the Treatment of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pappas, E P; Makris, D; Lahanas, V

2016-06-15

Purpose: To validate dose calculation and delivery accuracy of a recently introduced mono-isocentric technique for the treatment of multiple brain metastases in a realistic clinical case. Methods: Anonymized CT scans of a patient were used to model a hollow phantom that duplicates anatomy of the skull. A 3D printer was used to construct the phantom of a radiologically bone-equivalent material. The hollow phantom was subsequently filled with a polymer gel 3D dosimeter which also acted as a water-equivalent material. Irradiation plan consisted of 5 targets and was identical to the one delivered to the specific patient except for the prescriptionmore » dose which was optimized to match the gel dose-response characteristics. Dose delivery was performed using a single setup isocenter dynamic conformal arcs technique. Gel dose read-out was carried out by a 1.5 T MRI scanner. All steps of the corresponding patient’s treatment protocol were strictly followed providing an end-to-end quality assurance test. Pseudo-in-vivo measured 3D dose distribution and calculated one were compared in terms of spatial agreement, dose profiles, 3D gamma indices (5%/2mm, 20% dose threshold), DVHs and DVH metrics. Results: MR-identified polymerized areas and calculated high dose regions were found to agree within 1.5 mm for all targets, taking into account all sources of spatial uncertainties involved (i.e., set-up errors, MR-related geometric distortions and registration inaccuracies). Good dosimetric agreement was observed in the vast majority of the examined profiles. 3D gamma index passing rate reached 91%. DVH and corresponding metrics comparison resulted in a satisfying agreement between measured and calculated datasets within targets and selected organs-at-risk. Conclusion: A novel, pseudo-in-vivo QA test was implemented to validate spatial and dosimetric accuracy in treatment of multiple metastases. End-to-end testing demonstrated that our gel dosimetry phantom is suited for such QA procedures, allowing for 3D analysis of both targeting placement and dose.« less

Adolescent Risk Factors for Child Maltreatment

PubMed Central

Matsuda, Mauri; Greenman, Sarah J.; Augustyn, Megan Bears; Henry, Kimberly L.; Smith, Carolyn A.; Ireland, Timothy O.

2014-01-01

We investigate adolescent risk factors, measured at both early and late adolescence, for involvement in child maltreatment during adulthood. Comprehensive assessments of risk factors for maltreatment that use representative samples with longitudinal data are scarce and can inform multilevel prevention. We use data from the Rochester Youth Development Study, a longitudinal study begun in 1988 with a sample of 1,000 seventh and eighth graders. Participants have been interviewed 14 times and, at the last assessment (age 31), 80% were retained. Risk factors represent 10 developmental domains: area characteristics, family background/structure, parent stressors, exposure to family violence, parent-child relationships, education, peer relationships, adolescent stressors, antisocial behaviors, and precocious transitions to adulthood. Maltreatment is measured by substantiated reports from Child Protective Services records. Many individual risk factors (20 at early adolescence and 14 at later adolescence) are significantly, albeit moderately, predictive of maltreatment. Several developmental domains stand out, including family background/structure, education, antisocial behaviors, and precocious transitions. In addition, there is a pronounced impact of cumulative risk on the likelihood of maltreatment. For example, only 3% of the youth with no risk domains in their background at early adolescence were involved in later maltreatment, but for those with risk in 9 developmental domains the rate was 45%. Prevention programs targeting youth at high risk for engaging in maltreatment should begin during early adolescence when risk factors are already at play. These programs need to be comprehensive, capable of addressing the multiple and interwoven nature of risk that is associated with maltreatment. PMID:24075569

Targeting multiple types of tumors using NKG2D-coated iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Wu, Ming-Ru; Cook, W. James; Zhang, Tong; Sentman, Charles L.

2014-11-01

Iron oxide nanoparticles (IONPs) hold great potential for cancer therapy. Actively targeting IONPs to tumor cells can further increase therapeutic efficacy and decrease off-target side effects. To target tumor cells, a natural killer (NK) cell activating receptor, NKG2D, was utilized to develop pan-tumor targeting IONPs. NKG2D ligands are expressed on many tumor types and its ligands are not found on most normal tissues under steady state conditions. The data showed that mouse and human fragment crystallizable (Fc)-fusion NKG2D (Fc-NKG2D) coated IONPs (NKG2D/NPs) can target multiple NKG2D ligand positive tumor types in vitro in a dose dependent manner by magnetic cell sorting. Tumor targeting effect was robust even under a very low tumor cell to normal cell ratio and targeting efficiency correlated with NKG2D ligand expression level on tumor cells. Furthermore, the magnetic separation platform utilized to test NKG2D/NP specificity has the potential to be developed into high throughput screening strategies to identify ideal fusion proteins or antibodies for targeting IONPs. In conclusion, NKG2D/NPs can be used to target multiple tumor types and magnetic separation platform can facilitate the proof-of-concept phase of tumor targeting IONP development.

Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma

PubMed Central

Yco, Lisette P; Mocz, Gabor; Opoku-Ansah, John; Bachmann, André S

2014-01-01

Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that has been implicated in many human cancers and has emerged as an ideal target for cancer therapy. Withaferin A (WFA) is a natural product with promising antiproliferative properties through its association with a number of molecular targets including STAT3. However, the effect of WFA in pediatric neuroblastoma (NB) and its interaction with STAT3 have not been reported. In this study, we found that WFA effectively induces dose-dependent cell death in high-risk and drug-resistant NB as well as multiple myeloma (MM) tumor cells, prevented interleukin-6 (IL-6)–mediated and persistently activated STAT3 phosphorylation at Y705, and blocked the transcriptional activity of STAT3. We further provide computational models that show that WFA binds STAT3 near the Y705 phospho-tyrosine residue of the STAT3 Src homology 2 (SH2) domain, suggesting that WFA prevents STAT3 dimer formation similar to BP-1-102, a well-established STAT3 inhibitor. Our findings propose that the antitumor activity of WFA is mediated at least in part through inhibition of STAT3 and provide a rationale for further drug development and clinical use in NB and MM. PMID:25452693

Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma.

PubMed

Yco, Lisette P; Mocz, Gabor; Opoku-Ansah, John; Bachmann, André S

2014-01-01

Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that has been implicated in many human cancers and has emerged as an ideal target for cancer therapy. Withaferin A (WFA) is a natural product with promising antiproliferative properties through its association with a number of molecular targets including STAT3. However, the effect of WFA in pediatric neuroblastoma (NB) and its interaction with STAT3 have not been reported. In this study, we found that WFA effectively induces dose-dependent cell death in high-risk and drug-resistant NB as well as multiple myeloma (MM) tumor cells, prevented interleukin-6 (IL-6)-mediated and persistently activated STAT3 phosphorylation at Y705, and blocked the transcriptional activity of STAT3. We further provide computational models that show that WFA binds STAT3 near the Y705 phospho-tyrosine residue of the STAT3 Src homology 2 (SH2) domain, suggesting that WFA prevents STAT3 dimer formation similar to BP-1-102, a well-established STAT3 inhibitor. Our findings propose that the antitumor activity of WFA is mediated at least in part through inhibition of STAT3 and provide a rationale for further drug development and clinical use in NB and MM.