Testicular Lumicrine Factors Regulate ERK, STAT, and NFKB Pathways in the Initial Segment of the Rat Epididymis to Prevent Apoptosis1

PubMed Central

Xu, Bingfang; Abdel-Fattah, Rana; Yang, Ling; Crenshaw, Sallie A.; Black, Michael B.; Hinton, Barry T.

2011-01-01

The initial segment of the epididymis is vital for male fertility; therefore, it is important to understand the mechanisms that regulate this important region. Deprival of testicular luminal fluid factors/lumicrine factors from the epididymis results in a wave of apoptosis in the initial segment. In this study, a combination of protein array and microarray analyses was used to examine the early changes in downstream signal transduction pathways following loss of lumicrine factors. We discovered the following cascade of events leading to the loss of protection and eventual apoptosis: in the first 6 h after loss of lumicrine factors, down-regulation of the ERK pathway components was observed at the mRNA expression and protein activity levels. Microarray analysis revealed that mRNA levels of several key components of the ERK pathway, Dusp6, Dusp5, and Etv5, decreased sharply, while the analysis from the protein array revealed a decline in the activities of MAP2K1/2 and MAPK1. Immunostaining of phospho-MAPK3/1 indicated that down-regulation of the ERK pathway was specific to the epithelial cells of the initial segment. Subsequently, after 12 h of loss of lumicrine factors, levels of mRNA expression of STAT and NFKB pathway components increased, mRNA levels of several genes encoding cell cycle inhibitors increased, and levels of protein expression of several proapoptotic phosphatases increased. Finally, after 18 h of loss of protection from lumicrine factors, apoptosis was observed. In conclusion, testicular lumicrine factors protect the cells of the initial segment by activating the ERK pathway, repressing STAT and NFKB pathways, and thereby preventing apoptosis. PMID:21311037

Role of Individual, Family, and Peers in Sexual Initiation Among Late Adolescents Attending Institutions of Higher Learning in Malaysia.

PubMed

Abdul Samad, Shazimah; Hairi, Noran Naqiah; Ismail, Maslinor

2016-05-01

This cross-sectional study aimed to determine the prevalence and the factors associated with sexual initiation among the late adolescents in 6 institutions of higher learning in Malaysia. A total of 1572 students completed self-administered questionnaires between April and September 2013. Hierarchical multivariate logistic regression analyses stratified by gender were employed to identify the correlates of sexual initiation. The analyses were further adjusted by sampling weights. The overall prevalence of sexual initiation was 9.8% (95% confidence interval [CI] = 8.3-11.6), 18.1% (95% CI = 15.1-21.5) among males, and 4.1% (95% CI = 2.9-5.9) among females. The risk factors identified in this study supported the influence of the individual, family, and peer factors in the social-ecological model on adolescents' behaviors. The findings suggest the need for risk-reduction strategies aimed at the individual, family, and peer levels as well as the importance of gender-specific focus in assuring better outcomes. © 2016 APJPH.

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.

PubMed

Marcus, Julia L; Neugebauer, Romain S; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

2016-04-01

Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction. We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m). Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0). Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

Delay of insulin initiation in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycemic agents (analysis of patient- and physician-related factors): A prospective observational DIPP-FACTOR study in Korea.

PubMed

Kim, Sin Gon; Kim, Nam Hoon; Ku, Bon Jeong; Shon, Ho Sang; Kim, Doo Man; Park, Tae Sun; Kim, Yong-Seong; Kim, In Joo; Choi, Dong Seop

2017-05-01

To assess the time to initiation of insulin therapy, and concurrently investigate both patient- and physician-related factors associated with delaying insulin therapy in Korean patients with type 2 diabetes uncontrolled by oral hypoglycemic agents (OHAs). This prospective, observational disease registry study was carried out across 69 centers in Korea. Type 2 diabetes patients who had received two or more OHAs within the past 5 years, had a glycated hemoglobin ≥8% in the past 6 months and had not received insulin were included. Data recorded on data collection forms during a 12-month period were analyzed. Of 2168 patients enrolled, 1959 were evaluated and classified as the insulin-initiated or insulin-delayed group. Insulin was prescribed for just 20% of the patients during a 1-year follow-up period, and less than half (44.5%) of the patients who were taking two OHAs started insulin after 6 years. Patient-related factors for delay in insulin initiation included older age, shorter duration of diabetes and lower glycated hemoglobin. Physician-related factors included age (~50 to <60 years), sex (women) and number (<1000) of patients consulted per month. Patient refusal (33.6%) and physicians' concerns of patient non-compliance (26.5%) were the major physician-reported reasons for delaying insulin therapy. Inconvenience of insulin therapy (51.6%) and fear of injection (48.2%) were the major reasons for patient refusal. Insulin initiation is delayed in patients with type 2 diabetes uncontrolled by two or more OHAs in Korea. Patient- and physician-related factors associated with this delay need to be addressed for better diabetes management. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Systematic Review of Smoking Initiation among Asian Adolescents, 20052015: Utilizing the Frameworks of Triadic Influence and Planned Behavior.

PubMed

Talip, Tajidah; Murang, Zaidah; Kifli, Nurolaini; Naing, Lin

2016-01-01

A recent WHO data report on mortality attributable to tobacco use including cigarette smoking indicated a very high burden of deaths in Asia and that people often initiate smoking as early as young adolescents. The objectives of this study were to systematically review peerreviewed articles on cigarette smoking initiation among Asian adolescents and to develop a conceptual model of factors influencing smoking initiation by integrating all relevant factors based on existing data. Following a PRISMA guideline, a systematic review of articles published between 2005 and June 2015 was conducted using 5 databases on cigarette smoking initiation among adolescents (aged 1019 years) living in Asia. We summarized the main findings of each study according to our research questions and data that emerged during the data extraction process. Analysis and categorization were based on the TTI and TPB models and classification of factors extracted from the study, were as follows: personal factors, social factors, broader environmental factors, mediators, and intention to initiate smoking and smoking behavior. Of 1,227 identified studies, only 20 were included in this review. Our findings found that the mean age of cigarette smoking initiation ranged from 10 to 14 years and those who are more likely to initiate smoking are male, older adolescents, adolescents with low parental SES, individuals with low parental monitoring, low parental education level and having no discussion on smoking at home, those living in public housing and those exhibiting healthrisk behavior. Our study also revealed that the risk of smoking initiation increased when they are exposed to smokers, influenced by peers, exposed to tobacco advertisements, receive pocket money, have lack of knowledge about smoking, have poor school performance, have a family conflict and have psychological problems. The conceptual model developed demonstrated complex networks of factors influencing initiation. This systematic review presents various factors influencing smoking initiation of the Asian adolescents and provides a conceptual framework to further analyze factors. Future studies should have a standard measure of smoking initiation, should analyze interactions and the intensity of relationships between different factors or variables in the conceptual model. This will in turn consolidate the understanding of the different factors affecting smoking initiation and will help to improve interventions in this area.

AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo.

PubMed Central

Butler, J S; Springer, M; Grunberg-Manago, M

1987-01-01

We previously showed that Escherichia coli translation initiation factor IF3 regulates the expression of its own gene infC at the translational level in vivo. Here we create two alterations in the infC gene and test their effects on translational autocontrol of infC expression in vivo by measuring beta-galactosidase activity expressed from infC-lacZ gene fusions under conditions of up to 4-fold derepression or 3-fold repression of infC expression. Replacement of the infC promoter with the trp promoter deletes 120 nucleotides of the infC mRNA 5' to the translation initiation site without affecting autogenous translational control. Mutation of the unusual AUU initiator codon of infC to the more common AUG initiator codon abolishes translation initiation factor IF3-dependent repression and derepression of infC expression in vivo. These results establish the AUU initiator codon of infC as an essential cis-acting element in autogenous translational control of translation initiation factor IF3 expression in vivo. PMID:2954162

AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo.

PubMed

Butler, J S; Springer, M; Grunberg-Manago, M

1987-06-01

We previously showed that Escherichia coli translation initiation factor IF3 regulates the expression of its own gene infC at the translational level in vivo. Here we create two alterations in the infC gene and test their effects on translational autocontrol of infC expression in vivo by measuring beta-galactosidase activity expressed from infC-lacZ gene fusions under conditions of up to 4-fold derepression or 3-fold repression of infC expression. Replacement of the infC promoter with the trp promoter deletes 120 nucleotides of the infC mRNA 5' to the translation initiation site without affecting autogenous translational control. Mutation of the unusual AUU initiator codon of infC to the more common AUG initiator codon abolishes translation initiation factor IF3-dependent repression and derepression of infC expression in vivo. These results establish the AUU initiator codon of infC as an essential cis-acting element in autogenous translational control of translation initiation factor IF3 expression in vivo.

Identification of Associations Between Genetic Factors and Asthma that are Modified by Obesity

DTIC Science & Technology

2016-06-01

AFRL-SA-WP-TR-2016-0010 Identification of Associations Between Genetic Factors and Asthma That Are Modified by Obesity Andrew T...Between Genetic Factors and Asthma That Are Modified by Obesity 5a. CONTRACT NUMBER FA8650-13-2-6371 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...among African American women in the Women’s Health Initiative study. 15. SUBJECT TERMS Body mass index, SNP, asthma, obesity , genome, genes 16

Online Tobacco Marketing and Subsequent Tobacco Use.

PubMed

Soneji, Samir; Yang, JaeWon; Knutzen, Kristin E; Moran, Meghan Bridgid; Tan, Andy S L; Sargent, James; Choi, Kelvin

2018-02-01

Nearly 2.9 million US adolescents engaged with online tobacco marketing in 2013 to 2014. We assess whether engagement is a risk factor for tobacco use initiation, increased frequency of use, progression to poly-product use, and cessation. We analyzed data from 11 996 adolescents sampled in the nationally representative, longitudinal Population Assessment for Tobacco and Health study. At baseline (2013-2014), we ascertained respondents' engagement with online tobacco marketing. At follow-up (2014-2015), we determined if respondents had initiated tobacco use, increased frequency of use, progressed to poly-product use, or quit. Accounting for known risk factors, we fit a multivariable logistic regression model among never-users who engaged at baseline to predict initiation at follow-up. We fit similar models to predict increased frequency of use, progression to poly-product use, and cessation. Compared with adolescents who did not engage, those who engaged reported higher incidences of initiation (19.5% vs 11.9%), increased frequency of use (10.3% vs 4.4%), and progression to poly-product use (5.8% vs 2.4%), and lower incidence of cessation at follow-up (16.1% vs 21.5%). Accounting for other risk factors, engagement was positively associated with initiation (adjusted odds ratio [aOR] = 1.26; 95% confidence interval [CI]: 1.01-1.57), increased frequency of use (aOR = 1.58; 95% CI: 1.24-2.00), progression to poly-product use (aOR = 1.70; 95% CI: 1.20-2.43), and negatively associated with cessation (aOR = 0.71; 95% CI: 0.50-1.00). Engagement with online tobacco marketing represents a risk factor for adolescent tobacco use. FDA marketing regulation and cooperation of social-networking sites could limit engagement. Copyright © 2018 by the American Academy of Pediatrics.

Factor Xa Activation of Factor V is of Paramount Importance in Initiating the Coagulation System: Lessons from a Tick Salivary Protein

PubMed Central

Schuijt, Tim J.; Bakhtiari, Kamran; Daffre, Sirlei; DePonte, Kathleen; Wielders, Simone J.H.; Marquart, J. Arnoud; Hovius, Joppe W.; van der Poll, Tom; Fikrig, Erol; Bunce, Matthew W.; Camire, Rodney M.; Nicolaes, Gerry A.F.; Meijers, Joost C.M.; van 't Veer, Cornelis

2013-01-01

Background Generation of active procoagulant cofactor FVa and its subsequent association with the enzyme FXa to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation and controversy. The current paradigm assumes that FV activation is initiated by limited proteolysis by traces of (meizo) thrombin. Methods and Results Recombinant tick salivary protein TIX-5 was produced and anticoagulant properties were studied using plasma, whole blood and purified systems. Here we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B-domain of FV and show that FXa activation of FV is pivotal for plasma and blood clotting. In line, tick feeding is impaired on TIX-5 immune rabbits displaying the in vivo importance of TIX-5. Conclusions Our data elucidate a unique molecular mechanism by which ticks inhibit the host's coagulation system. Based on our data we propose a revised blood coagulation scheme wherein direct FXa-mediated FV activation occurs in the initiation phase during which thrombin-mediated FV activation is restrained by fibrinogen and inhibitors. PMID:23817575

Early smoking initiation and associated factors among in-school male and female adolescents in seven African countries.

PubMed

Peltzer, K

2011-09-01

This report examines the prevalence and common correlates of early smoking initiation among male and female school children across seven African countries. The total sample included 17,725 school children aged 13 to 15 years from nationally representative samples in seven African countries. Univariate and multivariate analyses were conducted to assess the relationship between early smoking initiation, health compromising behaviours, mental distress, protective factors and socio-economic status variables. Overall 15.5% had experienced smoking initiation before age 14, with the percentages 20.1% among boys and 10.9% among girls. In multivariable analysis, early smoking initiation was among boys associated with ever drunk from alcohol use (OR = 4.73, p = 0.001), ever used drugs (OR = 2.36, p = 0.04) and ever had sex (OR = 1.63, p = 0.04). Among girls, it was associated with higher education (OR = 5.77, p = 0.001), ever drunk from alcohol use (OR = 4.76, p = 0.002), parental or guardian tobacco use (OR = 2.83, p = 0.001) and suicide ideation (OR = 2.05, p = 0.02). The study found a high prevalence of early smoking initiation among 13-15 year-olds in seven African countries. Various risk factors have been identified in boys and girls who initiate smoking before age 14, forming a distinct risk group in this setting. Specific interventions are needed for boys and girls in the preteen years, before smoking initiation.

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Can demographic, clinical and treatment-related factors available at hormonal therapy initiation predict non-persistence in women with stage I-III breast cancer?

PubMed

Cahir, Caitriona; Barron, Thomas I; Sharp, Linda; Bennett, Kathleen

2017-03-01

To investigate whether demographic, clinical and treatment-related risk factors known at treatment initiation can be used to reliably predict future hormonal therapy non-persistence in women with breast cancer, and to inform intervention development. Women with stage I-III breast cancer diagnosed 2000-2012 and prescribed hormonal therapy were identified from the National Cancer Registry Ireland (NCRI) and linked to pharmacy claims data from Ireland's Primary Care Reimbursement Services (PCRS). Non-persistence was defined as a treatment gap of ≥180 days within 5 years of initiation. Seventeen demographic, clinical and treatment-related risk factors, identified from a systematic review, were abstracted from the NCRI-PCRS dataset. Multivariate binomial models were used to estimate relative risks (RR) and risk differences (RD) for associations between risk factors and non-persistence. Calibration and discriminative performance of the models were assessed. The analysis was repeated for early non-persistence (<1 year of initiation). Within 5 years of treatment initiation 680 women (19.9%) were non-persistent. Women aged <50 years (adjusted RR 1.41, 95% CI 1.16-1.70) and those prescribed antidepressants (RR 1.22, 95% CI 1.04-1.45) had increased risk of non-persistence. Married women (RR 0.82 95% CI 0.71-0.94) and those with prior medication use (RR 0.62 95% CI 0.51-0.75) had reduced risk of non-persistence. The area under the receiver-operating characteristic (ROC) curve for non-persistence was 0.61. Findings were similar for early non-persistence. The risk prediction model did not discriminate well between women at higher and lower risk of non-persistence at treatment initiation. Future studies should consider other factors, such as psychological characteristics and experience of side-effects.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

PubMed Central

Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin

2013-01-01

Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary. PMID:23875073

Preoperative short hookwire placement for small pulmonary lesions: evaluation of technical success and risk factors for initial placement failure.

PubMed

Iguchi, Toshihiro; Hiraki, Takao; Matsui, Yusuke; Fujiwara, Hiroyasu; Masaoka, Yoshihisa; Tanaka, Takashi; Sato, Takuya; Gobara, Hideo; Toyooka, Shinichi; Kanazawa, Susumu

2018-05-01

To retrospectively evaluate the technical success of computed tomography fluoroscopy-guided short hookwire placement before video-assisted thoracoscopic surgery and to identify the risk factors for initial placement failure. In total, 401 short hookwire placements for 401 lesions (mean diameter 9.3 mm) were reviewed. Technical success was defined as correct positioning of the hookwire. Possible risk factors for initial placement failure (i.e., requirement for placement of an additional hookwire or to abort the attempt) were evaluated using logistic regression analysis for all procedures, and for procedures performed via the conventional route separately. Of the 401 initial placements, 383 were successful and 18 failed. Short hookwires were finally placed for 399 of 401 lesions (99.5%). Univariate logistic regression analyses revealed that in all 401 procedures only the transfissural approach was a significant independent predictor of initial placement failure (odds ratio, OR, 15.326; 95% confidence interval, CI, 5.429-43.267; p < 0.001) and for the 374 procedures performed via the conventional route only lesion size was a significant independent predictor of failure (OR 0.793, 95% CI 0.631-0.996; p = 0.046). The technical success of preoperative short hookwire placement was extremely high. The transfissural approach was a predictor initial placement failure for all procedures and small lesion size was a predictor of initial placement failure for procedures performed via the conventional route. • Technical success of preoperative short hookwire placement was extremely high. • The transfissural approach was a significant independent predictor of initial placement failure for all procedures. • Small lesion size was a significant independent predictor of initial placement failure for procedures performed via the conventional route.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

PubMed

Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

PubMed Central

Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (∼65% vs. ∼35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5′-end of mRNA. PMID:15630022

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

Murooka, Thomas T.; Rahbar, Ramtin; Department of Immunology, University of Toronto, Ont.

The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase inmore » high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage.« less

Generational status and social factors predicting initiation of partnered sexual activity among Latino/a youth.

PubMed

Cabral, Patricia; Wallander, Jan L; Song, Anna V; Elliott, Marc N; Tortolero, Susan R; Reisner, Sari L; Schuster, Mark A

2017-02-01

Examine the longitudinal association of generational status (first = child and parent born outside the United States; second = child born in the United States, parent born outside the United States; third = child and parent born in the United States) and parent and peer social factors considered in 5th grade with subsequent oral, vaginal, and anal intercourse initiation by 7th and 10th grade among Latino/a youth. Using data from Latino/a participants (N = 1,790) in the Healthy Passages™ study, the authors measured generational status (first = 18.4%, second = 57.3%, third-generation = 24.3%) and parental (i.e., monitoring, involvement, nurturance) and peer (i.e., friendship quality, social interaction, peer norms) influences in 5th grade and oral, vaginal, and anal intercourse initiation by 7th and 10th (retention = 89%) grade. Among girls, parental monitoring, social interaction, friendship quality, and peer norms predicted sexual initiation. Among boys, parental involvement, social interaction, and peer norms predicted sexual initiation (ps < .05). When ≥1 friend was perceived to have initiated sexual intercourse, third-generation Latinas were more than twice as likely as first- and second-generation Latinas (ps < .05) to initiate vaginal intercourse by 10th grade and almost 5 times as likely as first-generation Latinas to initiate oral intercourse by 7th grade. Among Latina youth, generational status plays a role in social influences on vaginal and oral intercourse initiation. Moreover, Latinas and Latinos differ in which social influences predict sexual intercourse initiation. Preventive efforts for Latino/a youth may need to differ by gender and generational status. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Gender differences in risk factors for cigarette smoking initiation in childhood.

PubMed

Sylvestre, Marie-Pierre; Wellman, Robert J; O'Loughlin, Erin K; Dugas, Erika N; O'Loughlin, Jennifer

2017-09-01

We investigated whether established risk factors for initiating cigarette smoking during adolescence (parents, siblings, friends smoke; home smoking rules, smokers at home, exposure to smoking in cars, academic performance, susceptibility to smoking, depressive symptoms, self-esteem, school connectedness, use of other tobacco products) are associated with initiation in preadolescents, and whether the effects of these factors differ by gender. In spring 2005, baseline data were collected in self-report questionnaires from 1801 5th grade students including 1553 never-smokers (mean age=10.7years), in the longitudinal AdoQuest I Study in Montréal, Canada. Follow-up data were collected in the fall and spring of 6th grade (2005-2006). Poisson regression analyses with robust variance estimated the effects of each risk factor on initiation and additive interactions with gender were computed to assess the excess risk of each risk factor in girls compared to boys. 101 of 1399 participants in the analytic sample (6.7% of boys; 7.7% of girls) initiated smoking during follow-up. After adjustment for age, gender and maternal education, all risk factors except academic performance and school connectedness were statistically significantly associated with initiation. Paternal and sibling smoking were associated with initiation in girls only, and girls with lower self-esteem had a significant excess risk of initiating smoking in 6th grade. Risk factors for smoking initiation in preadolescents mirror those in adolescents; their effects do not differ markedly by gender. Preventive programs targeting children should focus on reducing smoking in the social environment and the dangers of poly-tobacco use. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

PubMed

Otto, Aline P; França, Marcela M; Correa, Fernanda A; Costalonga, Everlayny F; Leite, Claudia C; Mendonca, Berenice B; Arnhold, Ivo J P; Carvalho, Luciani R S; Jorge, Alexander A L

2015-08-01

Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

Spanish version of the Talent Development Environment Questionnaire for sport: Cultural adaptation and initial validation

PubMed Central

Olivares, Pedro R.; Andronikos, Georgios; Martindale, Russell J. J.

2017-01-01

This study aimed to translate the Talent Development Environment Questionnaire into Spanish and provide an initial validation. A recommended methodology for translation and cultural adaptation of questionnaires was applied. Once this had been completed, three hundred and thirty-two young athletes completed the Talent Development Environment Questionnaire. The results revealed that the five factor solution Talent Development Environment Questionnaire was confirmed. With the exclusion of one item due to low factor loading, the Talent Development Environment Questionnaire-5 had robust statistical support for its factor structure (χ2 (df = 305) = 499.64, p<0.01, CFI = 0.90, RMSEA = 0.045, SRMR = 0.055). It also demonstrated adequate convergent and discriminant validity. While the internal reliability was lower than in previous studies, it revealed acceptable levels. Specifically the overall 27 item Talent Development Environment Questionnaire-5 had a Cronbach α score of .877, and the reliability scores for individual factors 1–5 were .622; .761; .658; .605; .602 respectively. As such, it is recommended that the Spanish Talent Development Environment Questionnaire-5 can be used with confidence in Spain in both applied and research settings. PMID:28582387

Spanish version of the Talent Development Environment Questionnaire for sport: Cultural adaptation and initial validation.

PubMed

Brazo-Sayavera, Javier; Olivares, Pedro R; Andronikos, Georgios; Martindale, Russell J J

2017-01-01

This study aimed to translate the Talent Development Environment Questionnaire into Spanish and provide an initial validation. A recommended methodology for translation and cultural adaptation of questionnaires was applied. Once this had been completed, three hundred and thirty-two young athletes completed the Talent Development Environment Questionnaire. The results revealed that the five factor solution Talent Development Environment Questionnaire was confirmed. With the exclusion of one item due to low factor loading, the Talent Development Environment Questionnaire-5 had robust statistical support for its factor structure (χ2 (df = 305) = 499.64, p<0.01, CFI = 0.90, RMSEA = 0.045, SRMR = 0.055). It also demonstrated adequate convergent and discriminant validity. While the internal reliability was lower than in previous studies, it revealed acceptable levels. Specifically the overall 27 item Talent Development Environment Questionnaire-5 had a Cronbach α score of .877, and the reliability scores for individual factors 1-5 were .622; .761; .658; .605; .602 respectively. As such, it is recommended that the Spanish Talent Development Environment Questionnaire-5 can be used with confidence in Spain in both applied and research settings.

An interferon regulatory factor binding site in the U5 region of the bovine leukemia virus long terminal repeat stimulates Tax-independent gene expression.

PubMed

Kiermer, V; Van Lint, C; Briclet, D; Vanhulle, C; Kettmann, R; Verdin, E; Burny, A; Droogmans, L

1998-07-01

Bovine leukemia virus (BLV) replication is controlled by both cis- and trans-acting elements. The virus-encoded transactivator, Tax, is necessary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequences that control Tax-independent transcription must play an important role in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gene expression directed by the BLV promoter. R-U5 was also stimulatory when inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5' half of U5 is principally responsible for the stimulation. This element exhibited enhancer activity when inserted upstream or downstream from the herpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expression. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication.

GAUGING THE EXTENT OF THYROIDECTOMY FOR INDETERMINATE THYROID NODULES: AN ONCOLOGIC PERSPECTIVE.

PubMed

Schneider, David F; Cherney Stafford, Linda M; Brys, Nicole; Greenberg, Caprice C; Balentine, Courtney J; Elfenbein, Dawn M; Pitt, Susan C

2017-04-02

Increasing emphasis is being placed on appropriateness of care and avoidance of over- and under-treatment. Indeterminate thyroid nodules (ITNs) present a particular risk for this problem because cancer found via diagnostic lobectomy (DL) often requires a completion thyroidectomy (CT). However, initial total thyroidectomy (TT) for benign ITN results in lifelong thyroid hormone replacement. We sought to measure the accuracy and factors associated with the extent of initial thyroidectomy for ITN. We queried a single institution thyroid surgery database for all adult patients undergoing an initial operation for ITN. Multivariate logistic regression identified factors associated with either oncologic under- or overtreatment at initial operation. There were 639 patients with ITN. The median age was 52 (range, 18 to 93) years, 78.4% were female, and final pathology revealed a cancer >1 cm in 24.7%. The most common cytology was follicular neoplasm (45.1%) followed by Hürthle cell neoplasm (20.2%). CT or initial oncologic undertreatment was required in 58 patients (9.3%). Excluding those with goiters, 19.0% were treated with TT for benign final pathology. Multivariate analysis failed to identify any factor that independently predicted the need for CT. Female gender was associated with TT in benign disease (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0 to 4.5; P = .05). Age >45 years predicted correct initial use of DL (OR, 2.6; 95% CI, 1.2 to 5.7; P = .02). Suspicious for papillary thyroid carcinoma (OR, 5.7; 95% CI, 2.1 to 15.3; P<.01) and frozen section (OR, 9.7; 95% CI, 2.5 to 38.6; P<.01) were associated with oncologically appropriate initial TT. The highest frequency of CT occurred in patients with follicular lesion of undetermined significance (11.6%). TT for benign final pathology occurred most frequently in patients with a Hürthle cell neoplasm (24.8%). In patients with ITN, nearly 30% received an inappropriate extent of initial thyroidectomy from an oncologic standpoint. Tools to pre-operatively identify both benign and malignant disease can assist in the complex decision making to gauge the proper extent of initial surgery for ITN. ATA = American Thyroid Association AUS = atypia of undetermined significance CI = confidence interval CT = completion thyroidectomy FLUS = follicular lesion of undetermined significance ITN = indeterminate thyroid nodule OR = odds ratio PTC = papillary thyroid carcinoma TT = total thyroidectomy.

The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication.

PubMed

Liu, Xiaofeng; Wang, Xiaoyu; Wang, Qian; Luo, Mingyang; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

2018-02-01

Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein, playing critical roles in viral RNA replication, translation and assembly. To further explore its functions in viral replication, interaction of NS5A with host factors was assayed using a his-tag "pull down" assay coupled with shotgun LC-MS/MS. Host protein translation initiation factor 3 subunit E was identified as a binding partner of NS5A, and confirmed by co-immunoprecipitation and co-localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic replication, viral protein expression and production of progeny virus, and downregulation of eIF3E by siRNA significantly decreased viral proliferation in PK-15 cells. Luciferase reporter assay showed an enhancement of translational activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in cellular translation by NS5A. These data indicate that eIF3E plays an important role in CSFV replication, thereby identifying it as a potential target for inhibition of the virus. Copyright © 2017 Elsevier Inc. All rights reserved.

One-year contraceptive continuation and pregnancy in adolescent girls and women initiating hormonal contraceptives.

PubMed

Raine, Tina R; Foster-Rosales, Anne; Upadhyay, Ushma D; Boyer, Cherrie B; Brown, Beth A; Sokoloff, Abby; Harper, Cynthia C

2011-02-01

To assess contraceptive discontinuation, switching, factors associated with method discontinuation, and pregnancy among women initiating hormonal contraceptives. This was a 12-month longitudinal cohort study of adolescent girls and women (n=1,387) aged 15 to 24 years attending public family planning clinics who did not desire pregnancy for at least 1 year and selected to initiate the patch, ring, depot medroxyprogesterone acetate, or pills. Participants completed follow-up assessments at 3, 6, and 12 months after baseline. Life table analysis was used to estimate survival rates for contraceptive continuation. Cox proportional hazards models were used to estimate factors associated with method discontinuation. The continuation rate (per 100 person-years) at 12 months was low for all methods; however, it was lowest for patch and depot medroxyprogesterone acetate initiators, 10.9 and 12.1 per 100 person years, respectively (P≤.003); continuation among ring initiators was comparable to pill initiators, 29.4 and 32.7 per 100 person-years, respectively (P=.06). Discontinuation was independently associated with method initiated and younger age. The only factors associated with lower risk of discontinuation were greater intent to use the method and being in school or working. The pregnancy rate (per 100 person-years) was highest for patch and ring initiators (30.1 and 30.5) and comparable for pill and depot medroxyprogesterone acetate initiators (16.5 and 16.1; P<.001). The patch and the ring may not be better options than the pill or depot medroxyprogesterone acetate for women at high risk for unintended pregnancy. This study highlights the need for counseling interventions to improve contraceptive continuation, education about longer-acting methods, and developing new contraceptives that women may be more likely to continue. II.

Optimization and modeling of laccase production by Trametes versicolor in a bioreactor using statistical experimental design.

PubMed

Tavares, A P M; Coelho, M A Z; Agapito, M S M; Coutinho, J A P; Xavier, A M R B

2006-09-01

Experimental design and response surface methodologies were applied to optimize laccase production by Trametes versicolor in a bioreactor. The effects of three factors, initial glucose concentration (0 and 9 g/L), agitation (100 and 180 rpm), and pH (3.0 and 5.0), were evaluated to identify the significant effects and its interactions in the laccase production. The pH of the medium was found to be the most important factor, followed by initial glucose concentration and the interaction of both factors. Agitation did not seem to play an important role in laccase production, nor did the interaction agitation x medium pH and agitation x initial glucose concentration. Response surface analysis showed that an initial glucose concentration of 11 g/L and pH controlled at 5.2 were the optimal conditions for laccase production by T. versicolor. Under these conditions, the predicted value for laccase activity was >10,000 U/L, which is in good agreement with the laccase activity obtained experimentally (11,403 U/L). In addition, a mathematical model for the bioprocess was developed. It is shown that it provides a good description of the experimental profile observed, and that it is capable of predicting biomass growth based on secondary process variables.

Ten-year changes in smoking among young adults: are racial differences explained by socioeconomic factors in the CARDIA study?

PubMed Central

Kiefe, C I; Williams, O D; Lewis, C E; Allison, J J; Sekar, P; Wagenknecht, L E

2001-01-01

OBJECTIVES: This study investigated whether socioeconomic factors explain racial/ethnic differences in regular smoking initiation and cessation. METHODS: Data were derived from the CARDIA study, a cohort of 5115 healthy adults aged 18 to 30 years at baseline (1985-1986) and recruited from the populations of 4 US cities. Respondents were followed over 10 years. RESULTS: Among 3950 respondents reexamined in 1995-1996, 20% of Whites and 33% of African Americans were smokers, as compared with 25% and 32%, respectively, in 1985-1986. On average, African Americans were of lower socioeconomic status. Ten-year regular smoking initiation rates for African American women, White women, African American men, and White men were 7.1%, 3.5%, 13.2%, and 5.1%, respectively, and the corresponding cessation rates were 25%, 35.1%, 19.2%, and 31.3%. After adjustment for socioeconomic factors, most 95% confidence intervals of the odds ratios for regular smoking initiation and cessation in African Americans vs Whites included 1. CONCLUSIONS: Less beneficial 10-year changes in smoking were observed in African Americans, but socioeconomic factors explained most of the racial disparity. PMID:11211629

Preoperative fat-free mass: a predictive factor of weight loss after gastric bypass.

PubMed

Robert, Maud; Pelascini, Elise; Disse, Emmanuel; Espalieu, Philippe; Poncet, Gilles; Laville, Martine; Gouillat, Christian

2013-04-01

Weight loss failure occurs in 8% to 40% of patients after gastric bypass (GBP). The aim of our study was to analyse the predictive factors of weight loss at 1 year so as to select the best candidates for this surgery and reduce the failures. We included 73 patients treated by laparoscopic GBP. We retrospectively analysed the predictive factors of weight loss in kilograms as well as excess weight loss in percentage (EWL%) at 1 year. The population was divided into tertiles so as to compare the sub-group with the highest weight loss with the sub-group with the least satisfactory results. The significantly predictive factors of a better weight loss in kilograms were male, higher initial weight (144 versus 118 kg, p = 0.002), a significant early weight loss and a higher preoperative percentage of fat-free mass (FFM%; p = 0.03). A higher FFM% was also associated with a better EWL% (p = 0.004). The preoperative FFM (in kilograms) was the principal factor accounting for the weight loss at 1 year regardless of age, gender, height and initial body mass index (BMI; p < 0.0001). There was a better correlation between FFM and weight loss (Spearman test, p = 0.0001) than between initial BMI and weight loss (p = 0.016). We estimated weight loss at 1 year according to initial FFM using the formula: 0.5 kg of lost weight per kilogram of initial FFM. The initial FFM appears to be a decisive factor in the success of GBP. Thus, the sarcopoenic patients would appear to be less suitable candidates for this surgery.

Reliability Estimating Procedures for Electric and Thermochemical Propulsion Systems. Volume 2

DTIC Science & Technology

1977-02-01

final form. For some components, the parameters are calculated from design factors (e.g., design life) that must be input when requested. Each component...Components Components are regarded as statis- tically identical if they are drawn from the same production lot because the initial and sub- sequent...table yields b 0.0023 The - factors are obtained from Tables 2.2.4-1 through 2.2.4-5: Factor Value rE Space, flight 1 JANTXV quality 0.5 7A Small signal

An investigation of bioecological influences associated with first use of methamphetamine in a rural state.

PubMed

Bowen, Anne; Moring, John; Williams, Mark; Hopper, Glenna; Daniel, Candice

2012-01-01

Methamphetamine (MA) addiction is a significant problem in rural areas of the United States. Yet, little theoretically driven formative research has been conducted on the interactions of factors influencing initiation. The study was guided by Bronfenbrenner's bioecological model. Eighty-three MA users participated in an interview. Quantitative data included sociodemographic characteristics, drug use history, and psychosocial functioning. Semistructured interviews examined MA use histories with a focus on initiation. Transcripts of the interviews were coded for 5 themes related to Bronfenbrenner's influences including individual motivation, family, peers, work or school, or community as factors influencing initiation of MA use. Five dummy variables representing the presence or absence of a mention of Bronfenbrenner's 5 influences were created from the qualitative codes and entered into a hierarchical cluster analysis. The analyses revealed 4 distinct clusters: (1) predominantly female, influenced by peers and individual curiosity, (2) predominantly female, youngest age of first use, influenced by a family culture of drug use, (3) predominantly male, older age at first use, influenced by work settings and family co-workers, and (4) predominantly male, older age at first use, in the school context with a desire to increase intimacy. Bronfenbrenner's bioecological model was useful for classifying initiating influences and grouping individuals based on different combinations of influences. Identifying combinations of initiating factors such as work and community may facilitate tailoring of prevention programs, which may maximize efficacy and cost-effectiveness. © 2011 National Rural Health Association.

High-mobility group 1/2 proteins are essential for initiating rolling-circle-type DNA replication at a parvovirus hairpin origin.

PubMed

Cotmore, S F; Tattersall, P

1998-11-01

Rolling-circle replication is initiated by a replicon-encoded endonuclease which introduces a single-strand nick into specific origin sequences, becoming covalently attached to the 5' end of the DNA at the nick and providing a 3' hydroxyl to prime unidirectional, leading-strand synthesis. Parvoviruses, such as minute virus of mice (MVM), have adapted this mechanism to amplify their linear single-stranded genomes by using hairpin telomeres which sequentially unfold and refold to shuttle the replication fork back and forth along the genome, creating a continuous, multimeric DNA strand. The viral initiator protein, NS1, then excises individual genomes from this continuum by nicking and reinitiating synthesis at specific origins present within the hairpin sequences. Using in vitro assays to study ATP-dependent initiation within the right-hand (5') MVM hairpin, we have characterized a HeLa cell factor which is absolutely required to allow NS1 to nick this origin. Unlike parvovirus initiation factor (PIF), the cellular complex which activates NS1 endonuclease activity at the left-hand (3') viral origin, the host factor which activates the right-hand hairpin elutes from phosphocellulose in high salt, has a molecular mass of around 25 kDa, and appears to bind preferentially to structured DNA, suggesting that it might be a member of the high-mobility group 1/2 (HMG1/2) protein family. This prediction was confirmed by showing that purified calf thymus HMG1 and recombinant human HMG1 or murine HMG2 could each substitute for the HeLa factor, activating the NS1 endonuclease in an origin-specific nicking reaction.

Is short stature associated with short cervical length?

PubMed

Gagel, Caroline K; Rafael, Timothy J; Berghella, Vincenzo

2010-10-01

We sought to estimate if there is a correlation between maternal height and cervical length in women at high risk for preterm birth. We studied a retrospective cohort of women with singleton gestation and risk factors for preterm birth. Maternal height was categorized as short (<157.5 cm) or not short stature (≥157.5 cm). Cervical length at 14 to 24 weeks was evaluated. Primary outcomes were incidence of initial cervical length <30 mm and incidence of shortest cervical length <25 mm. Four hundred sixteen women met the inclusion criteria. Twenty-two (22.6%) of the short women and 79 (24.5%) of the nonshort women had an initial cervical length <30 mm ( P = 0.81). Twenty-two (23.7%) of the short women and 104 (32.2%) of the nonshort women had a cervical length <25 mm for shortest cervical length measurement ( P = 0.15). In women with singleton gestation and risk factors for preterm birth, no statistically significant relationship exists between maternal height and initial or shortest cervical length. © Thieme Medical Publishers.

Phosphorylation of Wheat Germ Initiation Factors and Ribosomal Proteins 1

PubMed Central

Browning, Karen S.; Yan, Tyan Fuh J.; Lauer, Stephen J.; Aquino, Lu Ann; Tao, Mariano; Ravel, Joanne M.

1985-01-01

The ability of the wheat germ initiation factors and ribosomes to serve as substrates for a wheat germ protein kinase (Yan and Tao 1982 J Biol Chem 257: 7037-7043) has been investigated. The wheat germ kinase catalyzes the phosphorylation of the 42,000 dalton subunit of eukaryotic initiation factor (eIF)-2 and the 107,000 dalton subunit of eIF-3. Other initiation factors, eIF-4B and eIF-4A, and elongation factors, EF-1 and EF-2, are not phosphorylated by the kinase. Quantitative analysis indicates that the kinase catalyzes the incorporation of about 0.5 to 0.6 mole of phosphate per mole of the 42,000 dalton subunit of eIF-2 and about 6 moles of phosphate per mole of the 107,000 dalton subunit of eIF-3. Three proteins (Mr = 38,000, 14,800, and 12,600) of the 60S ribosomal subunit are phosphorylated by the kinase, but none of the 40S ribosomal proteins are substrates of the kinase. No effects of phosphorylation on the activities of eIF-2, eIF-3, or 60S ribosomal subunits could be demonstrated in vitro. Images Fig. 1 Fig. 3 Fig. 4 PMID:16664060

HIV infection and obesity: where did all the wasting go?

PubMed

Tate, Tyler; Willig, Amanda L; Willig, James H; Raper, James L; Moneyham, Linda; Kempf, Mirjam-Colette; Saag, Michael S; Mugavero, Michael J

2012-01-01

The success of antiretroviral therapy (ART) has led to dramatic changes in causes of morbidity and mortality in HIV-infected individuals. As chronic diseases rates have increased in HIV+ populations, modifiable risk factors such as obesity have increased in importance. Our objective was to evaluate factors associated with weight change among patients receiving ART. ART-naïve patients initiating therapy at the University of Alabama - Birmingham 1917 HIV/AIDS Clinic from 2000- 2008 were included. Body Mass Index (BMI) was categorized as: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9) and obese (≥30). Linear regression models were used to evaluate overall change in BMI and factors associated with increased BMI category 24 months following ART initiation. Among 681 patients, the mean baseline BMI was 25.4 ± 6.1; 44% of patients were overweight/obese. At 24 months, 20% of patients moved from normal to overweight/obese or overweight to obese BMI categories. Greater increases in BMI were observed in patients with baseline CD4 count < 50 cells/µl (3.4 ± 4.1, P<0.01) and boosted protease inhibitor use (2.5±4.1 P=0.01), but did not account for all of the variation observed in weight change. The findings that almost half of patients were overweight or obese at ART initiation, and 1 in 5 patients moved to a deleterious BMI category within 2 years of ART initiation are alarming. ART therapy provides only a modest contribution to weight gain in patients. Obesity represents a highly prevalent condition in patients with HIV infection and an important target for intervention.

Mortality and loss to follow-up among HIV-infected persons on long-term antiretroviral therapy in Latin America and the Caribbean

PubMed Central

Carriquiry, Gabriela; Fink, Valeria; Koethe, John Robert; Giganti, Mark Joseph; Jayathilake, Karu; Blevins, Meridith; Cahn, Pedro; Grinsztejn, Beatriz; Wolff, Marcelo; Pape, Jean William; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; McGowan, Catherine Carey; Shepherd, Bryan Earl

2015-01-01

Introduction Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). Methods We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63–2.32) for 50 vs. 350 cells/µL; p<0.001) and older age (HR=1.47 (95% CI 1.29–1.69) for 50 vs. 30 years at ART initiation; p<0.001). Conclusions In this large, long-term study of mortality among HIV-positive adults initiating ART in Latin America and the Caribbean, overall estimates of mortality were heterogeneous, generally falling between those reported in high-income countries and sub-Saharan Africa. PMID:26165322

Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

PubMed

Gonzalez Calzada, Nuria; Prats Soro, Enric; Mateu Gomez, Lluis; Giro Bulta, Esther; Cordoba Izquierdo, Ana; Povedano Panades, Monica; Dorca Sargatal, Jordi; Farrero Muñoz, Eva

2016-01-01

Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

Hydrocarbon polymeric binder for advanced solid propellant

NASA Technical Reports Server (NTRS)

Potts, J. E. (Editor); Ashcraft, A. C., Jr.; Wise, E. W.

1971-01-01

Various experimental factors were examined to determine the source of difficulty in an isoprene polymerization in the 5-gallon reactor which gave a non-uniform product of low functionality. It was concluded that process improvements relating to initiator and monomer purity were desirable, but that the main difficulty was in the initiator feed system. A new pumping system was installed and an analog simulation of the reactor, feed system and initiator decomposition kinetics was devised which permits the selection of initial initiator concentrations and feed rates to use to give a nearly uniform initiator concentration throughout a polymerization run. An isoprene polymerization was run in which the process improvements were implemented.

Overall Impact of Speed-Related Initiatives and Factors on Crash Outcomes

PubMed Central

D’Elia, A.; Newstead, S.; Cameron, M.

2007-01-01

From December 2000 until July 2002 a package of speed-related initiatives and factors took place in Victoria, Australia. The broad aim of this study was to evaluate the overall impact of the package on crash outcomes. Monthly crash counts and injury severity proportions were assessed using Poisson and logistic regression models respectively. The model measured the overall effect of the package after adjusting as far as possible for non-speed road safety initiatives and socio-economic factors. The speed-related package was associated with statistically significant estimated reductions in casualty crashes and suggested reductions in injury severity with trends towards increased reductions over time. From December 2000 until July 2002, three new speed enforcement initiatives were implemented in Victoria, Australia. These initiatives were introduced in stages and involved the following key components: More covert operations of mobile speed cameras, including flash-less operations; 50% increase in speed camera operating hours; and lowering of cameras’ speed detection threshold. In addition, during the period 2001 to 2002, the 50 km/h General Urban Speed Limit (GUSL) was introduced (January 2001), there was an increase in speed-related advertising including the “Wipe Off 5” campaign, media announcements were made related to the above enforcement initiatives and there was a speeding penalty restructure. The above elements combine to make up a package of speed-related initiatives and factors. The package represents a broad, long term program by Victorian government agencies to reduce speed based on three linked strategies: more intensive Police enforcement of speed limits to deter potential offenders, i.e. the three new speed enforcement initiatives just described - supported by higher penalties; a reduction in the speed limit on local streets throughout Victoria from 60 km/h to 50 km/h; and provision of information using the mass media (television, radio and billboard) to reinforce the benefits of reducing low level speeding - the central message of “Wipe Off 5”. These strategies were implemented across the entire state of Victoria with the intention of covering as many road users as possible. PMID:18184508

Factors affecting the lung perfused blood volume in patients with intrapulmonary clots after anti-coagulation therapy.

PubMed

Okada, Munemasa; Masuda, Yu; Nakashima, Yoshiteru; Nomura, Takafumi; Nakao, Sei; Suga, Kazuyoshi; Kido, Shoji; Matsunaga, Naofumi

2015-08-01

Factors affecting the improvement in the lung perfused blood volume (LPBV) were evaluated based on the presence of intrapulmonary clots (IPCs) after anti-coagulation therapy using 64-slice dual-energy CT. 96 patients exhibiting venous thromboembolism underwent initial and repeated LPBV examinations between December 2008 and July 2014. Fifteen patients were excluded due to pulmonary comorbidities, and a total of 81 patients were included in this study. Acute pulmonary embolism (PE) was diagnosed in 46 of the patients (56.7%). LPBV images were three-dimensionally reconstructed with two threshold ranges: 1-120 HU (V120) and 1-5 HU (V5), and the relative value of V5 per V120 expressed as %V5. These values were subsequently compared with indicators of the severity of PE, such as the D-dimer level, heart rate and CT measurements. This study was approved by the local ethics committee. In patients with IPCs, the D-dimer, V5 and %V5values were significantly larger (p≤0.01) in the initial LPBV, although these differences disappeared in subsequent LPBV after treatment. The right ventricular (RV) diameter, RV/left ventricular (RV/LV) diameter ratio and %V5 values were also significantly reduced, whereas the V5 value did not significantly decrease (p=0.07), but V120 value significantly increased (p<0.001) after treatment. However, in patients with IPCs the change rate in %V5 [(subsequent-initial)/initial %V5] showed a better correlation with that in V5 (r=0.94, p<0.001) rate than that in V120 (r=0.19, p=0.19) after treatment. Increased whole lung perfusion (V120) and a decreased low perfusion volume (V5) affect the improvement in the %V5 values after treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CT fluoroscopy-guided renal tumour cutting needle biopsy: retrospective evaluation of diagnostic yield, safety, and risk factors for diagnostic failure.

PubMed

Iguchi, Toshihiro; Hiraki, Takao; Matsui, Yusuke; Fujiwara, Hiroyasu; Sakurai, Jun; Masaoka, Yoshihisa; Gobara, Hideo; Kanazawa, Susumu

2018-01-01

To evaluate retrospectively the diagnostic yield, safety, and risk factors for diagnostic failure of computed tomography (CT) fluoroscopy-guided renal tumour biopsy. Biopsies were performed for 208 tumours (mean diameter 2.3 cm; median diameter 2.1 cm; range 0.9-8.5 cm) in 199 patients. One hundred and ninety-nine tumours were ≤4 cm. All 208 initial procedures were divided into diagnostic success and failure groups. Multiple variables related to the patients, lesions, and procedures were assessed to determine the risk factors for diagnostic failure. After performing 208 initial and nine repeat biopsies, 180 malignancies and 15 benign tumours were pathologically diagnosed, whereas 13 were not diagnosed. In 117 procedures, 118 Grade I and one Grade IIIa adverse events (AEs) occurred. Neither Grade ≥IIIb AEs nor tumour seeding were observed within a median follow-up period of 13.7 months. Logistic regression analysis revealed only small tumour size (≤1.5 cm; odds ratio 3.750; 95% confidence interval 1.362-10.326; P = 0.011) to be a significant risk factor for diagnostic failure. CT fluoroscopy-guided renal tumour biopsy is a safe procedure with a high diagnostic yield. A small tumour size (≤1.5 cm) is a significant risk factor for diagnostic failure. • CT fluoroscopy-guided renal tumour biopsy has a high diagnostic yield. • CT fluoroscopy-guided renal tumour biopsy is safe. • Small tumour size (≤1.5 cm) is a risk factor for diagnostic failure.

Factors associated with initial incomplete ablation for benign thyroid nodules after radiofrequency ablation: First results of CEUS evaluation.

PubMed

Zhao, Chong-Ke; Xu, Hui-Xiong; Lu, Feng; Sun, Li-Ping; He, Ya-Ping; Guo, Le-Hang; Li, Xiao-Long; Bo, Xiao-Wan; Yue, Wen-Wen

2017-01-01

To assess the factors associated with initial incomplete ablation (ICA) after radiofrequency ablation for benign thyroid nodules (BTNs). 69 BTNs (mean volume 6.35±5.66 ml, range 1.00-25.04 ml) confirmed by fine-needle aspiration cytology (FNAC) in fifty-four patients were treated with ultrasound-guided percutaneous radiofrequency ablation (RFA) and the local treatment efficacy was immediately assessed by intra-procedural contrast-enhanced ultrasound (CEUS). The RFA was performed with a bipolar electrode (CelonProSurge 150-T20, output power: 20 W). CEUS was performed with a second generation contrast agent under low acoustic power (i.e. coded phase inversion, CPI). Characteristics of clinical factors, findings on conventional gray-scale ultrasound, color-Doppler ultrasound, and CEUS were evaluated preoperatively. Factors associated with initial ICA and initial ICA patterns on CEUS were assessed. Volume reduction ratios (VRRs) of ICA nodules were compared with those with complete ablation (CA). The RFA procedures were accomplished with a mean ablation time and mean total energy deposition of 11.13±3.39 min (range, 5.38-22.13 min) and 12612±4466 J (range, 6310-26130 J) respectively. CEUS detected initial ICA in 21 of 69 (30.8%) BTNs and 16 (76.2%) of the 21 BTNs with initial ICA achieved CA after additional RFA, leading to a final CA rate of 92.8% (64/69). The factors associated with initial ICA were predominantly solid nodule, nodule close to danger triangle area, nodule close to carotid artery, and peripheral blood flow on color-Doppler ultrasound (all P < 0.05). The mean VRRs of all BTNs were 23.4%, 54.4% and 81.9% at the 1-, 3- and 6-month follow-up, respectively. All BTNs achieved therapeutic success in this series in that all had VRRs of >50% at the 6-month follow-up, among which 7 nodules (10.1%) had VRRs of >90%. There were significant differences in VRRs between ICA nodules and CA nodules at the 3- and 6-month follow-up (all P < 0.05). The factors associated with initial ICA after RFA for BTNs were predominantly solid nodules, nodule close to danger triangle area, nodule close to carotid artery, and peripheral blood flow on color-Doppler ultrasound. CEUS assists quick treatment response evaluation and facilitates subsequent additional RFA and final CA of the nodules. Nodules with CA achieve a better outcome in terms of VRR in comparison with those with ICA.

Eukaryotic Initiation Factor 4E Binding Protien Family of Protiens: Sentinels at a Translational Control Checkpoint in Lung Tumor Defense

PubMed Central

Kim, Yong Y; Von Weymarn, Linda; Larsson, Ola; Fan, Danhua; Underwood, Jon M; Hecht, Stephen S; Polunovsky, Vitaly A; Bitterman, Peter B

2009-01-01

The usurping of translational control by sustained activation of translation initiation factors is oncogenic. Here we show that the primary negative regulators of these oncogenic initiation factors - the 4E-BP protein family - operate as guardians of a translational control checkpoint in lung tumor defense. When challenged with the tobacco carcinogen NNK, 4ebp1−/−/4ebp2−/− mice showed increased sensitivity to tumorigenesis compared to their wild type counterparts. The 4E-BP deficient state per se creates pro-oncogenic, genome-wide skewing of the molecular landscape - with translational activation of genes governing angiogenesis, growth and proliferation; and translational activation of the precise cytochrome p450 enzyme isoform (CYP2A5) that bioactivates NNK into mutagenic metabolites. Our study provides in vivo proof for a translational control checkpoint in lung tumor defense. PMID:19843855

Predictors of Cigarette Smoking Initiation in Early, Middle, and Late Adolescence.

PubMed

O'Loughlin, Jennifer; O'Loughlin, Erin K; Wellman, Robert J; Sylvestre, Marie-Pierre; Dugas, Erika N; Chagnon, Miguel; Dutczak, Hartley; Laguë, Johanne; McGrath, Jennifer J

2017-09-01

Little is known about age-related differences in risk factors for cigarette smoking initiation. We identified predictors of initiation in early, middle, and late adolescence from among sociodemographic factors, indicators of smoking in the social environment, psychological characteristics, lifestyle indicators, and perceived need for cigarettes. Data were drawn from a longitudinal study of 1,801 children recruited at age 10-11 years from 29 elementary schools in Montreal, Canada. Multivariable logistic regression within a generalized estimating equations framework was used to identify predictors among never smokers across three 2-year windows: age 11-13 years (n = 1,221); age 13-15 years (n = 737); and age 15-17 years (n = 690). Among the 18 risk factors investigated, two differed across age. Friends' smoking, a strong risk factor in early adolescence (odds ratio [95% confidence interval] = 5.78 [3.90-8.58]), lost potency in late adolescence (1.83 [1.31-2.57]). Depressive symptoms, a risk factor in early and middle adolescence (1.60 [1.26-2.02] and 1.92 [1.45-2.54], respectively), were inversely associated in late adolescence (.76 [.58-1.00]). Sex, TV viewing, and weight-related goals were not associated with initiation at any age. All other factors were significant in two or three age groups. Most risk factors for smoking initiation were stable across age. Tobacco control interventions may be robust for risk factors across age groups and may not need adjustment. At all ages, interventions should focus on eliminating smoking in the social environment and on reducing the availability of tobacco products. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Cadmium removal by Lemna minor and Spirodela polyrhiza.

PubMed

Chaudhuri, Devaleena; Majumder, Arunabha; Misra, Amal K; Bandyopadhyay, Kaushik

2014-01-01

The present study investigates the ability of two genus of duckweed (Lemna minor and Spirodela polyrhiza) to phytoremediate cadmium from aqueous solution. Duckweed was exposed to six different cadmium concentrations, such as, 0.5,1.0,1.5, 2.0, 2.5, and 3.0 mg/L and the experiment was continued for 22 days. Water samples were collected periodically for estimation of residual cadmium content in aqueous solution. At the end of treatment period plant samples were collected and accumulated cadmium content was measured. Cadmium toxicity was observed through relative growth factor and changes in chlorophyll content Experimental results showed that Lemna minor and Spirodela polyrhiza were capable of removing 42-78% and 52-75% cadmium from media depending upon initial cadmium concentrations. Cadmium was removed following pseudo second order kinetic model Maximum cadmium accumulation in Lemna minor was 4734.56 mg/kg at 2 mg/L initial cadmium concentration and 7711.00 mg/kg in Spirodela polyrhiza at 3 mg/L initial cadmium concentration at the end of treatment period. Conversely in both cases maximum bioconcentration factor obtained at lowest initial cadmium concentrations, i.e., 0.5 mg/L, were 3295.61 and 4752.00 for Lemna minor and Spirodela polyrhiza respectively. The present study revealed that both Lemna minor and Spirodela polyrhiza was potential cadmium accumulator.

Hypusine modification in eukaryotic initiation factor 5A in rodent cells selected for resistance to growth inhibition by ornithine decarboxylase-inhibiting drugs.

PubMed Central

Tome, M E; Gerner, E W

1996-01-01

Selection of HTC cells in drugs that inhibit ornithine decarboxylase (ODC) has produced two cell lines, HMOA and DH23A/b, that contain increased amounts of more stable ODC. In addition to alterations in ODC, these cells appear to produce modified eukaryotic initiation factor 5A (eIF-5A) at different rates, a reaction that both requires spermidine and is essential for proliferation. Alterations to the modification of eIF-5A by spermidine cannot be accounted for by changes in eIF-5A protein or modified eIF-5A turnover. Deoxyhypusine synthetase activity is similar in the parental and variant cell lines and is unaltered by growth into plateau phase or by spermidine depletion. The increased rate of eIF-5A modification in DH23A/b cells is due to an increased accumulation of the unmodified eIF-5A precursor. Increased precursor accumulation is not due to increased eIF-5A transcription, but rather it can be attributed to a metabolic accumulation caused by growth under conditions of chronically limiting spermidine. Selection using drugs that inhibit ODC apparently does not cause alterations in the eIF-5A modification pathway. These data support the hypothesis that one of the main effects of spermidine depletion is depletion of the modified eIF-5A pool, and that this is a critical factor in the cytostasis often observed after depletion of cellular polyamines. PMID:8947467

Cell proteins bind to multiple sites within the 5' untranslated region of poliovirus RNA.

PubMed Central

del Angel, R M; Papavassiliou, A G; Fernández-Tomás, C; Silverstein, S J; Racaniello, V R

1989-01-01

The 5' noncoding region of poliovirus RNA contains sequences necessary for translation and replication. These functions are probably carried out by recognition of poliovirus RNA by cellular and/or viral proteins. Using a mobility-shift electrophoresis assay and 1,10-phenanthroline/Cu+ footprinting, we demonstrate specific binding of cytoplasmic factors with a sequence from nucleotides 510-629 within the 5' untranslated region (UTR). Complex formation was also observed with a second sequence (nucleotides 97-182) within the 5' UTR. These two regions of the 5' UTR appear to be recognized by distinct cell factors as determined by competition analysis and the effects of ionic strength on complex formation. However, both complexes contain eukaryotic initiation factor 2 alpha, as revealed by their reaction with specific antibody. Images PMID:2554308

Initial validation of the Spanish childhood trauma questionnaire-short form: factor structure, reliability and association with parenting.

PubMed

Hernandez, Ana; Gallardo-Pujol, David; Pereda, Noemí; Arntz, Arnoud; Bernstein, David P; Gaviria, Ana M; Labad, Antonio; Valero, Joaquín; Gutiérrez-Zotes, Jose Alfonso

2013-05-01

The present study examines the internal consistency and factor structure of the Spanish version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the association between the CTQ-SF subscales and parenting style. Cronbach's α and confirmatory factor analyses (CFA) were performed in a female clinical sample (n = 185). Kendall's ι correlations were calculated between the maltreatment and parenting scales in a subsample of 109 patients. The Spanish CTQ-SF showed adequate psychometric properties and a good fit of the 5-factor structure. The neglect and abuse scales were negatively associated with parental care and positively associated with overprotection scales. The results of this study provide initial support for the reliability and validity of the Spanish CTQ-SF.

Periods of Child Growth up to age 8 Years in Ethiopia, India, Peru and Vietnam: Key Distal Household and Community Factors

PubMed Central

Schott, Whitney B.; Crookston, Benjamin T.; Lundeen, Elizabeth A.; Stein, Aryeh D.; Behrman, Jere R.

2013-01-01

Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7,266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40 to 71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26 to 47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers’ height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child’s starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. PMID:23769211

Periods of child growth up to age 8 years in Ethiopia, India, Peru and Vietnam: key distal household and community factors.

PubMed

Schott, Whitney B; Crookston, Benjamin T; Lundeen, Elizabeth A; Stein, Aryeh D; Behrman, Jere R

2013-11-01

Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40-71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26-47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers' height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child's starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. Copyright © 2013 Elsevier Ltd. All rights reserved.

Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

PubMed

Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

2014-08-01

Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

PubMed

Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

2016-02-01

The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Kinase Independent Role for EGF Receptor in Autophagy Initiation

PubMed Central

Tan, Xiaojun; Thapa, Narendra; Sun, Yue; Anderson, Richard A

2014-01-01

The Epidermal Growth Factor Receptor (EGFR) is upregulated in numerous human cancers. Inhibition of EGFR signaling induces autophagy in tumor cells. Here we report an unanticipated role for the inactive EGFR in autophagy initiation. Inactive EGFR interacts with the oncoprotein LAPTM4B that is required for the endosomal accumulation of EGFR upon serum starvation. Inactive EGFR and LAPTM4B stabilize each other at endosomes and recruit the exocyst subcomplex containing Sec5. We show that inactive EGFR, LAPTM4B, and the Sec5 subcomplex are required for basal and starvation induced autophagy. LAPTM4B and Sec5 promote EGFR association with the autophagy inhibitor Rubicon, which in turn disassociates Beclin 1 from Rubicon to initiate autophagy. Thus, the oncoprotein LAPTM4B facilitates the role of inactive EGFR in autophagy initiation. This pathway is positioned to control tumor metabolism and promote tumor cell survival upon serum deprivation or metabolic stress. PMID:25594178

eIF4B stimulates translation of long mRNAs with structured 5′ UTRs and low closed-loop potential but weak dependence on eIF4G

PubMed Central

Sen, Neelam Dabas; Zhou, Fujun; Harris, Michael S.; Ingolia, Nicholas T.

2016-01-01

DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. However, either eliminating eIF4B or inactivating eIF4A preferentially impacts mRNAs with longer, more structured 5′ untranslated regions (UTRs). These findings reveal an eIF4A-independent role for eIF4B in addition to its function as eIF4A cofactor in promoting PIC attachment or scanning on structured mRNAs. eIF4B, eIF4A, and Ded1 mutations also preferentially impair translation of longer mRNAs in a fashion mitigated by the ability to form closed-loop messenger ribonucleoprotein particles (mRNPs) via eIF4F–poly(A)-binding protein 1 (Pab1) association, suggesting cooperation between closed-loop assembly and eIF4B/helicase functions. Remarkably, depleting eukaryotic translation initiation factor 4G (eIF4G), the scaffold subunit of eukaryotic translation initiation factor 4F (eIF4F), preferentially impacts short mRNAs with strong closed-loop potential and unstructured 5′ UTRs, exactly the opposite features associated with hyperdependence on the eIF4B/helicases. We propose that short, highly efficient mRNAs preferentially depend on the stimulatory effects of eIF4G-dependent closed-loop assembly. PMID:27601676

Validation of the Adolescent Concerns Measure (ACM): evidence from exploratory and confirmatory factor analysis.

PubMed

Ang, Rebecca P; Chong, Wan Har; Huan, Vivien S; Yeo, Lay See

2007-01-01

This article reports the development and initial validation of scores obtained from the Adolescent Concerns Measure (ACM), a scale which assesses concerns of Asian adolescent students. In Study 1, findings from exploratory factor analysis using 619 adolescents suggested a 24-item scale with four correlated factors--Family Concerns (9 items), Peer Concerns (5 items), Personal Concerns (6 items), and School Concerns (4 items). Initial estimates of convergent validity for ACM scores were also reported. The four-factor structure of ACM scores derived from Study 1 was confirmed via confirmatory factor analysis in Study 2 using a two-fold cross-validation procedure with a separate sample of 811 adolescents. Support was found for both the multidimensional and hierarchical models of adolescent concerns using the ACM. Internal consistency and test-retest reliability estimates were adequate for research purposes. ACM scores show promise as a reliable and potentially valid measure of Asian adolescents' concerns.

Expression of Eukaryotic Initiation Factor 5A and Hypusine Forming Enzymes in Glioblastoma Patient Samples: Implications for New Targeted Therapies

PubMed Central

Preukschas, Michael; Hagel, Christian; Schulte, Alexander; Weber, Kristoffer; Lamszus, Katrin; Sievert, Henning; Pällmann, Nora; Bokemeyer, Carsten; Hauber, Joachim; Braig, Melanie; Balabanov, Stefan

2012-01-01

Glioblastomas are highly aggressive brain tumors of adults with poor clinical outcome. Despite a broad range of new and more specific treatment strategies, therapy of glioblastomas remains challenging and tumors relapse in all cases. Recent work demonstrated that the posttranslational hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is a crucial regulator of cell proliferation, differentiation and an important factor in tumor formation, progression and maintenance. Here we report that eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient samples. Importantly, targeting eIF-5A and its hypusine modification with GC7, a specific DHS-inhibitor, showed a strong antiproliferative effect in glioblastoma cell lines in vitro, while normal human astrocytes were not affected. Furthermore, we identified p53 dependent premature senescence, a permanent cell cycle arrest, as the primary outcome in U87-MG cells after treatment with GC7. Strikingly, combined treatment with clinically relevant alkylating agents and GC7 had an additive antiproliferative effect in glioblastoma cell lines. In addition, stable knockdown of eIF-5A and DHS by short hairpin RNA (shRNA) could mimic the antiproliferative effects of GC7. These findings suggest that pharmacological inhibition of eIF-5A may represent a novel concept to treat glioblastomas and may help to substantially improve the clinical course of this tumor entity. PMID:22927971

Factors associated with late ANC initiation among pregnant women in select public health centers of Addis Ababa, Ethiopia: unmatched case-control study design.

PubMed

Gebrekidan, Kahasse; Worku, Alemayehu

2017-01-01

Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country. The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia. A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case-control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation. The odds of attending ANC late were significantly higher for mothers with a monthly household income of $8.50 to start the ANC service (AOR=3.04; 95% CI: 1.98, 4.67). Low educational level, low income of the household, unplanned pregnancy, stay for <5 years in Addis Ababa, not getting advice from health extension workers or local TV/radio and higher cost associated with initiation of the first ANC service were the main predictors of late ANC initiation. Therefore, any intervention which would need to improve early ANC initiation should focus on economic empowerment of women, and tailored health education for migrant women should be strengthened.

Factors associated with late ANC initiation among pregnant women in select public health centers of Addis Ababa, Ethiopia: unmatched case–control study design

PubMed Central

Gebrekidan, Kahasse; Worku, Alemayehu

2017-01-01

Background Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country. Objective The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia. Subjects and methods A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case–control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation. Results The odds of attending ANC late were significantly higher for mothers with a monthly household income of $8.50 to start the ANC service (AOR=3.04; 95% CI: 1.98, 4.67). Conclusion Low educational level, low income of the household, unplanned pregnancy, stay for <5 years in Addis Ababa, not getting advice from health extension workers or local TV/radio and higher cost associated with initiation of the first ANC service were the main predictors of late ANC initiation. Therefore, any intervention which would need to improve early ANC initiation should focus on economic empowerment of women, and tailored health education for migrant women should be strengthened. PMID:29138615

Population attributable risk of key modifiable risk factors associated with non-exclusive breastfeeding in Nigeria.

PubMed

Ogbo, Felix Akpojene; Page, Andrew; Idoko, John; Agho, Kingsley E

2018-02-13

Non-exclusive breastfeeding (non-EBF) is a risk factor for many of the 2300 under-five deaths occurring daily in Nigeria - a developing country with approximately 40 million children. This study aimed to quantify and compare the attributable burden of key modifiable risk factors associated with non-EBF in Nigeria to inform strategic policy responses and initiatives. Relative risk and exposure prevalence for selected modifiable risk factors were used to calculate population attributable fractions based on Nigeria Demographic and Health Surveys data for the period (1999-2013). Scenarios based on feasible impact of community-based interventions in reducing exposure prevalence were also considered to calculate comparative potential impact fractions. In Nigeria, an estimated 22.8% (95% Confidence Interval, CI: 9.2-37.0%) of non-EBF was attributable to primary and no maternal education; 24.7% (95% CI: 9.5-39.5%) to middle and poor household wealth, 9.7% (1.7-18.1%) to lower number (1-3) and no antenatal care visits; 18.8% (95% CI: 6.9-30.8%) to home delivery and 16.6% (95% CI: 3.0-31.3%) to delivery assisted by a non-health professional. In combination, more than half of all cases of non-EBF (64.5%; 95% CI: 50.0-76.4%) could be attributed to those modifiable risk factors. Scenarios based on feasible impacts of community-based approaches to improve health service access and human capacity suggest that an avoidable burden of non-EBF practice of approximately 11% (95% CI: -5.4; 24.7) is achievable. Key modifiable risk factors contribute significantly to non-EBF in Nigerian women. Community-based initiatives and appropriate socio-economic government policies that specifically consider those modifiable risk factors could substantially reduce non-EBF practice in Nigeria.

Quantitative assessment of orthodontic mini-implant displacement: the effect of initial force application.

PubMed

Holst, Alexandra Ioana; Karl, Matthias; Karolczak, Marek; Goellner, Matthias; Holst, Stefan

2010-01-01

Primary stability and micromovement of orthodontic mini-implants depends on a number of factors and influences clinical success or failure. The purpose of this study was to assess the behavior of orthodontic mini-implants upon initial load application. Orthodontic mini-implants (n = 39) were inserted in the alveolar process of maxillary human cadaver specimens (n = 10). Increasing horizontal forces (up to 2.5 N) were applied, and triggered images were taken in 0.5-N load intervals. Additionally, peri-implant parameters based on micro-CT volume data were recorded. Data were subjected to a two-sided nonparametric Wilcoxon signed rank test, and between-group comparisons were assessed with a Mann-Whitney test (alpha = .05). Initial load application led to displacement beyond elastic recovery of the surrounding bone after force release (P < .001). Cortical thickness and insertion depth, despite numeric differences, did not reveal any statistical differences, while displacement of mini-implants was significantly affected by contact to neighboring teeth (P < .001). Insertion technique and initial load application on orthodontic mini-implants may be regarded as two crucial factors for success, while repeated application of orthodontic force does not seem to increase screw mobility.

Structure of the initiation-competent RNA polymerase I and its implication for transcription

NASA Astrophysics Data System (ADS)

Pilsl, Michael; Crucifix, Corinne; Papai, Gabor; Krupp, Ferdinand; Steinbauer, Robert; Griesenbeck, Joachim; Milkereit, Philipp; Tschochner, Herbert; Schultz, Patrick

2016-07-01

Eukaryotic RNA polymerase I (Pol I) is specialized in rRNA gene transcription synthesizing up to 60% of cellular RNA. High level rRNA production relies on efficient binding of initiation factors to the rRNA gene promoter and recruitment of Pol I complexes containing initiation factor Rrn3. Here, we determine the cryo-EM structure of the Pol I-Rrn3 complex at 7.5 Å resolution, and compare it with Rrn3-free monomeric and dimeric Pol I. We observe that Rrn3 contacts the Pol I A43/A14 stalk and subunits A190 and AC40, that association re-organizes the Rrn3 interaction interface, thereby preventing Pol I dimerization; and Rrn3-bound and monomeric Pol I differ from the dimeric enzyme in cleft opening, and localization of the A12.2 C-terminus in the active centre. Our findings thus support a dual role for Rrn3 in transcription initiation to stabilize a monomeric initiation competent Pol I and to drive pre-initiation complex formation.

Sport and scholastic factors in relation to smoking and smoking initiation in older adolescents: a prospective cohort study in Bosnia and Herzegovina

PubMed Central

Sekulic, Damir; Sisic, Nedim; Terzic, Admir; Jasarevic, Indira; Ostojic, Ljerka; Pojskic, Haris; Zenic, Natasa

2017-01-01

Objective Sport and scholastic factors are known to be associated with cigarette smoking in adolescence, but little is known about the causality of this association. The aim of this study was to prospectively explore the relationships of different sport and scholastic factors with smoking prevalence initiation in older adolescents from Bosnia and Herzegovina. Methods In this 2-year prospective cohort study, there were 872 adolescent participants (16 years at baseline; 46% females). The study consisted of baseline tests at the beginning of the third year (September 2013) and follow-up at the end of the fourth year of high school (late May to early June 2015). The independent variables were scholastic and sport-related factors. The dependent variables were (1) smoking at baseline, (2) smoking at follow-up and (3) smoking initiation over the course of the study. Logistic regressions controlling for age, gender and socioeconomic status were applied to define the relationships between independent and dependent variables. Results School absence at the baseline study was a significant predictor of smoking initiation during the course of the study (OR 1.4, 95% CI 1.1 to 1.8). Those who reported quitting sports at baseline showed an increased risk of smoking at the end of the study (OR 1.4, 95% CI 1.1 to 2.0) and of smoking initiation (OR 1.8, 95% CI 1.3 to 2.0). Adolescents who reported lower competitive achievements in sport were at a higher risk of (1) smoking at baseline (OR 1.5, 95% CI 1.1 to 2.1), (2) smoking at follow-up (OR 1.5, 95% CI 1.1 to 2.1) and (3) smoking initiation (OR 1.6, 95% CI 1.1 to 2.6). Conclusions In developing accurate antismoking public health policies for older adolescents, the most vulnerable groups should be targeted. The results showed that most participants initiated smoking before 16 years of age. Therefore, further investigations should evaluate the predictors of smoking in younger ages. PMID:28336745

Risk factors associated with recurrent hemorrhage after the initial improvement of colonic diverticular bleeding.

PubMed

Nishikawa, Hiroki; Maruo, Takanori; Tsumura, Takehiko; Sekikawa, Akira; Kanesaka, Takashi; Osaki, Yukio

2013-03-01

We elucidated risk factors contributing to recurrent hemorrhage after initial improvement of colonic diverticular bleeding. 172 consecutive hospitalized patients diagnosed with colonic diverticular bleeding were analyzed. Recurrent hemorrhage after initial improvement of colonic diverticular bleeding is main outcome measure. We analyzed factors contributing to recurrent hemorrhage risk in univariate and multivariate analyses. The length of the observation period after improvement of colonic diverticular bleeding was 26.4 +/- 14.6 months (range, 1-79 months). The cumulative recurrent hemorrhage rate in all patients at 1 and 2 years was 34.8% and 41.8%, respectively. By univariate analysis, age > 70 years (P = 0.021), BMI > 25 kg/m2 (P = 0.013), the use of anticoagulant drugs (P = 0.034), the use of NSAIDs (P = 0.040), history of hypertension (P = 0.011), history of smoking (P = 0.030) and serum creatinine level > 1.5 mg/dL (P < 0.001) were found to be significant risk factors for recurrent colonic diverticular bleeding. By multivariate analysis, age > 70 years (Hazard ratio (HR), 1.905, 95% confidence interval (CI), 1.067-3.403, P = 0.029), history of hypertension (HR, 0.493, 95% CI, 0.245-0.993, P = 0.048) and serum creatinine level > 1.5 mg/dL (HR, 95% CI, 0.288-0.964, P = 0.044) were shown to be significant independent risk factors. Close observation after the initial improvement of colonic diverticular bleeding is needed, especially in elderly patients or patients with history of hypertension or renal deficiency.

A prospective observational cohort study in primary care practices to identify factors associated with treatment failure in Staphylococcus aureus skin and soft tissue infections.

PubMed

Lee, Grace C; Hall, Ronald G; Boyd, Natalie K; Dallas, Steven D; Du, Liem C; Treviño, Lucina B; Treviño, Sylvia B; Retzloff, Chad; Lawson, Kenneth A; Wilson, James; Olsen, Randall J; Wang, Yufeng; Frei, Christopher R

2016-11-22

The incidence of outpatient visits for skin and soft tissue infections (SSTIs) has substantially increased over the last decade. The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has made the management of S. aureus SSTIs complex and challenging. The objective of this study was to identify risk factors contributing to treatment failures associated with community-associated S. aureus skin and soft tissue infections SSTIs. This was a prospective, observational study among 14 primary care clinics within the South Texas Ambulatory Research Network. The primary outcome was treatment failure within 90 days of the initial visit. Univariate associations between the explanatory variables and treatment failure were examined. A generalized linear mixed-effect model was developed to identify independent risk factors associated with treatment failure. Overall, 21% (22/106) patients with S. aureus SSTIs experienced treatment failure. The occurrence of treatment failure was similar among patients with methicillin-resistant S. aureus and those with methicillin-susceptible S. aureus SSTIs (19 vs. 24%; p = 0.70). Independent predictors of treatment failure among cases with S. aureus SSTIs was a duration of infection of ≥7 days prior to initial visit [aOR, 6.02 (95% CI 1.74-19.61)] and a lesion diameter size ≥5 cm [5.25 (1.58-17.20)]. Predictors for treatment failure included a duration of infection for ≥7 days prior to the initial visit and a wound diameter of ≥5 cm. A heightened awareness of these risk factors could help direct targeted interventions in high-risk populations.

Overall impact of speed-related initiatives and factors on crash outcomes.

PubMed

D'Elia, A; Newstead, S; Cameron, M

2007-01-01

From December 2000 until July 2002 a package of speed-related initiatives and factors took place in Victoria, Australia. The broad aim of this study was to evaluate the overall impact of the package on crash outcomes. Monthly crash counts and injury severity proportions were assessed using Poisson and logistic regression models respectively. The model measured the overall effect of the package after adjusting as far as possible for non-speed road safety initiatives and socio-economic factors. The speed-related package was associated with statistically significant estimated reductions in casualty crashes and suggested reductions in injury severity with trends towards increased reductions over time. From December 2000 until July 2002, three new speed enforcement initiatives were implemented in Victoria, Australia. These initiatives were introduced in stages and involved the following key components: More covert operations of mobile speed cameras, including flash-less operations; 50% increase in speed camera operating hours; and lowering of cameras' speed detection threshold. In addition, during the period 2001 to 2002, the 50 km/h General Urban Speed Limit (GUSL) was introduced (January 2001), there was an increase in speed-related advertising including the "Wipe Off 5" campaign, media announcements were made related to the above enforcement initiatives and there was a speeding penalty restructure. The above elements combine to make up a package of speed-related initiatives and factors. The package represents a broad, long term program by Victorian government agencies to reduce speed based on three linked strategies: more intensive Police enforcement of speed limits to deter potential offenders, i.e. the three new speed enforcement initiatives just described - supported by higher penalties; a reduction in the speed limit on local streets throughout Victoria from 60 km/h to 50 km/h; and provision of information using the mass media (television, radio and billboard) to reinforce the benefits of reducing low level speeding - the central message of "Wipe Off 5". These strategies were implemented across the entire state of Victoria with the intention of covering as many road users as possible. This study aimed to evaluate the overall effectiveness of the speed-related package. The study objectives were: to document the increased speed camera activity in each speed limit zone and in Melbourne compared with the rest of Victoria; to evaluate the overall effect on crash outcomes of the package; to account as far as possible for the effect on crash outcomes of non-speed road safety initiatives and socio-economic factors, which would otherwise influence the speed-related package evaluation; and to examine speed trends in Melbourne and on Victorian rural highways, especially the proportions of vehicles travelling at excessive speeds. This paper presents the results of the evaluation of the overall impact on crash outcomes associated with the speed-related package, after adjusting as far as possible for the effect of non-speed road safety initiatives and socio-economic factors. D'Elia, Newstead and Cameron (2007) document the study results in full.

Factors associated with early marijuana initiation in a criminal justice population.

PubMed

Savage, Rebekah J; King, Vinetra L; Clark, C Brendan; Cropsey, Karen L

2017-01-01

Initiation of marijuana during adolescence is associated with negative outcomes and is more common among those with criminal justice involvement. We sought to determine demographics, psychosocial factors, mental health factors, and criminal outcomes associated with earlier age at first marijuana use in a criminal justice population. Data from structured, in-person interviews of adults in a criminal corrections program were analyzed. Participants (689 men and women ages 19 and older) were recruited for a larger smoking cessation trial (2009-2013) as a volunteer sample by flyers at a community corrections site. 516 had smoked both nicotine and marijuana and were included in the analysis. We determined associations between self-reported age at first marijuana use and sex, race, income, educational attainment, history of abuse, family problems, psychiatric problems, criminal record, and age of nicotine and alcohol initiation. Of 516 participants, 68% were men, and 64.5% were Black. No participants were of Hispanic ethnicity. Average age of marijuana initiation was 15.1years (SD 3.7years). After linear regression, earlier age at marijuana initiation was associated with male sex and more criminal offenses (person/violent and court). Race and psychiatric problems were not associated with earlier marijuana initiation. Earlier adolescent marijuana initiation is associated with more criminal offenses in a criminal justice population. Men initiate marijuana earlier than women. Adolescents at high risk of justice involvement may benefit from delayed initiation of marijuana, specifically men. Additional studies should examine prevention strategies for adolescent marijuana use that target those at highest risk. Copyright © 2016. Published by Elsevier Ltd.

Functional genomics of fuzzless-lintless mutant of Gossypium hirsutum L. cv. MCU5 reveal key genes and pathways involved in cotton fibre initiation and elongation

PubMed Central

2012-01-01

Background Fuzzless-lintless cotton mutants are considered to be the ideal material to understand the molecular mechanisms involved in fibre cell development. Although there are few reports on transcriptome and proteome analyses in cotton at fibre initiation and elongation stages, there is no comprehensive comparative transcriptome analysis of fibre-bearing and fuzzless-lintless cotton ovules covering fibre initiation to secondary cell wall (SCW) synthesis stages. In the present study, a comparative transcriptome analysis was carried out using G. hirsutum L. cv. MCU5 wild-type (WT) and it’s near isogenic fuzzless-lintless (fl) mutant at fibre initiation (0 dpa/days post anthesis), elongation (5, 10 and 15 dpa) and SCW synthesis (20 dpa) stages. Results Scanning electron microscopy study revealed the delay in the initiation of fibre cells and lack of any further development after 2 dpa in the fl mutant. Transcriptome analysis showed major down regulation of transcripts (90%) at fibre initiation and early elongation (5 dpa) stages in the fl mutant. Majority of the down regulated transcripts at fibre initiation stage in the fl mutant represent calcium and phytohormone mediated signal transduction pathways, biosynthesis of auxin and ethylene and stress responsive transcription factors (TFs). Further, transcripts involved in carbohydrate and lipid metabolisms, mitochondrial electron transport system (mETS) and cell wall loosening and elongation were highly down-regulated at fibre elongation stage (5–15 dpa) in the fl mutant. In addition, cellulose synthases and sucrose synthase C were down-regulated at SCW biosynthesis stage (15–20 dpa). Interestingly, some of the transcripts (~50%) involved in phytohormone signalling and stress responsive transcription factors that were up-regulated at fibre initiation stage in the WT were found to be up-regulated at much later stage (15 dpa) in fl mutant. Conclusions Comparative transcriptome analysis of WT and its near isogenic fl mutant revealed key genes and pathways involved at various stages of fibre development. Our data implicated the significant role of mitochondria mediated energy metabolism during fibre elongation process. The delayed expression of genes involved in phytohormone signalling and stress responsive TFs in the fl mutant suggests the need for a coordinated expression of regulatory mechanisms in fibre cell initiation and differentiation. PMID:23151214

Interference Fit Life Factors for Roller Bearings

NASA Technical Reports Server (NTRS)

Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

2008-01-01

The effect of hoop stresses in reducing cylindrical roller bearing fatigue life was determined for various classes of inner ring interference fit. Calculations were performed for up to seven interference fit classes for each of ten bearing sizes. Each fit was taken at tightest, average and loosest values within the fit class for RBEC-5 tolerance, thus requiring 486 separate analyses. The hoop stresses were superimposed on the Hertzian principal stresses created by the applied radial load to calculate roller bearing fatigue life. The method was developed through a series of equations to calculate the life reduction for cylindrical roller bearings based on interference fit. All calculated lives are for zero initial bearing internal clearance. Any reduction in bearing clearance due to interference fit was compensated by increasing the initial (unmounted) clearance. Results are presented as tables and charts of life factors for bearings with light, moderate and heavy loads and interference fits ranging from extremely light to extremely heavy and for bearing accuracy class RBEC 5 (ISO class 5). Interference fits on the inner bearing ring of a cylindrical roller bearing can significantly reduce bearing fatigue life. In general, life factors are smaller (lower life) for bearings running under light load where the unfactored life is highest. The various bearing series within a particular bore size had almost identical interference fit life factors for a particular fit. The tightest fit at the high end of the RBEC-5 tolerance band defined in ANSI/ABMA shaft fit tables produces a life factor of approximately 0.40 for an inner-race maximum Hertz stress of 1200 MPa (175 ksi) and a life factor of 0.60 for an inner-race maximum Hertz stress of 2200 MPa (320 ksi). Interference fits also impact the maximum Hertz stress-life relation.

5 CFR 317.501 - Recruitment and selection for initial SES career appointment be achieved from the brightest and...

Code of Federal Regulations, 2010 CFR

2010-01-01

... political or other non-job-related factors. If a candidate is a current SES career appointee or an SES... the knowledges, skills, abilities, and other job-related factors in the qualifications standard for...) Retention of documentation. Agencies must keep such documentation as OPM prescribes for 2 years to permit...

Risk factors for DSM-5 posttraumatic stress symptoms (PTSS) among Israeli civilians during the 2014 Israel-Hamas war.

PubMed

Gil, Sharon; Weinberg, Michael; Shamai, Michal; Ron, Pnina; Harel, Hila; Or-Chen, Keren

2016-01-01

In light of current modifications in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for posttraumatic stress disorder (PTSD), this study aimed to revalidate well-known PTSD risk factors related to terrorism and war in Israel, namely, proximity to the Gaza Strip, dissociative symptoms, acute stress disorder (ASD) symptoms, and social support. One hundred and sixty Israeli civilians were assessed during the 2014 Israel-Hamas war at 2 time points: 1 week after the beginning of the operation (t1) and 1 month after initial evaluation (t2), using the DSM-5 PTSD Symptom Levels Scale (PSLS; Gil, Weinberg, Or-Chen, & Harel, 2015). A paired t test analysis showed significant reduction in the respondents' posttraumatic stress symptoms (PTSS) 1 month after the initial assessment point. A structural equation model (SEM) showed that higher ASD symptoms at t1 and higher dissociative symptoms at t2 increased the risk for PTSS at t2. Conversely, higher peritraumatic dissociation at t1 decreased the risk for PTSS at t2. Proximity to the Gaza Strip, and social support, failed to demonstrate significant association with PTSS at t2. DSM-5 PTSS 1 month after prolonged traumatic exposure are strongly associated with high ASD symptoms at 1 week as a risk factor; high levels of peritraumatic dissociation at 1 week as a protective factor; and high levels of dissociative symptoms at 1 month as a risk factor. Theoretically and clinically the findings of the study further suggest that ongoing massive terrorism and war cannot be viewed or treated as identical to other traumas. (c) 2016 APA, all rights reserved).

Teacher Involvement as a Protective Factor from the Association between Race-Based Bullying and Smoking Initiation.

PubMed

Earnshaw, Valerie A; Rosenthal, Lisa; Carroll-Scott, Amy; Peters, Susan M; McCaslin, Catherine; Ickovics, Jeannette R

2014-06-01

Experiencing bullying as a victim is associated with negative health and health behavior outcomes, including substance use, among adolescents. However, understandings of protective factors - factors that enhance adolescents' resilience to the negative consequences of bullying - remain limited. The current study investigates whether teacher involvement protects adolescent students from the association between being bullied due to race and smoking initiation. Students were recruited from 12 Kindergarten through 8 th grade schools in an urban school district in the Northeast United States. The analytic sample included 769 students who responded to surveys in 5 th or 6 th grade (2009), and two years later in 7 th or 8 th grade (2011). Students primarily identified as Latino and/or Black, and 90% were eligible for free or reduced lunch. Fifty-four (7%) students initiated smoking between survey time points. Among students reporting lower teacher involvement, race-based bullying was associated with higher likelihood of smoking initiation (OR = 1.69, p = .03). In contrast, among students reporting higher teacher involvement, racebased bullying was not associated with higher likelihood of smoking initiation (OR = 0.95, p = .81). Results suggest that teacher involvement may protect students from the association between race-based bullying and smoking initiation. Enhancing teacher involvement among students experiencing race-based bullying in schools may limit smoking initiation.

Use of natural mRNAs in the cell-free protein-synthesizing systems of the moderate halophile Vibrio costicola.

PubMed

Choquet, C G; Kushner, D J

1990-06-01

In vitro protein synthesis was studied in extracts of the moderate halophile Vibrio costicola by using as mRNAs the endogenous mRNA of V. costicola and the RNA of the R17 bacteriophage of Escherichia coli. Protein synthesis (amino acid incorporation) was dependent on the messenger, ribosomes, soluble cytoplasmic factors, energy source, and tRNA(FMet) (in the R17 RNA system) and was inhibited by certain antibiotics. These properties indicated de novo protein synthesis. In the V. costicola system directed by R17 RNA, a protein of the same electrophoretic mobility as the major coat protein of the R17 phage was synthesized. Antibiotic action and the response to added tRNA(FMet) showed that protein synthesis in the R17 RNA system, but not in the endogenous messenger system, absolutely depended on initiation. Optimal activity of both systems was observed in 250 to 300 mM NH4+ (as glutamate). Higher salt concentrations, especially those with Cl- as anion, were generally inhibitory. The R17 RNA-directed system was more sensitive to Cl- ions than the endogenous system was. Glycine betaine stimulated both systems and partly overcame the toxic effects of Cl- ions. Both systems required Mg2+, but in lower concentrations than the polyuridylic acid-directed system previously studied. Initiation factors were removed from ribosomes by washing with 3.0 to 3.5 M NH4Cl, concentrations about three times as high as that needed to remove initiation factors from E. coli ribosomes. Washing with 4.0 M NH4Cl damaged V. costicola ribosomes, although the initiation factors still functioned. Cl- ions inhibited the attachment of initiation factors to tRNA(FMet) but had little effect on binding of initiation factors to R17 RNA.

The Psychometric Properties of the French Version of the Personality Inventory for DSM-5

PubMed Central

Roskam, Isabelle; Galdiolo, Sarah; Hansenne, Michel; Massoudi, Koorosh; Rossier, Jérôme; Gicquel, Ludovic; Rolland, Jean-Pierre

2015-01-01

In the context of the publication of DSM-5, the Personality Inventory for DSM-5 (PID-5) has been proposed as a new dimensional assessment tool for personality disorders. This instrument includes a pool of 220 items organized around 25 facets included in a five-factor second-order domain structure. The examination of the replicability of the trait structure across methods and populations is of primary importance. In view of this need, the main objective of the current study was to validate the French version of the PID-5 among French-speaking adults from a European community sample (N=2,532). In particular, the assumption of unidimensionality of the 25 facet and the five domain scales was tested, as well as the extent to which the five-factor structure of the PID-5 and the DSM-5 personality trait hierarchical structure are replicated in the current sample. The results support the assumption of unidimensionality of both the facets and the domains. Exploratory factor and hierarchical analyses replicated the five-factor structure as initially proposed in the PID-5. PMID:26193699

The Psychometric Properties of the French Version of the Personality Inventory for DSM-5.

PubMed

Roskam, Isabelle; Galdiolo, Sarah; Hansenne, Michel; Massoudi, Koorosh; Rossier, Jérôme; Gicquel, Ludovic; Rolland, Jean-Pierre

2015-01-01

In the context of the publication of DSM-5, the Personality Inventory for DSM-5 (PID-5) has been proposed as a new dimensional assessment tool for personality disorders. This instrument includes a pool of 220 items organized around 25 facets included in a five-factor second-order domain structure. The examination of the replicability of the trait structure across methods and populations is of primary importance. In view of this need, the main objective of the current study was to validate the French version of the PID-5 among French-speaking adults from a European community sample (N=2,532). In particular, the assumption of unidimensionality of the 25 facet and the five domain scales was tested, as well as the extent to which the five-factor structure of the PID-5 and the DSM-5 personality trait hierarchical structure are replicated in the current sample. The results support the assumption of unidimensionality of both the facets and the domains. Exploratory factor and hierarchical analyses replicated the five-factor structure as initially proposed in the PID-5.

The dynamic role of parental influences in preventing adolescent smoking initiation.

PubMed

Mahabee-Gittens, E Melinda; Xiao, Yang; Gordon, Judith S; Khoury, Jane C

2013-04-01

As adolescents grow, protective parental influences become less important and peer influences take precedence in adolescent's initiation of smoking. It is unknown how and when this occurs. We sought to: prospectively estimate incidence rates of smoking initiation from late childhood through mid-adolescence, identify important risk and protective parental influences on smoking initiation, and examine their dynamic nature in order to identify key ages. Longitudinal data from the National Survey of Parents and Youth of 8 nationally representative age cohorts (9-16 years) of never smokers in the U.S. were used (N=5705 dyads at baseline). Analysis involved a series of lagged logistic regression models using a cohort-sequential design. The mean sample cumulative incidence rates of tobacco use increased from 1.8% to 22.5% between the 9 and 16 years old age cohorts. Among risk factors, peer smoking was the most important across all ages; 11-15 year-olds who spent time with peers who smoked had 2 to 6.5 times higher odds of initiating smoking. Parent-youth connectedness significantly decreased the odds of smoking initiation by 14-37% in 11-14 year-olds; parental monitoring and punishment for smoking decreased the odds of smoking initiation risk by 36-59% in 10-15 year-olds, and by 15-28% in 12-14 year-olds, respectively. Parental influences are important in protecting against smoking initiation across adolescence. At the same time, association with peers who smoke is a very strong risk factor. Our findings provide empirical evidence to suggest that in order to prevent youth from initiating smoking, parents should be actively involved in their adolescents' lives and guard them against association with peers who smoke. Copyright © 2013 Elsevier Ltd. All rights reserved.

Factors affecting UV/H2O2 inactivation of Bacillus atrophaeus spores in drinking water.

PubMed

Zhang, Yongji; Zhang, Yiqing; Zhou, Lingling; Tan, Chaoqun

2014-05-05

This study aims at estimating the performance of the Bacillus atrophaeus spores inactivation by the UV treatment with addition of H2O2. The effect of factors affecting the inactivation was investigated, including initial H2O2 dose, UV irradiance, initial cell density, initial solution pH and various inorganic anions. Under the experimental conditions, the B. atrophaeus spores inactivation followed both the modified Hom Model and the Chick's Model. The results revealed that the H2O2 played dual roles in the reactions, while the optimum reduction of 5.88lg was received at 0.5mM H2O2 for 10min. The inactivation effect was affected by the UV irradiance, while better inactivation effect was achieved at higher irradiance. An increase in the initial cell density slowed down the inactivation process. A slight acid condition at pH 5 was considered as the optimal pH value. The inactivation effect within 10min followed the order of pH 5>pH 7>pH 9>pH 3>pH 11. The effects of three added inorganic anions were investigated and compared, including sulfate (SO4(2)(-)), nitrate (NO3(-)) and carbonate (CO3(2)(-)). The sequence of inactivation effect within 10min followed the order of control group>SO4(2)(-)>NO3(-)>CO3(2)(-). Copyright © 2014 Elsevier B.V. All rights reserved.

Demographic and clinical features of gout patients in Turkey: a multicenter study.

PubMed

Öztürk, Mehmet Akif; Kaya, Arif; Şenel, Soner; Dönmez, Salim; Balkarlı, Ayşe; Çobankara, Veli; Erhan, Çiğdem; Sayarlıoğlu, Mehmet; Ugan, Yunus; Tunç, Ş Ercan; Pehlivan, Yavuz; Kısacık, Bünyamin; Tufan, Abdurrahman; Onat, Ahmet Mesut; Tezcan, Engin; Yıldırım Çetin, Gözde; Pamuk, Omer Nuri

2013-04-01

Gout results from multifactor interactions between gender, age, genetic and environmental factors. Environmental factors underlying gout and precipitating factors triggering acute attacks might vary in different populations with different lifestyles. In this study, we aimed to collect data regarding the demographic and clinical features, comorbid factors, and precipitating factors associated with the initiation of acute attacks in gout patients in Turkey. A total of 312 patients were included in this study (mean age, 58.8 ± 13.8 years; female/male ratio, 55/257). The demographic features, alcohol intake, clinical and laboratory features, and comorbid conditions including obesity, diabetes mellitus, hyperlipidemia, hypertension, and coronary heart disease were noted in a standard questionnaire. Precipitating factors initiating acute attacks (if any) were also noted. The patients were divided into 4 groups according to the region of location as central Anatolian region, southeast Anatolian region, Aegean region, and Trakya region. Our results were compared according to the gender and the location of the patients. The mean age at the start of the symptoms was 10 years higher in women (60.4 ± 14.8 and 50.6 ± 13.5 years in women and men, respectively, p < 0.001).Obesity was present in 40.1 %, diabetes mellitus in 17.9 %, hyperlipidemia in 30.1 %, hypertension in 53.5 %, coronary artery disease in 17 %, and nephrolithiasis in 21.8 % of patients. Precipitating factors triggering gout flares were as follows: diet (high consumption of meat or fish) in 46.5 %, alcohol consumption in 15.7 %, diuretics in 8.3 %, diet or diuretics in 5.1 %, diet or alcohol in 4.5 %, diet or alcohol or diuretics in 1.6 %, others in 4.2 %, and none in 14.1 %. The presence of diabetes and diuretic use was more common among women. Use of diuretics is a more common trigger for gout flares among women. On the other hand, various comorbid conditions, such as obesity and hypertension, and triggers for gout flares may differ between patients living in different geographic regions. In summary, we reported the first data regarding clinical and demographic characteristics of gout in Turkey. The majority of our patients could describe at least one "trigger" that initiated gout flare. Both comorbid conditions and triggers of attack might differ between men and women, and in different geographic areas. Better knowledge of the modifiable risk factors can be useful for the management strategy to optimize long-term patient outcomes in local clinics.

Prognostic factors in pemphigus vulgaris and pemphigus foliaceus.

PubMed

Saha, M; Bhogal, B; Black, M M; Cooper, D; Vaughan, R W; Groves, R W

2014-01-01

Pemphigus typically has a chronic course, although there is great variability in disease duration (DD) and time taken to disease remission (DR) between individuals with the disease. The reasons for this are unclear. To explore the prognostic influence of epidemiological, clinical, immunological and genetic factors on disease course and remission in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). This was a retrospective study of patients with PV and PF, recruited from a single UK centre. Direct and indirect immunofluorescence and enzyme-linked immunosorbent assay studies for antidesmoglein (Dsg) antibodies were used to assess immunological factors. Polymerase chain reaction with sequence specific primers (PCR-SSP) was used to assess the Class II human leukocyte antigen status of patients. Prognostic endpoints investigated were time to initial first DR and total DD. Ninety-five patients were recruited (79 PV and 16 PF). Patients of Indo-Asian origin were significantly associated with longer DD than White-British patients (P = 0.029). In addition, younger age at onset was associated with a worse prognosis in terms of DD: the mean age at presentation of patients with DD of < 5 years was 49 years (SEM = 3.4) compared with 40 years (SEM = 1.9) in those with DD > 5 years (P = 0.039). A higher initial intercellular antibody titre on normal human skin substrate was associated with a greater time to initial DR (P = 0.007) and high anti-Dsg 3 levels at baseline were associated with a longer total DD (P = 0.03). Ethnic group, age at presentation, initial intercellular antibody titre and initial Dsg 3 antibody levels all had a significant impact on prognosis of pemphigus. © 2013 British Association of Dermatologists.

Maternity staff perspectives regarding resource demands of breastfeeding supportive practices in accordance with the Baby-Friendly Hospital Initiative accreditation: a Q methodology approach.

PubMed

Huang, Chiu-Mieh; Hung, Wei-Shu; Lai, Jung-Nien; Kao, Yu-Hsiu; Wang, Ching-Ling; Guo, Jong-Long

2016-06-01

To explore the resource demands of implementing the Baby-Friendly Hospital Initiative among maternity staff. Implementing the Baby-Friendly Hospital Initiative is the most recognized global strategy for ensuring that hospital routines support breastfeeding. The maternity services of Baby-Friendly Hospital Initiative accredited hospitals are evaluated according to the Ten Steps to Successful Breastfeeding. Q methodology was applied to investigate the perspectives of 60 maternity staff in Northern Taiwan. Data were collected from May - December 2014. An online Q-sort platform was designed for the participants to perform sorting. The Q-sorts were subjected to factor analysis by using PQ Method software. Factors were extracted using principal component analysis with a varimax rotation. A combination of eigenvalues and a scree plot were employed to determine the number of retained factors. Four factors retained in the final model accounted for 56% of the total variance: (1) emphasis on implementing an institutional policy; (2) emphasis on providing supportive practices for breastfeeding mothers; (3) emphasis on establishing continual breastfeeding support; and (4) emphasis on managing breastfeeding supportive practices concerning a designated time period. The participants that were associated with Factors 1 and 3 emphasized the necessity of allocating resources to Steps 1, 2 and 10 of the Ten Steps. The participants associated with Factors 2 and 4 emphasized allocating resources to Steps 2-5 and 7. This study revealed the various perspectives of maternity staff regarding the resource demands of implementing the Baby-Friendly Hospital Initiative. These perspectives may serve as a reference for decision-makers in prioritizing resource allocation. © 2016 John Wiley & Sons Ltd.

Predictors of pain medication selection among patients diagnosed with fibromyalgia.

PubMed

Boulanger, Luke; Wu, Ning; Chen, Shih-Yin; Nagar, Saurabh; Fraser, Kimberly; Bernauer, Mark J; Zhao, Zhenxiang; Zhao, Yang

2012-04-01

Several pharmacologic therapies have been recommended for managing fibromyalgia. However, the factors associated with each treatment initiation have not been well established. This study assessed factors that were associated with the use of duloxetine vs. other pain medications among patients with fibromyalgia. Administrative claims from a large, U.S. commercially insured population were analyzed using a retrospective cohort design. Patients with fibromyalgia who were 18 to 64 years old and initiated duloxetine vs. selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, tramadol, or nontramadol opioids between January 1, 2007 and December 12, 2008 were selected. Treatment initiation was defined as no access to the same medication over the previous 90 days, with the most recent initiation date as the index date. All patients selected had at least one fibromyalgia diagnosis (ICD-9-CM: 729.1) in the 12 months prior to initiation of each study medication. Multiple logistic regression models were estimated to assess the predictors of initiating duloxetine vs. each of the other medications. The study included 117,305 patients with fibromyalgia (48 years of age on average; 76% women) who initiated duloxetine (n = 5,827), SSRIs (n = 8,620), TCAs (n = 5,424), venlafaxine (n = 2,038), gabapentin (n = 5,733), pregabalin (n = 11,152), tramadol (n = 7,312), or nontramadol opioids (n = 71,199). Common fibromyalgia-related comorbidities were low back pain (31% to 49%), osteoarthritis (14% to 21%), and sleep disturbance (10% to 15%). Controlling for demographic and clinical characteristics, patients who received pregabalin in the prior 12-month period were more likely to initiate duloxetine. Patients from other treatment cohorts, except for those in the pregabalin and nontramadol opioid cohorts, were more likely to re-initiate the same prior medication than to begin treatment with duloxetine. Other predictors of duloxetine initiation included history of rheumatoid and sleep disturbance. The presence of select comorbidities and prior use of certain medications were associated with the duloxetine initiation among working-age, commercially insured patients with fibromyalgia. © 2011 The Authors. Pain Practice © 2011 World Institute of Pain.

[Determinants of early sexual initiation in the Pelotas birth cohort from 1982 to 2004-5, Southern Brazil].

PubMed

Gonçalves, Helen; Béhague, Dominique P; Gigante, Denise P; Minten, Gicele C; Horta, Bernardo L; Victora, Cesar G; Barros, Fernando C

2008-12-01

To analyze social determinants of early sexual initiation among young adults from a birth cohort. Individuals from the 1982 birth cohort (N=4,297) were interviewed in 2004-5, city of Pelotas, Southern Brazil. Early sexual initiation (<13 years of age) was the outcome. Descriptive and stratified analyses were performed according to sex. Variables analyzed were family income in 1982, ethnicity, young adult's level of education and change in income (between 1982 and 2004-5). Ethnographic data were used to complement result analysis. Prevalence of early sexual initiation was higher among black and mixed men, and those with low level of education and low family income in 1982 and 2004-5. More traditional male sexual role requirements, such as virility and sexual initiative, showed more repercussion and adherence from an early age among men. Young family women with higher income and level of education tended to delay their sexual initiation. Imposition of traditional values was found to influence early sexual initiation among men and women with lower level of education and income. Results found re-established the economic factor as a determinant of behavior or uses of sexuality for both sexes. To focus on political efforts that help the economically disadvantaged to have opportunities and egalitarian future perspectives is an important strategy for health outcomes.

Determinants of early sexual initiation in the Pelotas birth cohort from 1982 to 2004-5, Southern Brazil

PubMed Central

Gonçalves, Helen; Béhague, Dominique P; Gigante, Denise P; Minten, Gicele C; Horta, Bernardo L; Victora, Cesar G; Barros, Fernando C

2009-01-01

OBJECTIVE To analyze social determinants of early sexual initiation among young adults from a birth cohort. METHODS Individuals from the 1982 birth cohort (N=4,297) were interviewed in 2004-5, city of Pelotas, Southern Brazil. Early sexual initiation (≤13 years of age) was the outcome. Descriptive and stratified analyses were performed according to sex. Variables analyzed were family income in 1982, ethnicity, young adult’s level of education and change in income (between 1982 and 2004-5). Ethnographic data were used to complement result analysis. RESULTS Prevalence of early sexual initiation was higher among black and mixed men, and those with low level of education and low family income in 1982 and 2004-5. More traditional male sexual role requirements, such as virility and sexual initiative, showed more repercussion and adherence from an early age among men. Young family women with higher income and level of education tended to delay their sexual initiation. Imposition of traditional values was found to influence early sexual initiation among men and women with lower level of education and income. CONCLUSIONS Results found re-established the economic factor as a determinant of behavior or uses of sexuality for both sexes. To focus on political efforts that help the economically disadvantaged to have opportunities and egalitarian future perspectives is an important strategy for health outcomes. PMID:19142343

Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.

PubMed

Papadopoulos, Evangelos; Jenni, Simon; Kabha, Eihab; Takrouri, Khuloud J; Yi, Tingfang; Salvi, Nicola; Luna, Rafael E; Gavathiotis, Evripidis; Mahalingam, Poornachandran; Arthanari, Haribabu; Rodriguez-Mias, Ricard; Yefidoff-Freedman, Revital; Aktas, Bertal H; Chorev, Michael; Halperin, Jose A; Wagner, Gerhard

2014-08-05

The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5' end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5' UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer-biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between β-sheet2 (L60-T68) and α-helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85 region. It acts by unfolding a short 310-helix (S82-L85) while extending α-helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E.

Flux-tunable heat sink for quantum electric circuits.

PubMed

Partanen, M; Tan, K Y; Masuda, S; Govenius, J; Lake, R E; Jenei, M; Grönberg, L; Hassel, J; Simbierowicz, S; Vesterinen, V; Tuorila, J; Ala-Nissila, T; Möttönen, M

2018-04-20

Superconducting microwave circuits show great potential for practical quantum technological applications such as quantum information processing. However, fast and on-demand initialization of the quantum degrees of freedom in these devices remains a challenge. Here, we experimentally implement a tunable heat sink that is potentially suitable for the initialization of superconducting qubits. Our device consists of two coupled resonators. The first resonator has a high quality factor and a fixed frequency whereas the second resonator is designed to have a low quality factor and a tunable resonance frequency. We engineer the low quality factor using an on-chip resistor and the frequency tunability using a superconducting quantum interference device. When the two resonators are in resonance, the photons in the high-quality resonator can be efficiently dissipated. We show that the corresponding loaded quality factor can be tuned from above 10 5 down to a few thousand at 10 GHz in good quantitative agreement with our theoretical model.

Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

PubMed

Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

2003-07-20

Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.

Initial apixaban dosing in patients with atrial fibrillation.

PubMed

Buchholz, Alexander; Ueberham, Laura; Gorczynska, Kaja; Dinov, Borislav; Hilbert, Sebastian; Dagres, Nikolaos; Husser, Daniela; Hindricks, Gerhard; Bollmann, Andreas

2018-05-01

Apixaban is a non-vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction. Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing-relevant secondary diagnoses and co-medication. We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664-0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076-1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881-0.940, P < 0.0001) were independent predictors for apixaban underdosage. In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction. © 2018 Wiley Periodicals, Inc.

Moderators of the Intervention Effects for a Dissonance-Based Eating Disorder Prevention Program; Results from an Amalgam of Three Randomized Trials

PubMed Central

Müller, Sina; Stice, Eric

2013-01-01

Objective To investigate factors hypothesized to moderate the effects of a dissonance-based eating disorder prevention program, including initial elevations in thin-ideal internalization, body dissatisfaction, eating disorder symptoms, and older participant age. Method Adolescent female high school and college students with body image concerns (N = 977; M age = 18.6) were randomized to a dissonance-based thin-ideal internalization reduction program or an assessment-only control condition in three prevention trials. Results The intervention produced (a) significantly stronger reductions in thin-ideal internalization for participants with initial elevations in thin-ideal internalization and a threshold/subthreshold DSM-5 eating disorder at baseline, (b) significantly greater reductions in eating disorder symptoms for participants with versus without a DSM-5 eating disorder at baseline, and (c) significantly stronger reductions in body dissatisfaction for late adolescence/young adulthood versus mid-adolescent participants. Baseline body dissatisfaction did not moderate the intervention effects. Conclusion Overall, intervention effects tended to be amplified for individuals with initial elevations in risk factors and a DSM-5 eating disorder at baseline. Results suggest that this prevention program is effective for a broad range of individuals, but is somewhat more beneficial for the subgroups identified in the moderation analyses. PMID:23337181

Greater stroke severity predominates over all other factors for the worse outcome of cardioembolic stroke.

PubMed

Hong, Keun-Sik; Lee, Juneyoung; Bae, Hee-Joon; Lee, Ji Sung; Kang, Dong-Wha; Yu, Kyung-Ho; Han, Moon-Ku; Cho, Yong-Jin; Song, Pamela; Park, Jong-Moo; Oh, Mi-Sun; Koo, Jaseong; Lee, Byung-Chul

2013-11-01

Cardioembolic (CE) strokes are more disabling and more fatal than non-CE strokes. Multiple prognostic factors have been recognized, but the magnitude of their relative contributions has not been well explored. Using a prospective stroke outcome database, we compared the 3-month outcomes of CE and non-CE strokes. We assessed the relative contribution of each prognostic factor of initial stroke severity, poststroke complications, and baseline characteristics with multivariable analyses and model fitness improvement using -2 log-likelihood and Nagelkerke R2. This study included 1233 patients with acute ischemic stroke: 193 CE strokes and 1040 non-CE strokes. Compared with the non-CE group, CE group had less modified Rankin Scale (mRS) 0-2 outcomes (47.2% versus 68.5%; odds ratio [95% confidence interval], .41 [.30-.56]), less mRS 0-1 outcomes (33.7% versus 53.5%; .44 [.32-.61]), more mRS 5-6 outcomes (32.1% versus 10.9%; 3.88 [2.71-5.56]), and higher mortality (19.2% versus 5.2%; 4.33 [2.76-6.80]) at 3 months. When adjusting either baseline characteristics or poststroke complications, the outcome differences between the 2 groups remained significant. However, adjusting initial National Institute of Health Stroke Scale (NIHSS) score alone abolished all outcome differences except for mortality. For mRS 0-2 outcomes, the decrement of -2 log-likelihood and the Nagelkerke R2 of the model adjusting initial NIHSS score alone approached 70.2% and 76.7% of the fully adjusting model. Greater stroke severity predominates over all other factors for the worse outcome of CE stroke. Primary prevention and more efficient acute therapy for stroke victims should be given top priorities to reduce the burden of CE strokes. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Adolescent Online Romantic Relationship Initiation: Differences by Sexual and Gender Identification

PubMed Central

Korchmaros, Josephine D.; Ybarra, Michele L.; Mitchell, Kimberly J.

2015-01-01

Data from the national Teen Health and Technology Study of adolescents 13-18 years old (N = 5,091) were used to examine online formation of romantic relationships. Results show that lesbian, gay, bisexual, transgender, and queer (LGBTQ) and non-LGBTQ adolescents similarly were most likely to have met their most recent boy/girlfriend in the past 12 months at school. However, they differed on many characteristics of romantic relationship initiation, including the extent to which they initiated romantic relationships online. LGBTQ and non-LGBTQ adolescents also differed on level of offline access to potential partners, offline popularity, and numerous other factors possibly related to online relationship initiation (e.g., Internet use and demographic factors). Even after adjusting for differences in these factors, LGBTQ adolescents were more likely than non-LGBTQ adolescents to find boy/girlfriends online in the past 12 months. The results support the rich-get-richer hypothesis as well as the social compensation hypothesis. PMID:25625753

Patient, physician, pharmacy, and pharmacy benefit design factors related to generic medication use.

PubMed

Shrank, William H; Stedman, Margaret; Ettner, Susan L; DeLapp, Dee; Dirstine, June; Brookhart, M Alan; Fischer, Michael A; Avorn, Jerry; Asch, Steven M

2007-09-01

Increased use of generic medications conserves insurer and patient financial resources and may increase patient adherence. The objective of the study is to evaluate whether physician, patient, pharmacy benefit design, or pharmacy characteristics influence the likelihood that patients will use generic drugs Observational analysis of 2001-2003 pharmacy claims from a large health plan in the Western United States. We evaluated claims for 5,399 patients who filled a new prescription in at least 1 of 5 classes of chronic medications with generic alternatives. We identified patients initiated on generic drugs and those started on branded medications who switched to generic drugs in the subsequent year. We used generalized estimating equations to perform separate analyses assessing the relationship between independent variables and the probability that patients were initiated on or switched to generic drugs. Of the 5,399 new prescriptions filled, 1,262 (23.4%) were generics. Of those initiated on branded medications, 606 (14.9%) switched to a generic drug in the same class in the subsequent year. After regression adjustment, patients residing in high-income zip codes were more likely to initiate treatment with a generic than patients in low-income regions (RR = 1.29; 95% C.I. 1.04-1.60); medical subspecialists (RR = 0.82; 0.69-0.95) and obstetrician/gynecologists (RR = 0.81; 0.69-0.98) were less likely than generalist physicians to initiate generics. Pharmacy benefit design and pharmacy type were not associated with initiation of generic medications. However, patients were over 2.5 times more likely to switch from branded to generic medications if they were enrolled in 3-tier pharmacy plans (95% C.I. 1.12-6.09), and patients who used mail-order pharmacies were 60% more likely to switch to a generic (95% C.I. 1.18-2.30) after initiating treatment with a branded drug. Physician and patient factors have an important influence on generic drug initiation, with the patients who live in the poorest zip codes paradoxically receiving generic drugs least often. While tiered pharmacy benefit designs and mail-order pharmacies helped steer patients towards generic medications once the first prescription has been filled, they had little effect on initial prescriptions. Providing patients and physicians with information about generic alternatives may reduce costs and lead to more equitable care.

Factors influencing warfarin response in hospitalized patients

PubMed Central

Abdel-Aziz, Mahmoud I.; Ali, Mostafa A. Sayed; Hassan, Ayman K.M.; Elfaham, Tahani H.

2015-01-01

The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range. Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8 mg ± 0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p = .034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72–0.94]), being a male patient (OR, 2.86 [95% CI, 1.05–7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07–0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28–10.9]). Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered. PMID:26702259

Transcription coactivator SAYP combines chromatin remodeler Brahma and transcription initiation factor TFIID into a single supercomplex

PubMed Central

Vorobyeva, Nadezhda E.; Soshnikova, Nataliya V.; Nikolenko, Julia V.; Kuzmina, Julia L.; Nabirochkina, Elena N.; Georgieva, Sofia G.; Shidlovskii, Yulii V.

2009-01-01

Transcription activation by RNA polymerase II is a complicated process driven by combined, precisely coordinated action of a wide array of coactivator complexes, which carry out chromatin-directed activities and nucleate the assembly of the preinitiation complex on the promoter. Using various techniques, we have shown the existence of a stable coactivator supercomplex consisting of the chromatin-remodeling factor Brahma (SWI/SNF) and the transcription initiation factor TFIID, named BTFly (Brahma and TFIID in one assembly). The coupling of Brahma and TFIID is mediated by the SAYP factor, whose evolutionarily conserved activation domain SAY can directly bind to both BAP170 subunit of Brahma and TAF5 subunit of TFIID. The integrity of BTFly is crucial for its ability to activate transcription. BTFly is distributed genome-wide and appears to be a means of effective transcription activation. PMID:19541607

Sources of Life Strengths as Predictors of Late-Life Mortality and Survivorship

ERIC Educational Resources Information Center

Fry, Prem S.; Debats, Dominique L.

2006-01-01

The aim of the research was to determine within a single study the extent to which demographic factors, self-rated-health and psychosocial factors present the strongest risks or benefits to older adults' mortality in the course of a 5.9-year longitudinal follow-up. The initial sample of 732 individuals was drawn randomly from the registry listings…

Preadolescent Conduct Problems in Girls and Boys

ERIC Educational Resources Information Center

Messer, Julie; Goodman, Robert; Rowe, Richard; Meltzer, Howard; Maughan, Barbara

2006-01-01

Objective: To examine sex differences in correlates of disruptive behavior disorders (DBDs) in preadolescent children using indicators of a wide range of well-established risk factors for DBDs and outcomes 3 years after initial assessment. Method: Analyses were based on data for 5- to 10-year-olds (n = 5,913) from the British Child and Adolescent…

Trends and factors associated with early initiation of breastfeeding in Namibia: analysis of the Demographic and Health Surveys 2000-2013.

PubMed

Ndirangu, M N; Gatimu, S M; Mwinyi, H M; Kibiwott, D C

2018-05-16

Early initiation of breastfeeding (EIBF) lowers the risk for all-cause mortality in babies, including those with low birth weight. However, rates of neonatal mortality and delayed initiation of breastfeeding remain high in most low- and middle-income countries. This study aimed to assess the trends and factors associated with EIBF in Namibia from 2000 to 2013. An analysis of EIBF trends was conducted using data from three Namibia Demographic Health Surveys. The present sample included singleton children younger than 2-years from 2000 (n = 1655), 2006-2007 (n = 2152) and 2013 (n = 2062) surveys. Descriptive statistics were used to analyse respondents' demographic, socioeconomic and obstetric characteristics. Factors associated with EIBF were assessed using univariate analysis and further evaluated using multivariable logistic regression analysis. EIBF significantly decreased from 82.5% (confidence interval [CI]: 79.5-85.0) in 2000 to 74.9% (72.5-77.2) in 2013. Factors associated with EIBF in 2000 were urban residence (adjusted odds ratio 0.58, 95% CI: 0.36-0.93), poorer household wealth index (1.82, 1.05-3.17), lack of antenatal care (0.14, 0.03-0.81), small birth size (0.38, 0.24-0.63) and large birth size (0.51, 0.37-0.79). In 2013, factors associated with EIBF were maternal age of 15-19 years (2.28, 1.22-4.24), vaginal delivery (2.74, 1.90-3.93), married mothers (1.57, 1.16-2.14), delivery assistance from health professionals (3.67, 1.23-10.9) and birth order of fourth or above (1.52, 1.03-2.26). Namibia has experienced a declining trend in EIBF rates from 2000 to 2013. Factors associated with EIBF differed between 2000 and 2013. The present findings highlight the importance of continued commitment to addressing neonatal health challenges and strengthening implementation of interventions to increase EIBF in Namibia.

Factores predictores de inicio y cesación de tabaquismo en una cohorte de mujeres chilenas con 5,5 años de seguimiento

PubMed Central

Puschel, Klaus; Thompson, Beti; Olcay, Fabiola; Frreccio, Catterina

2014-01-01

Background Chilean women have one of the highest smoking prevalence in the world. Aim To estimate the main factors associated with smoking initiation and quitting among a cohort of adult women living in a low socioeconomic status area of Santiago, Chile. Material and methods A random population-based sample of 1,100 women, 18 years and older, were selected from a community located in the South East area of Santiago. Sociodemographic, as well as smoking, beliefs, behaviors, stages of change and nicotine addiction level were recorded during a personal interview. After an average follow-up period of 5.5 years, women were re-evaluated. Results Seventy-three percent of women completed the study. At baseline, 39% of women were smokers. At the end of the study, there was an absolute smoking rate reduction of 7.1% (p<0.001). The main variables associated with smoking initiation were younger age (Odds ratio (OR): 1.08, 95% confidence intervals (CI): 1.05–1.12), higher education level (OR: 1.2, 95% CI: 1.07–1.35), and having fewer children (OR: 1.3 95% CI: 1.01–1.66). Factors related with quitting were younger age of onset (OR: 1.06 95% CI: 1.02–1.1), higher level of nicotine dependence (OR: 4.22, 95% CI: 1.74–10.27), and higher perception of smoking addiction (OR: 4.34, 95% CI: 2–9.09). Stage of change was associated with smoking cessation but its effect was diluted after adjusting for the level of nicotine addiction. Conclusions Sociodemographic and family factors were the main variables related with initiation, whereas age of onset, belief of addiction, and nicotine dependence were the main factors related with cessation. Women with a high motivation for quitting should be evaluated for nicotine addiction level to define the best strategy for intervention (Rev Méd Chile 2009; 137: 1001–9). PMID:19915762

Functional Characterization of the Role of the N-terminal Domain of the c/Nip1 Subunit of Eukaryotic Initiation Factor 3 (eIF3) in AUG Recognition*

PubMed Central

Karásková, Martina; Gunišová, Stanislava; Herrmannová, Anna; Wagner, Susan; Munzarová, Vanda; Valášek, Leoš Shivaya

2012-01-01

In eukaryotes, for a protein to be synthesized, the 40 S subunit has to first scan the 5′-UTR of the mRNA until it has encountered the AUG start codon. Several initiation factors that ensure high fidelity of AUG recognition were identified previously, including eIF1A, eIF1, eIF2, and eIF5. In addition, eIF3 was proposed to coordinate their functions in this process as well as to promote their initial binding to 40 S subunits. Here we subjected several previously identified segments of the N-terminal domain (NTD) of the eIF3c/Nip1 subunit, which mediates eIF3 binding to eIF1 and eIF5, to semirandom mutagenesis to investigate the molecular mechanism of eIF3 involvement in these reactions. Three major classes of mutant substitutions or internal deletions were isolated that affect either the assembly of preinitiation complexes (PICs), scanning for AUG, or both. We show that eIF5 binds to the extreme c/Nip1-NTD (residues 1–45) and that impairing this interaction predominantly affects the PIC formation. eIF1 interacts with the region (60–137) that immediately follows, and altering this contact deregulates AUG recognition. Together, our data indicate that binding of eIF1 to the c/Nip1-NTD is equally important for its initial recruitment to PICs and for its proper functioning in selecting the translational start site. PMID:22718758

Comparing Factor, Class, and Mixture Models of Cannabis Initiation and DSM Cannabis Use Disorder Criteria, Including Craving, in the Brisbane Longitudinal Twin Study

PubMed Central

Kubarych, Thomas S.; Kendler, Kenneth S.; Aggen, Steven H.; Estabrook, Ryne; Edwards, Alexis C.; Clark, Shaunna L.; Martin, Nicholas G.; Hickie, Ian B.; Neale, Michael C.; Gillespie, Nathan A.

2014-01-01

Accumulating evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying factor. However, it remains possible that models with additional factors, or latent class models or hybrid models, may better explain the data. Using structured interviews, 626 adult male and female twins provided complete data on symptoms of cannabis abuse and dependence, plus a craving criterion. We compared latent factor analysis, latent class analysis, and factor mixture modeling using normal theory marginal maximum likelihood for ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5 craving loads onto a general factor. When compared with latent class and mixture models, factor models provided a better fit to the data. When conditioned on initiation and cannabis use, the association between criteria for abuse, dependence, withdrawal, and craving were best explained by two correlated latent factors for males and females: a general risk factor to CUD and a factor capturing the symptoms of social and occupational impairment as a consequence of frequent use. Secondary analyses revealed a modest increase in the prevalence of DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded that, in addition to a general factor with loadings on cannabis use and symptoms of abuse, dependence, withdrawal, and craving, a second clinically relevant factor defined by features of social and occupational impairment was also found for frequent cannabis use. PMID:24588857

Electronics Controls Assessment for the PATRIOT Air Conditioner System. Revision

DTIC Science & Technology

1986-04-28

electronic controls in Army Air Conditioner Systems. This assessment used criteria which included: cost (initial and life cycle), efficiency, weight ...each of the twelve selected controllers as to cost and size Iqualifications was accomplished b) assigning reasonable weight factors according to the...following table:I COST SIZE5 WEIGHT FACTOR (Per Unit Price Range) (Volumetric Range) 1 Under $1000 Under 700 in 3 3 $1000 to $1500 700-1000 in 3 5 $1501

Early childhood predictors of age of initiation to use of cannabis: a birth prospective study.

PubMed

Hayatbakhsh, Reza; Williams, Gail M; Bor, William; Najman, Jake M

2013-05-01

Early age of cannabis use predicts subsequent illicit drug abuse and other psychosocial problems. Identification of factors associated with early cannabis use may contribute to the development of preventive interventions. This study aimed to examine the early life predictors of age of initiation to cannabis. Data were from Mater Hospital and University of Queensland Study of Pregnancy, a population-based prospective birth cohort study. Participants were a cohort of 3488 young adults who self-reported frequency and age of onset of cannabis use at the 21 year follow up. Of 3488 young adults, 48.9% (51.8% men and 46.4% women) reported having ever used cannabis. For those who had ever used cannabis, age of onset had mean and median of 15.8 and 16.0 years, respectively. In multivariate analysis child's gender, change in maternal marital status, quality of marital relationship, maternal cigarette smoking and alcohol consumption and maternal depression when the child was 5 years statistically significantly predicted age of initiation to cannabis use. The present study explores the impact of early childhood factors associated with age of onset of cannabis use. It is suggested that the family environment within which children are reared, including factors such as parents' marital circumstances, has a major influence on initiation to cannabis use in adolescence. Research is needed to disentangle the pathways of association between these early life factors and early initiation to use of cannabis. © 2012 Australasian Professional Society on Alcohol and other Drugs.

Early and Late Recurrent Epistaxis Admissions: Patterns of Incidence and Risk Factors.

PubMed

Cohen, Oded; Shoffel-Havakuk, Hagit; Warman, Meir; Tzelnick, Sharon; Haimovich, Yaara; Kohlberg, Gavriel D; Halperin, Doron; Lahav, Yonatan

2017-09-01

Objective Epistaxis is a common complaint, yet few studies have focused on the incidence and risk factors of recurrent epistaxis. Our objective was to determine the patterns of incidence and risk factors for recurrent epistaxis admission (REA). Study Design Case series with chart review. Settings Single academic center. Subjects and Methods The medical records of patients admitted for epistaxis between 1999 and 2015 were reviewed. The follow-up period was defined as 3 years following initial admission. REAs were categorized as early (30 days) and late (31 days to 3 years) following initial admission. Logistic regression was used to identify potential predictors of REAs. Results A total of 653 patients were included. Eighty-six patients (14%) had REAs: 48 (7.5%) early and 38 (6.5%) late. Nonlinear incidence curve was demonstrated for both early and late REAs. Based on logistic regression, prior nasal surgery and anemia were independent risk factors for early REAs. According to multivariate analysis, thrombocytopenia was significantly associated with late REAs. Conclusion Early and late REAs demonstrate different risk predictors. Knowledge of such risk factors may help in risk stratification for this selected group of patients. All patients at risk should be advised on possible preventive measures. Patients at risk for early REA may benefit from a more proactive approach.

How does low temperature coupled with different pressures affect initiation mechanisms and subsequent decompositions in nitramine explosive HMX?

PubMed

Wu, Qiong; Xiong, Guolin; Zhu, Weihua; Xiao, Heming

2015-09-21

We have performed ab initio molecular dynamics simulations to study coupling effects of temperature (534-873 K) and pressure (1-20 GPa) on the initiation mechanisms and subsequent chemical decompositions of nitramine explosive 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). A new initiation decomposition mechanism of HMX was found to be the unimolecular C-H bond breaking, and this mechanism was independent of the coupling effects of different temperatures and pressures. The formed hydrogen radicals could promote subsequent decompositions of HMX. Subsequent decompositions were very sensitive to the pressure at low temperatures (534 and 608 K), while the temperature became the foremost factor that affected the decomposition at a high temperature (873 K) instead of the pressure. Our study may provide a new insight into understanding the coupling effects of the temperature and pressure on the initiation decomposition mechanisms of nitramine explosives.

Testing and screening for chlamydia in general practice: a cross-sectional analysis.

PubMed

Thomson, Allison; Morgan, Simon; Henderson, Kim; Tapley, Amanda; Spike, Neil; Scott, John; van Driel, Mieke; Magin, Parker

2014-12-01

Chlamydia screening is widely advocated. General practice registrars are an important stage of clinical behaviour development. This study aimed to determine rates of, and factors associated with, registrars' chlamydia testing including asymptomatic screening. A cross-sectional analysis of data from Registrars Clinical Encounters in Training (ReCEnT), a cohort study of registrars' consultations. Registrars record details of 60 consecutive consultations in each GP-term of training. Outcome factors were chlamydia testing, asymptomatic screening and doctor-initiated screening. Testing occurred in 2.5% of 29,112 consultations (398 registrars) and in 5.8% of patients aged 15-25. Asymptomatic screening comprised 47.5% of chlamydia tests, and 55.6% of screening tests were doctor-initiated. Chlamydia testing was associated with female gender of doctor and patient, younger patient age, and patients new to doctor or practice. Asymptomatic screening was associated with practices where patients incur no fees, and in patients new to doctor or practice. Screening of female patients was more often doctor-initiated. GP registrars screen for chlamydia disproportionately in younger females and new patients. Our findings highlight potential opportunities to improve uptake of screening for chlamydia, including targeted education and training for registrars, campaigns targeting male patients, and addressing financial barriers to accessing screening services. © 2014 Public Health Association of Australia.

Effect of a prenatal nutritional intervention program on initiation and duration of breastfeeding.

PubMed

Léger-Leblanc, Gisèle; Rioux, France M

2008-01-01

To evaluate initiation and duration of breastfeeding of infants born to mothers who participated in the Early Childhood Initiative (ECI) program. Factors affecting the initiation and the early cessation of breastfeeding were also explored. Twenty-five pregnant women participating in the ECI program completed this prospective study. At 36 weeks' gestation, a questionnaire was administered to assess socioeconomic status, intention to breastfeed and breastfeeding experience. When the infants were three and six months of age, feeding practices were assessed with a questionnaire. The breastfeeding initiation rate was 62.5%. At one and three months postpartum, exclusive breastfeeding rates were 39% and 4%, respectively. At six months, none of the women was exclusively breastfeeding. Primiparity, prenatal classes, having been breastfed and intention to breastfeed at 36 weeks' gestation were positively associated with breastfeeding initiation. Father's education, intention to breastfeed at 36 weeks' gestation, no water or formula given to the infant during hospitalization and higher maternal hemoglobin level at 36 weeks' gestation were positively associated with the duration of breastfeeding. The rate of initiation and duration of breastfeeding for ECI participants were low. To achieve successful interventions, it is important to target modifiable factors known to influence the initiation and duration of breastfeeding within this population.

Quantitative studies of mRNA recruitment to the eukaryotic ribosome.

PubMed

Fraser, Christopher S

2015-07-01

The process of peptide bond synthesis by ribosomes is conserved between species, but the initiation step differs greatly between the three kingdoms of life. This is illustrated by the evolution of roughly an order of magnitude more initiation factor mass found in humans compared with bacteria. Eukaryotic initiation of translation is comprised of a number of sub-steps: (i) recruitment of an mRNA and initiator methionyl-tRNA to the 40S ribosomal subunit; (ii) migration of the 40S subunit along the 5' UTR to locate the initiation codon; and (iii) recruitment of the 60S subunit to form the 80S initiation complex. Although the mechanism and regulation of initiation has been studied for decades, many aspects of the pathway remain unclear. In this review, I will focus discussion on what is known about the mechanism of mRNA selection and its recruitment to the 40S subunit. I will summarize how the 43S preinitiation complex (PIC) is formed and stabilized by interactions between its components. I will discuss what is known about the mechanism of mRNA selection by the eukaryotic initiation factor 4F (eIF4F) complex and how the selected mRNA is recruited to the 43S PIC. The regulation of this process by secondary structure located in the 5' UTR of an mRNA will also be discussed. Finally, I present a possible kinetic model with which to explain the process of mRNA selection and recruitment to the eukaryotic ribosome. Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Should particle size analysis data be combined with EPA approved sampling method data in the development of AP-42 emission factors?

USDA-ARS?s Scientific Manuscript database

A cotton ginning industry-supported project was initiated in 2008 and completed in 2013 to collect additional data for U.S. Environmental Protection Agency’s (EPA) Compilation of Air Pollution Emission Factors (AP-42) for PM10 and PM2.5. Stack emissions were collected using particle size distributio...

Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.

PubMed

Zhang, Chuanzhao; Zhi, Wanqing Iris; Lu, Haiquan; Samanta, Debangshu; Chen, Ivan; Gabrielson, Edward; Semenza, Gregg L

2016-10-04

Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification. Although hypoxia induced the BCSC phenotype in all breast-cancer cell lines analyzed, it did so through variable induction of pluripotency factors and ALKBH5 or ZNF217. However, in every breast cancer line, the hypoxic induction of pluripotency factor and ALKBH5 or ZNF217 expression was HIF-dependent. Immunohistochemistry revealed that expression of HIF-1α and ALKBH5 was concordant in all human breast cancer biopsies analyzed. ALKBH5 knockdown in MDA-MB-231 breast cancer cells significantly decreased metastasis from breast to lungs in immunodeficient mice. Thus, HIFs stimulate pluripotency factor expression and BCSC specification by negative regulation of RNA methylation.

Canonical Initiation Factor Requirements of the Myc Family of Internal Ribosome Entry Segments▿ †

PubMed Central

Spriggs, Keith A.; Cobbold, Laura C.; Jopling, Catherine L.; Cooper, Rebecca E.; Wilson, Lindsay A.; Stoneley, Mark; Coldwell, Mark J.; Poncet, Didier; Shen, Ya-Ching; Morley, Simon J.; Bushell, Martin; Willis, Anne E.

2009-01-01

Initiation of protein synthesis in eukaryotes requires recruitment of the ribosome to the mRNA and its translocation to the start codon. There are at least two distinct mechanisms by which this process can be achieved; the ribosome can be recruited either to the cap structure at the 5′ end of the message or to an internal ribosome entry segment (IRES), a complex RNA structural element located in the 5′ untranslated region (5′-UTR) of the mRNA. However, it is not well understood how cellular IRESs function to recruit the ribosome or how the 40S ribosomal subunits translocate from the initial recruitment site on the mRNA to the AUG initiation codon. We have investigated the canonical factors that are required by the IRESs found in the 5′-UTRs of c-, L-, and N-myc, using specific inhibitors and a tissue culture-based assay system, and have shown that they differ considerably in their requirements. The L-myc IRES requires the eIF4F complex and the association of PABP and eIF3 with eIF4G for activity. The minimum requirements of the N- and c-myc IRESs are the C-terminal domain of eIF4G to which eIF4A is bound and eIF3, although interestingly this protein does not appear to be recruited to the IRES RNA via eIF4G. Finally, our data show that all three IRESs require a ternary complex, although in contrast to c- and L-myc IRESs, the N-myc IRES has a lesser requirement for a ternary complex. PMID:19124605

Psychosocial factors associated with early initiation and frequency of antenatal care (ANC) visits in a rural and urban setting in South Africa: a cross-sectional survey.

PubMed

Muhwava, Lorrein Shamiso; Morojele, Neo; London, Leslie

2016-01-25

Late booking and infrequent antenatal care (ANC) are common but avoidable patient-related risk factors for maternal deaths in South Africa. The aim of the study was to examine the association of psychosocial factors with early initiation of ANC and adequate frequency of attendance of ANC clinics among women in an urban and rural location in South Africa. Data from a 2006 cross-sectional household survey of 363 women from the rural Western Cape and 466 women from urban Gauteng provinces of South Africa for risk of alcohol-exposed pregnancy were analysed. We examined associations between psychosocial variables (self-esteem, cultural influences, religiosity, social capital, social support, pregnancy desire (wanted versus unwanted pregnancy), partner characteristics and mental health) and both early ANC first visit (before 16 weeks) and adequate frequency of ANC visits (4 or more visits) for respondents' last pregnancy. Overall prevalence among urban women of early ANC initiation was 46% and 84% for adequate ANC frequency. Overall prevalence among rural women of early ANC initiation was 45% and 78% for adequate ANC frequency. After adjusting for clustering, psychosocial factors associated with early ANC initiation in the urban site were being employed (OR 1.6; 95% CI 1.0-2.5) and wanted pregnancy (OR 1.8; 95% CI 1.1-3.0). For the rural site, early ANC initiation was significantly associated with being married (OR 1.93; 95% CI 1.0-3.6) but inversely associated with high religiosity (OR 0.5; 95% CI 0.3-0.8). Adequate frequency of ANC attendance in the rural site was associated with wanted pregnancy (OR 4.2; 95% CI 1.9-9.3) and the father of the child being present in the respondent's life (OR 3.0; 95% CI 1.0-9.0) but inversely associated with having a previous miscarriage (OR 0.4; 95% CI 0.2-0.8). There were no significant associations between adequate ANC attendance and the psychosocial factors in the urban site. The majority of women from both sites attended ANC frequently but less than 50% initiated ANC before the recommended 16 weeks gestational age. Interventions to reduce prevalence of late ANC booking and inadequate ANC attendance should engage religious leaders, address unintended pregnancy through family planning education and involve male partners in women's reproductive health.

Socioeconomic thresholds that affect use of customary fisheries management tools.

PubMed

Cinner, Joshua E; Sutton, Stephen G; Bond, Trevor G

2007-12-01

Customary forms of resource management, such as taboos, have received considerable attention as a potential basis for conservation initiatives in the Indo-Pacific. Yet little is known about how socioeconomic factors influence the ability of communities to use customary management practices and whether socioeconomic transformations within communities will weaken conservation initiatives with a customary foundation. We used a comparative approach to examine how socioeconomic factors may influence whether communities use customary fisheries management in Papua New Guinea. We examined levels of material wealth (modernization), dependence on marine resources, population, and distance to market in 15 coastal communities. We compared these socioeconomic conditions in 5 communities that used a customary method of closing their fishing ground with 10 communities that did not use this type of management. There were apparent threshold levels of dependence on marine resources, modernization, distance to markets (<16.5 km), and population (>600 people) beyond which communities did not use customary fisheries closures. Nevertheless, economic inequality, rather than mean modernization levels seemed to influence the use of closures. Our results suggest that customary management institutions are not resilient to factors such as population growth and economic modernization. If customary management is to be used as a basis for modern conservation initiatives, cross-scale institutional arrangements such as networks and bridging organizations may be required to help filter the impacts of socioeconomic transformations.

Clustering of chronic disease risk factors with tobacco smoking habits among adults in the work place in Sousse, Tunisia.

PubMed

Sonia, Hmad; Jihene, Maatoug; Imed, Harrabi; Rim, Ghammem; Mylene, Belkacem; Mounir, Saadi; Souad, Amimi; Khaoula, Knani; Mustafa, Al'Absi; Harry, Lando; Najib, Mrizak; Hassen, Ghannem

2016-01-01

The aim of our study was to explore the major non-communicable risk factors (unhealthy diet, sedentarily, alcohol consumption) of smokers and nonsmokers in workplaces. A cross-sectional study was derived from an initial assessment in workplaces which was part of a community-based intervention to prevent chronic disease risk factors conducted in 2009 in the region of Sousse, Tunisia. The surveyed subjects were employees in six factories spread across three delegations in the region. Overall, 1770 of 2250 employees participated in the assessment. In this study, the clustering of non-communicable diseases risk factors with smoking habits was made only for male employees including in this study 1099 among 2250. Data were collected at worksites by a questionnaire, via interview or self-report. The main items assessed socio-demographics characteristics, smoking status, eating habits, level of physical activity and alcohol use of the participants. The percentage of male smokers was 54.0%(n=594). Their average age of daily smoking initiation was 19.22 (±4.24 years). The percentage of male smokers consuming 5 fruits and vegetables per day was significantly lower than nonsmokers (57.2% vs 63.5%, p=0.04). The proportion of male smokers consuming alcohol was about three times that of nonsmokers (16.5% vs 5.8%, p=0.001). The proportion of male employees who agree with anti-smoking laws in work places was higher for nonsmokers than for smokers. A strong association existed between smoking and risky lifestyles factors in the work place. Such findings are potentially useful in directing intervention efforts regarding smoking cessation in occupational settings.

Clustering of chronic disease risk factors with tobacco smoking habits among adults in the work place in Sousse, Tunisia

PubMed Central

Sonia, Hmad; Jihene, Maatoug; Imed, Harrabi; Rim, Ghammem; Mylene, Belkacem; Mounir, Saadi; Souad, Amimi; Khaoula, Knani; Mustafa, Al’Absi; Harry, Lando; Najib, Mrizak; Hassen, Ghannem

2016-01-01

Introduction The aim of our study was to explore the major non-communicable risk factors (unhealthy diet, sedentarily, alcohol consumption) of smokers and nonsmokers in workplaces. Methods A cross-sectional study was derived from an initial assessment in workplaces which was part of a community-based intervention to prevent chronic disease risk factors conducted in 2009 in the region of Sousse, Tunisia. The surveyed subjects were employees in six factories spread across three delegations in the region. Overall, 1770 of 2250 employees participated in the assessment. In this study, the clustering of non-communicable diseases risk factors with smoking habits was made only for male employees including in this study 1099 among 2250. Data were collected at worksites by a questionnaire, via interview or self-report. The main items assessed socio-demographics characteristics, smoking status, eating habits, level of physical activity and alcohol use of the participants. Results The percentage of male smokers was 54.0%(n=594). Their average age of daily smoking initiation was 19.22 (±4.24 years). The percentage of male smokers consuming 5 fruits and vegetables per day was significantly lower than nonsmokers (57.2% vs 63.5%, p=0.04). The proportion of male smokers consuming alcohol was about three times that of nonsmokers (16.5% vs 5.8%, p=0.001). The proportion of male employees who agree with anti-smoking laws in work places was higher for nonsmokers than for smokers. Conclusion A strong association existed between smoking and risky lifestyles factors in the work place. Such findings are potentially useful in directing intervention efforts regarding smoking cessation in occupational settings. PMID:27800075

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

PubMed

Zappitelli, Michael; Goldstein, Stuart L; Symons, Jordan M; Somers, Michael J G; Baum, Michelle A; Brophy, Patrick D; Blowey, Douglas; Fortenberry, James D; Chua, Annabelle N; Flores, Francisco X; Benfield, Mark R; Alexander, Steven R; Askenazi, David; Hackbarth, Richard; Bunchman, Timothy E

2008-12-01

Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. Retrospective database study. Multicenter study in pediatric critical care units. Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. None. Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Sport and scholastic factors in relation to smoking and smoking initiation in older adolescents: a prospective cohort study in Bosnia and Herzegovina.

PubMed

Sekulic, Damir; Sisic, Nedim; Terzic, Admir; Jasarevic, Indira; Ostojic, Ljerka; Pojskic, Haris; Zenic, Natasa

2017-03-22

Sport and scholastic factors are known to be associated with cigarette smoking in adolescence, but little is known about the causality of this association. The aim of this study was to prospectively explore the relationships of different sport and scholastic factors with smoking prevalence initiation in older adolescents from Bosnia and Herzegovina. In this 2-year prospective cohort study, there were 872 adolescent participants (16 years at baseline; 46% females). The study consisted of baseline tests at the beginning of the third year (September 2013) and follow-up at the end of the fourth year of high school (late May to early June 2015). The independent variables were scholastic and sport-related factors. The dependent variables were (1) smoking at baseline, (2) smoking at follow-up and (3) smoking initiation over the course of the study. Logistic regressions controlling for age, gender and socioeconomic status were applied to define the relationships between independent and dependent variables. School absence at the baseline study was a significant predictor of smoking initiation during the course of the study (OR 1.4, 95% CI 1.1 to 1.8). Those who reported quitting sports at baseline showed an increased risk of smoking at the end of the study (OR 1.4, 95% CI 1.1 to 2.0) and of smoking initiation (OR 1.8, 95% CI 1.3 to 2.0). Adolescents who reported lower competitive achievements in sport were at a higher risk of (1) smoking at baseline (OR 1.5, 95% CI 1.1 to 2.1), (2) smoking at follow-up (OR 1.5, 95% CI 1.1 to 2.1) and (3) smoking initiation (OR 1.6, 95% CI 1.1 to 2.6). In developing accurate antismoking public health policies for older adolescents, the most vulnerable groups should be targeted. The results showed that most participants initiated smoking before 16 years of age. Therefore, further investigations should evaluate the predictors of smoking in younger ages. 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/.

Identification of controlling factors for the initiation of corrosion of fresh concrete sewers.

PubMed

Jiang, Guangming; Sun, Xiaoyan; Keller, Jurg; Bond, Philip L

2015-09-01

The development of concrete corrosion in new sewer pipes undergoes an initiation process before reaching an active corrosion stage. This initiation period is assumed to last several months to years but the key factors affecting the process, and its duration, are not well understood. This study is therefore focused on this initial stage of the corrosion process and the effect of key environmental factors. Such knowledge is important for the effective management of corrosion in new sewers, as every year of life extension of such systems has a very high financial benefit. This long-term (4.5 year) study has been conducted in purpose-built corrosion chambers that closely simulated the sewer environment, but with control of three key environmental factors being hydrogen sulfide (H2S) gas phase concentration, relative humidity and air temperature. Fresh concrete coupons, cut from an industry-standard sewer pipe, were exposed to the corrosive conditions in the chambers, both in the gas phase and partially submerged in wastewater. A total of 36 exposure conditions were investigated to determine the controlling factors by regular retrieval of concrete coupons for detailed analysis of surface pH, sulfur compounds (elemental sulfur and sulfate) and concrete mass loss. Corrosion initiation times were thus determined for different exposure conditions. It was found that the corrosion initiation time of both gas-phase and partially-submerged coupons was positively correlated with the gas phase H2S concentration, but only at levels of 10 ppm or below, indicating that sulfide oxidation rate rather than the H2S concentration was the limiting factor during the initiation stage. Relative humidity also played a role for the corrosion initiation of the gas-phase coupons. However, the partially-submerged coupons were not affected by humidity as these coupons were in direct contact with the sewage and hence did have sufficient moisture to enable the microbial processes to proceed. The corrosion initiation time was also shortened by higher gas temperature due to its positive impact on reaction kinetics. These findings provide real opportunities for pro-active sewer asset management with the aim to delay the on-set of the corrosion processes, and hence extend the service life of sewers, through improved prediction and optimization capacity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age at smoking initiation and self-rated health among second grade high school boys and girls in Scania, Sweden, a cross-sectional study.

PubMed

Hansen, Kristina; Lindström, Martin; Rosvall, Maria

2015-11-18

Smoking is usually initiated early in life and most adult regular smokers have started smoking before 18 years of age. A younger age at smoking initiation is associated with risk taking behaviours and worse health outcomes regarding psychological and somatic conditions, suggested to be caused by exposure during critical developmental periods. The present study aims to investigate self-rated health among second grade high school boys and girls related to age at smoking initiation (<14 years of age and ≥ 14 years of age) among current and former smokers, compared to never smokers. Data was derived from the Scania public health survey among children and adolescents in 2012. The study was cross-sectional with retrospective information about first time cigarette smoking experiences among 3245 boys and 3434 girls in second grade of high school. Self-rated health was assessed with the question "How do you rate your general health". Associations of age at smoking initiation, current smoking status and poor self-rated health were investigated with logistic regression models. Crude odds ratios of poor self-rated health were increased for all smoking groups compared to never smokers. Former smoking boys and currently smoking girls with early smoking initiation had the highest odds ratios of poor self-rated health, with odds ratios (OR) 2.4 (95 % confidence interval (CI): 1.5-3.7) and OR 2.9 (95 % CI: 2.3-3.6), respectively. After adjustments for sociodemographic factors, health-related behaviours, psychosocial factors, weight and functional disabilities, the results were attenuated, but remained statistically significant regarding former and current smoking boys with early smoking initiation, OR 2.0 (95 % CI: 1.1-3.7) and OR 1.7 (95 % CI: 1.1-2.4) and for current smoking girls with early and later smoking initiation, OR 2.1 (95 % CI: 1.5-2.8) and OR 1.5 (95 % CI: 1.1-2.0). Boys and girls in second grade of high school with early smoking initiation reported poorer self-rated health than later initiators and never smokers. Poorer self-rated health persisted also after smoking cessation among early initiating boys. Further studies are needed to understand the adverse health effects associated with timing of smoking initiation.

Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea

PubMed Central

Graf, Michael; Blaby, Ian K.; Makkay, Andrea M.; Starosta, Agata L.; Papke, R. Thane; Oshima, Tairo; Wilson, Daniel N.

2016-01-01

Translation initiation factor 5A (IF5A) is essential and highly conserved in Eukarya (eIF5A) and Archaea (aIF5A). The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced in Haloferax volcanii in minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification in Hfx. volcanii that was experimentally tested. Analysis of aIF5A from Hfx. volcanii by LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene (HVO_1958) in agmatine synthesis. The agmatinase-like gene (HVO_2299) was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS) from S. cerevisiae was shown to transfer 4-aminobutyl moiety from spermidine to aIF5A from Hfx. volcanii in vitro. However, at least under conditions tested, this transfer was not observed with the Hfx. volcanii DHS. Furthermore, the growth of Hfx. volcanii was not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis in Hfx. volcanii that differs from the canonical eukaryotic pathway, paving the way for further studies. PMID:28053595

Two-Stage Design Method for Enhanced Inductive Energy Transmission with Q-Constrained Planar Square Loops.

PubMed

Eteng, Akaa Agbaeze; Abdul Rahim, Sharul Kamal; Leow, Chee Yen; Chew, Beng Wah; Vandenbosch, Guy A E

2016-01-01

Q-factor constraints are usually imposed on conductor loops employed as proximity range High Frequency Radio Frequency Identification (HF-RFID) reader antennas to ensure adequate data bandwidth. However, pairing such low Q-factor loops in inductive energy transmission links restricts the link transmission performance. The contribution of this paper is to assess the improvement that is reached with a two-stage design method, concerning the transmission performance of a planar square loop relative to an initial design, without compromise to a Q-factor constraint. The first stage of the synthesis flow is analytical in approach, and determines the number and spacing of turns by which coupling between similar paired square loops can be enhanced with low deviation from the Q-factor limit presented by an initial design. The second stage applies full-wave electromagnetic simulations to determine more appropriate turn spacing and widths to match the Q-factor constraint, and achieve improved coupling relative to the initial design. Evaluating the design method in a test scenario yielded a more than 5% increase in link transmission efficiency, as well as an improvement in the link fractional bandwidth by more than 3%, without violating the loop Q-factor limit. These transmission performance enhancements are indicative of a potential for modifying proximity HF-RFID reader antennas for efficient inductive energy transfer and data telemetry links.

Natural Course of Initially Non-Operated Cases of Acute Subdural Hematoma : The Risk Factors of Hematoma Progression

PubMed Central

Son, Seong; Lee, Sang Gu; Kim, Eun Young; Park, Chan Woo; Kim, Woo Kyung

2013-01-01

Objective The objectives of the present study were to characterize the natural course of initially non-operated traumatic acute subdural hematoma (ASDH) and to identify the risk factors of hematoma progression. Methods Retrospective analysis was performed using sequential computed tomography (CT) images maintained in a prospective observational database containing 177 ASDH cases treated from 2005 to 2011. Patients were allocated to four groups as followings; 136 (76.8%) patients to the spontaneous resolution group, 12 (6.8%) who underwent operation between 4 hours and 7 days to the rapid worsening group (RWG), 24 (13.6%) who experienced an increase of hematoma and that underwent operation between 7 and 28 days to the subacute worsening group (SWG), and 5 (2.8%) who developed delayed aggravation requiring surgery from one month after onset to the delayed worsening group (DWG). Groups were compared with respect to various factors. Results No significant intergroup difference was found with respect to age, mechanism of injury, or initial Glasgow Coma Scale. The presence of combined cerebral contusion or subarachnoid hemorrhage was found to be a significant prognostic factor. Regarding CT findings, mixed density was common in the RWG and the SWG. Midline shifting, hematoma thickness, and numbers of CT slices containing hematoma were significant prognostic factors of the RWG and the SWG. Brain atrophy was more severe in the SWG and the DWG. Conclusion A large proportion of initially non-operated ASDHs worsen in the acute or subacute phase. Patients with risk factors should be monitored carefully for progression by repeat CT imaging. PMID:24278650

Rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk.

PubMed

Kim, Eunjoo; Davidson, Laurie A; Zoh, Roger S; Hensel, Martha E; Salinas, Michael L; Patil, Bhimanagouda S; Jayaprakasha, Guddadarangavvanahally K; Callaway, Evelyn S; Allred, Clinton D; Turner, Nancy D; Weeks, Brad R; Chapkin, Robert S

2016-11-10

The majority of colon tumors are driven by aberrant Wnt signaling in intestinal stem cells, which mediates an efficient route toward initiating intestinal cancer. Natural lipophilic polyphenols and long-chain polyunsaturated fatty acids (PUFAs) generally suppress Wnt- and NF-κB- (nuclear factor-κ light-chain enhancer of activated B-cell) related pathways. However, the effects of these extrinsic agents on colonic leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5 + ) stem cells, the cells of origin of colon cancer, have not been documented to date. Therefore, we examined the effect of n-3 PUFA and polyphenol (curcumin) combination on Lgr5 + stem cells during tumor initiation and progression in the colon compared with an n-6 PUFA-enriched control diet. Lgr5-EGFP-IRES- creERT2 knock-in mice were fed diets containing n-6 PUFA (control), n-3 PUFA, n-6 PUFA+curcumin or n-3 PUFA+curcumin for 3 weeks, followed by 6 azoxymethane (AOM) injections, and terminated 17 weeks after the last injection. To further elucidate the effects of the dietary bioactives at the tumor initiation stage, Lgr5 + stem cells were also assessed at 12 and 24 h post AOM injection. Only n-3 PUFA+curcumin feeding reduced nuclear β-catenin in aberrant crypt foci (by threefold) compared with control at the progression time point. n-3 PUFA+curcumin synergistically increased targeted apoptosis in DNA-damaged Lgr5 + stem cells by 4.5-fold compared with control at 12 h and maximally reduced damaged Lgr5 + stem cells at 24 h, down to the level observed in saline-treated mice. Finally, RNAseq analysis indicated that p53 signaling in Lgr5 + stem cells from mice exposed to AOM was uniquely upregulated only following n-3 PUFA+curcumin cotreatment. These novel findings demonstrate that Lgr5 + stem cells are uniquely responsive to external dietary cues following the induction of DNA damage, providing a therapeutic strategy for eliminating damaged Lgr5 + stem cells to reduce colon cancer initiation.

Rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk

PubMed Central

Kim, Eunjoo; Davidson, Laurie A; Zoh, Roger S; Hensel, Martha E; Salinas, Michael L; Patil, Bhimanagouda S; Jayaprakasha, Guddadarangavvanahally K; Callaway, Evelyn S; Allred, Clinton D; Turner, Nancy D; Weeks, Brad R; Chapkin, Robert S

2016-01-01

The majority of colon tumors are driven by aberrant Wnt signaling in intestinal stem cells, which mediates an efficient route toward initiating intestinal cancer. Natural lipophilic polyphenols and long-chain polyunsaturated fatty acids (PUFAs) generally suppress Wnt- and NF-κB- (nuclear factor-κ light-chain enhancer of activated B-cell) related pathways. However, the effects of these extrinsic agents on colonic leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5+) stem cells, the cells of origin of colon cancer, have not been documented to date. Therefore, we examined the effect of n-3 PUFA and polyphenol (curcumin) combination on Lgr5+ stem cells during tumor initiation and progression in the colon compared with an n-6 PUFA-enriched control diet. Lgr5-EGFP-IRES-creERT2 knock-in mice were fed diets containing n-6 PUFA (control), n-3 PUFA, n-6 PUFA+curcumin or n-3 PUFA+curcumin for 3 weeks, followed by 6 azoxymethane (AOM) injections, and terminated 17 weeks after the last injection. To further elucidate the effects of the dietary bioactives at the tumor initiation stage, Lgr5+ stem cells were also assessed at 12 and 24 h post AOM injection. Only n-3 PUFA+curcumin feeding reduced nuclear β-catenin in aberrant crypt foci (by threefold) compared with control at the progression time point. n-3 PUFA+curcumin synergistically increased targeted apoptosis in DNA-damaged Lgr5+ stem cells by 4.5-fold compared with control at 12 h and maximally reduced damaged Lgr5+ stem cells at 24 h, down to the level observed in saline-treated mice. Finally, RNAseq analysis indicated that p53 signaling in Lgr5+ stem cells from mice exposed to AOM was uniquely upregulated only following n-3 PUFA+curcumin cotreatment. These novel findings demonstrate that Lgr5+ stem cells are uniquely responsive to external dietary cues following the induction of DNA damage, providing a therapeutic strategy for eliminating damaged Lgr5+ stem cells to reduce colon cancer initiation. PMID:27831561

Relationship between personality traits and vocational choice.

PubMed

Garcia-Sedeño, Manuel; Navarro, Jose I; Menacho, Inmaculada

2009-10-01

Summary.-The relationship between occupational preferences and personality traits was examined. A randomly chosen sample of 735 students (age range = 17 to 23 years; 50.5% male) in their last year of high school participated in this study. Participants completed Cattell's Sixteen Personality Factor-5 Questionnaire (16PF-5 Questionnaire) and the Kuder-C Professional Tendencies Questionnaire. Initial hierarchical cluster analysis categorized the participants into two groups by Kuder-C vocational factors: one showed a predilection for scientific or technological careers and the other a bias toward the humanities and social sciences. Based on these groupings, differences in 16PF-5 personality traits were analyzed and differences associated with three first-order personality traits (warmth, dominance, and sensitivity), three second-order factors (extraversion, control, and independence), and some areas of professional interest (mechanical, arithmetical artistic, persuasive, and welfare) were identified. The data indicated that there was congruency between personality profiles and vocational interests.

Reproductive Risk Factors and Coronary Heart Disease in the Women’s Health Initiative Observational Study

PubMed Central

Parikh, Nisha I.; Jeppson, Rebecca P.; Berger, Jeffrey S.; Eaton, Charles B.; Kroenke, Candyce H.; LeBlanc, Erin S.; Lewis, Cora E.; Loucks, Eric B.; Parker, Donna R.; Rillamas-Sun, Eileen; Ryckman, Kelli K; Waring, Molly E.; Schenken, Robert S.; Johnson, Karen C; Edstedt-Bonamy, Anna-Karin; Allison, Matthew A.; Howard, Barbara V.

2016-01-01

Background Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk, however their contribution to CHD risk stratification is uncertain. Methods and Results In the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥ 1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C-statistic, net reclassification index (or NRI with risk categories of <5%, 5–<10%, and ≥10% 10-year risk of CHD) and integrated discriminatory index (IDI) were assessed. Among 72,982 women [n=4607 CHD events, median follow-up=12.0 (IQR=8.3–13.7) years, mean (SD) age 63.2 (7.2) years], an age-adjusted reproductive risk factor model had a C-statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C-statistic increased from 0.726 to 0.730; IDI=0.0013, p-value < 0.0001). Net reclassification for women with events was not improved (NRI events=0.007, p-value=0.18); and for women without events was marginally improved (NRI non-events=0.002, p-value=0.04) Conclusions Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination and do not materially improve net reclassification. PMID:27143682

Binary Cell Fate Decisions and Fate Transformation in the Drosophila Larval Eye

PubMed Central

Rister, Jens; Ng, June; Celik, Arzu; Sprecher, Simon G.

2013-01-01

The functionality of sensory neurons is defined by the expression of specific sensory receptor genes. During the development of the Drosophila larval eye, photoreceptor neurons (PRs) make a binary choice to express either the blue-sensitive Rhodopsin 5 (Rh5) or the green-sensitive Rhodopsin 6 (Rh6). Later during metamorphosis, ecdysone signaling induces a cell fate and sensory receptor switch: Rh5-PRs are re-programmed to express Rh6 and become the eyelet, a small group of extraretinal PRs involved in circadian entrainment. However, the genetic and molecular mechanisms of how the binary cell fate decisions are made and switched remain poorly understood. We show that interplay of two transcription factors Senseless (Sens) and Hazy control cell fate decisions, terminal differentiation of the larval eye and its transformation into eyelet. During initial differentiation, a pulse of Sens expression in primary precursors regulates their differentiation into Rh5-PRs and repression of an alternative Rh6-cell fate. Later, during the transformation of the larval eye into the adult eyelet, Sens serves as an anti-apoptotic factor in Rh5-PRs, which helps in promoting survival of Rh5-PRs during metamorphosis and is subsequently required for Rh6 expression. Comparably, during PR differentiation Hazy functions in initiation and maintenance of rhodopsin expression. Hazy represses Sens specifically in the Rh6-PRs, allowing them to die during metamorphosis. Our findings show that the same transcription factors regulate diverse aspects of larval and adult PR development at different stages and in a context-dependent manner. PMID:24385925

Binary cell fate decisions and fate transformation in the Drosophila larval eye.

PubMed

Mishra, Abhishek Kumar; Tsachaki, Maria; Rister, Jens; Ng, June; Celik, Arzu; Sprecher, Simon G

2013-01-01

The functionality of sensory neurons is defined by the expression of specific sensory receptor genes. During the development of the Drosophila larval eye, photoreceptor neurons (PRs) make a binary choice to express either the blue-sensitive Rhodopsin 5 (Rh5) or the green-sensitive Rhodopsin 6 (Rh6). Later during metamorphosis, ecdysone signaling induces a cell fate and sensory receptor switch: Rh5-PRs are re-programmed to express Rh6 and become the eyelet, a small group of extraretinal PRs involved in circadian entrainment. However, the genetic and molecular mechanisms of how the binary cell fate decisions are made and switched remain poorly understood. We show that interplay of two transcription factors Senseless (Sens) and Hazy control cell fate decisions, terminal differentiation of the larval eye and its transformation into eyelet. During initial differentiation, a pulse of Sens expression in primary precursors regulates their differentiation into Rh5-PRs and repression of an alternative Rh6-cell fate. Later, during the transformation of the larval eye into the adult eyelet, Sens serves as an anti-apoptotic factor in Rh5-PRs, which helps in promoting survival of Rh5-PRs during metamorphosis and is subsequently required for Rh6 expression. Comparably, during PR differentiation Hazy functions in initiation and maintenance of rhodopsin expression. Hazy represses Sens specifically in the Rh6-PRs, allowing them to die during metamorphosis. Our findings show that the same transcription factors regulate diverse aspects of larval and adult PR development at different stages and in a context-dependent manner.

A Review of the Factors Associated With the Timely Initiation of Breastfeeding and Exclusive Breastfeeding in the Middle East

PubMed Central

Alzaheb, Riyadh A

2017-01-01

Background: Breastfeeding supplies all the nutrients that infants need for their healthy development. Breastfeeding practice is multifactorial, and numerous variables influence mothers’ decisions and ability to breastfeed. This review identifies the factors potentially affecting the timely initiation of breastfeeding within an hour after birth and exclusive breastfeeding in the first 6 months in Middle Eastern countries. Methods: The Medline, ScienceDirect, and Web of Science databases were keyword-searched for primary studies meeting the following inclusion criteria: (1) publication in the English language between January 2001 and May 2017, (2) original research articles reporting primary data on the factors influencing the timely initiation of breastfeeding and/or exclusive breastfeeding, (3) the use of World Health Organization definitions, and (4) Middle Eastern research contexts. A random effect model was used to establish the average prevalence of the timely initiation of breastfeeding and exclusive breastfeeding in the Middle East. Results: The review identified 19 studies conducted in Saudi Arabia (7), Iran (3), Egypt (2), Turkey (2), Kuwait (1), the United Arab Emirates (1), Qatar (1), Lebanon (1), and Syria (1). The meta-analysis established that 34.3% (confidence interval [CI]: 20.2%-51.9%) of Middle Eastern newborns received breastfeeding initiated within an hour of birth, and only 20.5% (CI: 14.5%-28.2%) were fed only breast milk for the first 6 months. The 8 studies exploring breastfeeding initiation most commonly associated it with the following: delivery mode, maternal employment, rooming-in, and prelacteal feeding. The 17 studies investigating exclusive breastfeeding most frequently linked it to the following: maternal age, maternal education, maternal employment, and delivery mode. Conclusions: Middle Eastern health care organizations should fully understand all the determinants of breastfeeding identified by this review to provide suitable practical guidance and advice to help new mothers to overcome barriers where possible and to contribute to improving infant and maternal health in the region. PMID:29317851

Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons.

PubMed

Holtyn, August F; Kaminski, Barbara J; Weerts, Elise M

2017-10-01

Baclofen, a GABA B receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8mg/kg) or naltrexone (1.0-5.6mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8mg/kg) and naltrexone (3.2 and 5.6mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6mg/kg), but not baclofen, significantly reduced alcohol seeking. Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection. Copyright © 2017 Elsevier B.V. All rights reserved.

Factors Influencing Hospital Stay for Pulmonary Embolism. A Cohort Study.

PubMed

Rodríguez-Núñez, Nuria; Ruano-Raviña, Alberto; Abelleira, Romina; Ferreiro, Lucía; Lama, Adriana; González-Barcala, Francisco J; Golpe, Antonio; Toubes, María E; Álvarez-Dobaño, José M; Valdés, Luis

2017-08-01

The aim of this study was to identify factors influencing hospital stay due to pulmonary embolism. We performed a retrospective cohort study of patients hospitalized between 2010 and 2015. Patients were identified using information recorded in hospital discharge reports (ICD-9-CM codes 415.11 and 415.19). We included 965 patients with a median stay of 8 days (IQR 6-13 days). Higher scores on the simplified Pulmonary Embolism Severity Index (sPESI) were associated with increased probability of longer hospital stay. The probability of a hospital stay longer than the median was 8.65 (95% CI 5.42-13.79) for patients referred to the Internal Medicine Department and 1.54 (95% CI 1.07-2.24) for patients hospitalized in other departments, compared to those referred to the Pneumology Department. Patients with grade 3 on the modified Medical Research Council dyspnea scale had an odds ratio of 1.63 (95% CI: 1.07-2.49). The likelihood of a longer than median hospital stay was 1.72 (95% CI: 0.85-3.48) when oral anticoagulation (OAC) was initiated 2-3 days after admission, and 2.43 (95% CI: 1.16-5.07) when initiated at 4-5 days, compared to OAC initiation at 0-1 days. sPESI grade, the department of referral from the Emergency Department, the grade of dyspnea and the time of initiating OAC were associated with a longer hospital stay. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

The Dissociative Subtype of PTSD Scale (DSPS): Initial Evaluation in a National Sample of Trauma-Exposed Veterans

PubMed Central

Wolf, Erika J.; Mitchell, Karen S.; Sadeh, Naomi; Hein, Christina; Fuhrman, Isaac; Pietrzak, Robert H.; Miller, Mark W.

2015-01-01

The fifth edition of the Diagnostic and Statistical Manual (DSM-5) includes a dissociative subtype of posttraumatic stress disorder (PTSD), but no existing measures specifically assess it. This paper describes the initial evaluation of a 15-item self-report measure of the subtype called the Dissociative Subtype of PTSD Scale (DSPS) in an on-line survey of 697 trauma-exposed military veterans representative of the US veteran population. Exploratory factor analyses of the lifetime DSPS items supported the intended structure of the measure consisting of three factors reflecting derealization/depersonalization, loss of awareness, and psychogenic amnesia. Consistent with prior research, latent profile analyses assigned 8.3% of the sample to a highly dissociative class distinguished by pronounced symptoms of derealization and depersonalization. Overall, results provide initial psychometric support for the lifetime DSPS scales; additional research in clinical and community samples is needed to further validate the measure. PMID:26603115

Risk factors of avascular necrosis of the femoral head and fixation failure in patients with valgus angulated femoral neck fractures over the age of 50 years.

PubMed

Song, Hyung Keun; Choi, Ho June; Yang, Kyu Hyun

2016-12-01

The aim of our study was to identify the risk factors for avascular necrosis of the femoral head (AVN) and fixation failure (FF) after screw osteosynthesis in patients with valgus angulated femoral neck fractures. We conducted a retrospective study of 308 patients (mean age, 72.5 years, range, 50-97 years), with a mean follow-up of 21.4 months (range, 12-64 months). The risk for failure in treatment (FIT) associated with patient- and fracture-related factors was evaluated by logistic regression analyses. FIT was identified in 32 cases (10.3%): 22 cases (7.1%) of AVN and 10 cases (3.2%) of FF. Initial valgus tilt>15° (p=0.023), posterior tilt>15° (p=0.012), and screw sliding distance (p=0.037) were significantly associated with FIT. FIT occurred in 7 patients (5.2%) with B1.2.1 fractures and 17 patients (48.6%) with B1.1.2 fractures (p<0.001). The odds of FIT were 17-fold higher in patients with initial valgus and posterior tilts>15° (B1.1.2) compared to patients with <15° of tilt in both planes (B1.2.1). The severity of initial deformity predicts AVN and FF in patients with valgus angulated femoral neck fractures. Patients with an initial valgus and posterior tilt>15° are reasonable candidates for primary arthroplasty due to high risk of FIT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Friction and wear of plasma-deposited diamond films

NASA Technical Reports Server (NTRS)

Miyoshi, Kazuhisa; Wu, Richard L. C.; Garscadden, Alan; Barnes, Paul N.; Jackson, Howard E.

1993-01-01

Reciprocating sliding friction experiments in humid air and in dry nitrogen and unidirectional sliding friction experiments in ultrahigh vacuum were conducted with a natural diamond pin in contact with microwave-plasma-deposited diamond films. Diamond films with a surface roughness (R rms) ranging from 15 to 160 nm were produced by microwave-plasma-assisted chemical vapor deposition. In humid air and in dry nitrogen, abrasion occurred when the diamond pin made grooves in the surfaces of diamond films, and thus the initial coefficients of friction increased with increasing initial surface roughness. The equilibrium coefficients of friction were independent of the initial surface roughness of the diamond films. In vacuum the friction for diamond films contacting a diamond pin arose primarily from adhesion between the sliding surfaces. In these cases, the initial and equilibrium coefficients of friction were independent of the initial surface roughness of the diamond films. The equilibrium coefficients of friction were 0.02 to 0.04 in humid air and in dry nitrogen, but 1.5 to 1.8 in vacuum. The wear factor of the diamond films depended on the initial surface roughness, regardless of environment; it increased with increasing initial surface roughness. The wear factors were considerably higher in vacuum than in humid air and in dry nitrogen.

Dual function of Rpn5 in two PCI complexes, the 26S proteasome and COP9 signalosome.

PubMed

Yu, Zanlin; Kleifeld, Oded; Lande-Atir, Avigail; Bsoul, Maisa; Kleiman, Maya; Krutauz, Daria; Book, Adam; Vierstra, Richard D; Hofmann, Kay; Reis, Noa; Glickman, Michael H; Pick, Elah

2011-04-01

Subunit composition and architectural structure of the 26S proteasome lid is strictly conserved between all eukaryotes. This eight-subunit complex bears high similarity to the eukaryotic translation initiation factor 3 and to the COP9 signalosome (CSN), which together define the proteasome CSN/COP9/initiation factor (PCI) troika. In some unicellular eukaryotes, the latter two complexes lack key subunits, encouraging questions about the conservation of their structural design. Here we demonstrate that, in Saccharomyces cerevisiae, Rpn5 plays dual roles by stabilizing proteasome and CSN structures independently. Proteasome and CSN complexes are easily dissected, with Rpn5 the only subunit in common. Together with Rpn5, we identified a total of six bona fide subunits at roughly stoichiometric ratios in isolated, affinity-purified CSN. Moreover, the copy of Rpn5 associated with the CSN is required for enzymatic hydrolysis of Rub1/Nedd8 conjugated to cullins. We propose that multitasking by a single subunit, Rpn5 in this case, allows it to function in different complexes simultaneously. These observations demonstrate that functional substitution of subunits by paralogues is feasible, implying that the canonical composition of the three PCI complexes in S. cerevisiae is more robust than hitherto appreciated.

Failure to initiate early insulin therapy - A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35).

PubMed

Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

2016-06-01

Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00-1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02-1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control.

[Family, friends, and other sources of information associated with the initiation of sexual relations by adolescents in El Salvador].

PubMed

Ruiz-Canela, Miguel; López-Del Burgo, Cristina; Carlos, Silvia; Calatrava, María; Osorio, Alfonso; Irala, Jokin de

2012-01-01

The objective of this study is to verify the influence of messages Salvadorian youth receive about sexuality, affection, and leisure from family, friends, and the media on the initiation of sexual activity. Cross-sectional study based on a representative sample of 2 615 students (from 13 to 19 years of age) in El Salvador. A random systematic sampling was used to select 30 schools. Sociodemographic aspects, lifestyles, and sources of information on sexuality and love used by the young people were collected. The average age of the young people studied was 15 (SD = 1.8). In all, 638 (24.4%) of the young people stated that they had had sexual relations. The following factors are associated with a greater probability of having had sexual relations: a perception that siblings (OR = 1.8, CI 95%: 1.2-2.7) or friends (OR = 1.7, CI 95%: 1.3-2.2) encourage them to have sex. Protective factors were found to be the supervision of parents (OR = 0.5, CI 95%: 0.4-0.7); messages received from friends that encourage abstinence (OR = 0.7, CI 95%: 0.6-1.0) or from siblings (OR = 0.7, CI 95%: 0.5-0.8); and favorable messages related to marriage received from parents (OR = 0.4, CI 95%: 0.3-0.6). Messages from family and friends are factors that seem to influence the initiation of sexual activity by young people. Sexual health promotion programs in El Salvador should take these factors into account.

Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children.

PubMed

Abrams, Elaine J; Woldesenbet, Selamawit; Soares Silva, Juliana; Coovadia, Ashraf; Black, Viviane; Technau, Karl-Günter; Kuhn, Louise

2017-06-01

Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access. We enrolled newly diagnosed HIV-infected children ≤24 months of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality. Of 272 children enrolled, median age 6.1 months, 69.5% were diagnosed during hospitalization. By 6 months postenrollment, 53 (19.5%) died and 73 (26.8%) were lost-to-follow-up. Using Kaplan-Meier analysis, the probability of death by 6 months after enrollment was 23.5%. The median age of death was 9.1 months [95% confidence interval (CI): 8.6-12.0]. Overall, 226 (83%) children initiated ART which was associated with a 71% reduction in risk of death [hazard ratio (HR) = 0.29 (95% CI: 0.15-0.58)]. In multivariable analysis of infant factors, weight-for-age Z score < -2 standard deviation (SD) [HR = 2.43 (95% CI: 1.03-5.73)], CD4 <20% [HR = 3.29 (95% CI: 1.60-6.76)] and identification during hospitalization [HR = 2.89 (95% CI: 1.16-7.25)] were independently associated with mortality. In multivariable analysis of maternal factors, CD4 ≤350/no maternal ART was associated with increased mortality risk [HR = 2.57 (95% CI: 1.19-5.59)] versus CD4 >350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk [HR = 0.53 (95% CI: 0.28-0.99)] versus no PMTCT. ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.

Mechanism of Promoter Melting by the Xeroderma Pigmentosum Complementation Group B Helicase of Transcription Factor IIH Revealed by Protein-DNA Photo-Cross-Linking

PubMed Central

Douziech, Maxime; Coin, Frédéric; Chipoulet, Jean-Marc; Arai, Yoko; Ohkuma, Yoshiaki; Egly, Jean-Marc; Coulombe, Benoit

2000-01-01

The p89/xeroderma pigmentosum complementation group B (XPB) ATPase-helicase of transcription factor IIH (TFIIH) is essential for promoter melting prior to transcription initiation by RNA polymerase II (RNAPII). By studying the topological organization of the initiation complex using site-specific protein-DNA photo-cross-linking, we have shown that p89/XPB makes promoter contacts both upstream and downstream of the initiation site. The upstream contact, which is in the region where promoter melting occurs (positions −9 to +2), requires tight DNA wrapping around RNAPII. The addition of hydrolyzable ATP tethers the template strand at positions −5 and +1 to RNAPII subunits. A mutation in p89/XPB found in a xeroderma pigmentosum patient impairs the ability of TFIIH to associate correctly with the complex and thereby melt promoter DNA. A model for open complex formation is proposed. PMID:11027286

Initiation and Maintenance of Fitness Center Utilization in an Incentive-Based Employer Wellness Program

PubMed Central

Abraham, Jean Marie; Crespin, Daniel; Rothman, Alexander

2015-01-01

Objective Investigate the initiation and maintenance of participation in an employer-based wellness program that provides financial incentives for fitness center utilization. Methods Using multivariate analysis, we investigated how employees’ demographics, health status, exercise-related factors, and lifestyle change preferences affect program participation. Results Forty-two percent of eligible employees participated in the program and 24% earned a $20 incentive at least once by utilizing a gym 8 times or more in a month. On average, participants utilized fitness centers 7.0 months each year and earned credit 4.5 months. Participants’ utilization diminished after their first year in the program. Conclusions Factors associated with initiation and maintenance of fitness center utilization were similar. Declining utilization over time raises concern about the long-run effectiveness of fitness-focused wellness programs. Employers may want to consider additional levers to positively reinforce participation. PMID:26340283

Incidence, risk factors and causes of death in an HIV care programme with a large proportion of injecting drug users.

PubMed

Spillane, Heidi; Nicholas, Sarala; Tang, Zhirong; Szumilin, Elisabeth; Balkan, Suna; Pujades-Rodriguez, Mar

2012-10-01

To identify factors influencing mortality in an HIV programme providing care to large numbers of injecting drug users (IDUs) and patients co-infected with hepatitis C (HCV). A longitudinal analysis of monitoring data from HIV-infected adults who started antiretroviral therapy (ART) between 2003 and 2009 was performed. Mortality and programme attrition rates within 2 years of ART initiation were estimated. Associations with individual-level factors were assessed with multivariable Cox and piece-wise Cox regression. A total of 1671 person-years of follow-up from 1014 individuals was analysed. Thirty-four percent of patients were women and 33% were current or ex-IDUs. 36.2% of patients (90.8% of IDUs) were co-infected with HCV. Two-year all-cause mortality rate was 5.4 per 100 person-years (95% CI, 4.4-6.7). Most HIV-related deaths occurred within 6 months of ART start (36, 67.9%), but only 5 (25.0%) non-HIV-related deaths were recorded during this period. Mortality was higher in older patients (HR = 2.50; 95% CI, 1.42-4.40 for ≥40 compared to 15-29 years), and in those with initial BMI < 18.5 kg/m(2) (HR = 3.38; 95% CI, 1.82-5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47-10.65 during the second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54-13.41 for <100 compared to ≥100 cells/μl). Risk of death was not associated with IDU status (P = 0.38). Increased mortality was associated with late presentation of patients. In this programme, death rates were similar regardless of injection drug exposure, supporting the notion that satisfactory treatment outcomes can be achieved when comprehensive care is provided to these patients. © 2012 Blackwell Publishing Ltd.

Breast-feeding initiation in women with pregestational diabetes mellitus.

PubMed

Cordero, Leandro; Thung, Stephen; Landon, Mark B; Nankervis, Craig A

2014-01-01

To examine feeding practices and factors associated with breast-feeding initiation (BFI) in women with pregestational diabetes mellitus (PGDM) and their infants. In all, 392 PGDM (135 late preterm and 257 term) pregnancies were studied. Infant feeding preference was ascertained on admission. After birth, 166 (42%) of the infants received well-baby care, whereas 226 (58%) were admitted to the newborn intensive care unit (NICU). Hypoglycemia (blood glucose <40 mg/dL), which occurred in 128 (33%) of all infants, did not influence BFI. Of 257 women who intended to BF, 55% initiated BF. Also, 5% of 105 women who intended to feed formula and 13% of the 30 undecided later initiated BF. The BFI rate for women with PGDM is remarkably low even among those who intended to BF. Factors associated with BFI failure in this population were primiparity, African American race, lower education, smoking, lack of intention to BF, and NICU admission.

Ion collection from a plasma by a pinhole

NASA Technical Reports Server (NTRS)

Snyder, David B.; Herr, Joel L.

1992-01-01

Ion focusing by a biased pinhole is studied numerically. Laplace's equation is solved in 3-D for cylindrical symmetry on a constant grid to determine the potential field produced by a biased pinhole in a dielectric material. Focusing factors are studied for ions of uniform incident velocity with a 3-D Maxwellian distribution superimposed. Ion currents to the pinhole are found by particle tracking. The focusing factor of positive ions as a function of initial velocity, temperature, injection radius, and hole size is reported. For a typical Space Station Freedom environment (oxygen ions having a 4.5 eV ram energy, 0.1 eV temperature, and a -140 V biased pinhole), a focusing factor of 13.35 is found for a 1.5 mm radius pinhole.

Transcription factor Etv5 is essential for the maintenance of alveolar type II cells.

PubMed

Zhang, Zhen; Newton, Kim; Kummerfeld, Sarah K; Webster, Joshua; Kirkpatrick, Donald S; Phu, Lilian; Eastham-Anderson, Jeffrey; Liu, Jinfeng; Lee, Wyne P; Wu, Jiansheng; Li, Hong; Junttila, Melissa R; Dixit, Vishva M

2017-04-11

Alveolar type II (AT2) cell dysfunction contributes to a number of significant human pathologies including respiratory distress syndrome, lung adenocarcinoma, and debilitating fibrotic diseases, but the critical transcription factors that maintain AT2 cell identity are unknown. Here we show that the E26 transformation-specific (ETS) family transcription factor Etv5 is essential to maintain AT2 cell identity. Deletion of Etv5 from AT2 cells produced gene and protein signatures characteristic of differentiated alveolar type I (AT1) cells. Consistent with a defect in the AT2 stem cell population, Etv5 deficiency markedly reduced recovery following bleomycin-induced lung injury. Lung tumorigenesis driven by mutant KrasG12D was also compromised by Etv5 deficiency. ERK activation downstream of Ras was found to stabilize Etv5 through inactivation of the cullin-RING ubiquitin ligase CRL4 COP1/DET1 that targets Etv5 for proteasomal degradation. These findings identify Etv5 as a critical output of Ras signaling in AT2 cells, contributing to both lung homeostasis and tumor initiation.

Differential Gene Expression of Longan Under Simulated Acid Rain Stress.

PubMed

Zheng, Shan; Pan, Tengfei; Ma, Cuilan; Qiu, Dongliang

2017-05-01

Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.

Factors determining when to start levodopa/carbidopa/entacapone treatment in Spanish patients with Parkinson's disease.

PubMed

Martínez-Martín, P; Hernández, B; Ricart, J

2014-04-01

Several therapeutic options are available for the symptomatic treatment of Parkinson's disease (PD).There is no reliable information about which factors are involved in the choice of treatment. To identify factors contributing to the decision to start treatment with levodopa/carbidopa/entacapone (LCE) in patients with PD. We completed a descriptive cross-sectional retrospective multicentre study of patients with idiopathic PD receiving LCE. Clinical data were collected with special attention to factors that could potentially determine when to initiate treatment with LCE in normal clinical practice. We studied 1050 patients with a mean age of 71.3±8.7 years (58.2% men). Average time from onset of symptoms to diagnosis was 13.8±12.9 months, with a latency time of 74.5±53.6 months before starting LCE treatment. The most common initial symptoms were tremor (70.6%), reduced dexterity (43.2%) and slowness of movement (41.5%). At the start of LCE treatment, most patients were in Hoehn and Yahr stage 2 (57.5%), with an average rating of 73.4% on the Schwab & England scale. Eight hundred twenty two patients (78.3%) received treatment with other drugs before starting LCE (mean time between starting any PD treatment and starting LCE was 40.5±47.2 months). Clinical factors with a moderate, marked, or crucial effect on the decision to start LCE treatment were bradykinesia (84.7%), daytime rigidity (72.2%), general decline (72.2%), difficulty walking (66.4%), tremor (62.7%), nocturnal rigidity (56.1%), and postural instability (53%). Difficulty performing activities of daily living was the only psychosocial factor identified as having an influence on the decision (84.3%). The decision to start patients with idiopathic PD on LCE treatment is mainly determined by motor deficits and disabilities associated with disease progression. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression

PubMed Central

Shives, Katherine D.; Massey, Aaron R.; May, Nicholas A.; Morrison, Thomas E.; Beckham, J. David

2016-01-01

West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome. PMID:27763553

The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA

PubMed Central

Sloan, Katherine E.; Bohnsack, Markus T.; Schneider, Claudia; Watkins, Nicholas J.

2014-01-01

During eukaryotic ribosome biogenesis, three of the mature ribosomal (r)RNAs are released from a single precursor transcript (pre-rRNA) by an ordered series of endonucleolytic cleavages and exonucleolytic processing steps. Production of the 18S rRNA requires the removal of the 5′ external transcribed spacer (5′ETS) by endonucleolytic cleavages at sites A0 and A1/site 1. In metazoans, an additional cleavage in the 5′ETS, at site A′, upstream of A0, has also been reported. Here, we have investigated how A′ processing is coordinated with assembly of the early preribosomal complex. We find that only the tUTP (UTP-A) complex is critical for A′ cleavage, while components of the bUTP (UTP-B) and U3 snoRNP are important, but not essential, for efficient processing at this site. All other factors involved in the early stages of 18S rRNA processing that were tested here function downstream from this processing step. Interestingly, we show that the RNA surveillance factors XRN2 and MTR4 are also involved in A′ cleavage in humans. A′ cleavage is largely bypassed when XRN2 is depleted, and we also discover that A′ cleavage is not always the initial processing event in all cell types. Together, our data suggest that A′ cleavage is not a prerequisite for downstream pre-rRNA processing steps and may, in fact, represent a quality control step for initial pre-rRNA transcripts. Furthermore, we show that components of the RNA surveillance machinery, including the exosome and TRAMP complexes, also play key roles in the recycling of excised spacer fragments and degradation of aberrant pre-rRNAs in human cells. PMID:24550520

Prevalence and risk factors related to preterm birth in Brazil.

PubMed

Leal, Maria do Carmo; Esteves-Pereira, Ana Paula; Nakamura-Pereira, Marcos; Torres, Jacqueline Alves; Theme-Filha, Mariza; Domingues, Rosa Maria Soares Madeira; Dias, Marcos Augusto Bastos; Moreira, Maria Elizabeth; Gama, Silvana Granado

2016-10-17

The rate of preterm birth has been increasing worldwide, including in Brazil. This constitutes a significant public health challenge because of the higher levels of morbidity and mortality and long-term health effects associated with preterm birth. This study describes and quantifies factors affecting spontaneous and provider-initiated preterm birth in Brazil. Data are from the 2011-2012 "Birth in Brazil" study, which used a national population-based sample of 23,940 women. We analyzed the variables following a three-level hierarchical methodology. For each level, we performed non-conditional multiple logistic regression for both spontaneous and provider-initiated preterm birth. The rate of preterm birth was 11.5 %, (95 % confidence 10.3 % to 12.9 %) 60.7 % spontaneous - with spontaneous onset of labor or premature preterm rupture of membranes - and 39.3 % provider-initiated, with more than 90 % of the last group being pre-labor cesarean deliveries. Socio-demographic factors associated with spontaneous preterm birth were adolescent pregnancy, low total years of schooling, and inadequate prenatal care. Other risk factors were previous preterm birth (OR 3.74; 95 % CI 2.92-4.79), multiple pregnancy (OR 16.42; 95 % CI 10.56-25.53), abruptio placentae (OR 2.38; 95 % CI 1.27-4.47) and infections (OR 4.89; 95 % CI 1.72-13.88). In contrast, provider-initiated preterm birth was associated with private childbirth healthcare (OR 1.47; 95 % CI 1.09-1.97), advanced-age pregnancy (OR 1.27; 95 % CI 1.01-1.59), two or more prior cesarean deliveries (OR 1.64; 95 % CI 1.19-2.26), multiple pregnancy (OR 20.29; 95 % CI 12.58-32.72) and any maternal or fetal pathology (OR 6.84; 95 % CI 5.56-8.42). The high proportion of provider-initiated preterm birth and its association with prior cesarean deliveries and all of the studied maternal/fetal pathologies suggest that a reduction of this type of prematurity may be possible. The association of spontaneous preterm birth with socially-disadvantaged groups reaffirms that the reduction of social and health inequalities should continue to be a national priority.

mRNA-Selective Translation Induced by FSH in Primary Sertoli Cells

PubMed Central

Musnier, Astrid; León, Kelly; Morales, Julia; Reiter, Eric; Boulo, Thomas; Costache, Vlad; Vourc'h, Patrick; Heitzler, Domitille; Oulhen, Nathalie; Poupon, Anne; Boulben, Sandrine; Cormier, Patrick

2012-01-01

FSH is a key hormonal regulator of Sertoli cell secretory activity, required to optimize sperm production. To fulfil its biological function, FSH binds a G protein-coupled receptor, the FSH-R. The FSH-R-transduced signaling network ultimately leads to the transcription or down-regulation of numerous genes. In addition, recent evidence has suggested that FSH might also regulate protein translation. However, this point has never been demonstrated conclusively yet. Here we have addressed this issue in primary rat Sertoli cells endogenously expressing physiological levels of FSH-R. We observed that, within 90 min of stimulation, FSH not only enhanced overall protein synthesis in a mammalian target of rapamycin-dependent manner but also increased the recruitment of mRNA to polysomes. m7GTP pull-down experiments revealed the functional recruitment of mammalian target of rapamycin and p70 S6 kinase to the 5′cap, further supported by the enhanced phosphorylation of one of p70 S6 kinase targets, the eukaryotic initiation factor 4B. Importantly, the scaffolding eukaryotic initiation factor 4G was also recruited, whereas eukaryotic initiation factor 4E-binding protein, the eukaryotic initiation factor 4E generic inhibitor, appeared to play a minor role in translational regulations induced by FSH, in contrast to what is generally observed in response to anabolic factors. This particular regulation of the translational machinery by FSH stimulation might support mRNA-selective translation, as shown here by quantitative RT-PCR amplification of the c-fos and vascular endothelial growth factor mRNA but not of all FSH target mRNA, in polysomal fractions. These findings add a new level of complexity to FSH biological roles in its natural target cells, which has been underappreciated so far. PMID:22383463

Poor replication validity of biomedical association studies reported by newspapers

PubMed Central

Smith, Andy; Boraud, Thomas; Gonon, François

2017-01-01

Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists preferentially cover initial findings although they are often contradicted by meta-analyses and rarely inform the public when they are disconfirmed. PMID:28222122

Poor replication validity of biomedical association studies reported by newspapers.

PubMed

Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

2017-01-01

To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings although they are often contradicted by meta-analyses and rarely inform the public when they are disconfirmed.

The guanosine nucleotide (p)ppGpp initiates development and A-factor production in myxococcus xanthus.

PubMed

Harris, B Z; Kaiser, D; Singer, M

1998-04-01

Guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp], synthesized in response to amino acid limitation, induce early gene expression leading to multicellular fruiting body formation in Myxococcus xanthus. A mutant (DK527) that fails to accumulate (p)ppGpp in response to starvation was found to be blocked in development prior to aggregation. By use of a series of developmentally regulated Tn5lac transcriptional fusion reporters, the time of developmental arrest in DK527 was narrowed to within the few hours of development, the period of starvation recognition. The mutant is also defective in the production of A-factor, an early extracellular cell-density signal. The relA gene from Escherichia coli, which encodes a ribosome-dependent (p)ppGpp synthetase, rescues this mutant. We also demonstrate that inactivation of the M. xanthus relA homolog blocks development and the accumulation of (p)ppGpp. Moreover, the wild-type allele of Myxococcus relA rescues DK527. These observations support a model in which accumulation of (p)ppGpp, in response to starvation, initiates the program of fruiting body development, including the production of A-factor.

The Lesbian, Gay and Bisexual Affirmative Counseling Self-Efficacy Inventory (LGB-CSI): Development, Validation, and Training Implications

ERIC Educational Resources Information Center

Dillon, Frank; Worthington, Roger L.

2003-01-01

Five studies on the development of the Lesbian, Gay, and Bisexual Affirmative Counseling Self-Efficacy Inventory (LGB-CSI) were conducted. Exploratory and confirmatory factor analyses of an initial pool of 64 items yielded 5 factors that assess counselor self-efficacy to perform lesbian, gay, and bisexual (LGB) affirmative counseling behaviors…

Experimental Adiabatic Quantum Factorization under Ambient Conditions Based on a Solid-State Single Spin System.

PubMed

Xu, Kebiao; Xie, Tianyu; Li, Zhaokai; Xu, Xiangkun; Wang, Mengqi; Ye, Xiangyu; Kong, Fei; Geng, Jianpei; Duan, Changkui; Shi, Fazhan; Du, Jiangfeng

2017-03-31

The adiabatic quantum computation is a universal and robust method of quantum computing. In this architecture, the problem can be solved by adiabatically evolving the quantum processor from the ground state of a simple initial Hamiltonian to that of a final one, which encodes the solution of the problem. Adiabatic quantum computation has been proved to be a compatible candidate for scalable quantum computation. In this Letter, we report on the experimental realization of an adiabatic quantum algorithm on a single solid spin system under ambient conditions. All elements of adiabatic quantum computation, including initial state preparation, adiabatic evolution (simulated by optimal control), and final state read-out, are realized experimentally. As an example, we found the ground state of the problem Hamiltonian S_{z}I_{z} on our adiabatic quantum processor, which can be mapped to the factorization of 35 into its prime factors 5 and 7.

Experimental Adiabatic Quantum Factorization under Ambient Conditions Based on a Solid-State Single Spin System

NASA Astrophysics Data System (ADS)

Xu, Kebiao; Xie, Tianyu; Li, Zhaokai; Xu, Xiangkun; Wang, Mengqi; Ye, Xiangyu; Kong, Fei; Geng, Jianpei; Duan, Changkui; Shi, Fazhan; Du, Jiangfeng

2017-03-01

The adiabatic quantum computation is a universal and robust method of quantum computing. In this architecture, the problem can be solved by adiabatically evolving the quantum processor from the ground state of a simple initial Hamiltonian to that of a final one, which encodes the solution of the problem. Adiabatic quantum computation has been proved to be a compatible candidate for scalable quantum computation. In this Letter, we report on the experimental realization of an adiabatic quantum algorithm on a single solid spin system under ambient conditions. All elements of adiabatic quantum computation, including initial state preparation, adiabatic evolution (simulated by optimal control), and final state read-out, are realized experimentally. As an example, we found the ground state of the problem Hamiltonian SzIz on our adiabatic quantum processor, which can be mapped to the factorization of 35 into its prime factors 5 and 7.

Clinicopathological Factors Affecting Survival and Recurrence after Initial Hepatectomy in Non-B Non-C Hepatocellular Carcinoma Patients with Comparison to Hepatitis B or C Virus

PubMed Central

Shiraishi, Taizou; Murata, Yasuhiro; Tanemura, Akihiro; Azumi, Yoshinori; Kuriyama, Naohisa; Kishiwada, Masashi; Usui, Masanobu; Tabata, Masami; Yamada, Tomomi

2014-01-01

We evaluated clinicopathological factors affecting survival and recurrence after initial hepatectomy in non-B non-C (NBNC) hepatocellular carcinoma (HCC) patients with comparison to hepatitis B or C virus, paying attention to relationship between alcohol consumption and histopathological findings. The medical records on the 201HCC patients who underwent initial hepatectomy between January 2000 and April 2013 were retrospectively reviewed. NBNC patients had higher prevalence of hypertension (47.4%), diabetes mellitus (35.5%), alcohol consumption (>20 g/day) (61.8%), and preserved liver function than hepatitis B or C patients. The 5-year survival rate of NBNC patients (74.1%) was significantly better than hepatitis B (49.1%) or C (65.0%) patients (NBNC versus B, P = 0.031). Among the NBNC patients, there was no relationship between alcohol consumption and clinicopathological findings including nonalcoholic fatty liver disease activity score (NAS). However, the 5-year OS and RFS rates in the alcohol-unrelated NBNC patients tend to be better than in the alcohol-related. By multivariate analysis, independent factors for OS in NBNC patients were Child-Pugh B/C, intrahepatic metastasis (im), and extrahepatic recurrence. NBNC patients, who were highly associated with lifestyle-related disease and preserved liver function, had significantly better prognosis compared to hepatitis B/C patients; however, there was no association between alcohol consumption and histopathological findings. PMID:24745029

A rapid and low energy consumption method to decolorize the high concentration triphenylmethane dye wastewater: operational parameters optimization for the ultrasonic-assisted ozone oxidation process.

PubMed

Zhou, Xian-Jiao; Guo, Wan-Qian; Yang, Shan-Shan; Ren, Nan-Qi

2012-02-01

This research set up an ultrasonic-assisted ozone oxidation process (UAOOP) to decolorize the triphenylmethane dyes wastewater. Five factors - temperature, initial pH, reaction time, ultrasonic power (low frequency 20 kHz), and ozone concentration - were investigated. Response surface methodology was used to find out the major factors influencing color removal rate and the interactions between these factors, and optimized the operating parameters as well. Under the experimental conditions: reaction temperature 39.81 °C, initial pH 5.29, ultrasonic power 60 W and ozone concentration 0.17 g/L, the highest color removals were achieved with 10 min reaction time and the initial concentration of the MG solution was 1000 mg/L. The optimal results indicated that the UAOOP was a rapid, efficient and low energy consumption technique to decolorize the high concentration MG wastewater. The predicted model was approximately in accordance with the experimental cases with correlation coefficients R(2) and R(adj)(2) of 0.9103 and 0.8386. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Improved survival in HIV treatment programs in Asia

PubMed Central

De La Mata, Nicole L; Kumarasamy, Nagalingeswaran; Khol, Vohith; Ng, Oon Tek; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Durier, Nicolas; Law, Matthew

2016-01-01

Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (p<0.001). Factors associated with higher mortality risk included initiating ART in earlier time periods, older age, male sex, injecting drug use as HIV exposure and lower pre-ART CD4 count. Concurrent with improved survival was increased tenofovir use, ART initiation at higher CD4 counts, and greater monitoring of CD4 and HIV viral load. Conclusions Our results suggest that HIV-positive patients from Asia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time. PMID:26961354

Relation Between Witnessing Violence and Drug Use Initiation Among Rural Adolescents: Parental Monitoring and Family Support as Protective Factors

ERIC Educational Resources Information Center

Sullivan, Terri N.; Kung, Eva M.; Farrell, Albert D.

2004-01-01

This study examined the relation between witnessing violence and drug use initiation among 6th graders attending middle schools in 5 rural counties and investigated the extent to which family support and parental monitoring moderated this relation. Data were obtained from 1,282 adolescents at 2 time points during the 6th grade. Witnessing violence…

Association Between the Lower Extremity Deep Venous Thrombosis, the Warfarin Maintenance Dose, and CYP2C9*3, CYP2D6*10, and CYP3A5*3 Genetic Polymorphisms: A Case-Control Study.

PubMed

Ju, Shang; Gao, Yu; Cao, Xin; Zhang, Xiao-Fu; Yan, Cheng-Cheng; Liu, Feng-Tong

2017-09-01

This study explored the association between the CYP2C9*3/CYP2D6*10/CYP3A5*3 genetic polymorphisms with lower extremity deep venous thrombosis (LEDVT) and the warfarin maintenance dose. Five hundred thirty-six patients who were pathologically diagnosed with LEDVT after surgery were included in the LEDVT group. At the same time, 540 patients without LEDVT who underwent surgery were recruited as the control group. Patients were given warfarin at an initial dose of 2.5-3.0 mg. Blood samples were collected to detect the initial and stable international normalized ratio (INR) values. The warfarin maintenance dose was obtained if the INR remained within a range of 2.0-3.0 for 3 consecutive days. The genotype distribution and haplotype analysis of the CYP2C9*3/CYP2D6*10/CYP3A5*3 alleles were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) testing and SHEsis software, respectively. Logistic regression analysis was used to analyze the risk and protective factors for LEDVT. The A/G genotypes, G/G genotypes, and G allele of CYP3A5*3 in the LEDVT group were observed with increased frequency compared with the control group. The LEDVT group displayed a higher ACG haplotype frequency, and lower ACA and ATA haplotype frequencies than the control group. Age, diabetes, low-density lipoprotein, CYP3A5*3 and the ACG haplotype were independent risk factors for LEDVT. High-density lipoprotein and the ACA haplotype were independent protective factors for LEDVT. The genotype distributions of the CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms were associated with the warfarin maintenance dose. The CYP3A5*3 genetic polymorphism may be an important risk factor for LEDVT. Moreover, CYP2C9*3, CYP2D6*10, and CYP3A5*3 are associated with the warfarin maintenance dose.

Outcomes and prognostic factors of multimodality treatment for locally recurrent rectal cancer with curative intent.

PubMed

Bird, Thomas G; Ngan, Samuel Y; Chu, Julie; Kroon, René; Lynch, Andrew C; Heriot, Alexander G

2018-04-01

Radical management of locally recurrent rectal cancer (LRRC) can lead to prolonged survival. This study aims to assess outcomes and identify prognostic factors for patients with LRRC treated using a multimodality treatment protocol. An analysis of a prospectively maintained institutional database of consecutive patients who underwent radical surgical resection for LRRC was performed. Potential prognostic factors were investigated using a Cox proportional hazards model. Ninety-eight patients were included in this study. A multimodality approach was taken in the majority, including preoperative chemoradiation (78%), intraoperative radiation therapy (47%) and adjuvant chemotherapy (41%). Extended resection was performed where required: bone resection (34%) and lateral pelvic sidewall dissection (31%). The rate of R0 resection was 66%. Estimated rates of 5-year overall survival (OS) and progression-free survival (PFS) were 41.8% (95% CI 32.5-53.7) and 22.5% (95% CI 15.3-33.1). On multivariate analysis, stage III disease at initial primary surgery, a positive margin at initial primary surgery, synchronous or previously resected oligometastases, a lateral or sacral invasive-type pelvic recurrence and the requirement for IORT all predicted for inferior PFS (p < 0.05). Eleven percent of patients subsequently underwent further pelvic surgery for pelvic re-recurrence and had an estimated 5-year OS rate of 54.5% (95% CI 29.0-100.0) from repeat surgery. Radical multimodality management of LRRC leads to prolonged survival in approximately 40% of patients. Those with sacral or lateral invasive-type recurrence or oligometastatic disease have inferior outcomes and further research is needed to optimise treatment for these groups.

Toilet training in Turkey: the factors that affect timing and duration in different sociocultural groups.

PubMed

Koc, I; Camurdan, A D; Beyazova, U; Ilhan, M N; Sahin, F

2008-07-01

The aim of the present study was to determine the patterns of toilet training and the factors that may be related to its timing and duration and the approaches of different sociocultural groups within a developing country. This cross-sectional survey was performed on 745 children who live in three different sociocultural settlements. The factors that might have affected initiation and completion age and duration of toilet training were assessed with t-test, ANOVA and logistic regression analysis. Mean initiation and completion ages were 22.05 +/- 6.73, 28.05 +/- 8.40 months respectively. The families living in rural and semi-urban settlements, mothers educated for less than 5 years, unoccupied mothers, children living in houses which do not have a toilet inside, families who use washable diapers, who use Turkish style toilets and who use punishment methods started training earlier. In the infants whose mothers had an education over 12 years, completion age was later than others and the earliest completion age was seen in families who used punishment method. Mean duration needed to complete toilet training was 6.84 +/- 7.16 months. The duration of training was longer in families living in rural and semi-urban settlements, mothers educated for less than 5 years, unoccupied mothers, children living in houses which do not have a toilet inside, families who use washable diapers and when the initiation was before the child was 18 months old. Toilet training shows differences among cultures. The age of initiation may be increased as the parents are educated better and a child-orientated approach becomes more popular than the parent-orientated approach.

Interaction of air shock waves and porous compressible materials

NASA Astrophysics Data System (ADS)

Gvozdeva, L. G.; Faresov, Yu. M.; Fokeyev, V. P.

1986-05-01

Interaction of air shock waves and porous compressible materials was studied in an experiment with two foam-plastic materials: PPU-3M-1 polyurethane (density 33 kg/cu m) and much more rigid PKhV-1 polyvinyl chloride (density 50 kg/cu m). Tests were performed in a shock tube with 0.1x0.1 m square cross-section, a single diaphragm separating its 8 m long low-pressure segment with inspection zone and 1.5 m long high-pressure segment. The instrumentation included an array of piezoelectric pressure transducers and a digital frequency meter for velocity measurements, a Tectronix 451A oscillograph, and IAB-451 shadowgraph, and a ZhFR camera with slit scanning. Air was used as compressing gas, its initial pressure being varied from 10(3) Pa to 10(5) Pa, helium and nitrogen were used as propelling gas. The impact velocity of shock waves was varied over the N(M) = 2-5 range of the Mach number. The maximum amplitude of the pressure pulse increased as the thickness of the foam layer was increased up to 80 mm and then remained constant with further increases of that thickness, at a level depending on the material and on the intitial conditions. A maximum pressure rise by a factor of approximately 10 was attained, with 1.3 x 10(3) Pa initial pressure and an impact velocity N(M) = 5. Reducing the initial pressure to below (0.1-0.3) x 10(3) Pa, with the impact velocity maintained at N(M) = 5, reduced the pressure rise to a factor below 3. The results are interpreted taking into account elasticity forces in the solid skeleton phase and gas filtration through the pores.

Functional equivalence of translation factor eIF5B from Candida albicans and Saccharomyces cerevisiae.

PubMed

Jun, Kyung Ok; Yang, Eun Ji; Lee, Byeong Jeong; Park, Jeong Ro; Lee, Joon H; Choi, Sang Ki

2008-04-30

Eukaryotic translation initiation factor 5B (eIF5B) plays a role in recognition of the AUG codon in conjunction with translation factor eIF2, and promotes joining of the 60S ribosomal subunit. To see whether the eIF5B proteins of other organisms function in Saccharomyces cerevisiae, we cloned the corresponding genes from Oryza sativa, Arabidopsis thaliana, Aspergillus nidulans and Candida albican and expressed them under the control of the galactose-inducible GAL promoter in the fun12Delta strain of Saccharomyces cerevisiae. Expression of Candida albicans eIF5B complemented the slow-growth phenotype of the fun12Delta strain, but that of Aspergillus nidulance did not, despite the fact that its protein was expressed better than that of Candida albicans. The Arabidopsis thaliana protein was also not functional in Saccharomyces. These results reveal that the eIF5B in Candida albicans has a close functional relationship with that of Sacharomyces cerevisiae, as also shown by a phylogenetic analysis based on the amino acid sequences of the eIF5Bs.

Impact of feeding and breastfeeding practices on the nutritional status of infants in a district of Andhra Pradesh, India.

PubMed

Meshram, I I; A, Laxmaiah; K, Venkaiah; N V, Brahmam G

2012-01-01

Infant feeding practices have a major role in determining the nutritional status of children and are associated with household socioeconomic and demographic factors. We did a cross-sectional household study to assess feeding practices of infants and young children in rural areas of Medak district, Andhra Pradesh. A total of 805 child-mother pairs were included using systematic random sampling. Age-specific feeding patterns were described using frequencies, proportions and survival analysis. Logistic regression was done with feeding practice as dependent and sociodemographic factors as independent variables. Breastfeeding was universal in the study area. Only 22% of mothers initiated breastfeeding within one hour whereas 44% initiated it within three hours after delivery. The median duration of exclusive breastfeeding was 5.5 months. Pre-lacteal use was high (44.7%). Only 41% of infants were exclusively breastfed for 6 months and 58% of infants (6-11 months) received complementary feeding at 6-9 months of age. Timely initiation of breastfeeding and exclusive breastfeeding for 6 months was significantly more likely among mothers belonging to scheduled castes and scheduled tribes (OR 0.27, 95% CI 0.10-0.76 and OR 0.24, 95% CI 0.08-0.76). Timely initiation of complementary feeding was more likely among scheduled caste and scheduled tribe communities (OR 0.24, 95% CI 0.11-0.54). Early initiation of breastfeeding (within an hour of birth) and other feeding practices were associated with community, type of family and education of mother. Efforts are needed to promote early initiation of breastfeeding, exclusive breastfeeding for 6 months and age-appropriate complementary feeding among infants. Copyright 2012, NMJI.

Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients.

PubMed

Xu, Guifang; Zhang, Weijie; Lv, Ying; Zhang, Bin; Sun, Qi; Ling, Tingsheng; Zhang, Xiaoqi; Zhou, Zhihua; Wang, Lei; Huang, Qin; Zou, Xiaoping

2016-07-01

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy

PubMed Central

Lin, Chen-Sung; Liu, Chao-Yu; Cheng, Chih-Tao; Tsai, Yu-Chen; Chiou, Lun-Wei; Lee, Ming-Yuan

2017-01-01

Background The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. Methods Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3–5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. Results Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3–5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all’s P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3–5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all’s P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. Conclusions Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion. PMID:29221296

Employment Opportunities for Family Members in Germany.

DTIC Science & Technology

1983-05-24

30 V . NEW INITIATIVES TO IMPROVE FAMILY MEMBER EMPLOYMENT OPPORTUNITIES ........ ...................... . 40 VI. OBSERVATIONS AND COMMENTS...I, II, V Local National Hire 9.94% 2.5% 6.52% 1.93% 12.07% NOTES 1. CONUS Hire Fringe Benefits include overseas unique estimated costs outlined in...from a survey of ODCSRM FY81 vouchers . 19 TABLE 3-4 FY83 GENERAL SCHEDULE CONUS HIRE CIVILIAN COST FACTORS This table provides cost factors for

Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007-2011): Evidence leading to policy enhancement.

PubMed

Parmar, Malik M; Sachdeva, Kuldeep Singh; Dewan, Puneet K; Rade, Kiran; Nair, Sreenivas A; Pant, Rashmi; Khaparde, Sunil D

2018-01-01

Globally, India has the world's highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92-125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202-381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model. India's initial MDR-TB patients' cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India.

Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007–2011): Evidence leading to policy enhancement

PubMed Central

Sachdeva, Kuldeep Singh; Dewan, Puneet K.; Rade, Kiran; Nair, Sreenivas A.; Pant, Rashmi; Khaparde, Sunil D.

2018-01-01

Background Globally, India has the world’s highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. Objective To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. Methods This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. Results In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92–125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202–381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model. Conclusion India’s initial MDR-TB patients’ cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India. PMID:29641576

Mesoscale Simulations of a Florida Sea Breeze Using the PLACE Land Surface Model Coupled to a 1.5-Order Turbulence Parameterization

NASA Technical Reports Server (NTRS)

Lynn, Barry H.; Stauffer, David R.; Wetzel, Peter J.; Tao, Wei-Kuo; Perlin, Natal; Baker, R. David; Munoz, Ricardo; Boone, Aaron; Jia, Yiqin

1999-01-01

A sophisticated land-surface model, PLACE, the Parameterization for Land Atmospheric Convective Exchange, has been coupled to a 1.5-order turbulent kinetic energy (TKE) turbulence sub-model. Both have been incorporated into the Penn State/National Center for Atmospheric Research (PSU/NCAR) mesoscale model MM5. Such model improvements should have their greatest effect in conditions where surface contrasts dominate over dynamic processes, such as the simulation of warm-season, convective events. A validation study used the newly coupled model, MM5 TKE-PLACE, to simulate the evolution of Florida sea-breeze moist convection during the Convection and Precipitation Electrification Experiment (CaPE). Overall, eight simulations tested the sensitivity of the MM5 model to combinations of the new and default model physics, and initialization of soil moisture and temperature. The TKE-PLACE model produced more realistic surface sensible heat flux, lower biases for surface variables, more realistic rainfall, and cloud cover than the default model. Of the 8 simulations with different factors (i.e., model physics or initialization), TKE-PLACE compared very well when each simulation was ranked in terms of biases of the surface variables and rainfall, and percent and root mean square of cloud cover. A factor separation analysis showed that a successful simulation required the inclusion of a multi-layered, land surface soil vegetation model, realistic initial soil moisture, and higher order closure of the planetary boundary layer (PBL). These were needed to realistically model the effect of individual, joint, and synergistic contributions from the land surface and PBL on the CAPE sea-breeze, Lake Okeechobee lake breeze, and moist convection.

In Situ Biogeochemical Treatment Demonstration: Lessons Learned from ESTCP Project ER 201124

DTIC Science & Technology

2015-12-09

vegetable oil fermentation to volatile fatty acids (VFA) also likely reduced the pH and this change could have reduced the FeS reactivity. 2.3.5...Initially about 6.5 ● Vegetable oil fermentation to VFAs ● Lower FeSx reactivity Need to balance iron and sulfur! 55 Critical Factors

Factors associated with self-reported need for treatment of sleeping difficulties: a survey of the general Swedish population.

PubMed

Sandlund, Christina; Westman, Jeanette; Hetta, Jerker

2016-06-01

This study aims to investigate factors associated with the self-reported need for treatment of sleeping difficulties in the general population. This study consisted of a cross-sectional telephone survey of 1550 people randomly selected from the total population of Sweden. The survey, conducted by the Swedish national statistics agency, Statistics Sweden, was completed by 1115 people aged 18-85 years. Participants were asked about sleep patterns, daytime symptoms, physical and mental health disorders, use of prescribed hypnotics, help-seeking behaviors, and sociodemographic characteristics. They were also asked whether they thought they needed treatment for sleeping difficulties. A total of 12.5% of the participants reported a need for treatment because of sleeping difficulties. Significantly more women than men reported such a need (OR 1.46, 95% CI 1.02-2.10). Additionally, in univariate analyses, older age (age 60-69), sick leave, retirement, and unemployment were associated with a self-reported need for treatment, as were several sleep complaints, daytime symptoms, and physical and mental health disorders. A logistic regression model showed that difficulty initiating sleep (OR 6.29, 95% CI 3.67-10.78) was the factor most strongly associated with a self-reported need for treatment for sleeping difficulties. Other important factors were nonrestorative sleep (OR 3.70, 95% CI 2.05-6.69), mental health disorders (OR 3.01, 95% CI 1.59-5.67), and fatigue (OR 2.95, 95% CI 1.53-5.68). There was considerable self-reported need for treatment for sleeping difficulties in the population. Difficulty initiating sleep was the factor most strongly associated with this need, followed by nonrestorative sleep, mental health disorders, and fatigue. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Number of Coronary Heart Disease Risk Factors and Mortality in Patients With First Myocardial Infarction

PubMed Central

Canto, John G.; Kiefe, Catarina I.; Rogers, William J.; Peterson, Eric D.; Frederick, Paul D.; French, William J.; Gibson, C. Michael; Pollack, Charles V.; Ornato, Joseph P.; Zalenski, Robert J.; Penney, Jan; Tiefenbrunn, Alan J.; Greenland, Philip

2013-01-01

Context Few studies have examined the association between the number of coronary heart disease risk factors and outcomes of acute myocardial infarction in community practice. Objective To determine the association between the number of coronary heart disease risk factors in patients with first myocardial infarction and hospital mortality. Design Observational study from the National Registry of Myocardial Infarction, 1994-2006. Patients We examined the presence and absence of 5 major traditional coronary heart disease risk factors (hypertension, smoking, dyslipidemia, diabetes, and family history of coronary heart disease) and hospital mortality among 542 008 patients with first myocardial infarction and without prior cardiovascular disease. Main Outcome Measure All-cause in-hospital mortality. Results A majority (85.6%) of patients who presented with initial myocardial infarction had at least 1 of the 5 coronary heart disease risk factors, and 14.4% had none of the 5 risk factors. Age varied inversely with the number of coronary heart disease risk factors, from a mean age of 71.5 years with 0 risk factors to 56.7 years with 5 risk factors (P for trend <.001). The total number of in-hospital deaths for all causes was 50 788. Unadjusted in-hospital mortality rates were 14.9%, 10.9%, 7.9%, 5.3%, 4.2%, and 3.6% for patients with 0, 1, 2, 3, 4, and 5 risk factors, respectively. After adjusting for age and other clinical factors, there was an inverse association between the number of coronary heart disease risk factors and hospital mortality adjusted odds ratio (1.54; 95% CI, 1.23-1.94) among individuals with 0 vs 5 risk factors. This association was consistent among several age strata and important patient subgroups. Conclusion Among patients with incident acute myocardial infarction without prior cardiovascular disease, in-hospital mortality was inversely related to the number of coronary heart disease risk factors. PMID:22089719

Timely initiation of breastfeeding and associated factors among mothers of infants under 12 months in South Gondar zone, Amhara regional state, Ethiopia; 2013.

PubMed

Mekonen, Liyew; Seifu, Wubareg; Shiferaw, Zemenu

2018-01-01

Timely initiation of breastfeeding is defined as putting the newborn to the breast within one hour of birth. Significant benefits in reducing neonatal mortality and morbidity can be attained with effective promotion of timely initiation of breastfeeding and exclusive breastfeeding during the first months of life. Therefore, this study was conducted to assess timely initiation of breastfeeding and associated factors among mothers in South Gondar, Amhara regional state, Northern Ethiopia. A community based cross-sectional study was employed. A multistage stratified sampling technique was used to select the sample of 845 mothers with 97.4% response rate. Moreover, data were collected by face to face interview using a semi structured questionnaire. The prevalence of timely initiation of breastfeeding was 48.7% (54.7% in urban and 25.1% in rural areas). The odds of initiation of breastfeeding within one hour was higher for urban mothers (Adjusted Odds Ratio [AOR] 2.1; 95% Confidence Interval [CI] 1.4, 3.3), multiparous mothers (AOR 2.8; 95% CI 2.0, 3.8), mothers who had antenatal care (AOR 3.2; 95% CI 2.0, 5.2), mothers delivered in health institution (AOR 3.1; 95% CI 2.2, 4.6) and mothers delivered vaginally (AOR 4.1; 95% CI 1.7, 9.8) than their respective counterparts. This study depicts the rate of timely initiation of breastfeeding was low in south Gondar zone. Factors which were positively associated with timely initiation of breastfeeding include urban residence, multiparity, having antenatal care, mother deliver in health institution and vaginal mode of delivery. Therefore, South Gondar health office and healthcare providers have to provide breastfeeding information during antenatal care by giving special emphasis to rural and primiparous mothers in which timely initiation of breastfeeding is poorly practiced. Further study is needed to assess the implementation of policies on timely initiation of breastfeeding.

Development and Validation of the Caring Loneliness Scale.

PubMed

Karhe, Liisa; Kaunonen, Marja; Koivisto, Anna-Maija

2016-12-01

The Caring Loneliness Scale (CARLOS) includes 5 categories derived from earlier qualitative research. This article assesses the reliability and construct validity of a scale designed to measure patient experiences of loneliness in a professional caring relationship. Statistical analysis with 4 different sample sizes included Cronbach's alpha and exploratory factor analysis with principal axis factoring extraction. The sample size of 250 gave the most useful and comprehensible structure, but all 4 samples yielded underlying content of loneliness experiences. The initial 5 categories were reduced to 4 factors with 24 items and Cronbach's alpha ranging from .77 to .90. The findings support the reliability and validity of CARLOS for the assessment of Finnish breast cancer and heart surgery patients' experiences but as all instruments, further validation is needed.

Automotive Test Rig Final Design Report. Volume 1. Design and Fabrication.

DTIC Science & Technology

1986-01-01

when the ATR overrides a three inch diameter tree . The force generated in accomplishing this is estimated as 500 lbs. The initial hull configuration...and tree , hut does not alter the fact that the contact point is along the welded joint of two hull plates. In the initial analysis, as discussed in R...the current nose structure is more than adequate to withstand the overriding of a three inch diameter tree . 2.8.5 Shock Factor Diagram In conjunction

Intrinsic Predictive Factors of Noncontact Lateral Ankle Sprain in Collegiate Athletes

PubMed Central

Kobayashi, Takumi; Yoshida, Masahiro; Yoshida, Makoto; Gamada, Kazuyoshi

2013-01-01

Background: Lateral ankle sprain (LAS) is one of the most common injuries in sports. Despite extensive research, intrinsic factors that predict initial and recurrent noncontact LAS remain undefined. Purpose: To identify the predictive factors of initial and recurrent noncontact LAS, focusing on ankle flexibility and/or alignment in collegiate athletes. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 191 athletes were assessed during the preseason for factors predictive of noncontact LAS. The baseline measurements included weightbearing dorsiflexion range of motion (ROM), leg-heel angle, foot internal rotation angle in plantar flexion, classification according to the mortise test, and navicular–medial malleolus (NMM) distance. Occurrence of noncontact LAS and participation in practice and games were prospectively recorded for 11 months. Results: Of the 191 athletes assessed, 169 (145 males, 24 females) completed the study; 125 athletes had a history of ankle sprain. During the observational period, 16 athletes suffered noncontact LAS (0.58 per 1000 athlete-exposures) consisting of 4 initial sprains and 12 recurrences. The hazard ratio estimated by a Cox regression analysis showed that athletes with an NMM distance ≥4.65 cm were 4.14 times more likely to suffer an initial noncontact LAS than were athletes with a shorter NMM distance (95% confidence interval, 1.12-14.30) and that athletes with a weightbearing dorsiflexion ROM >49.5° were 1.12 times as likely to suffer a recurrent noncontact LAS compared with athletes with a lower ROM (95% confidence interval, 1.05-1.20). Conclusion: NMM distance predicts initial noncontact LAS, and weightbearing dorsiflexion ROM predicts recurrent noncontact LAS. PMID:26535263

[Tuberculin test responses of tuberculosis patients].

PubMed

Pina, J M; Domínguez, A; Alcaide, J; Alvarez, J; Camps, N; Díez, M; Godoy, P; Jansá, J M; Minguell, S

2002-12-01

To determine the response of tuberculosis patients to tuberculin skin tests. The results of skin tests used for initial assessment of tuberculosis patients in Catalonia were reviewed (Multicenter Tuberculosis Research Project). Negative skin tests were those with indurations < 5 mm; positive tests were those with indurations measuring > or = 5 mm. Individuals were classed as having or not having risk factors for developing tuberculosis and those without risk factors were classified by age, location and extension of tuberculosis. Negative skin tests were seen in 1,566 patients (23%). Negative tests were more common in patients with risk factors, significantly so in those undergoing immunosuppressant therapy (50%) or with HIV infection (61%). Negative tests were less prevalent in patients with no risk factors (13%) and, among them, in children (1%), in patients between 15 and 29 years of age (10%) or in those with non-pulmonary forms (10%). Negative tests were significantly more prevalent among patients 60 to 74 years of age (27%), those over 74 (44%), and those whose disease was pulmonary and extrapulmonary (26%) or disseminated (64%). No significant differences in induration size of positive skin tests were observed for patients with and without risk factors (including HIV infection or non-infection). A normal distribution of induration size was observed in all groups. A negative tuberculin skin test for initial assessment should be interpreted in function of the presence or absence of risk factors, age, location or extension of tuberculosis. When a skin test is positive, the response will be similar whether or not an immunodepressant factor is present.

A retrospective analysis of negative diffusion-weighted image results in patients with acute cerebral infarction

PubMed Central

Zuo, Lian; Zhang, Yue; Xu, Xiahong; Li, Ying; Bao, Huan; Hao, Junjie; Wang, Xin; Li, Gang

2015-01-01

We aimed to investigate the clinicoradiologic determinants of negative diffusion-weighted image (DWI) results in patients with acute cerebral infarction (ACI). The medical records were reviewed of ACI patients. Patients were divided to the DWI positive and negative group. Positive DWI was used as independent variable and patients' clinicoradiologic factors were used as co-variables for multivariate logistic regression analysis. 349 patients received initial cerebral MRI within 72 hours of admission. Lacunar infarction was most common (42.1%) followed by posterior circulation infarction (30.1%) and partial anterior circulation infarction (18.1%). The majority of the patients (72.2%) had an NIHSS score of less than 5 at admission. 316 patients (90.54%) were positive on initial DWI. Patients with smoking, initial SBP ≥ 140 or DBP ≥ 90 mmHg, initial fasting plasma glucose (FPG) ≥7.0 mmol/L, initial MRI from onset of disease >1 d and anterior circulation infarction were liable to show positive DWI. Furthermore, DWI negative patients had significantly lower NIHSS scores (IQR 0,1,2) than DWI positive patients (IQR 1,2,4) (P = 0.000) at two weeks post onset of acute cerebral infarction. In conclusion, multiple clinicoradiologic factors are associated with negative and positive DWI and further delineation of these factors is required in future prospective studies. PMID:25777182

The Epidemiology of IRIS in Southern India: An Observational Cohort Study

PubMed Central

Thambuchetty, Nisha; Mehta, Kayur; Arumugam, Karthika; Shekarappa, Umadevi G.; Idiculla, Jyothi; Shet, Anita

2018-01-01

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon but dynamic phenomenon seen among patients initiating antiretroviral therapy (ART). We aimed to describe incidence, risk factors, clinical spectrum, and outcomes among ART-naive patients experiencing IRIS in southern India. Among 599 eligible patients monitored prospectively between 2012 and 2014, there were 59.3% males, with mean age 36.6 ± 7.8 years. Immune reconstitution inflammatory syndrome incidence rate was 51.3 per 100 person-years (95% confidence interval: 44.5-59.2). One-third (31.4%) experienced at least 1 IRIS event, at a median of 27 days since ART initiation. Mucocutaneous infections and candidiasis were common IRIS events, followed by tuberculosis. Significant risk factors included age >40 years, body mass index <18.5 kg/m2, CD4 count <100 cells/mm3, viral load >10 000 copies/mL, hemoglobin <1 g/dL, and erythrocyte sedimentation rate >50 mm/h. Immune reconstitution inflammatory syndrome–related morality was 1.3% (8 of 599); 3 patients died of complicated diarrhea. These findings highlight the current spectrum of IRIS in South India and underscore the importance of heightened vigilance for anemia and treatment of diarrhea and candidiasis during ART initiation. PMID:28399724

An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

PubMed Central

Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

2016-01-01

The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

Region-specific role of growth differentiation factor-5 in the establishment of sympathetic innervation.

PubMed

O'Keeffe, Gerard W; Gutierrez, Humberto; Howard, Laura; Laurie, Christopher W; Osorio, Catarina; Gavaldà, Núria; Wyatt, Sean L; Davies, Alun M

2016-02-15

Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching. Here report that growth differentiation factor 5 (GDF5), a widely expressed member of the transforming growth factor beta (TGFβ) superfamily required for limb development, promoted axon growth from mouse superior cervical ganglion (SCG) neurons independently of NGF and enhanced axon growth in combination with NGF. GDF5 had no effect on neuronal survival and influenced axon growth during a narrow window of postnatal development when sympathetic axons are ramifying extensively in their targets in vivo. SCG neurons expressed all receptors capable of participating in GDF5 signaling at this stage of development. Using compartment cultures, we demonstrated that GDF5 exerted its growth promoting effect by acting directly on axons and by initiating retrograde canonical Smad signalling to the nucleus. GDF5 is synthesized in sympathetic targets, and examination of several anatomically circumscribed tissues in Gdf5 null mice revealed regional deficits in sympathetic innervation. There was a marked, highly significant reduction in the sympathetic innervation density of the iris, a smaller though significant reduction in the trachea, but no reduction in the submandibular salivary gland. There was no reduction in the number of neurons in the SCG. These findings show that GDF5 is a novel target-derived factor that promotes sympathetic axon growth and branching and makes a distinctive regional contribution to the establishment of sympathetic innervation, but unlike NGF, plays no role in regulating sympathetic neuron survival.

SU-E-T-169: Initial Investigation into the Use of Optically Stimulated Luminescent Dosimeters (OSLDs) for In-Vivo Dosimetry of TBI Patients.

PubMed

Paloor, S; Aland, T; Mathew, J; Al-Hammadi, N; Hammoud, R

2012-06-01

To report on an initial investigation into the use of optically stimulated luminescent dosimeters (OSLDs) for in-vivo dosimetry for total body irradiation (TBI) treatments. Specifically, we report on the determination of angular dependence, sensitivity correction factors and the dose calibration factors. The OSLD investigated in our work was InLight/OSL nanoDot dosimeters (Landauer Inc.). Nanodots are 5 mm diameter, 0.2 mm thick disk-shaped Carbon-doped Al2O3, and were read using a Landauer InLight microstar reader and associated software.OSLDs were irradiated under two setup conditions: a) typical clinical reference conditions (95cm SSD, 5cm depth in solid water, 10×10 cm field size), and b) TBI conditions (520cm SSD, 5cm depth in solid water, 40×40 cm field size,). The angular dependence was checked for angles ranging ±60 degree from normal incidence. In order to directly compare the sensitivity correction factors, a common dose was delivered to the OSLDs for the two setups. Pre- and post-irradiation readings were acquired. OSLDs were optically annealed under various techniques (1) by keeping over a film view box, (2) Using multiple scan on a flat bed optical scanner and (3) Using natural room light. Under reference conditions, the calculated sensitivity correction factors of the OSLDs had a SD of 2.2% and a range of 5%. Under TBI conditions, the SD increased to 3.4% and the range to 6.0%. The variation in sensitivity correction factors between individual OSLDs across the two measurement conditions was up to 10.3%. Angular dependence of less than 1% is observed. The best bleaching method we found is to keep OSLDs for more than 3 hours on a film viewer which will reduce normalized response to less than 1%. In order to obtain the most accurate results when using OSLDs for in-vivo dosimetry for TBI treatments, sensitivity correction factors and dose calibration factors should all be determined under clinical TBI conditions. © 2012 American Association of Physicists in Medicine.

The hierarchical structure of DSM-5 pathological personality traits.

PubMed

Wright, Aidan G C; Thomas, Katherine M; Hopwood, Christopher J; Markon, Kristian E; Pincus, Aaron L; Krueger, Robert F

2012-11-01

A multidimensional trait system has been proposed for representing personality disorder (PD) features in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to address problematic classification issues such as comorbidity. In this model, which may also assist in providing scaffolding for the underlying structure of major forms of psychopathology more generally, 25 primary traits are organized by 5 higher order dimensions: Negative Affect, Detachment, Antagonism, Disinhibition, and Psychoticism. We examined (a) the generalizability of the structure proposed for DSM-5 PD traits, and (b) the potential for an integrative hierarchy based upon DSM-5 PD traits to represent the dimensions scaffolding psychopathology more generally. A large sample of student participants (N = 2,461) completed the Personality Inventory for DSM-5, which operationalizes the DSM-5 traits. Exploratory factor analysis replicated the initially reported 5-factor structure, as indicated by high factor congruencies. The 2-, 3-, and 4-factor solutions estimated in the hierarchy of the DSM-5 traits bear close resemblance to existing models of common mental disorders, temperament, and personality pathology. Thus, beyond the description of individual differences in personality disorder, the trait dimensions might provide a framework for the metastructure of psychopathology in the DSM-5 and the integration of a number of ostensibly competing models of personality trait covariation. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Small self-RNA generated by RNase L amplifies antiviral innate immunity

PubMed Central

Malathi, Krishnamurthy; Dong, Beihua; Gale, Michael; Silverman, Robert H.

2013-01-01

Antiviral innate immunity is initiated in response to RNA molecules that are produced in virus-infected cells1. These RNAs activate signalling cascades that activate the genes that encode α- and β-interferon (IFN). Signalling occurs through the interaction of the RNAs with either of two pathogen recognition receptors, retinoic acid-inducible gene-I (RIG-I, also known as DDX58) and melanoma differentiation associated gene-5 (MDA5, also known as IFIH1), which contain amino-terminal caspase activation and recruitment domains (CARD) and carboxy-terminal DExD/H Box RNA helicase motifs2-5. RIG-I and MDA5 interact with another CARD protein, interferon-β promotor stimulator protein-1 (IPS-1, also known as MAVS, VISA and Cardif), in the mitochondrial membrane, which relays the signal through the transcription factors interferon regulatory factor 3 (IRF-3) and nuclear factor (NF)-κB to the IFN-β gene6-10. Although the signalling pathway is well understood, the origin of the RNA molecules that initiate these processes is not. Here we show that activation of the antiviral endoribonuclease, RNase L11, by 2′,5′-linked oligoadenylate (2-5A)12 produces small RNA cleavage products from self-RNA that initiate IFN production. Accordingly, mouse embryonic fibroblasts lacking RNase L were resistant to the induction of IFN-β expression in response to 2-5A, dsRNA or viral infection. Single-stranded regions of RNA are cleaved 3′ of UpUp and UpAp sequences by RNase L during viral infections, resulting in small, often duplex, RNAs13,14. We show that small self-RNAs produced by the action of RNase L on cellular RNA induce IFN-β expression and that the signalling involves RIG-I, MDA5 and IPS-1. Mice lacking RNase L produce significantly less IFN-β during viral infections than infected wild-type mice. Furthermore, activation of RNase L with 2-5A in vivo induced the expression of IFN-β in wild-type but not RNase L-deficient mice. Our results indicate that RNase L has an essential role in the innate antiviral immune response that relieves the requirement for direct sensing of non-self RNA. PMID:17653195

Does the cerebellum initiate movement?

PubMed

Thach, W T

2014-02-01

Opinion is divided on what the exact function of the cerebellum is. Experiments are summarized that support the following views: (1) the cerebellum is a combiner of multiple movement factors; (2) it contains anatomically fixed permanent focal representation of individual body parts (muscles and segments) and movement modes (e.g., vestibular driven vs. cognitive driven); (3) it contains flexible changing representations/memory of physical properties of the body parts including muscle strength, segment inertia, joint viscosity, and segmental interaction torques (dynamics); (4) it contains mechanisms for learning and storage of the properties in item no. 3 through trial-and-error practice; (5) it provides for linkage of body parts, motor modes, and motordynamics via the parallel fiber system; (6) it combines and integrates the many factors so as to initiate coordinated movements of the many body parts; (7) it is thus enabled to play the unique role of initiating coordinated movements; and (8) this unique causative role is evidenced by the fact that: (a) electrical stimulation of the cerebellum can initiate compound coordinated movements; (b) in naturally initiated compound movements, cerebellar discharge precedes that in downstream target structures such as motor cerebral cortex; and (c) cerebellar ablation abolishes the natural production of compound movements in the awake alert individuals.

Initial stability of cementless acetabular cups: press-fit and screw fixation interaction--an in vitro biomechanical study.

PubMed

Tabata, Tomonori; Kaku, Nobuhiro; Hara, Katsutoshi; Tsumura, Hiroshi

2015-04-01

Press-fit and screw fixation are important technical factors to achieve initial stability of a cementless acetabular cup for good clinical results of total hip arthroplasty. However, how these factors affect one another in initial cup fixation remains unclear. Therefore, this study aimed to evaluate the mutual influence between press-fit and screw fixation on initial cup stability. Foam bone was subjected to exact hemispherical-shape machining to diameters of 48, 48.5 and 49 mm. A compressive force was applied to ensure seating of a 48-mm-diameter acetabular cup in the foam bone prior to testing. Screws were inserted in six different conditions and tightened in a radial direction at the same torque strength. Then, the socket was rotated with a twist-testing machine, and the torque value at the start of axial rotation between the socket and the foam bone was measured under each screw condition. The torque values for the 48-mm-diameter reaming were >20 N m higher than those for the 48.5- and 49-mm-diameter reaming in each screw condition, indicating that press-fit fixation is stronger than screw fixation. Meanwhile, torque values for the 48.5- and 49-mm-diameter reaming tended to increase with increasing the number of screws. According to our experiment, press-fit fixation of a cementless acetabular cup achieved rigid stability. Although the supplemental screws increased stability of the implant under good press-fit conditions, they showed little impact on whole-cup stability. In the case of insufficient press-fit fixation, cup stability depends on screw stability and increasing the number of additional screws increases cup stability.

Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5

PubMed Central

Ng, Ray Kit; Dean, Wendy; Dawson, Claire; Lucifero, Diana; Madeja, Zofia; Reik, Wolf; Hemberger, Myriam

2008-01-01

Mouse ES cells can differentiate into all three germ layers of the embryo but are generally excluded from the trophoblast lineage. Here we show that ES cells deficient in DNA methylation can differentiate efficiently into trophoblast derivatives. In a genome-wide screen we identify the transcription factor Elf5 as methylated and repressed in ES cells, and hypomethylated and expressed in TS and methylation-deficient ES cells. Elf5 creates a positive feedback loop with TS cell determinants Cdx2 and Eomes that is restricted to the trophoblast lineage by epigenetic regulation of Elf5. Importantly, the late-acting function of Elf5 allows initial plasticity and regulation in the early blastocyst. Thus, Elf5 acts downstream of initial lineage determination as a gatekeeper to reinforce commitment to the trophoblast lineage, or to abort this pathway in epiblast cells. This epigenetic restriction of cell lineage fate provides a molecular mechanism for Waddington’s concept of canalization of developmental pathways. PMID:18836439

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

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

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2more » is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.« less

Inhibition of PKR Activation by the Proline-Rich RNA Binding Domain of the Herpes Simplex Virus Type 1 Us11 Protein

PubMed Central

Poppers, Jeremy; Mulvey, Matthew; Khoo, David; Mohr, Ian

2000-01-01

Upon activation by double-stranded RNA in virus-infected cells, the cellular PKR kinase phosphorylates the translation initiation factor eukaryotic initiation factor 2 (eIF2) and thereby inhibits protein synthesis. The γ34.5 and Us11 gene products encoded by herpes simplex virus type 1 (HSV-1) are dedicated to preventing the accumulation of phosphorylated eIF2. While the γ34.5 gene specifies a regulatory subunit for protein phosphatase 1α, the Us11 gene encodes an RNA binding protein that also prevents PKR activation. γ34.5 mutants fail to grow on a variety of human cells as phosphorylated eIF2 accumulates and protein synthesis ceases prior to the completion of the viral life cycle. We demonstrate that expression of a 68-amino-acid fragment of Us11 containing a novel proline-rich basic RNA binding domain allows for sustained protein synthesis and enhanced growth of γ34.5 mutants. Furthermore, this fragment is sufficient to inhibit activation of the cellular PKR kinase in a cell-free system, suggesting that the intrinsic activities of this small fragment, notably RNA binding and ribosome association, may be required to prevent PKR activation. PMID:11070019

Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein.

PubMed

Poppers, J; Mulvey, M; Khoo, D; Mohr, I

2000-12-01

Upon activation by double-stranded RNA in virus-infected cells, the cellular PKR kinase phosphorylates the translation initiation factor eukaryotic initiation factor 2 (eIF2) and thereby inhibits protein synthesis. The gamma 34.5 and Us11 gene products encoded by herpes simplex virus type 1 (HSV-1) are dedicated to preventing the accumulation of phosphorylated eIF2. While the gamma 34.5 gene specifies a regulatory subunit for protein phosphatase 1 alpha, the Us11 gene encodes an RNA binding protein that also prevents PKR activation. gamma 34.5 mutants fail to grow on a variety of human cells as phosphorylated eIF2 accumulates and protein synthesis ceases prior to the completion of the viral life cycle. We demonstrate that expression of a 68-amino-acid fragment of Us11 containing a novel proline-rich basic RNA binding domain allows for sustained protein synthesis and enhanced growth of gamma 34.5 mutants. Furthermore, this fragment is sufficient to inhibit activation of the cellular PKR kinase in a cell-free system, suggesting that the intrinsic activities of this small fragment, notably RNA binding and ribosome association, may be required to prevent PKR activation.

A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR-Dependent Mechanism for Stomatal Development.

PubMed

de Marcos, Alberto; Houbaert, Anaxi; Triviño, Magdalena; Delgado, Dolores; Martín-Trillo, Mar; Russinova, Eugenia; Fenoll, Carmen; Mena, Montaña

2017-06-01

The asymmetric cell divisions necessary for stomatal lineage initiation and progression in Arabidopsis ( Arabidopsis thaliana ) require the function of the basic helix-loop-helix (bHLH) transcription factor SPEECHLESS ( SPCH ). Mutants lacking SPCH do not produce stomata or lineages. Here, we isolated a new spch-5 allele carrying a point mutation in the bHLH domain that displayed normal growth, but had an extremely low number of sometimes clustered stomata in the leaves, whereas the hypocotyls did not have any stomata. In vivo tracking of leaf epidermal cell divisions, combined with marker lines and genetic analysis, showed that the spch-5 leaf phenotype is dosage dependent and results from the decreased ability to initiate and amplify lineages, defects in asymmetric cell fate allocation, and misorientation of asymmetric division planes. Notably, application of brassinosteroids (BRs) partly rescued the stomatal leaf phenotype of spch-5 Transcriptomic analysis combining spch-5 with BR treatments revealed that the expression of a set of SPCH target genes was restored by BRs. Our results also show that BR-dependent stomata formation and expression of some, but not all, SPCH target genes require the integrity of the bHLH domain of SPCH. © 2017 American Society of Plant Biologists. All Rights Reserved.

A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR-Dependent Mechanism for Stomatal Development1

PubMed Central

Triviño, Magdalena; Delgado, Dolores; Martín-Trillo, Mar

2017-01-01

The asymmetric cell divisions necessary for stomatal lineage initiation and progression in Arabidopsis (Arabidopsis thaliana) require the function of the basic helix-loop-helix (bHLH) transcription factor SPEECHLESS (SPCH). Mutants lacking SPCH do not produce stomata or lineages. Here, we isolated a new spch-5 allele carrying a point mutation in the bHLH domain that displayed normal growth, but had an extremely low number of sometimes clustered stomata in the leaves, whereas the hypocotyls did not have any stomata. In vivo tracking of leaf epidermal cell divisions, combined with marker lines and genetic analysis, showed that the spch-5 leaf phenotype is dosage dependent and results from the decreased ability to initiate and amplify lineages, defects in asymmetric cell fate allocation, and misorientation of asymmetric division planes. Notably, application of brassinosteroids (BRs) partly rescued the stomatal leaf phenotype of spch-5. Transcriptomic analysis combining spch-5 with BR treatments revealed that the expression of a set of SPCH target genes was restored by BRs. Our results also show that BR-dependent stomata formation and expression of some, but not all, SPCH target genes require the integrity of the bHLH domain of SPCH. PMID:28507175

How Long Are Cancer Patients Waiting for Oncological Therapy in Poland?

PubMed

Osowiecka, Karolina; Rucinska, Monika; Nowakowski, Jacek J; Nawrocki, Sergiusz

2018-03-23

The five-year relative survival rate in Poland is approximately 10% lower compared with the average for Europe. One of the factors that may contribute to the inferior treatment results in Poland could be the long time between cancer suspicion and the beginning of treatment. The aim of the study was to determine the real waiting time for cancer diagnosis and treatment in Poland. The study was carried out in six cancer centers on a group of 1373 patients, using a questionnaire to interview patients. The median waiting time was estimated as follows: (A) from suspicion (the date of the first visit, with symptoms, to a doctor or a preventive or screening test) until histopathological diagnosis; (B) from suspicion until initial treatment; and (C) from diagnosis until initial treatment. The median times from suspicion to treatment, from suspicion to diagnosis, and from diagnosis to treatment, were 10.6, 5.6, and 5.0 weeks, respectively. Using multivariate analysis, the strongest influence was estimated, in a case of tumor localization, to be the method of initial treatment and facilities. The waiting time for cancer treatment in Poland is too long. The highest influence on waiting time was determined, in the case of tumors, as the type of cancer and factors related to the health care system.

The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar

PubMed Central

Dorrell, Craig; Tarlow, Branden; Wang, Yuhan; Canaday, Pamela S; Haft, Annelise; Schug, Jonathan; Streeter, Philip R; Finegold, Milton J; Shenje, Lincoln T; Kaestner, Klaus H; Grompe, Markus

2014-01-01

Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5+ organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3+/CD133+/CD26− in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah-/- mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination. PMID:25151611

Sociocultural Determinants of Tobacco Smoking Initiation among University Students in Bucaramanga, Colombia, 2012.

PubMed

Afanador, Laura Del Pilar Cadena; Radi, Daniel Sebastián Salazar; Pinto, Luis Enrique Vásquez; Pinzón, Cristian Eduardo Pérez; Carreño, Manuel Felipe Castro

2014-09-01

Tobacco smoking is the leading cause of preventable mortality. The prevalence of smoking in adolescents in high schools ranges from 23.5% to 41%, respectively. In Colombia, these figures are similar and students entering the University are exposed to initiate smoking. The purpose of this study was to establish the determinants associated with the initiation of tobacco smoking among university students. A case-control paired by sex and age study design was used. The study population was the students of a private university of Bucaramanga, Santander, Colombia. The final sample consisted of 167 cases and 314 controls randomly select undergraduate university students. Data analysis was performed using a Logistic regression model adjusted by gender and age; using the initiation of tobacco smoking as the dependent variable, and as independent variables relationship with parents, history of parental smoking, university social environment, being away from hometown, steady girlfriend/boyfriend who smokes, alcohol consumption, physical activity, and Francis Score. THE SOCIAL ENVIRONMENT (ODDS RATIO [OR]: 32.70, 7.40-144.55), being away from hometown (OR: 3.06, 1.55-6.07), history of steady girlfriend/boyfriend who smoke (OR: 2.87, 1.43-5.76), a bad relationship with the father (OR: 8.01, 2.01-31.83), history of tobacco consumption of the mother (OR: 2.66, 1.37-5.17) and alcohol consumption (OR: 4.79, 1.91-12.00) appeared as determinants of initiation of tobacco smoking. As protector factors we found media advertisement (OR: 0.19, 0.05-0.71), light physical activity 2-3 times a week (OR: 0.33, 0.12-0.88), and a high result in Francis score (OR: 0.95, 0.919-0.99). University efforts for tobacco-free policies should focus on preventive advertisement, promoting physical activity and awareness among young students of social environmental factors that could influence their decision to start smoking tobacco.

Interference-Fit Life Factors for Roller Bearings

NASA Technical Reports Server (NTRS)

Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

2009-01-01

The effect of hoop stresses in reducing cylindrical roller bearing fatigue life was determined for various classes of inner-ring interference fit. Calculations were performed for up to 7 fit classes for each of 10 bearing sizes. The hoop stresses were superimposed on the Hertzian principal stresses created by the applied radial load to calculate roller bearing fatigue life. A method was developed through a series of equations to calculate the life reduction for cylindrical roller bearings. All calculated lives are for zero initial internal clearance. Any reduction in bearing clearance due to interference fit would be compensated by increasing the initial (unmounted) clearance. Results are presented as tables and charts of life factors for bearings with light, moderate, and heavy loads and interference fits ranging from extremely light to extremely heavy for bearing accuracy class RBEC-5 (ISO class 5). Interference fits on the inner ring of a cylindrical roller bearing can significantly reduce bearing fatigue life. In general, life factors are smaller (lower life) for bearings running under light load where the unfactored life is highest. The various bearing series within a particular bore size had almost identical interference-fit life factors for a particular fit. The tightest fit at the high end of the tolerance band produces a life factor of approximately 0.40 for an inner-race maximum Hertz stress of 1200 MPa (175 ksi) and a life factor of 0.60 for an inner-race maximum Hertz stress of 2200 MPa (320 ksi). Interference fits also impact the maximum Hertz stress-life relation.

Application of response surface methodology for optimization of biosorption of fluoride from groundwater using Shorea robusta flower petal

NASA Astrophysics Data System (ADS)

Biswas, G.; Kumari, M.; Adhikari, K.; Dutta, S.

2017-12-01

Fluoride pollution in groundwater is a major concern in rural areas. The flower petal of Shorea robusta, commonly known as sal tree, is used in the present study both in its native form and Ca-impregnated activated form to eradicate excess fluoride from simulated wastewater. Response surface methodology (RSM) was used for experimental designing and analyzing optimum condition for carbonization vis-à-vis calcium impregnation for preparation of adsorbent. During carbonization, temperature, time and weight ratio of calcium chloride to sal flower petal (SFP) have been considered as input factors and percentage removal of fluoride as response. Optimum condition for carbonization has been obtained as temperature, 500 °C; time, 1 h and weight ratio, 2.5 and the sample prepared has been termed as calcium-impregnated carbonized sal flower petal (CCSFP). Optimum condition as analyzed by one-factor-at-a-time (OFAT) method is initial fluoride concentration, 2.91 mg/L; pH 3 and adsorbent dose, 4 g/L. CCSFP shows maximum removal of 98.5% at this condition. RSM has also been used for finding out optimum condition for defluoridation considering initial concentration, pH and adsorbent dose as input parameters. The optimum condition as analyzed by RSM is: initial concentration, 5 mg/L; pH 3.5 and adsorbent dose, 2 g/L. Kinetic and equilibrium data follow Ho pseudo-second-order kinetic model and Freundlich isotherm model, respectively. Adsorption capacity of CCSFP has been found to be 5.465 mg/g. At optimized condition, CCSFP has been found to remove fluoride (80.4%) efficiently from groundwater collected from Bankura district in West Bengal, a fluoride-contaminated province in India.

Development of the Professional Self-Care Scale.

PubMed

Dorociak, Katherine E; Rupert, Patricia A; Bryant, Fred B; Zahniser, Evan

2017-04-01

In recent years, there has been an increased emphasis on the importance of self-care for psychologists and other mental health professionals. With the growth of positive psychology and preventive medicine, self-care is an emerging topic, promulgated as a means of avoiding the adverse effects of stress and promoting professional functioning and well-being. However, the research on self-care is limited because of the lack of an empirically based, psychometrically sound measure of this construct. Thus, the purpose of this project was to develop a measure of professional self-care. Professional psychologists were the focus of study, with the goal being to develop a measure that can be used in this population and similar groups of professionals. Based on expert feedback and a preliminary study of 422 licensed psychologists in Illinois, a 5-factor, 21-item scale was created. Factor analysis identified the following self-care factors: Professional Support, Professional Development, Life Balance, Cognitive Awareness, and Daily Balance. Preliminary analyses provided initial support for the validity of the 5 factors. A follow-up study was conducted with a second sample of clinical psychologists. The 5-factor structure provided a good fit to the data with the second sample. Thus, based on factor analysis and validity data, a 5-factor, 21-item Professional Self-Care Scale was established for further study and use in future research. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

C-reactive protein as a prognostic indicator for rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

PubMed

Lee, Han Hee; Park, Jae Myung; Lee, Soon-Wook; Kang, Seung Hun; Lim, Chul-Hyun; Cho, Yu Kyung; Lee, Bo-In; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gyu

2015-05-01

In patients with acute nonvariceal upper gastrointestinal bleeding, rebleeding after an initial treatment is observed in 10-20% and is associated with mortality. To investigate whether the initial serum C-reactive protein level could predict the risk of rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding. This was a retrospective study using prospectively collected data for upper gastrointestinal bleeding. Initial clinical characteristics, endoscopic features, and C-reactive protein levels were compared between those with and without 30-day rebleeding. A total of 453 patients were included (mean age, 62 years; male, 70.9%). The incidence of 30-day rebleeding was 15.9%. The mean serum C-reactive protein level was significantly higher in these patients than in those without rebleeding (P<0.001). The area under the receiver operating characteristics curve with a cutoff value of 0.5mg/dL was 0.689 (P<0.001). High serum C-reactive protein level (odds ratio, 2.98; confidence interval, 1.65-5.40) was independently associated with the 30-day rebleeding risk after adjustment for the main confounding risk factors, including age, blood pressure, and initial haemoglobin level. The serum C-reactive protein was an independent risk factor for 30-day rebleeding in patients with acute nonvariceal upper gastrointestinal bleeding, indicating a possible role as a useful screening indicator for predicting the risk of rebleeding. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Intensive exposure as a risk factor for severe polio: a study of multiple family cases.

PubMed

Nielsen, N M; Aaby, P; Wohlfahrt, J; Pedersen, J B; Melbye, M; Mølbak, K

2001-01-01

To examine the importance of intensity of exposure for the outcome of the poliomyelitis infection 429 polio cases were identified belonging to families with 2, 3 or 4 polio cases, all hospitalized in Copenhagen from 1919 to 1953. Furthermore, 87 pairs of polio cases living on the same stairway, but not in the same household, were identified. Severity among multiple cases in families analysed according to time of appearance showed a U-shaped curve. Initial cases had a higher risk of developing paralysis [relative risk (RR) = 1.5, 95% confidence interval (CI) 1.2-1.91 and of dying (RR = 2.5, 95% CI 0.9-6.9). Decreased severity was observed among subsequent cases appearing within 11 d after the initial case (RR = 1.0); however, severity increased again, with higher mortality for cases likely to have been infected by the initial case (cases appearing more than 11 d later) (RR = 5.7, 95% CI 1.8-17.8). The pattern described among multiple family cases was not found among cases from the same stairway. Since family cases appearing within 11 d were probably infected simultaneously, a short incubation period is associated with severe disease and a prolonged incubation period with milder infections. Furthermore, intensive exposure from being infected in the household increased severity. These observations therefore suggest that intensity of exposure and dose of infection are important factors in the severity of poliomyelitis.

The Nematode Eukaryotic Translation Initiation Factor 4E/G Complex Works with a trans-Spliced Leader Stem-Loop To Enable Efficient Translation of Trimethylguanosine-Capped RNAs ▿ †

PubMed Central

Wallace, Adam; Filbin, Megan E.; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E.

2010-01-01

Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5′ end through the eIF4F initiation complex binding to the 5′ m7G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5′ end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m7G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5′ untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs. PMID:20154140

The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs.

PubMed

Wallace, Adam; Filbin, Megan E; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E

2010-04-01

Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m(7)G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5' untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs.

Mobile computing initiatives within pharmacy education.

PubMed

Cain, Jeff; Bird, Eleanora R; Jones, Mikael

2008-08-15

To identify mobile computing initiatives within pharmacy education, including how devices are obtained, supported, and utilized within the curriculum. An 18-item questionnaire was developed and delivered to academic affairs deans (or closest equivalent) of 98 colleges and schools of pharmacy. Fifty-four colleges and schools completed the questionnaire for a 55% completion rate. Thirteen of those schools have implemented mobile computing requirements for students. Twenty schools reported they were likely to formally consider implementing a mobile computing initiative within 5 years. Numerous models of mobile computing initiatives exist in terms of device obtainment, technical support, infrastructure, and utilization within the curriculum. Responders identified flexibility in teaching and learning as the most positive aspect of the initiatives and computer-aided distraction as the most negative, Numerous factors should be taken into consideration when deciding if and how a mobile computing requirement should be implemented.

MicroRNA-9 enhances sensitivity to cetuximab in epithelial phenotype hepatocellular carcinoma cells through regulation of the eukaryotic translation initiation factor 5A-2.

PubMed

Xue, Fei; Liang, Yuntian; Li, Zhenrong; Liu, Yanhui; Zhang, Hongwei; Wen, Yu; Yan, Lei; Tang, Qiang; Xiao, Erhui; Zhang, Dongyi

2018-01-01

Hepatocellular carcinoma (HCC) is one of the most widespread malignant human tumors worldwide. Treatment options include radiotherapy, surgical intervention and chemotherapy; however, drug resistance is an ongoing treatment concern. In the present study, the effects of a microRNA (miR/miRNA), miR-9, on the sensitivity of HCC cell lines to the epidermal growth factor receptor inhibitor, cetuximab, were examined. miR-9 has been proposed to serve a role in tumorigenesis and tumor progression. In the present study, bioinformatics analyses identified the eukaryotic translation initiation factor 5A2 (eIF-5A-2) as a target of miR-9. The expression levels of miR-9 and eIF-5A-2 were examined by reverse transcription-quantitative polymerase chain reaction and HCC cell lines were transfected with miR-9 mimics and inhibitors to determine the effects of the miRNA on cell proliferation and viability. The miR-9 mimic was revealed to significantly increase the sensitivity of epithelial phenotype HCC cells (Hep3B and Huh7) to cetuximab, while the miR-9 inhibitor triggered the opposite effect. There were no significant differences in sensitivity to cetuximab observed in mesenchymal phenotype HCC cells (SNU387 and SNU449). Cells lines displaying high expression levels of eIF-5A-2 were more resistant to cetuximab. Transfection of cells with a miR-9 mimic resulted in downregulation of the expression of eIF-5A-2 mRNA, while an miR-9 inhibitor increased expression. When expression of eIF-5A-2 was knocked down with siRNA, the effects of miR-9 on cetuximab sensitivity were no longer observed. Taken together, these data support a role for miR-9 in enhancing the sensitivity of epithelial phenotype HCC cells to cetuximab through regulation of eIF-5A-2.

Influencing Factors of the Initiation Point in the Parachute-Bomb Dynamic Detonation System

NASA Astrophysics Data System (ADS)

Qizhong, Li; Ye, Wang; Zhongqi, Wang; Chunhua, Bai

2017-12-01

The parachute system has been widely applied in modern armament design, especially for the fuel-air explosives. Because detonation of fuel-air explosives occurs during flight, it is necessary to investigate the influences of the initiation point to ensure successful dynamic detonation. In fact, the initiating position exist the falling area in the fuels, due to the error of influencing factors. In this paper, the major influencing factors of initiation point were explored with airdrop and the regularity between initiation point area and factors were obtained. Based on the regularity, the volume equation of initiation point area was established to predict the range of initiation point in the fuel. The analysis results showed that the initiation point appeared area, scattered on account of the error of attitude angle, secondary initiation charge velocity, and delay time. The attitude angle was the major influencing factors on a horizontal axis. On the contrary, secondary initiation charge velocity and delay time were the major influencing factors on a horizontal axis. Overall, the geometries of initiation point area were sector coupled with the errors of the attitude angle, secondary initiation charge velocity, and delay time.

Dimensions of Oppositional Defiant Disorder in Young Children: Heterotypic Continuity with Anxiety and Depression

PubMed Central

Lavigne, John V.; Gouze, Karen R.; Bryant, Fred B.; Hopkins, Joyce

2014-01-01

There are distinct dimensions of Oppositional Defiant Disorder (ODD) that have been associated with symptoms of other disorders (heterotypic continuity). The present study compared the heterotypic continuity of a two-factor (Pitt-2) model and the three-factor model incorporated into DSM-5 with symptoms of anxiety and depression. Participants were a diverse community sample of 796 children (38.8% minority, 49.1% boys) assessed at ages 4, 5 and 6 years. Symptoms were assessed with the dimensional scales of the Diagnostic Interview Schedule for Children-Young Child version and the Child Symptom Inventory. Dimensions of both the two- and three-factor DSM-5 models were associated with later symptoms of anxiety and depression. The association, however, was weak when accounting for initial levels of internalizing symptoms: thus there was little evidence for the unique contributions of ODD dimensions to symptoms of subsequent internalizing disorders for either model. PMID:24497230

Real-time observation of the initiation of RNA polymerase II transcription.

PubMed

Fazal, Furqan M; Meng, Cong A; Murakami, Kenji; Kornberg, Roger D; Block, Steven M

2015-09-10

Biochemical and structural studies have shown that the initiation of RNA polymerase II transcription proceeds in the following stages: assembly of the polymerase with general transcription factors and promoter DNA in a 'closed' preinitiation complex (PIC); unwinding of about 15 base pairs of the promoter DNA to form an 'open' complex; scanning downstream to a transcription start site; synthesis of a short transcript, thought to be about 10 nucleotides long; and promoter escape. Here we have assembled a 32-protein, 1.5-megadalton PIC derived from Saccharomyces cerevisiae, and observe subsequent initiation processes in real time with optical tweezers. Contrary to expectation, scanning driven by the transcription factor IIH involved the rapid opening of an extended transcription bubble, averaging 85 base pairs, accompanied by the synthesis of a transcript up to the entire length of the extended bubble, followed by promoter escape. PICs that failed to achieve promoter escape nevertheless formed open complexes and extended bubbles, which collapsed back to closed or open complexes, resulting in repeated futile scanning.

Syntactic Language Correlates of Written Communication Apprehension.

ERIC Educational Resources Information Center

Stacks, Don W.; And Others

A study provided the initial test of a multidimensional instrument based on the idea that syntactic language choice might predict writing apprehension. The test measured six factors: (1) blank page paralysis, (2) general affect toward writing, (3) positive/negative business affect, (4) alternative modes, (5) attitude toward writing competence, and…

Negative and Translation Termination-Dependent Positive Control of FLI-1 Protein Synthesis by Conserved Overlapping 5′ Upstream Open Reading Frames in Fli-1 mRNA

PubMed Central

Sarrazin, Sandrine; Starck, Joëlle; Gonnet, Colette; Doubeikovski, Alexandre; Melet, Fabrice; Morle, François

2000-01-01

The proto-oncogene Fli-1 encodes a transcription factor of the ets family whose overexpression is associated with multiple virally induced leukemias in mouse, inhibits murine and avian erythroid cell differentiation, and induces drastic perturbations of early development in Xenopus. This study demonstrates the surprisingly sophisticated regulation of Fli-1 mRNA translation. We establish that two FLI-1 protein isoforms (of 51 and 48 kDa) detected by Western blotting in vivo are synthesized by alternative translation initiation through the use of two highly conserved in-frame initiation codons, AUG +1 and AUG +100. Furthermore, we show that the synthesis of these two FLI-1 isoforms is regulated by two short overlapping 5′ upstream open reading frames (uORF) beginning at two highly conserved upstream initiation codons, AUG −41 and GUG −37, and terminating at two highly conserved stop codons, UGA +35 and UAA +15. The mutational analysis of these two 5′ uORF revealed that each of them negatively regulates FLI-1 protein synthesis by precluding cap-dependent scanning to the 48- and 51-kDa AUG codons. Simultaneously, the translation termination of the two 5′ uORF appears to enhance 48-kDa protein synthesis, by allowing downstream reinitiation at the 48-kDa AUG codon, and 51-kDa protein synthesis, by allowing scanning ribosomes to pile up and consequently allowing upstream initiation at the 51-kDa AUG codon. To our knowledge, this is the first example of a cellular mRNA displaying overlapping 5′ uORF whose translation termination appears to be involved in the positive control of translation initiation at both downstream and upstream initiation codons. PMID:10757781

Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

PubMed Central

Seeley, Todd W; Sternlicht, Mark D; Klaus, Stephen J; Neff, Thomas B; Liu, David Y

2017-01-01

The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. PMID:28331872

Epidemiology and Risk Factors for Cancer After Lung Transplantation.

PubMed

Berastegui, C; LaPorta, R; López-Meseguer, M; Romero, L; Gómez-Ollés, S; Riera, J; Monforte, V; Sáez, B; Bravo, C; Roman, A; Ussetti, P

2017-12-01

Cancer is the third most common cause of death among lung transplant (LT) recipients who survive for more than 1 year. The purpose of this study was to analyze the incidence and risk factors for cancer after LT in a Spanish cohort. The epidemiology and risk factors for cancer were retrospectively analyzed in LT recipients from 2 cities in Spain, Madrid and Barcelona. Of the 1353 LT patients initially included in the study, 125 (9.2%) developed cancer after a mean of 3.7 years. This frequency was 5-fold higher than in the general population. The most prevalent tumors were skin cancer (32%), lymphoproliferative disease (18%), and lung cancer (16.5%). In 4 patients, lung cancer was diagnosed on the day of the operation. The risk of cancer increased with age >55 year (hazard ratio [HR] 2.89 [1.64-5.09]; P < .001), in men (HR 2.8 [1.4-5.6]; P = .004), and in heavy smokers (>20 pack-years) (HR 2.94 [1.64-5.27]; P < .001). Other factors such as sun exposure were not found to be risk factors. In conclusion, prevalence of cancer is high in LT recipients in a Mediterranean country. Skin tumors, lymphoproliferative disease, and lung cancer are the most prevalent cancers. Age, male sex, and smoking were the main risk factors for cancer in this population. Copyright © 2017. Published by Elsevier Inc.

Definition of Two Angiogenic Pathways by Distinct α_v Integrins

NASA Astrophysics Data System (ADS)

Friedlander, Martin; Brooks, Peter C.; Shaffer, Robert W.; Kincaid, Christine M.; Varner, Judith A.; Cheresh, David A.

1995-12-01

Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist and were defined by their dependency on distinct vascular cell integrins. In vivo angiogenesis in corneal or chorioallantoic membrane models induced by basic fibroblast growth factor or by tumor necrosis factor-α depended on α_vβ_3, whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-α, or phorbol ester depended on α_vβ_5. Antibody to each integrin selectively blocked one of these pathways, and a cyclic peptide antagonist of both integrins blocked angiogenesis stimulated by each cytokine tested. These pathways are further distinguished by their sensitivity to calphostin C, an inhibitor of protein kinase C that blocked angiogenesis potentiated by α_vβ_5 but not by α_vβ_3.

Visual outcome in Japanese patients with Acanthamoeba keratitis.

PubMed

Yamazoe, K; Yamamoto, Y; Shimazaki-Den, S; Shimazaki, J

2012-04-01

To identify prognostic factors affecting visual outcome in Acanthamoeba keratitis (AK) treated with topical chlorhexidine gluconate (CHG). A total of 35 eyes in 34 patients with AK were treated with 0.02% topical CHG. Patients were divided into two groups according to the final visual outcome: Group 1, final visual acuity (VA) of 20/25 or greater (22 eyes); Group 2, less than 20/25 (13 eyes). We compared these groups and evaluated the effectiveness of topical CHG compared with outcomes in previous reports. Ring infiltrate was observed more often in Group 2 (4.5% vs 61.5%, OR 33.6, 95% confidence interval (CI) 3.4-333.9, P<0.01). The duration between onset and diagnosis of AK was significantly longer (24.9 days vs 48.4 days, OR 1.03, 95% CI 1.00-1.06, P = 0.04) and VA at initial examination (log MAR) significantly lower (0.47 vs 1.59, OR 25.5, 95% CI 3.4-186.7, P<0.01) in Group 2 (visual outcome <20/25). Multivariate analysis revealed that only VA at initial examination was independently associated with worse visual outcome (adjusted OR 24.5, 95% CI 1.9-312.6, P=0.01). Seventeen (85.0%) of the 20 eyes diagnosed within 1 month and 24 (82.8%) of 29 eyes diagnosed within 2 months achieved a VA of 20/40 or greater. VA at initial examination was the most predictive factors for final visual outcome in AK. Topical CHG was comparably effective to other treatments, including polyhexamethyl biguanide and propamidine isethionate.

A National Cohort Study of U.S. Medical School Students Who Initially Failed Step 1 of the United States Medical Licensing Examination

PubMed Central

Andriole, Dorothy A.; Jeffe, Donna B.

2012-01-01

Purpose To describe educational outcomes for a national cohort of U.S. medical students who initially failed Step 1 of the United States Medical Licensing Examination Method The authors analyzed de-identified, individualized records for the 1993–2000 cohort of U.S. medical school matriculants who both initially failed Step l and were no longer in medical school as of March 2, 2009, using multivariable logistic regression to identify factors associated with attempting, and initially passing, Step 2 Clinical Knowledge (CK). Results Of 6,594 students who failed Step l, 5,985 (90.8%) took Step 2CK. Women and Asian/Pacific Islander students were more likely to attempt Step 2CK; more recent matriculants and students with lower failing Step 1 scores were less likely. Of the 5,985 students who attempted Step 2CK, 4,168 (69.6%) initially passed. Women, students with higher Medical College Admission Test scores, and more recent matriculants were more likely to pass Step 2CK; Asian/Pacific Islander students, underrepresented minority students, older students, and students with lower failing Step 1 scores were less likely. Ninety percent of students in the study sample (5,952/6,594) ultimately graduated from medical school, including 99.5% (4,148/4,168) of those who initially passed, 96.7% (1,757/1,817) of those who initially failed, and 7.7% (47/609) of those who never attempted Step 2CK. Conclusions The authors identified variables associated with educational outcomes among students who failed Step l. These findings can inform medical schools’ efforts to develop tailored interventions to maximize the likelihood that students will take Step 2CK and pass it on the first attempt. PMID:22361789

NLRC5: a key regulator of MHC class I-dependent immune responses.

PubMed

Kobayashi, Koichi S; van den Elsen, Peter J

2012-12-01

The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction.

PubMed

Miki, Takanori; Kusaka, Takashi; Yokoyama, Toshifumi; Ohta, Ken-ichi; Suzuki, Shingo; Warita, Katsuhiko; Jamal, Mostofa; Wang, Zhi-Yu; Ueki, Masaaki; Liu, Jun-Qian; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

2014-02-01

Alcohol ingestion affects both motor and cognitive functions. One brain system that is influenced by ethanol is the basal forebrain (BF) cholinergic projection system, which projects to diverse neocortical and limbic areas. The BF is associated with memory and cognitive function. Our primary interest is the examination of how regions that receive BF cholinergic projections are influenced by short-term ethanol exposure through alterations in the mRNA levels of neurotrophic factors [nerve growth factor/TrkA, brain-derived neurotrophic factor/TrkB, and glial-derived neurotrophic factor (GDNF)/GDNF family receptor α1]. Male BALB/C mice were fed a liquid diet containing 5 % (v/v) ethanol. Pair-fed control mice were maintained on an identical liquid diet, except that the ethanol was isocalorically substituted with sucrose. Mice exhibiting signs of ethanol intoxication (stages 1-2) were used for real-time reverse transcription-polymerase chain reaction analyses. Among the BF cholinergic projection regions, decreased levels of GDNF mRNA and increased levels of TrkB mRNA were observed in the basal nucleus, and increased levels of TrkB mRNA were observed in the cerebral cortex. There were no significant alterations in the levels of expression of relevant neurotrophic factors in the septal nucleus and hippocampus. Given that neurotrophic factors function in retrograde/anterograde or autocrine/paracrine mechanisms and that BF cholinergic projection regions are neuroanatomically connected, these findings suggested that an imbalanced allocation of neurotrophic factor ligands and receptors is an initial phenomenon in alcohol addiction. The exact mechanisms underlying this phenomenon in the BF cholinergic system are unknown. However, our results provide a novel notion for the understanding of the initial processes in alcohol addiction.

Immigration, race/ethnicity, and social and economic factors as predictors of breastfeeding initiation.

PubMed

Celi, Ann C; Rich-Edwards, Janet W; Richardson, Marcie K; Kleinman, Ken P; Gillman, Matthew W

2005-03-01

To determine the impact of immigration status as well as race/ethnicity and social and economic factors on breastfeeding initiation. Cohort. Multisite group practice in eastern Massachusetts. One thousand eight hundred twenty-nine pregnant women prospectively followed up in Project Viva. Whether the participant breastfed her infant. The overall breastfeeding initiation rate was 83%. In multivariate models that included race/ethnicity and social, economic, and demographic factors, foreign-born women were more likely to initiate breastfeeding than US-born women (odds ratio [OR], 3.2 [95% confidence interval (CI), 2.0-5.2]). In models stratified by both race/ethnicity and immigration status, and further adjusted for whether the mother herself was breastfed as an infant and the mother's parents' immigration status, US-born and foreign-born black and Hispanic women initiated breastfeeding at rates at least as high as US-born white women (US-born black vs US-born white women, OR, 1.2 [95% CI, 0.8-1.9], US-born Hispanic vs US-born white women, OR, 1.1 [95% CI, 0.6-1.9], foreign-born black vs US-born white women, OR, 2.6 [95% CI, 1.1-6.0], and foreign-born Hispanic vs US-born white women, OR, 1.8 [95% CI, 0.7-4.8]). Calculations of predicted prevalences showed that, for example, the 2.6-fold increase in odds for the foreign-born black vs US-born white women translated to an increase in probability of approximately 1.4. Higher maternal education and household income also predicted higher initiation rates. Immigration status was strongly associated with increased breastfeeding initiation in this cohort, implying that cultural factors are important in the decision to breastfeed. Immigrants of all races/ethnicities initiated breastfeeding more often than their US-born counterparts. In addition, US-born minority groups initiated breastfeeding at rates at least as high as their white counterparts, likely due in part to high levels of education and income as well as to access to a medical care system that explicitly supports breastfeeding.

Initial Development and Validation of the Mexican Intercultural Competence Scale

PubMed Central

Torres, Lucas

2013-01-01

The current project sought to develop the Mexican Intercultural Competence Scale (MICS), which assesses group-specific skills and attributes that facilitate effective cultural interactions, among adults of Mexican descent. Study 1 involved an Exploratory Factor Analysis (N = 184) that identified five factors including Ambition/Perseverance, Networking, the Traditional Latino Culture, Family Relationships, and Communication. In Study 2, a Confirmatory Factor Analysis provided evidence for the 5-factor model for adults of Mexican origin living in the Midwest (N = 341) region of the U.S. The general findings are discussed in terms of a competence-based formulation of cultural adaptation and include theoretical and clinical implications. PMID:24058890

Initial Development and Validation of the Mexican Intercultural Competence Scale.

PubMed

Torres, Lucas

2013-01-01

The current project sought to develop the Mexican Intercultural Competence Scale (MICS), which assesses group-specific skills and attributes that facilitate effective cultural interactions, among adults of Mexican descent. Study 1 involved an Exploratory Factor Analysis ( N = 184) that identified five factors including Ambition/Perseverance, Networking, the Traditional Latino Culture, Family Relationships, and Communication. In Study 2, a Confirmatory Factor Analysis provided evidence for the 5-factor model for adults of Mexican origin living in the Midwest ( N = 341) region of the U.S. The general findings are discussed in terms of a competence-based formulation of cultural adaptation and include theoretical and clinical implications.

Absence of airway secretion accumulation predicts tolerance of noninvasive ventilation in subjects with amyotrophic lateral sclerosis.

PubMed

Vandenberghe, Nadia; Vallet, Anne-Evelyne; Petitjean, Thierry; Le Cam, Pierre; Peysson, Stéphane; Guérin, Claude; Dailler, Frédéric; Jay, Sylvie; Cadiergue, Vincent; Bouhour, Françoise; Court-Fortune, Isabelle; Camdessanche, Jean-Philippe; Antoine, Jean-Christophe; Philit, François; Beuret, Pascal; Bin-Dorel, Sylvie; Vial, Christophe; Broussolle, Emmanuel

2013-09-01

To assess factors that predict good tolerance of noninvasive ventilation (NIV), in order to improve survival and quality of life in subjects with amyotrophic lateral sclerosis. We conducted a prospective study in subjects with amyotrophic lateral sclerosis and requiring NIV. The primary end point was NIV tolerance at 1 month. Subjects, several of whom failed to complete the study, were classified as "tolerant" or "poorly tolerant," according to the number of hours of NIV use (more or less than 4 h per night, respectively). Eighty-one subjects, 73 of whom also attended the 1-month follow-up visit, participated over 34 months. NIV tolerance after the first day of utilization predicted tolerance at 1 month (77.6% and 75.3% of subjects, respectively). Multivariate analysis disclosed 3 factors predicting good NIV tolerance: absence of airway secretions accumulation prior to NIV onset (odds ratio 11.5); normal bulbar function at initiation of NIV (odds ratio 8.5); and older age (weakly significant, odds ratio 1.1). Our study reveals 3 factors that are predictive of good NIV tolerance, in particular the absence of airway secretion accumulation, which should prompt NIV initiation before its appearance.

Germ cell pluripotency, premature differentiation and susceptibility to testicular teratomas in mice

PubMed Central

Heaney, Jason D.; Anderson, Ericka L.; Michelson, Megan V.; Zechel, Jennifer L.; Conrad, Patricia A.; Page, David C.; Nadeau, Joseph H.

2012-01-01

Testicular teratomas result from anomalies in germ cell development during embryogenesis. In the 129 family of inbred strains of mice, teratomas initiate around embryonic day (E) 13.5 during the same developmental period in which female germ cells initiate meiosis and male germ cells enter mitotic arrest. Here, we report that three germ cell developmental abnormalities, namely continued proliferation, retention of pluripotency, and premature induction of differentiation, associate with teratoma susceptibility. Using mouse strains with low versus high teratoma incidence (129 versus 129-Chr19MOLF/Ei), and resistant to teratoma formation (FVB), we found that germ cell proliferation and expression of the pluripotency factor Nanog at a specific time point, E15.5, were directly related with increased tumor risk. Additionally, we discovered that genes expressed in pre-meiotic embryonic female and adult male germ cells, including cyclin D1 (Ccnd1) and stimulated by retinoic acid 8 (Stra8), were prematurely expressed in teratoma-susceptible germ cells and, in rare instances, induced entry into meiosis. As with Nanog, expression of differentiation-associated factors at a specific time point, E15.5, increased with tumor risk. Furthermore, Nanog and Ccnd1, genes with known roles in testicular cancer risk and tumorigenesis, respectively, were co-expressed in teratoma-susceptible germ cells and tumor stem cells, suggesting that retention of pluripotency and premature germ cell differentiation both contribute to tumorigenesis. Importantly, Stra8-deficient mice had an 88% decrease in teratoma incidence, providing direct evidence that premature initiation of the meiotic program contributes to tumorigenesis. These results show that deregulation of the mitotic-meiotic switch in XY germ cells contributes to teratoma initiation. PMID:22438569

Drying kinetic of industrial cassava flour: Experimental data in view.

PubMed

Odetunmibi, Oluwole A; Adejumo, Oluyemisi A; Oguntunde, Pelumi E; Okagbue, Hilary I; Adejumo, Adebowale O; Suleiman, Esivue A

2017-12-01

In this data article, laboratory experimental investigation results on drying kinetic properties: the drying temperature ( T ), drying air velocity ( V ) and dewatering time (Te), each of the factors has five levels, and the experiment was replicated three times and the output: drying rate and drying time obtained, were observed. The experiment was conducted at National Centre for Agricultural Mechanization (NCAM) for a period of eight months, in 2014. Analysis of variance was carried out using randomized complete block design with factorial experiment on each of the outputs: drying rate and drying times of the industrial cassava flour. A clear picture on each of these outputs was provided separately using tables and figures. It was observed that all the main factors as well as two and three ways interactions are significant at 5% level for both drying time and rate. This also implies that the rate of drying grated unfermented cassava mash, to produce industrial cassava flour, depend on the dewatering time (the initial moisture content), temperature of drying, velocity of drying air as well as the combinations of these factors altogether. It was also discovered that all the levels of each of these factors are significantly difference from one another. In summary, the time of drying is a function of the dewatering time which was responsible for the initial moisture content. The higher the initial moisture content the longer the time of drying, and the lower the initial moisture content, the lower the time of drying. Also, the higher the temperature of drying the shorter the time of drying and vice versa. Also, the air velocity effect on the drying process was significant. As velocity increases, rate of drying also increases and vice versa. Finally, it can be deduced that the drying kinetics are influenced by these processing factors.

2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma

PubMed Central

Cerci, Juliano J; Linardi, Camila C G; Pracchia, Luís F; Junior, José Soares; Trindade, Evelinda; Delbeke, Dominique; Cerci, Rodrigo J; Carr, Robert; Meneghetti, José C; Buccheri, Valeria

2013-01-01

AIM: To assess the prognostic value and risk classification improvement of metabolic staging (MS) with Initial 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography (FDG-PET) in initial staging of Hodgkin’s Lymphoma (HL) patients to predict 5 years overall survival (5y-OS) and event free survival (EFS). METHODS: A total of 275 patients were included in this retrospective study, 155 patients were staged with conventional anatomical staging (AS), and 120 also submitted to MS (FDG-PET). Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS. Risk-adjusted models incorporated clinical risk factors, computed tomography and FDG-PET staging. RESULTS: During the follow up of 267 evaluated patients, 220 (122 AS and 98 MS) achieved complete remission after first-line therapy (median follow-up: 70 ± 29 mo), treatment failure occurred in 79 patients and 34 died. The 5y-EFS for early vs advanced disease in AS patients was 79.3% and 66.7%, and 85.6% and 53.6% in MS patients, respectively (P < 0.01). The 5y-OS for early and advanced disease with AS was 91.3% and 81.5%, and 97.5% and 80.7% for patients staged with MS, respectively. Cox proportional hazards analysis demonstrated that FDG-PET added significant prognostic information and improved risk prediction (P = 0.02). CONCLUSION: Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL, with impact in 5y-EFS and OS. PMID:24379935

Tissue expression analysis, cloning and characterization of the 5'-regulatory region of the bovine FABP3 gene.

PubMed

Li, Anning; Wu, Lijuan; Wang, Xiaoyu; Xin, Yaping; Zan, Linsen

2016-09-01

Fatty acid binding protein 3 (FABP3) is a member of the FABP family which bind fatty acids and have an important role in fatty acid metabolism. A large number of studies have shown that the genetic polymorphisms of FABP3 are positively correlated with intramuscular fat (IMF) content in domestic animals, however, the function and transcriptional characteristics of FABP3 in cattle remain unclear. Real-time PCR analysis revealed that bovine FABP3 was highly expressed in cardiac tissue. The 5'-regulatory region of bovine FABP3 was cloned and its transcription initiation sites were identified. Sequence analysis showed that many transcriptional factor binding sites including TATA-box and CCAAT-box were present on the 5'-flanking region of bovine FABP3, and four CpG islands were found on nucleotides from -891 to +118. Seven serial deletion constructs of the 5'-regulatory region evaluated in dual-luciferase reporter assay indicated that its core promoter was 384 base pairs upstream from the transcription initiation site. The transcriptional factor binding sites RXRα, KLF15, CREB and Sp1 were conserved in the core promoter of cattle, sheep, pigs and dogs. These results provide further understanding of the function and regulation mechanism of bovine FABP3.

An instrumental variable approach finds no associated harm or benefit from early dialysis initiation in the United States

PubMed Central

Scialla, Julia J.; Liu, Jiannong; Crews, Deidra C.; Guo, Haifeng; Bandeen-Roche, Karen; Ephraim, Patti L.; Tangri, Navdeep; Sozio, Stephen M.; Shafi, Tariq; Miskulin, Dana C.; Michels, Wieneke M.; Jaar, Bernard G.; Wu, Albert W.; Powe, Neil R.; Boulware, L. Ebony

2014-01-01

The estimated glomerular filtration rate (eGFR) at dialysis initiation has been rising. Observational studies suggest harm, but may be confounded by unmeasured factors. As instrumental variable methods may be less biased we performed a retrospective cohort study of 310,932 patients starting dialysis between 2006 to 2008 and registered in the United States Renal Data System in order to describe geographic variation in eGFR at dialysis initiation and determine its association with mortality. Patients were grouped into 804 health service areas by zip code. Individual eGFR at dialysis initiation averaged 10.8 ml/min/1.73m2 but varied geographically. Only 11% of the variation in mean health service areas-level eGFR at dialysis initiation was accounted for by patient characteristics. We calculated demographic-adjusted mean eGFR at dialysis initiation in the health service areas using the 2006 and 2007 incident cohort as our instrument and estimated the association between individual eGFR at dialysis initiation and mortality in the 2008 incident cohort using the 2 stage residual inclusion method. Among 89,547 patients starting dialysis in 2008 with eGFR 5 to 20 ml/min/1.73m2, eGFR at initiation was not associated with mortality over a median of 15.5 months [hazard ratio 1.025 per 1 ml/min/1.73m2 for eGFR 5 to 14 ml/min/1.73m2; and 0.973 per 1 ml/min/1.73m2 for eGFR 14 to 20 ml/min/1.73m2]. Thus, there was no associated harm or benefit from early dialysis initiation in the United States. PMID:24786707

Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni) for Chronic HCV Infection in a Real-World Cohort: A New Barrier in the HCV Care Cascade

PubMed Central

Liapakis, AnnMarie; Cohen, Elizabeth; Chau, Hong; Bertuccio, Claudia; Sapir, Dana; Wright, Jessica; Eggers, Carol; Drozd, Kristine; Ciarleglio, Maria; Deng, Yanhong; Lim, Joseph K.

2015-01-01

Background New treatments for hepatitis C (HCV) infection hold great promise for cure, but numerous challenges to diagnosing, establishing care, and receiving therapy exist. There are limited data on insurance authorization for these medications. Materials and Methods We performed a retrospective chart review of patients receiving sofosbuvir/ledipasvir (SOF/LED) from October 11-December 31, 2014 to determine rates and timing of drug authorization. We also determined predictors of approval, and those factors associated with faster decision and approval times. Results Of 174 patients prescribed HCV therapy during this period, 129 requests were made for SOF/LED, of whom 100 (77.5%) received initial approval, and an additional 17 patients (13.9%) ultimately received approval through the appeals process. Faster approval times were seen in patients with Child-Pugh Class B disease (14.4 vs. 24.7 days, p = 0.048). A higher proportion of patients were initially approved in those with Medicare/Medicaid coverage (92.2% vs. 71.4%, p = 0.002) and those with baseline viral load ≥6 million IU/mL (84.1% vs. 62.5%, p = 0.040). Linear regression modeling identified advanced fibrosis, high Model of End Stage Liver Disease (MELD) score, and female gender as significant predictors of shorter decision and approval times. On logistic regression, Medicare/Medicaid coverage (OR 5.96, 95% CI 1.66–21.48) and high viral load (OR 4.52, 95% CI 1.08–19.08) were significant predictors for initial approval. Conclusions Early analysis of real-world drug authorization outcomes between October-December 2014 reveals that nearly one in four patients are initially denied access to SOF/LED upon initial prescription, although most patients are eventually approved through appeal, which delays treatment initiation. Having Medicare/Medicaid and advanced liver disease resulted in a higher likelihood of approval as well as earlier decision and approval times. More studies are needed to determine factors resulting in higher likelihood of denial and to evaluate approval rates and times after implementation of restrictive prior authorization guidelines. PMID:26312999

Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni) for Chronic HCV Infection in a Real-World Cohort: A New Barrier in the HCV Care Cascade.

PubMed

Do, Albert; Mittal, Yash; Liapakis, AnnMarie; Cohen, Elizabeth; Chau, Hong; Bertuccio, Claudia; Sapir, Dana; Wright, Jessica; Eggers, Carol; Drozd, Kristine; Ciarleglio, Maria; Deng, Yanhong; Lim, Joseph K

2015-01-01

New treatments for hepatitis C (HCV) infection hold great promise for cure, but numerous challenges to diagnosing, establishing care, and receiving therapy exist. There are limited data on insurance authorization for these medications. We performed a retrospective chart review of patients receiving sofosbuvir/ledipasvir (SOF/LED) from October 11-December 31, 2014 to determine rates and timing of drug authorization. We also determined predictors of approval, and those factors associated with faster decision and approval times. Of 174 patients prescribed HCV therapy during this period, 129 requests were made for SOF/LED, of whom 100 (77.5%) received initial approval, and an additional 17 patients (13.9%) ultimately received approval through the appeals process. Faster approval times were seen in patients with Child-Pugh Class B disease (14.4 vs. 24.7 days, p = 0.048). A higher proportion of patients were initially approved in those with Medicare/Medicaid coverage (92.2% vs. 71.4%, p = 0.002) and those with baseline viral load ≥ 6 million IU/mL (84.1% vs. 62.5%, p = 0.040). Linear regression modeling identified advanced fibrosis, high Model of End Stage Liver Disease (MELD) score, and female gender as significant predictors of shorter decision and approval times. On logistic regression, Medicare/Medicaid coverage (OR 5.96, 95% CI 1.66-21.48) and high viral load (OR 4.52, 95% CI 1.08-19.08) were significant predictors for initial approval. Early analysis of real-world drug authorization outcomes between October-December 2014 reveals that nearly one in four patients are initially denied access to SOF/LED upon initial prescription, although most patients are eventually approved through appeal, which delays treatment initiation. Having Medicare/Medicaid and advanced liver disease resulted in a higher likelihood of approval as well as earlier decision and approval times. More studies are needed to determine factors resulting in higher likelihood of denial and to evaluate approval rates and times after implementation of restrictive prior authorization guidelines.

Near-Surface PM2.5 Concentrations Derived from Satellites, Simulation and Ground Monitors

NASA Astrophysics Data System (ADS)

van Donkelaar, A.; Martin, R.; Hsu, N. Y. C.; Kahn, R. A.; Levy, R. C.; Lyapustin, A.; Sayer, A. M.; Brauer, M.

2015-12-01

Exposure to fine particulate matter (PM2.5) is globally associated with 3.2 million premature deaths annually. Satellite retrievals of total column aerosol optical depth (AOD) from instruments such as MODIS, MISR and SeaWiFS are related to PM2.5 through local aerosol vertical profiles and optical properties. A globally applicable and geophysically-based AOD to PM2.5 relationship can be calculated from chemical transport model (CTM) simulations. This approach, while effective, ignores the wealth of ground monitoring data that exist in some regions of the world. We therefore use ground monitors to develop a geographically weighted regression (GWR) that predicts the residual bias in geophysically-based satellite-derived PM2.5. Predictors such as the AOD to PM2.5 relationship resolution, land cover type, and chemical composition are used to predict this bias, which can then be used to improve the initial PM2.5 estimates. This approach not only allows for direct bias correction, but also provides insight into factors biasing the initial CTM-derived AOD to PM2.5 relationship. Over North America, we find significant improvement in bias-corrected PM2.5 (r2=0.82 versus r2=0.62), with evidence that fine-scale variability in surface elevation and urban factors are major sources of error in the CTM-derived relationships. Agreement remains high (r2=0.78) even when a large fraction of ground monitors (70%) are withheld from the GWR, suggesting this technique may add value in regions with even sparse ground monitoring networks, and potentially worldwide.

Socio-economic status and time trends associated with early ART initiation following primary HIV infection in Montreal, Canada: 1996 to 2015.

PubMed

Mehraj, Vikram; Cox, Joseph; Lebouché, Bertrand; Costiniuk, Cecilia; Cao, Wei; Li, Taisheng; Ponte, Rosalie; Thomas, Réjean; Szabo, Jason; Baril, Jean-Guy; Trottier, Benoit; Côté, Pierre; LeBlanc, Roger; Bruneau, Julie; Tremblay, Cécile; Routy, Jean-Pierre

2018-02-01

Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study. The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs). Recently diagnosed HIV-infected adults were categorized as receiving early (vs. delayed) ART if ART was initiated within 180 days of the baseline visit. Associations between early ART initiation and socio-demographic, socio-economic and behavioural information were examined. Independent associations of factors linked with early ART initiation were determined using multivariable binary logistic regression analysis. A total of 348 participants had a documented date of HIV acquisition of <180 days. The median interquartile range (IQR) age of participants was 35 (28; 42) years and the majority were male (96%), having paid employment (63%), men who have sex with men (MSM) (78%) and one to four sexual partners in the last three months (70%). Participants presented with a median IQR HIV plasma viral load of 4.6 (3.7; 5.3) log 10 copies/ml, CD4 count of 510 (387; 660) cells/μl and were recruited in CMCs (52%) or UMCs (48%). Early ART initiation was observed in 47% of the participants and the trend followed a V-shaped curve with peaks in 1996 to 1997 (89%) and 2013 to 2015 (88%) with a dip in 2007 to 2009 (22%). Multivariable analyses showed that having a paid employment adjusted odds ratio (aOR: 2.43; 95% CI: 1.19, 4.95), lower CD4 count (aOR per 50 cell increase: 0.93; 95% CI: 0.87, 0.99) and care at UMCs (aOR: 2.03; 95% CI: 1.06 to 3.90) were independently associated with early ART initiation. Early ART initiation during primary HIV infection was associated with diminished biological prognostic factors and calendar time mirroring evolution of treatment guidelines. In addition, socio-economic factors such as having a paid employment, contribute to early ART initiation in the context of universal access to care in Canada. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

40 CFR 61.165 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... adjustments; (4) The occurrence and duration of all startups, shutdowns, and malfunctions of the furnace; (5... in production rates, types of glass produced, and other factors that would affect the uncontrolled... days after the effective date of this subpart for a source that has an initial startup date preceding...

40 CFR 61.165 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... adjustments; (4) The occurrence and duration of all startups, shutdowns, and malfunctions of the furnace; (5... in production rates, types of glass produced, and other factors that would affect the uncontrolled... days after the effective date of this subpart for a source that has an initial startup date preceding...

40 CFR 61.165 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... adjustments; (4) The occurrence and duration of all startups, shutdowns, and malfunctions of the furnace; (5... in production rates, types of glass produced, and other factors that would affect the uncontrolled... days after the effective date of this subpart for a source that has an initial startup date preceding...

40 CFR 61.165 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... adjustments; (4) The occurrence and duration of all startups, shutdowns, and malfunctions of the furnace; (5... in production rates, types of glass produced, and other factors that would affect the uncontrolled... days after the effective date of this subpart for a source that has an initial startup date preceding...

40 CFR 61.165 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... adjustments; (4) The occurrence and duration of all startups, shutdowns, and malfunctions of the furnace; (5... in production rates, types of glass produced, and other factors that would affect the uncontrolled... days after the effective date of this subpart for a source that has an initial startup date preceding...

Gender difference in early initiation of methamphetamine use among current methamphetamine users in Muse, Northern Shan State, Myanmar.

PubMed

Saw, Yu Mon; Saw, Thu Nandar; Yasuoka, Junko; Chan, Nyein; Kham, Nang Pann Ei; Khine, Wint; Cho, Su Myat; Jimba, Masamine

2017-05-08

Globally, methamphetamine (MA) use is a significant public health concern due to unprecedented health effects of its use. However, gender similarities and differences in early age of MA initiation and its risk factors among current MA users have been understudied in a developing country setting. A community-based, cross-sectional study was conducted using a computer assisted self-interviewing program from January to March 2013 in Muse, Northern Shan State, Myanmar. A total of 1362 (775 male and 587 female) self-reported current MA users aged between 18 and 35 years were recruited using respondent-driven sampling. Two gender-stratified multiple logistic regression models (models I and II) were done for analysis. For similarities, 73.0% of males and 60.5% of females initiated MA before their 18th birthday. The early age of MA initiation was positively associated with the reasons and places of the first time MA use among both genders. For differences, males [hazard ratio 1.35; 95% confidence interval, 1.18-1.54] had a significantly higher risk than females to initiate MA at earlier age. Among male users, participants who had bisexual/homosexual preferences were more likely to initiate MA use earlier. In contrast, female users who exchanged sex for money and/or drugs were more likely to initiate MA in earlier age. More than 60.0% of male and female participants initiated MA use early; however, males initiated use earlier than females. Although similarities were found among both genders, differences found in key risk factors for early age MA initiation suggest that gender-specific, MA prevention programs are urgently needed in Myanmar.

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia

PubMed Central

Lee, Hao-Yuan; Chen, Chyi-Liang; Liu, Shu-Ying; Yan, Yu-Shan; Chang, Chee-Jen; Chiu, Cheng-Hsun

2015-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. Methods A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed. Results Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759). Conclusions Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality. PMID:26295150

Gateways to the FANTOM5 promoter level mammalian expression atlas

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

Lizio, Marina; Harshbarger, Jayson; Shimoji, Hisashi

The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). In conclusion, this resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas.

Gateways to the FANTOM5 promoter level mammalian expression atlas

DOE PAGES

Lizio, Marina; Harshbarger, Jayson; Shimoji, Hisashi; ...

2015-01-05

The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). In conclusion, this resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas.

Arsenic uptake by Lemna minor in hydroponic system.

PubMed

Goswami, Chandrima; Majumder, Arunabha; Misra, Amal Kanti; Bandyopadhyay, Kaushik

2014-01-01

Arsenic is hazardous and causes several ill effects on human beings. Phytoremediation is the use of aquatic plants for the removal of toxic pollutants from external media. In the present research work, the removal efficiency as well as the arsenic uptake capacity of duckweed Lemna minor has been studied. Arsenic concentration in water samples and plant biomass were determined by AAS. The relative growth factor of Lemna minor was determined. The duckweed had potential to remove as well as uptake arsenic from the aqueous medium. Maximum removal of more than 70% arsenic was achieved atinitial concentration of 0.5 mg/1 arsenic on 15th day of experimental period of 22 days. Removal percentage was found to decrease with the increase in initial concentration. From BCF value, Lemna minor was found to be a hyperaccumulator of arsenic at initial concentration of 0.5 mg/L, such that accumulation decreased with increase in initial arsenic concentration.

Distribution and diversity of ribosome binding sites in prokaryotic genomes.

PubMed

Omotajo, Damilola; Tate, Travis; Cho, Hyuk; Choudhary, Madhusudan

2015-08-14

Prokaryotic translation initiation involves the proper docking, anchoring, and accommodation of mRNA to the 30S ribosomal subunit. Three initiation factors (IF1, IF2, and IF3) and some ribosomal proteins mediate the assembly and activation of the translation initiation complex. Although the interaction between Shine-Dalgarno (SD) sequence and its complementary sequence in the 16S rRNA is important in initiation, some genes lacking an SD ribosome binding site (RBS) are still well expressed. The objective of this study is to examine the pattern of distribution and diversity of RBS in fully sequenced bacterial genomes. The following three hypotheses were tested: SD motifs are prevalent in bacterial genomes; all previously identified SD motifs are uniformly distributed across prokaryotes; and genes with specific cluster of orthologous gene (COG) functions differ in their use of SD motifs. Data for 2,458 bacterial genomes, previously generated by Prodigal (PROkaryotic DYnamic programming Gene-finding ALgorithm) and currently available at the National Center for Biotechnology Information (NCBI), were analyzed. Of the total genes examined, ~77.0% use an SD RBS, while ~23.0% have no RBS. Majority of the genes with the most common SD motifs are distributed in a manner that is representative of their abundance for each COG functional category, while motifs 13 (5'-GGA-3'/5'-GAG-3'/5'-AGG-3') and 27 (5'-AGGAGG-3') appear to be predominantly used by genes for information storage and processing, and translation and ribosome biogenesis, respectively. These findings suggest that an SD sequence is not obligatory for translation initiation; instead, other signals, such as the RBS spacer, may have an overarching influence on translation of mRNAs. Subsequent analyses of the 5' secondary structure of these mRNAs may provide further insight into the translation initiation mechanism.

Association Between Short Sleep Duration and Risk Behavior Factors in Middle School Students.

PubMed

Owens, Judith; Wang, Guanghai; Lewin, Daniel; Skora, Elizabeth; Baylor, Allison

2017-01-01

To examine the association between self-reported sleep duration (SD) and peer/individual factors predictive of risky behaviors (risk behavior factors) in a large socioeconomically diverse school-based sample of early adolescents. Survey data collected from 10718 and 11240 eighth-grade students in 2010 and 2012, respectively, were analyzed. N/A. Self-reported school night SD was grouped as ≤4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, and ≥10 hours. Scores on 10 peer/individual risk behavior factor scales were dichotomized according to national eigth-grade cut points. The percentage of students reporting an "optimal" SD of 9 hours was 14.8% and 15.6% in 2010 and 2012, respectively; 45.6% and 46.1% reported <7 hours. Adjusted for covariates of gender, race, and SES, multilevel logistic regression results showed that odds ratios (ORs) for 9 of 10 risk factor scales increased with SD <7 hours, with a dose-response effect for each hour less sleep compared to an SD of 9 hours. For example, ORs for students sleeping <7 hours ranged from 1.3 (early initiation of antisocial behavior) to 1.8 (early initiation of drug use). The risk factor scale ORs for <5 hours SD ranged from 3.0 (sensation seeking) to 6.4 (gang involvement). Middle school students are at high risk of insufficient sleep; in particular, an SD <7 hours is associated with increased risk behavior factors. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Measuring and managing risk improves strategic financial planning.

PubMed

Kleinmuntz, D N; Kleinmuntz, C E; Stephen, R G; Nordlund, D S

1999-06-01

Strategic financial risk assessment is a practical technique that can enable healthcare strategic decision makers to perform quantitative analyses of the financial risks associated with a given strategic initiative. The technique comprises six steps: (1) list risk factors that might significantly influence the outcomes, (2) establish best-guess estimates for assumptions regarding how each risk factor will affect its financial outcomes, (3) identify risk factors that are likely to have the greatest impact, (4) assign probabilities to assumptions, (5) determine potential scenarios associated with combined assumptions, and (6) determine the probability-weighted average of the potential scenarios.

Durability of Adherence to Antiretroviral Therapy on Initial and Subsequent Regimens

PubMed Central

GARDNER, EDWARD M.; BURMAN, WILLIAM J.; MARAVI, MOISES E.; DAVIDSON, ARTHUR J.

2007-01-01

There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, −43% per year), followed by patients with intermediate regimen duration (16 to <28 months, −19% per year), and then patients with longer regimens (≥28 months, −5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed. PMID:16987049

MicroRNA-9 regulates non-small cell lung cancer cell invasion and migration by targeting eukaryotic translation initiation factor 5A2.

PubMed

Xu, Guodong; Shao, Guofeng; Pan, Qiaoling; Sun, Lebo; Zheng, Dawei; Li, Minghui; Li, Ni; Shi, Huoshun; Ni, Yiming

2017-01-01

MicroRNAs (miRNAs) play a critical role in cancer development and progression. Bioinformatics analyses has identified eukaryotic translation initiation factor 5A2 (eIF5A2) as a target of miR-9. In this study, we attempted to determine whether miR-9 regulates non-small cell lung cancer (NSCLC) cell invasion and migration by targeting eIF5A2 We examined eIF5A2 expression using reverse transcription-quantitative PCR (RT-qPCR) and subsequently transfected A549 and NCI-H1299 NSCLC cells with a miR-9 mimic or miR-9 inhibitor to determine the migration and invasive capability of the cells via wound healing assay and Transwell invasion assay, respectively. E-cadherin and vimentin expression was detected with western blotting. The miR-9 mimic significantly reduced NSCLC cell invasive and metastatic ability, and the miR-9 inhibitor enhanced NSCLC cell migration activity, increasing the number of migrated cells. There was no significant difference between the negative control siRNA and miR-9 mimic groups after knockdown of eIF5A2; western blotting showed that miR-9 regulated E-cadherin and vimentin expression. These data show that miR-9 regulates NSCLC cell invasion and migration through regulating eIF5A2 expression. Taken together, our findings suggest that the mechanism of miR-9-regulated NSCLC cell invasion and migration may be related to epithelial-mesenchymal transition.

Facilitating Learning in SPI through Co-design

NASA Astrophysics Data System (ADS)

Seigerroth, Ulf; Lind, Mikael

Information system development (ISD) is not a stable discipline. On the contrary, ISD must constantly cope with rapidly changing and diversifying technologies, application domains, and organizational contexts [14]. ISD is a complex and a multi dimensional phenomenon [5, 15]. As a consequence of this. Software Process Improvement (SPI) can also be regarded as a complex and multi dimensional phenomenon [16]. Problems that are accentuated in relation to SPI are: SPI is in its current shape a quite young discipline [15], there is a sparse amount of SPI-theories that can guide SPI initiatives [19], SPI-initiatives often focus on the system development (SD)-process, methods and tools which is a narrow focus that leave out important aspects such as business orientation [6], organization and social factors [4, 5] and the learning process [19]. Arguments have therefore been raised that there is a need for both researchers and practitioners to better understand SD-organisations and their practice [5].

Determinants of change in polypharmacy status in Switzerland: the population-based CoLaus study.

PubMed

Abolhassani, Nazanin; Castioni, Julien; Marques-Vidal, Pedro; Vollenweider, Peter; Waeber, Gérard

2017-09-01

This study aimed to assess the prevalence, the change, and the determinants of change in polypharmacy in a population-based sample. Baseline (2003-2006) and follow-up (2009-2012) data are from 4679 participants aged between 35 and 75 years (53.5% women, mean age 52.6 ± 10.6 years) from the population of Lausanne, Switzerland. Polypharmacy was defined by the regular use of ≥5 drugs. Four categories of change were defined: never (no polypharmacy at baseline and follow-up), initiating (no polypharmacy at baseline but at follow-up), maintaining, or quitting. Polypharmacy increased from 7.7% at baseline to 15.3% at follow-up. Cardiovascular drugs were the most prescribed medicines at baseline and follow-up. Gender, age, obesity, smoking, previously diagnosed hypertension, or diabetes or dyslipidemia were significantly and independently associated with initiating and maintaining polypharmacy. In a population-based sample, prevalence of polypharmacy doubled over a 5.6-year period. The main determinants of initiating polypharmacy were age, overweight and obesity, smoking status, and previously diagnosed cardiovascular risk factors.

3′ Cap-Independent Translation Enhancers of Plant Viruses

PubMed Central

Simon, Anne E.; Miller, W. Allen

2014-01-01

In the absence of a 5′ cap, plant positive-strand RNA viruses have evolved a number of different elements in their 3′ untranslated region (UTR) to attract initiation factors and/or ribosomes to their templates. These 3′ cap-independent translational enhancers (3′ CITEs) take different forms, such as I-shaped, Y-shaped, T-shaped, or pseudoknotted structures, or radiate multiple helices from a central hub. Common features of most 3′ CITEs include the ability to bind a component of the translation initiation factor eIF4F complex and to engage in an RNA-RNA kissing-loop interaction with a hairpin loop located at the 5′ end of the RNA. The two T-shaped structures can bind to ribosomes and ribosomal subunits, with one structure also able to engage in a simultaneous long-distance RNA-RNA interaction. Several of these 3′ CITEs are interchangeable and there is evidence that natural recombination allows exchange of modular CITE units, which may overcome genetic resistance or extend the virus’s host range. PMID:23682606

Predictors of Optimal Cognitive Aging in 80+ Women: The Women's Health Initiative Memory Study.

PubMed

Goveas, Joseph S; Rapp, Stephen R; Hogan, Patricia E; Driscoll, Ira; Tindle, Hilary A; Smith, J Carson; Kesler, Shelli R; Zaslavsky, Oleg; Rossom, Rebecca C; Ockene, Judith K; Yaffe, Kristine; Manson, JoAnn E; Resnick, Susan M; Espeland, Mark A

2016-03-01

Independent predictors of preserved cognitive functioning and factors associated with maintaining high preserved cognitive function in women ≥ 80 years remain elusive. Two thousand two hundred twenty-eight women with a mean age of 85 years who participated in the Women's Health Initiative Memory Study were classified as cognitively normal (n = 1,905, 85.5%), mild cognitive impairment (n = 88, 3.9%), dementia (n = 121, 5.4%) or other cognitive impairment (n = 114, n = 5.1%) by central adjudication. Global cognitive functioning was assessed using telephone interview for cognitive status-modified in those women who did not meet cognitive impairment criteria. Differences between women grouped by cognitive status with respect to each potential risk factor were assessed using chi-squared tests and t-tests. Backward stepwise logistic regression was used to select factors that were independently associated with cognitive status. Factors associated with preserved cognitive functioning were younger age, higher education, and family incomes, being non-Hispanic white, better emotional wellbeing, fewer depressive symptoms, more insomnia complaints, being free of diabetes, and not carrying the apolipoprotein E-epsilon 4 allele. Cognitively normal women who demonstrated sustained high preserved cognition were younger, more educated, and endorsed better self-reported general health, emotional wellbeing, and higher physical functioning. Addressing sociodemographic disparities such as income inequality, and targeting interventions to improve depressive symptoms and vascular risk factors, including diabetes, may play an important role in preserving cognition among women who survive to 80 years of age. Person-centered approaches that combine interventions to improve physical, cognitive, and psychosocial functioning may promote maintenance of high preserved cognitive health in the oldest-old. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Predictors of Optimal Cognitive Aging in 80+ Women: The Women’s Health Initiative Memory Study

PubMed Central

Rapp, Stephen R.; Hogan, Patricia E.; Driscoll, Ira; Tindle, Hilary A.; Smith, J. Carson; Kesler, Shelli R.; Zaslavsky, Oleg; Rossom, Rebecca C.; Ockene, Judith K.; Yaffe, Kristine; Manson, JoAnn E.; Resnick, Susan M.; Espeland, Mark A.

2016-01-01

Background. Independent predictors of preserved cognitive functioning and factors associated with maintaining high preserved cognitive function in women ≥80 years remain elusive. Methods. Two thousand two hundred twenty-eight women with a mean age of 85 years who participated in the Women’s Health Initiative Memory Study were classified as cognitively normal (n = 1,905, 85.5%), mild cognitive impairment (n = 88, 3.9%), dementia (n = 121, 5.4%) or other cognitive impairment (n = 114, n = 5.1%) by central adjudication. Global cognitive functioning was assessed using telephone interview for cognitive status-modified in those women who did not meet cognitive impairment criteria. Differences between women grouped by cognitive status with respect to each potential risk factor were assessed using chi-squared tests and t-tests. Backward stepwise logistic regression was used to select factors that were independently associated with cognitive status. Results. Factors associated with preserved cognitive functioning were younger age, higher education, and family incomes, being non-Hispanic white, better emotional wellbeing, fewer depressive symptoms, more insomnia complaints, being free of diabetes, and not carrying the apolipoprotein E-epsilon 4 allele. Cognitively normal women who demonstrated sustained high preserved cognition were younger, more educated, and endorsed better self-reported general health, emotional wellbeing, and higher physical functioning. Conclusions. Addressing sociodemographic disparities such as income inequality, and targeting interventions to improve depressive symptoms and vascular risk factors, including diabetes, may play an important role in preserving cognition among women who survive to 80 years of age. Person-centered approaches that combine interventions to improve physical, cognitive, and psychosocial functioning may promote maintenance of high preserved cognitive health in the oldest-old. PMID:26858326

Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy for Patients With Metastatic or Recurrent Esophageal Cancer.

PubMed

Kishida, Yoshihiro; Tsushima, Takahiro; Endo, Masahiro; Hamauchi, Satoshi; Todaka, Akiko; Yokota, Tomoya; Machida, Nozomu; Yamazaki, Kentaro; Fukutomi, Akira; Onozawa, Yusuke; Yasui, Hirofumi

2018-01-01

Taxane chemotherapy for esophageal cancer causes pneumonitis, not only by itself but also by radiation recall. This study aimed to clarify the risk of pneumonitis in patients with esophageal cancer who receive taxane therapy after chemoradiotherapy. The data of 129 patients with metastatic or recurrent esophageal cancer who initiated taxane therapy between September 2002 and June 2013 were retrospectively analyzed. Patient selection criteria were as follows: performance status ≤2, preserved organ functions, previous chemoradiotherapy with a radiation dose of ≥50 Gy, grade 0 or 1 pneumonitis at taxane initiation, and no concomitant malignancy. Logistic regression analysis was performed to identify risk factors for pneumonitis. Patient characteristics were as follows: males/females, 116/13; median age, 63 years (range, 44 to 80 y); performance status of 0/1/2, 61/60/8; smoking history, 112 (88%); location of the primary tumor Ce/Ut/Mt/Lt/Ae 12/30/66/20/1; median radiation dose, 60 Gy; history of radiation pneumonitis, 39 (30%); history of other pulmonary disease, 4 (3%); and median duration between the last radiation therapy (RT) exposure and taxane initiation, 6.1 months (range, 1.0 to 71 mo). During the median observation period of 7.8 months from taxane initiation, the incidence of grade 2 and 3 pneumonitis was observed in 7 (5.4%) and 3 (2.3%) patients, respectively. No patient died of pneumonitis. The only independent risk factor for pneumonitis was a ≤4-month period between the last RT exposure and taxane initiation (P=0.03). A short period between the last RT exposure and taxane initiation is an independent risk factor for pneumonitis development.

Timely initiation of breastfeeding and associated factors among mothers in Motta town, East Gojjam zone, Amhara regional state, Ethiopia, 2015: a cross-sectional study.

PubMed

Tewabe, Tilahun

2016-10-19

Timely initiation of breastfeeding within one hour after birth and exclusive breastfeeding is recommended for the first six months of infant life along with continuation of breastfeeding up to two years. Timely initiation of breastfeeding has the potential to prevent 22 % of neonatal deaths. The objective of this study was to assess timely initiation of breastfeeding and associated factors among mothers who have infants less than six months of age in Motta town, East Gojjam, Amhara Regional State, Ethiopia. Community based quantitative cross-sectional study was conducted from April 7, 2015 to May 7, 2015. Simple random sampling technique was applied after taking all registered mothers who have infants less than 6 months old from local health extension workers of each kebele. A total of 423 mothers with infant less than six month old were included in this study. The data was collected from all four Kebeles using interviewer administered questionnaire. Descriptive and inferential statistics were used to present the data. Both bivariate and multivariate logistic regression analyses were used to identify factors associated with timely initiation breastfeeding. Prevalence of timely initiation of breastfeeding was78.8 % [95 % CL: 74.88 %, 82.72 %]. Mothers who gave birth to their infant in a health institution [AOR = 3.486(1.253, 9.700)], birthed vaginally [AOR = 5.722(3.134, 11.246)] and didn't give prelacteal food [AOR = 4.627(2.095, 10.220)] were more likely to initiate breastfeeding early than their counterparts. Prevalence of timely initiation of breastfeeding in the study area was 78.8 %. Place of delivery, mode of delivery and prelactal feeding were the independent predictors of timely initiation of breastfeeding. Recommendations to increase timely initiation of breastfeeding were: encouraging mothers to deliver their child in a health institution, minimizing caesarean delivery as much as possible and educating mothers and community as a whole to avoid traditional prelactal feeding practice.

Rotational biomechanics of the elite golf swing: benchmarks for amateurs.

PubMed

Meister, David W; Ladd, Amy L; Butler, Erin E; Zhao, Betty; Rogers, Andrew P; Ray, Conrad J; Rose, Jessica

2011-08-01

The purpose of this study was to determine biomechanical factors that may influence golf swing power generation. Three-dimensional kinematics and kinetics were examined in 10 professional and 5 amateur male golfers. Upper-torso rotation, pelvic rotation, X-factor (relative hip-shoulder rotation), O-factor (pelvic obliquity), S-factor (shoulder obliquity), and normalized free moment were assessed in relation to clubhead speed at impact (CSI). Among professional golfers, results revealed that peak free moment per kilogram, peak X-factor, and peak S-factor were highly consistent, with coefficients of variation of 6.8%, 7.4%, and 8.4%, respectively. Downswing was initiated by reversal of pelvic rotation, followed by reversal of upper-torso rotation. Peak X-factor preceded peak free moment in all swings for all golfers, and occurred during initial downswing. Peak free moment per kilogram, X-factor at impact, peak X-factor, and peak upper-torso rotation were highly correlated to CSI (median correlation coefficients of 0.943, 0.943, 0.900, and 0.900, respectively). Benchmark curves revealed kinematic and kinetic temporal and spatial differences of amateurs compared with professional golfers. For amateurs, the number of factors that fell outside 1-2 standard deviations of professional means increased with handicap. This study identified biomechanical factors highly correlated to golf swing power generation and may provide a basis for strategic training and injury prevention.

Top-down Versus Step-up Prescribing Strategies for Tumor Necrosis Factor Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease.

PubMed

Lee, Wan-Ju; Briars, Leslie; Lee, Todd A; Calip, Gregory S; Suda, Katie J; Schumock, Glen T

2016-10-01

Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%). Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

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

Mizuta, Akira; Ioka, Kunihito

We investigate the jet propagation and breakout from the stellar progenitor for gamma-ray burst (GRB) collapsars by performing two-dimensional relativistic hydrodynamic simulations and analytical modeling. We find that the jet opening angle is given by θ{sub j} ∼ 1/5Γ{sub 0} and infer the initial Lorentz factor of the jet at the central engine, Γ{sub 0}, is a few for existing observations of θ{sub j}. The jet keeps the Lorentz factor low inside the star by converging cylindrically via collimation shocks under the cocoon pressure and accelerates at jet breakout before the free expansion to a hollow-cone structure. In this newmore » picture, the GRB duration is determined by the sound crossing time of the cocoon, after which the opening angle widens, reducing the apparent luminosity. Some bursts violating the maximum opening angle θ{sub j,{sub max}} ∼ 1/5 ∼ 12° imply the existence of a baryon-rich sheath or a long-acting jet. We can explain the slopes in both Amati and Yonetoku spectral relations using an off-centered photosphere model, if we make only one assumption that the total jet luminosity is proportional to the initial Lorentz factor of the jet. We also numerically calibrate the pre-breakout model (Bromberg et al.) for later use.« less

Characterization of Transcription from TATA-Less Promoters: Identification of a New Core Promoter Element XCPE2 and Analysis of Factor Requirements

PubMed Central

Anish, Ramakrishnan; Hossain, Mohammad B.; Jacobson, Raymond H.; Takada, Shinako

2009-01-01

Background More than 80% of mammalian protein-coding genes are driven by TATA-less promoters which often show multiple transcriptional start sites (TSSs). However, little is known about the core promoter DNA sequences or mechanisms of transcriptional initiation for this class of promoters. Methodology/Principal Findings Here we identify a new core promoter element XCPE2 (X core promoter element 2) (consensus sequence: A/C/G-C-C/T-C-G/A-T-T-G/A-C-C/A+1-C/T) that can direct specific transcription from the second TSS of hepatitis B virus X gene mRNA. XCPE2 sequences can also be found in human promoter regions and typically appear to drive one of the start sites within multiple TSS-containing TATA-less promoters. To gain insight into mechanisms of transcriptional initiation from this class of promoters, we examined requirements of several general transcription factors by in vitro transcription experiments using immunodepleted nuclear extracts and purified factors. Our results show that XCPE2-driven transcription uses at least TFIIB, either TFIID or free TBP, RNA polymerase II (RNA pol II) and the MED26-containing mediator complex but not Gcn5. Therefore, XCPE2-driven transcription can be carried out by a mechanism which differs from previously described TAF-dependent mechanisms for initiator (Inr)- or downstream promoter element (DPE)-containing promoters, the TBP- and SAGA (Spt-Ada-Gcn5-acetyltransferase)-dependent mechanism for yeast TATA-containing promoters, or the TFTC (TBP-free-TAF-containing complex)-dependent mechanism for certain Inr-containing TATA-less promoters. EMSA assays using XCPE2 promoter and purified factors further suggest that XCPE2 promoter recognition requires a set of factors different from those for TATA box, Inr, or DPE promoter recognition. Conclusions/Significance We identified a new core promoter element XCPE2 that are found in multiple TSS-containing TATA-less promoters. Mechanisms of promoter recognition and transcriptional initiation for XCPE2-driven promoters appear different from previously shown mechanisms for classical promoters that show single “focused” TSSs. Our studies provide insight into novel mechanisms of RNA Pol II transcription from multiple TSS-containing TATA-less promoters. PMID:19337366

Examining the dimensional structure models of secondary traumatic stress based on DSM-5 symptoms.

PubMed

Mordeno, Imelu G; Go, Geraldine P; Yangson-Serondo, April

2017-02-01

Latent factor structure of Secondary Traumatic Stress (STS) has been examined using Diagnostic Statistic Manual-IV (DSM-IV)'s Posttraumatic Stress Disorder (PTSD) nomenclature. With the advent of Diagnostic Statistic Manual-5 (DSM-5), there is an impending need to reexamine STS using DSM-5 symptoms in light of the most updated PTSD models in the literature. The study investigated and determined the best fitted PTSD models using DSM-5 PTSD criteria symptoms. Confirmatory factor analysis (CFA) was conducted to examine model fit using the Secondary Traumatic Stress Scale in 241 registered and practicing Filipino nurses (166 females and 75 males) who worked in the Philippines and gave direct nursing services to patients. Based on multiple fit indices, the results showed the 7-factor hybrid model, comprising of intrusion, avoidance, negative affect, anhedonia, externalizing behavior, anxious arousal, and dysphoric arousal factors has excellent fit to STS. This model asserts that: (1) hyperarousal criterion needs to be divided into anxious and dysphoric arousal factors; (2) symptoms characterizing negative and positive affect need to be separated to two separate factors, and; (3) a new factor would categorize externalized, self-initiated impulse and control-deficit behaviors. Comparison of nested and non-nested models showed Hybrid model to have superior fit over other models. The specificity of the symptom structure of STS based on DSM-5 PTSD criteria suggests having more specific interventions addressing the more elaborate symptom-groupings that would alleviate the condition of nurses exposed to STS on a daily basis. Copyright © 2016 Elsevier B.V. All rights reserved.

Onset time of hyperkalaemia after angiotensin receptor blocker initiation: when should we start serum potassium monitoring?

PubMed

Park, I-W; Sheen, S S; Yoon, D; Lee, S-H; Shin, G-T; Kim, H; Park, R W

2014-02-01

Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high-risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy. We carried out a retrospective analysis to determine the onset time of hyperkalaemia (serum potassium >5·5 mm) among hospitalized patients newly starting ARB therapy between 2004 and 2012, in a tertiary teaching hospital. Predefined possible risk factors and concomitant medications were evaluated. During the 97-month study period, a total of 4267 hospitalized patients started ARBs as new drugs and 225 patients showed hyperkalaemia. A significantly increased risk of hyperkalaemia was detected among patients with a high baseline potassium [odds ratio (OR) 6·0] and those who took non-potassium-sparing diuretics (OR 2·2) or potassium supplements (OR 1·6). A high glomerular filtration rate (GFR) was associated with a lower risk of hyperkalaemia (OR 0·992). Fifty-two percentage of hyperkalaemic events occurred within the first week after initiation of ARB therapy. The highest frequency of hyperkalaemia occurred on the first day after initiation of ARBs. Hyperkalaemia occurred earlier in patients with a high baseline serum potassium level, reduced GFR, diabetes and in those without heart failure. Hyperkalaemia occurs most frequently at the beginning of ARB therapy in hospitalized patients. Monitoring of serum potassium and estimated GFR after initiation of ARBs should be started within a few days or not later than 1 week, especially in patients with risk factors. © 2013 John Wiley & Sons Ltd.

Safety and immunogenicity of a booster dose of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults: A randomized phase 1 study.

PubMed

Marshall, Helen; Nissen, Michael; Richmond, Peter; Shakib, Sepehr; Jiang, Qin; Cooper, David; Rill, Denise; Baber, James; Eiden, Joseph; Gruber, William C; Jansen, Kathrin U; Anderson, Annaliesa S; Zito, Edward T; Girgenti, Douglas

2016-11-01

A 2-stage, phase 1, randomized, placebo-controlled study in healthy adults to assess immunogenicity and safety of a booster dose at three dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) containing recombinant clumping factor A (ClfA) and capsular polysaccharides 5 and 8 (CP5 and CP8) conjugated to a diphtheria toxoid. Six months after initial single vaccination, in Stage 2, SA3Ag recipients were randomized (1:1) to booster vaccination or placebo, while Stage 1 placebo recipients received placebo again. Pre- and post-vaccination blood samples were analyzed. In Stage 2 (n = 345), pre-booster CP5 and CP8 titers remained high with no increase post-booster. ClfA titers remained high after initial vaccination and increased post-booster, approaching the peak response to the initial dose. Post-booster local reactions were more frequent and of greater severity than reported after the initial vaccination, particularly for the high-dose level recipients. Post hoc analysis showed no dose-response pattern and no obvious association between diphtheria toxoid titers and local reactions after initial or booster vaccination. Immune responses after the initial vaccination persisted for the 12 months studied, with little additional response after the booster dose at 6 months. Post-booster injection site reactions were more frequent and more severe but self-limiting. CLINICALTRIALS. NCT01018641. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia.

PubMed

Prouvot, Catherine; Golfier, François; Massardier, Jérôme; You, Benoit; Lotz, Jean-Pierre; Patrier, Sophie; Devouassoux, Mojgan; Schott, Anne-Marie; Hajri, Touria; Bolze, Pierre-Adrien

2018-06-01

The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate. From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure. A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3-83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post-dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98-50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%). Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

Positive long-term effects of Pilates exercise on the aged-related decline in balance and strength in older, community-dwelling men and women.

PubMed

Bird, Marie-Louise; Fell, James

2014-07-01

This study investigated the effect of Pilates exercise on physical fall risk factors 12 months after an initial 5-week Pilates intervention. The authors hypothesized that ongoing Pilates participation would have a positive effect on physical fall risk factors in those who continued with Pilates exercise compared with those who ceased. Thirty older ambulatory adults (M = 69 years, SD = 7) participated in Pilates classes for 5 weeks with testing preintevention (Time 1 [T1]) and postintervention (Time 2 [T2]) and 12 months later (Time 3 [T3]). Balance and leg strength were compared using a 2-way analysis of variance with repeated measures. Postural sway, dynamic balance, and function improvements evident after the initial Pilates training (T1-T2) were maintained at T3 (p < .01). Significant differences existed at T3 for dynamic balance and strength between participants who continued performing Pilates (n = 14) and those who had ceased. Balance improvements after a short Pilates intervention were maintained 1 year later in all participants, with increased benefits from ongoing participation.

Crystal Structures of the E. coli Transcription Initiation Complexes with a Complete Bubble

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

Zuo, Yuhong; Steitz, Thomas A.

2015-05-01

During transcription initiation, RNA polymerase binds to promoter DNA to form an initiation complex containing a DNA bubble and enters into abortive cycles of RNA synthesis before escaping the promoter to transit into the elongation phase for processive RNA synthesis. Here we present the crystal structures of E. coli transcription initiation complexes containing a complete transcription bubble and de novo synthesized RNA oligonucleotides at about 6-Å resolution. The structures show how RNA polymerase recognizes DNA promoters that contain spacers of different lengths and reveal a bridging interaction between the 5'-triphosphate of the nascent RNA and the σ factor that maymore » function to stabilize the short RNA-DNA hybrids during the early stage of transcription initiation. The conformation of the RNA oligonucleotides and the paths of the DNA strands in the complete initiation complexes provide insights into the mechanism that controls both the abortive and productive RNA synthesis.« less

Spanish adaptation of the Creative Potential and Practised Creativity scale (CPPC-17) in the workplace and inside the organization.

PubMed

Boada-Grau, Joan; Sánchez-García, José-Carlos; Prizmic-Kuzmica, Aldo-Javier; Vigil-Colet, Andreu

2014-01-01

This study follows the theoretical framework put forward by Hinton on creative potential and practised creativity. The objective was to adapt the 17-item Creative Potential and Practised Creativity scale into Spanish and examine its psychometric properties. The study sample was made up of 975 Spanish employees (48.5% men and 51.5% women). After performing a confirmatory factor analysis, the findings revealed a three-factor structure: Creative potential, Practised creativity and Perception of organizational support. Furthermore, appropriate reliability was found for all three factors as well as initial evidence of construct validity in relation to certain external correlates and a series of scales measuring workaholism, irritation, burnout and personality. The present scale may prove ideal for adequately identifying Creative potential, Practised creativity and Perceived organizational support.

Recurrent skin and soft tissue infections in HIV-infected patients during a 5-year period: incidence and risk factors in a retrospective cohort study.

PubMed

Hemmige, Vagish; McNulty, Moira; Silverman, Ethan; David, Michael Z

2015-10-26

Skin and soft tissue infections (SSTIs) are common in the era of community-associated methicillin resistant Staphylococcus aureus among HIV-infected patients. Recurrent infections are frequent. Risk factors for recurrence after an initial SSTI have not been well-studied. Retrospective cohort study, single center, 2005-2009. Paper and electronic medical records were reviewed by one of several physicians. Subjects with initial SSTI were followed until the time of SSTI recurrence. Standard descriptive statistics were calculated to describe the characteristics of subjects who did and did not develop a recurrent SSTI. Kaplan-Meier methods were used to estimate the risk of recurrent SSTI. A Cox regression model was developed to identify predictors of SSTI recurrence. 133 SSTIs occurred in 87 individuals. 85 subjects were followed after their initial SSTI, of whom 30 (35.3 %) had a recurrent SSTI in 118.3 person-years of follow-up, for an incidence of second SSTI of 253.6 SSTIs/1000 person-years (95 % CI 166.8-385.7). The 1-year Kaplan-Meier estimated risk of a second SSTI was 29.2 % (95 % CI 20.3-41.0 %), while the 3-year risk was 47.0 % (95 % CI 34.4-61.6 %). Risk factors for recurrent SSTI in a multivariable Cox regression model were non-hepatitis liver disease (HR 3.44; 95 % CI 1.02-11.5; p = 0.05), the presence of an intravenous catheter (HR 6.50; 95 % CI 1.47-28.7; p = 0.01), and a history of intravenous drug use (IVDU) (HR 2.80; 95 % CI 1.02-7.65; p = 0.05); African-American race was associated with decreased risk of recurrent SSTI (HR 0.12; 95 % CI 0.04-0.41; p < 0.01). Some evidence was present for HIV viral load ≥ 1000 copies/mL as an independent risk factor for recurrent SSTI (HR 2.21; 95 % CI 0.99-4.94; p = 0.05). Hemodialysis, currently taking HAART, CD4+ count, trimethoprim-sulfamethoxazole or azithromycin use, initial SSTI type, diabetes mellitus, incision and drainage of the original SSTI, or self-report of being a man who has sex with men were not associated with recurrence. Of HIV-infected patients with an SSTI, nearly 1/3 had a recurrent SSTI within 1 year. Risk factors for recurrent SSTI were non-hepatitis liver disease, intravenous catheter presence, a history of IVDU, and non-African-American race. Low CD4+ count was not a significant risk factor for recurrence.

Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development

PubMed Central

Jäckel, Sven; Saffarzadeh, Mona; Langer, Florian

2017-01-01

Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)–dependent model of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expression by myeloid cells, but did not require neutrophil extracellular trap formation involving peptidyl arginine deiminase 4. In contrast to C3−/− mice, C5-deficient mice had no apparent defect in platelet activation in vitro, and vessel wall platelet deposition and initial hemostasis in vivo. However, fibrin formation, the exposure of negatively charged phosphatidylserine (PS) on adherent leukocytes, and clot burden after 48 hours were significantly reduced in C5−/− mice compared with wild-type controls. These results delineate that C3 plays specific roles in platelet activation independent of formation of the terminal complement complex and provide in vivo evidence for contributions of complement-dependent membrane perturbations to prothrombotic TF activation on myeloid cells. PMID:28223279

Development and validation of the simulation-based learning evaluation scale.

PubMed

Hung, Chang-Chiao; Liu, Hsiu-Chen; Lin, Chun-Chih; Lee, Bih-O

2016-05-01

The instruments that evaluate a student's perception of receiving simulated training are English versions and have not been tested for reliability or validity. The aim of this study was to develop and validate a Chinese version Simulation-Based Learning Evaluation Scale (SBLES). Four stages were conducted to develop and validate the SBLES. First, specific desired competencies were identified according to the National League for Nursing and Taiwan Nursing Accreditation Council core competencies. Next, the initial item pool was comprised of 50 items related to simulation that were drawn from the literature of core competencies. Content validity was established by use of an expert panel. Finally, exploratory factor analysis and confirmatory factor analysis were conducted for construct validity, and Cronbach's coefficient alpha determined the scale's internal consistency reliability. Two hundred and fifty students who had experienced simulation-based learning were invited to participate in this study. Two hundred and twenty-five students completed and returned questionnaires (response rate=90%). Six items were deleted from the initial item pool and one was added after an expert panel review. Exploratory factor analysis with varimax rotation revealed 37 items remaining in five factors which accounted for 67% of the variance. The construct validity of SBLES was substantiated in a confirmatory factor analysis that revealed a good fit of the hypothesized factor structure. The findings tally with the criterion of convergent and discriminant validity. The range of internal consistency for five subscales was .90 to .93. Items were rated on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree). The results of this study indicate that the SBLES is valid and reliable. The authors recommend that the scale could be applied in the nursing school to evaluate the effectiveness of simulation-based learning curricula. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ELAV RNA-stability factor HuR binds the 5′-untranslated region of the human IGF-IR transcript and differentially represses cap-dependent and IRES-mediated translation

PubMed Central

Meng, Zheng; King, Peter H.; Nabors, L. Burt; Jackson, Nateka L.; Chen, Ching-Yi; Emanuel, Peter D.; Blume, Scott W.

2005-01-01

The type I insulin-like growth factor receptor (IGF-IR) is an integral component in the control of cell proliferation, differentiation and apoptosis. The IGF-IR mRNA contains an extraordinarily long (1038 nt) 5′-untranslated region (5′-UTR), and we have characterized a diverse series of proteins interacting with this RNA sequence which may provide for intricate regulation of IGF-IR gene expression at the translational level. Here, we report the purification and identification of one of these IGF-IR 5′-UTR-binding proteins as HuR, using a novel RNA crosslinking/RNase elution strategy. Because HuR has been predominantly characterized as a 3′-UTR-binding protein, enhancing mRNA stability and generally increasing gene expression, we sought to determine whether HuR might serve a different function in the context of its binding the IGF-IR 5′-UTR. We found that HuR consistently repressed translation initiation through the IGF-IR 5′-UTR. The inhibition of translation by HuR was concentration dependent, and could be reversed in trans by addition of a fragment of the IGF-IR 5′-UTR containing the HuR binding sites as a specific competitor, or abrogated by deletion of the third RNA recognition motif of HuR. We determined that HuR repressed translation initiation through the IGF-IR 5′-UTR in cells as well, and that siRNA knockdown of HuR markedly increased IGF-IR protein levels. Interestingly, we also found that HuR potently inhibited IGF-IR translation mediated through internal ribosome entry. Kinetic assays were performed to investigate the mechanism of translation repression by HuR and the dynamic interplay between HuR and the translation apparatus. We found that HuR, occupying a cap-distal position, significantly delayed translation initiation mediated by cap-dependent scanning, but was eventually displaced from its binding site, directly or indirectly, as a consequence of ribosomal scanning. However, HuR perpetually blocked the activity of the IGF-IR IRES, apparently arresting the IRES-associated translation pre-initiation complex in an inactive state. This function of HuR as a 5′-UTR-binding protein and dual-purpose translation repressor may be critical for the precise regulation of IGF-IR expression essential to normal cellular homeostasis. PMID:15914670

[Long-term destiny of adolescents and young adults with de novo acute lymphoblastic leukemia treated with a pediatric protocol type].

PubMed

López-Hernández, Manuel Antonio; Alvarado-Ibarra, Martha; Álvarez-Veral, José Luis; Ortiz-Zepeda, Maricela; Guajardo-Leal, Martha Lilia; Cota-Range, Xochitl

The prognosis, in the long term, of adolescents and young adults with acute de novo lymphoblastic leukemia, treated with a pediatric type protocol. To analyze the efficacy and tolerability of a chemotherapy regimen of pediatric type on patients 15-35 years old with de novo acute lymphoblastic leukemia, Ph(-). A retrospective study of patients received from 2001 to 2013, without initial infiltration of the central nervous system. They received the regimen called LALÍN. Terminal goals: frequency of initial remission, probability of survival free of leukemia and event-free survival for five years. We included 101 patients; there were 29 relapses and 19 deaths. There was initial remission in 97% of the cases; survival free of leukemia of 0.58 and event-free survival 0.44. No difference in patients aged 16-21 years vs. 22-35 (p > 0.55). Negative prognostic factors: abnormal karyotypes, except hyperdiploids (p = 0.001); > 5% of blasts, on 14 day induction (p = 0. 0001); delay in the punctuality of the courses of the chemotherapy regimen (p = 0.0001). A pediatric type regimen is applicable to patients aged from 16 to 35 years with acute lymphoblastic leukemia, without greater toxicity and a best survival free of leukemia. The count of > 5% of blasts and the delay in the execution of the stages of the chemotherapy regimen are the stronger negative prognostic factors.

Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study.

PubMed

Taylor, Peter N; Iqbal, Ahmed; Minassian, Caroline; Sayers, Adrian; Draman, Mohd S; Greenwood, Rosemary; Hamilton, William; Okosieme, Onyebuchi; Panicker, Vijay; Thomas, Sara L; Dayan, Colin

2014-01-01

Rates of thyroid hormone prescribing in the United States and the United Kingdom have increased substantially. If some of the increase is due to lowering the thyrotropin threshold for treatment, this may result in less benefit and greater harm. To define trends in thyrotropin levels at the initiation of levothyroxine sodium therapy and the risk of developing a suppressed thyrotropin level following treatment. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. Among 52,298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009, we extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. We excluded persons who had a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking thyroid-altering medication or if the levothyroxine prescription was related to pregnancy; and those who did not have a thyrotropin level measured within 3 months before the initiation of levothyroxine. The median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy. Between 2001 and 2009, the median thyrotropin level at the initiation of levothyroxine therapy fell from 8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in population demographics) was 1.30 (95% CI, 1.19-1.42; P < .001). Older individuals and individuals with cardiac risk factors had higher odds of initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less. At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin level of <0.1 mIU/L. Individuals with depression or tiredness at baseline had increased odds of developing a suppressed thyrotropin level, whereas individuals with cardiac risk factors (eg, atrial fibrillation, diabetes mellitus, hypertension, and raised lipid levels) did not. We observed a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism and a substantial risk of developing a suppressed thyrotropin level following therapy. Large-scale prospective studies are required to assess the risk-benefit ratio of current practice.

Prediction of Febrile Neutropenia after Chemotherapy Based on Pretreatment Risk Factors among Cancer Patients

PubMed Central

Aagaard, Theis; Roen, Ashley; Daugaard, Gedske; Brown, Peter; Sengeløv, Henrik; Mocroft, Amanda; Lundgren, Jens; Helleberg, Marie

2017-01-01

Abstract Background Febrile neutropenia (FN) is a common complication to chemotherapy associated with a high burden of morbidity and mortality. Reliable prediction of individual risk based on pretreatment risk factors allows for stratification of preventive interventions. We aimed to develop such a risk stratification model to predict FN in the 30 days after initiation of chemotherapy. Methods We included consecutive treatment-naïve patients with solid cancers and diffuse large B-cell lymphomas at Copenhagen University Hospital, 2010–2015. Data were obtained from the PERSIMUNE repository of electronic health records. FN was defined as neutrophils ≤0.5 × 10E9/L ​at the time of either a blood culture sample or death. Time from initiation of chemotherapy to FN was analyzed using Fine-Gray models with death as a competing event. Risk factors investigated were: age, sex, body surface area, haemoglobin, albumin, neutrophil-to-lymphocyte ratio, Charlson Comorbidity Index (CCI) and chemotherapy drugs. Parameter estimates were scaled and summed to create the risk score. The scores were grouped into four: low, intermediate, high and very high risk. Results Among 8,585 patients, 467 experienced FN, incidence rate/30 person-days 0.05 (95% CI, 0.05–0.06). Age (1 point if > 65 years), albumin (1 point if < 39 g/L), CCI (1 point if > 2) and chemotherapy (range -5 to 6 points/drug) predicted FN. Median score at inclusion was 2 points (range –5 to 9). The cumulative incidence and the incidence rates and hazard ratios of FN are shown in Figure 1 and Table 1, respectively. Conclusion We developed a risk score to predict FN the first month after initiation of chemotherapy. The score is easy to use and provides good differentiation of risk groups; the score needs independent validation before routine use. Disclosures All authors: No reported disclosures.

Breastfeeding Progression in Preterm Infants Is Influenced by Factors in Infants, Mothers and Clinical Practice: The Results of a National Cohort Study with High Breastfeeding Initiation Rates

PubMed Central

Maastrup, Ragnhild; Hansen, Bo Moelholm; Kronborg, Hanne; Bojesen, Susanne Norby; Hallum, Karin; Frandsen, Annemi; Kyhnaeb, Anne; Svarer, Inge; Hallström, Inger

2014-01-01

Background and Aim Many preterm infants are not capable of exclusive breastfeeding from birth. To guide mothers in breastfeeding, it is important to know when preterm infants can initiate breastfeeding and progress. The aim was to analyse postmenstrual age (PMA) at breastfeeding milestones in different preterm gestational age (GA) groups, to describe rates of breastfeeding duration at pre-defined times, as well as analyse factors associated with PMA at the establishment of exclusive breastfeeding. Methods The study was part of a prospective survey of a national Danish cohort of preterm infants based on questionnaires and structured telephone interviews, including 1,221 mothers and their 1,488 preterm infants with GA of 24–36 weeks. Results Of the preterm infants, 99% initiated breastfeeding and 68% were discharged exclusively breastfed. Breastfeeding milestones were generally reached at different PMAs for different GA groups, but preterm infants were able to initiate breastfeeding at early times, with some delay in infants less than GA 32 weeks. Very preterm infants had lowest mean PMA (35.5 weeks) at first complete breastfeed, and moderate preterm infants had lowest mean PMA at the establishment of exclusive breastfeeding (36.4 weeks). Admitting mothers to the NICU together with the infant and minimising the use of a pacifier during breastfeeding transition were associated with 1.6 (95% CI 0.4–2.8) and 1.2 days (95% CI 0.1–2.3) earlier establishment of exclusive breastfeeding respectively. Infants that were small for gestational age were associated with 5.6 days (95% CI 4.1–7.0) later establishment of exclusive breastfeeding. Conclusion Breastfeeding competence is not developed at a fixed PMA, but is influenced by multiple factors in infants, mothers and clinical practice. Admitting mothers together with their infants to the NICU and minimising the use of pacifiers may contribute to earlier establishment of exclusive breastfeeding. PMID:25251690

Patients living in impoverished areas have more severe ischemic strokes.

PubMed

Kleindorfer, Dawn; Lindsell, Christopher; Alwell, Kathleen A; Moomaw, Charles J; Woo, Daniel; Flaherty, Matthew L; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Kissela, Brett M

2012-08-01

Initial stroke severity is one of the strongest predictors of eventual stroke outcome. However, predictors of initial stroke severity have not been well-described within a population. We hypothesized that poorer patients would have a higher initial stroke severity on presentation to medical attention. We identified all cases of hospital-ascertained ischemic stroke occurring in 2005 within a biracial population of 1.3 million. "Community" socioecomic status was determined for each patient based on the percentage below poverty in the census tract in which the patient resided. Linear regression was used to model the effect of socioeconomic status on stroke severity. Models were adjusted for race, gender, age, prestroke disability, and history of medical comorbidities. There were 1895 ischemic stroke events detected in 2005 included in this analysis; 22% were black, 52% were female, and the mean age was 71 years (range, 19-104). The median National Institutes of Health Stroke Scale was 3 (range, 0-40). The poorest community socioeconomic status was associated with a significantly increased initial National Institutes of Health Stroke Scale by 1.5 points (95% confidence interval, 0.5-2.6; P<0.001) compared with the richest category in the univariate analysis, which increased to 2.2 points after adjustment for demographics and comorbidities. We found that increasing community poverty was associated with worse stroke severity at presentation, independent of other known factors associated with stroke outcomes. Socioeconomic status may impact stroke severity via medication compliance, access to care, and cultural factors, or may be a proxy measure for undiagnosed disease states.

Effect of applied voltage, initial concentration and natural organic matter on sequential reduction/oxidation of nitrobenzene by graphite electrodes

PubMed Central

Sun, Mei; Reible, Danny D.; Lowry, Gregory V.; Gregory, Kelvin B.

2012-01-01

Carbon electrodes are proposed in reactive sediment caps for in situ treatment of contaminants. The electrodes produce reducing conditions and H2 at the cathode and oxidizing conditions and O2 at the anode. Emplaced perpendicular to seepage flow, the electrodes provide the opportunity for sequential reduction and oxidation of contaminants. The objectives of this study are to demonstrate degradation of nitrobenzene (NB) as a probe compound for sequential electrochemical reduction and oxidation, and to determine the effect of applied voltage, initial concentration and natural organic matter on the degradation rate. In H-cell reactors with graphite electrodes and buffer solution, NB was reduced stoichiometrically to aniline (AN) at the cathode with nitrosobenzene (NSB) as the intermediate. AN was then removed at the anode, faster than the reduction step. No common AN oxidation intermediate was detected in the system. Both the first order reduction rate constants of NB (kNB) and NSB (kNSB) increased with applied voltage between 2V and 3.5 V (when the initial NB concentration was 100 µM, kNB=0.3 d−1 and kNSB=0.04 d−1at 2V; kNB=1.6 d−1 and kNSB=0.64 d−1at 3.5 V) but stopped increasing beyond the threshold of 3.5V. When initial NB concentration decreased from 100 to 5 µM, kNB and kNSB became 9 and 5 times faster, respectively, suggesting that competition for active sites on the electrode surface is an important factor in NB degradation. Presence of natural organic matter (in forms of either humic acid or Anacostia River sediment porewater) decreased kNB while slightly increased kNSB, but only to a limited extent (~factor of 3) for dissolved organic carbon content up to 100 mg/l. These findings suggest that electrode-based reactive sediment capping via sequential reduction/oxidation is a potentially robust and tunable technology for in situ contaminants degradation. PMID:22571797

Risk Analyses of Pressure Ulcer in Tetraplegic Spinal Cord-Injured Persons: A French Long-Term Survey.

PubMed

Le Fort, Marc; Espagnacq, Maude; Perrouin-Verbe, Brigitte; Ravaud, Jean-François

2017-09-01

To identify the long-term clinical, individual, and social risk factors for the development of pressure ulcers (PUs) in traumatic spinal cord-injured persons with tetraplegia (TSCIt). Cohort survey with self-applied questionnaires in 1995 and 2006. Thirty-five French-speaking European physical medicine and rehabilitation centers participating in the Tetrafigap surveys. Tetraplegic adults (N=1641) were surveyed after an initial posttraumatic period of at least 2 years. Eleven years later, a follow-up was done for 1327 TSCIt, among whom 221 had died and 547 could be surveyed again. Not applicable. The proportion of PUs documented at the various defined time points, relative to the medical and social situations of the TSCIt, by using univariate analyses followed by logistic regression. Of the participants, 73.4% presented with a PU during at least 1 period after their injury. Four factors had an effect on the occurrence of PUs in the long-term. Protective features for this population were incomplete motor impairment (odds ratio, 0.5) and the ability to walk (odds ratio, 0.2), whereas a strong predictive factor was the development of a PU during the initial posttrauma phase (odds ratio, 2.7). Finally, a significant situational factor was the lack of a social network (odds ratio, 3.1). We believe that the highlighting of a motor incomplete feature of SCI (protective against the development of a PU) and of a medical risk factor, an early PU (which served as a definitive marker of the trajectory of TSCIt), together with a social situational factor, indicates the crucial role of initial management and long-term follow-up. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Factors associated with interest in receiving prison-based methadone maintenance therapy in Malaysia.

PubMed

Mukherjee, Trena I; Wickersham, Jeffrey A; Desai, Mayur M; Pillai, Veena; Kamarulzaman, Adeeba; Altice, Frederick L

2016-07-01

Methadone maintenance therapy (MMT) is crucial for HIV prevention and treatment in people who inject opioids. In Malaysia, a large proportion of the prison population is affected by both HIV and opioid use disorders. This study assessed individual preferences and factors associated with interest in receiving MMT among male prisoners meeting criteria for opioid dependence in Malaysia. A convenience sample of 96 HIV-positive and 104 HIV-negative incarcerated men who met pre-incarceration criteria for opioid dependence was interviewed using a structured questionnaire to examine participant characteristics and attitudes toward MMT. Factors associated with interest in prison-based MMT initiation were identified using logistic regression analysis. Among all participants, 85 (42.5%) were interested in receiving MMT within prison. Independent correlates of interest in prison-based MMT were being previously married (AOR=4.15, 95% CI: 1.15, 15.02), previously incarcerated (AOR=5.68, 95% CI: 1.54, 21.02), depression (AOR=3.66, 95% CI: 1.68, 7.98), daily heroin use in the 30days prior to incarceration (AOR=5.53, 95% CI: 1.65, 18.58), and more favorable attitudes toward MMT (AOR=19.82, 95% CI: 6.07, 64.74). Overall, interest in receiving prison-based MMT was low, and was associated with adverse social, mental health, and drug use consequences. Incarceration provides a unique opportunity to initiate MMT for those who need it, however, optimal scale-up efforts must be systemic and address modifiable factors like improving attitudes toward and motivation for MMT. Informed or shared decision-making tools may be useful in improving expectations and acceptability of MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Factors associated with interest in receiving prison-based methadone maintenance therapy in Malaysia

PubMed Central

Mukherjee, Trena I.; Wickersham, Jeffrey A.; Desai, Mayur M.; Pillai, Veena; Kamarulzaman, Adeeba; Altice, Frederick L.

2017-01-01

Introduction Methadone maintenance therapy (MMT) is crucial for HIV prevention and treatment in people who inject opioids. In Malaysia, a large proportion of the prison population is affected by both HIV and opioid use disorders. This study assessed individual preferences and factors associated with interest in receiving MMT among male prisoners meeting criteria for opioid dependence in Malaysia. Methods A convenience sample of 96 HIV-positive and 104 HIV-negative incarcerated men who met pre-incarceration criteria for opioid dependence was interviewed using a structured questionnaire to examine participant characteristics and attitudes toward MMT. Factors associated with interest in prison-based MMT initiation were identified using logistic regression analysis. Results Among all participants, 85 (42.5%) were interested in receiving MMT within prison. Independent correlates of interest in prison-based MMT were being previously married (AOR = 4.15, 95% CI: 1.15, 15.02), previously incarcerated (AOR = 5.68, 95% CI: 1.54, 21.02), depression (AOR = 3.66, 95% CI: 1.68, 7.98), daily heroin use in the 30 days prior to incarceration (AOR = 5.53, 95% CI: 1.65, 18.58), and more favorable attitudes toward MMT (AOR = 19.82, 95% CI: 6.07, 64.74). Conclusions Overall, interest in receiving prison-based MMT was low, and was associated with adverse social, mental health, and drug use consequences. Incarceration provides a unique opportunity to initiate MMT for those who need it, however, optimal scale-up efforts must be systemic and address modifiable factors like improving attitudes toward and motivation for MMT. Informed or shared decision-making tools may be useful in improving expectations and acceptability of MMT. PMID:27207155

Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva.

PubMed

Cracchiolo, Bernadette M; Heller, Debra S; Clement, Paul M J; Wolff, Edith C; Park, Myung-Hee; Hanauske-Abel, Hartmut M

2004-07-01

The mature eukaryotic translation initiation factor 5A contains the unusual amino acid hypusine, formed post-translationally from a specific lysine residue and essential for proliferation of eukaryotic cells. We hypothesized that the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH-353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was used to test this proposal in biopsies of vulvar high-grade intraepithelial neoplasia (VIN), characterized by the presence of proliferating cells throughout the thickness of the epithelium. Methods. Formalin-fixed and paraffin-embedded archival samples with an independently established diagnosis of VIN 3 were stained immunohistochemically after antigen retrieval, employing NIH-353 and, for comparison, the standard Ki-67 antibody. NIH-353 labeled neoplastic keratinocytes throughout the thickness of the epithelium in all VIN 3 samples. Malignant cells in a case of focally invasive squamous cell carcinoma also stained strongly for mature, hypusine-containing eIF5A-1. Epithelium adjacent to these lesions, though still of apparently normal morphology, was immunoreactive throughout its full thickness. At inflammatory foci of lesional sites, solitary reactive lymphocytes were positive, as were individual proliferating cells within dermal appendages. The submucosal stroma lacked reactive cells. NIH-353 identifies mature eIF5A-1 as an in situ biomarker for proliferation. Like Ki-67, this immunoreagent promises broad applicability in histopathological diagnosis and may be helpful in outcome prediction. In contrast to Ki-67, NIH-353 visualizes a molecular target for antineoplastic therapy, and thus may guide the development and clinical testing of drugs that, like the fungicide ciclopirox, inhibit hypusine formation and cell proliferation.

pH controls spermatozoa motility in the Pacific oyster (Crassostrea gigas)

PubMed Central

Suquet, Marc; Malo, Florent; Queau, Isabelle; Pignet, Patricia; Ratiskol, Dominique; Le Grand, Jacqueline; Huber, Matthias; Cosson, Jacky

2018-01-01

ABSTRACT Investigating the roles of chemical factors stimulating and inhibiting sperm motility is required to understand the mechanisms of spermatozoa movement. In this study, we described the composition of the seminal fluid (osmotic pressure, pH, and ions) and investigated the roles of these factors and salinity in initiating spermatozoa movement in the Pacific oyster, Crassostrea gigas. The acidic pH of the gonad (5.82±0.22) maintained sperm in the quiescent stage and initiation of flagellar movement was triggered by a sudden increase of spermatozoa external pH (pHe) when released in seawater (SW). At pH 6.4, percentage of motile spermatozoa was three times higher when they were activated in SW containing 30 mM NH4Cl, which alkalinizes internal pH (pHi) of spermatozoa, compared to NH4Cl-free SW, revealing the role of pHi in triggering sperm movement. Percentage of motile spermatozoa activated in Na+-free artificial seawater (ASW) was highly reduced compared to ASW, suggesting that change of pHi triggering sperm motility was mediated by a Na+/H+ exchanger. Motility and swimming speed were highest in salinities between 33.8 and 42.7‰ (within a range of 0 to 50 ‰), and pH values above 7.5 (within a range of 4.5 to 9.5). PMID:29483075

A theoretical study of OH radical-initiated atmospheric oxidation of 1-chloronaphthalene

NASA Astrophysics Data System (ADS)

Cui, Yang; Ding, Zhezheng; Sun, Yanhui; Yi, Yayi; Xu, Fei; Zhang, Qingzhu; Wang, Wenxing

2018-05-01

OH-initiated atmospheric oxidation mechanism of 1-chloronaphthalene (1-CN) was investigated using density functional theory (DFT) calculations. The oxidation is predicted to be initiated by OH addition to the α-positions, and the additions to C4 and C5 are more favorable. 1-CN-OH adducts tend to react with ambient O2 to produce peroxy intermediates, followed by intramolecular H-shifts producing C10H7OCl and diketone or unimolecular ring closure forming methyl glyoxal and Cl-substituted phthalaldialdehyde. Despite that the rate constants are influenced by the tunneling factors, intramolecular H-shift reactions are suggested to be more favorable. The OH-determined lifetime of 1-CN is 0.62 days.

Medical and sociodemographic factors associated with human papillomavirus (HPV) vaccination adherence among female survivors of childhood cancer.

PubMed

Klosky, James L; Russell, Kathryn M; Simmons, Jessica L; Foster, Rebecca H; Peck, Kelly; Green, Daniel M; Hudson, Melissa M

2015-09-01

Among those 9-26 years of age, vaccination can prevent specific types of genital human papillomavirus (HPV), the most common sexually transmitted infection and cause of cervical and other cancers. The objective of this study was to estimate the prevalence of and factors associated with HPV vaccine initiation and completion among females surviving childhood cancer. One-hundred fourteen young adults and 230 mothers with daughters surviving childhood cancer completed surveys querying HPV vaccination history along with medical and sociodemographic factors potentially associated with vaccination outcomes. Vaccination rate differences by age necessitated analysis of outcomes by age group: 9-13 years (preadolescents), 14-17 years (adolescents), and 18-26 years (young adults). Multivariable logistic regression was utilized to identify factors associated with HPV vaccination outcomes. Overall, 34.6% (119/344) of survivors initiated and 20.9% (72/344) completed HPV vaccination. Preadolescents were least likely to have initiated vaccination (P < 0.001). Physician recommendation was associated with initiation across age groups (OR = 6.81-11.96, Ps < 0.001-.01), whereas older age at diagnosis (≥12 years of age) was associated with lower vaccination initiation among young adults only (OR = 0.28; 95%CI, 0.10-0.76, P = 0.012). Physician recommendation (OR = 7.54; 95%CI, 1.19-47.69, P = 0.032; adolescent group) and greater treatment intensity (OR = 5.25; 95%CI, 1.00-27.61, P = 0.050; young adult group) were associated with vaccine completion, whereas being non-White was associated with decreased vaccination completion (OR = 0.17; 95%CI, 0.05-0.66, P = 0.010; adolescent group). A minority of youths surviving childhood cancer have initiated or completed HPV vaccination. Strategies to increase vaccination among survivors are discussed. © 2015 Wiley Periodicals, Inc.

Benzocaine-induced methaemoglobinaemia: a case study.

PubMed

Bittmann, Stefan; Krüger, Carsten

Benzocaine is a widely used topical anaesthetic and has been reported to cause toxic methaemoglobinaemia in otherwise healthy individuals with no predisposing risk factors. This article reports on a rare case of benzocaine-induced methaemoglobinaemia following adenotonsillectomy in a 5-year-old girl. Topical benzocaine was applied orally for the relief of postoperative wound pain on the eighth postoperative day. Two hours after application, generalized cyanosis, mild dyspnoea and some degree of agitation developed. The methaemoglobin level was 38.5%. Treatment with methylene blue was initiated immediately. Symptoms completely disappeared 4 hours after initiation of methylene blue therapy. The further course was uneventful. Therefore, all health professionals should be aware that topical anaesthetics after surgery can induce methaemoglobinaemia in children, even after a prolonged interval, and especially when applied on wound surfaces.

Afebrile seizure subsequent to initial febrile seizure.

PubMed

Fallah, Razieh; Razieh, Fallah; Akhavan Karbasi, Sedighah; Sedighah, Akhavan Karbasi; Golestan, Motahhareh; Motahhareh, Golestan

2012-05-01

Febrile seizure (FS) is the most common paediatric neurological problem. The purpose of this study was to determine the frequency of afebrile seizures subsequent to FS in children with initial FS and to evaluate its risk factors. A prospective study was conducted on all children (age 6 months to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran, between August 2004 and March 2006, who were followed up for at least 15 months for the occurrence of subsequent afebrile seizures. 161 boys and 120 girls (mean age 2.12 ± 1.33 years) were followed up for 34.1 ± 7.8 months. 87 (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile seizure, with a mean occurrence time of 10.6 ± 6.4 months. Univariate analysis using chi-square test showed that initial FS within one hour of developing fever (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. Special attention should be paid to children with FS during history-taking and developmental assessments to identify high-risk patients and those who might need prophylactic anticonvulsants.

Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non-Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center.

PubMed

Dinglin, Xiao-Xiao; Ma, Shu-Xiang; Wang, Fang; Li, De-Lan; Liang, Jian-Zhong; Chen, Xin-Ru; Liu, Qing; Zeng, Yin-Duo; Chen, Li-Kun

2017-05-01

The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non-small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs. Copyright © 2017 Elsevier Inc. All rights reserved.

QCD for Postgraduates (3/5)

ScienceCinema

Zanderighi, Giulia

2018-04-27

Modern QCD - Lecture 3 We will introduce processes with initial-state hadrons and discuss parton distributions, sum rules, as well as the need for a factorization scale once radiative corrections are taken into account. We will then discuss the DGLAP equation, the evolution of parton densities, as well as ways in which parton densities are extracted from data.

Effects of Psychological and Social Work Factors on Self-Reported Sleep Disturbance and Difficulties Initiating Sleep

PubMed Central

Vleeshouwers, Jolien; Knardahl, Stein; Christensen, Jan Olav

2016-01-01

Study Objectives: This prospective cohort study examined previously underexplored relations between psychological/social work factors and troubled sleep in order to provide practical information about specific, modifiable factors at work. Methods: A comprehensive evaluation of a range of psychological/social work factors was obtained by several designs; i.e., cross-sectional analyses at baseline and follow-up, prospective analyses with baseline predictors (T1), prospective analyses with average exposure across waves as predictor ([T1 + T2] / 2), and prospective analyses with change in exposure from baseline to follow-up as predictor. Participants consisted of a sample of Norwegian employees from a broad spectrum of occupations, who completed a questionnaire at two points in time, approximately two years apart. Cross-sectional analyses at T1 comprised 7,459 participants, cross-sectional analyses at T2 included 6,688 participants. Prospective analyses comprised a sample 5,070 of participants who responded at both T1 and T2. Univariable and multivariable ordinal logistic regressions were performed. Results: Thirteen psychological/social work factors and two aspects of troubled sleep, namely difficulties initiating sleep and disturbed sleep, were studied. Ordinal logistic regressions revealed statistically significant associations for all psychological and social work factors in at least one of the analyses. Psychological and social work factors predicted sleep problems in the short term as well as the long term. Conclusions: All work factors investigated showed statistically significant associations with both sleep items, however quantitative job demands, decision control, role conflict, and support from superior were the most robust predictors and may therefore be suitable targets of interventions aimed at improving employee sleep. Citation: Vleeshouwers J, Knardahl S, Christensen JO. Effects of psychological and social work factors on self-reported sleep disturbance and difficulties initiating sleep. SLEEP 2016;39(4):833–846. PMID:26446114

Developing a Tool to Assess the Capacity of Out-of-School Time Program Providers to Implement Policy, Systems, and Environmental Change.

PubMed

Leeman, Jennifer; Blitstein, Jonathan L; Goetz, Joshua; Moore, Alexis; Tessman, Nell; Wiecha, Jean L

2016-08-11

Little is known about public health practitioners' capacity to change policies, systems, or environments (PSEs), in part due to the absence of measures. To address this need, we partnered with the Alliance for a Healthier Generation (Alliance) to develop and test a theory-derived measure of the capacity of out-of-school time program providers to improve students' level of nutrition and physical activity through changes in PSEs. The measure was developed and tested through an engaged partnership with staff working on the Alliance's Healthy Out-of-School Time (HOST) Initiative. In total, approximately 2,000 sites nationwide are engaged in the HOST Initiative, which serves predominantly high-need children and youths. We partnered with the Alliance to conduct formative work that would help develop a survey that assessed attitudes/beliefs, social norms, external resources/supports, and self-efficacy. The survey was administered to providers of out-of-school time programs who were implementing the Alliance's HOST Initiative. Survey respondents were 185 out-of-school time program providers (53% response rate). Exploratory factor analysis yielded a 4-factor model that explained 44.7% of the variance. Factors pertained to perceptions of social norms (6 items) and self-efficacy to build support and engage a team (4 items) and create (5 items) and implement (3 items) an action plan. We report initial development and factor analysis of a tool that the Alliance can use to assess the capacity of after-school time program providers, which is critical to targeting capacity-building interventions and assessing their effectiveness. Study findings also will inform the development of measures to assess individual capacity to plan and implement other PSE interventions.

Polygenic risk scores for smoking: predictors for alcohol and cannabis use?

PubMed

Vink, Jacqueline M; Hottenga, Jouke Jan; de Geus, Eco J C; Willemsen, Gonneke; Neale, Michael C; Furberg, Helena; Boomsma, Dorret I

2014-07-01

A strong correlation exists between smoking and the use of alcohol and cannabis. This paper uses polygenic risk scores to explore the possibility of overlapping genetic factors. Those scores reflect a combined effect of selected risk alleles for smoking. Summary-level P-values were available for smoking initiation, age at onset of smoking, cigarettes per day and smoking cessation from the Tobacco and Genetics Consortium (n between 22,000 and 70,000 subjects). Using different P-value thresholds (0.1, 0.2 and 0.5) from the meta-analysis, sets of 'risk alleles' were defined and used to generate a polygenic risk score (weighted sum of the alleles) for each subject in an independent target sample from the Netherlands Twin Register (n = 1583). The association between polygenic smoking scores and alcohol/cannabis use was investigated with regression analysis. The polygenic scores for 'cigarettes per day' were associated significantly with the number of glasses alcohol per week (P = 0.005, R2 = 0.4-0.5%) and cannabis initiation (P = 0.004, R2 = 0.6-0.9%). The polygenic scores for 'age at onset of smoking' were associated significantly with 'age at regular drinking' (P = 0.001, R2 = 1.1-1.5%), while the scores for 'smoking initiation' and 'smoking cessation' did not significantly predict alcohol or cannabis use. Smoking, alcohol and cannabis use are influenced by aggregated genetic risk factors shared between these substances. The many common genetic variants each have a very small individual effect size. © 2014 Society for the Study of Addiction.

Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators.

PubMed

Svensson, Elisabeth; Baggesen, Lisbeth M; Johnsen, Søren P; Pedersen, Lars; Nørrelund, Helene; Buhl, Esben S; Haase, Christiane L; Thomsen, Reimar W

2017-06-01

We investigated the association of early achieved HbA 1c level and magnitude of HbA 1c reduction with subsequent risk of cardiovascular events or death in patients with type 2 diabetes who initiate metformin. This was a population-based cohort study including all metformin initiators with HbA 1c tests in Northern Denmark, 2000-2012. Six months after metformin initiation, we classified patients by HbA 1c achieved (<6.5% or higher) and by magnitude of HbA 1c change from the pretreatment baseline. We used Cox regression to examine subsequent rates of acute myocardial infarction, stroke, or death, controlling for baseline HbA 1c and other confounding factors. We included 24,752 metformin initiators (median age 62.5 years, 55% males) with a median follow-up of 2.6 years. The risk of a combined outcome event gradually increased with rising levels of HbA 1c achieved compared with a target HbA 1c of <6.5%: adjusted hazard ratio (HR) 1.18 (95% CI 1.07-1.30) for 6.5-6.99%, HR 1.23 (1.09-1.40) for 7.0-7.49%, HR 1.34 (1.14-1.57) for 7.5-7.99%, and HR 1.59 (1.37-1.84) for ≥8%. Results were consistent for individual outcome events and robust by age-group and other patient characteristics. A large absolute HbA 1c reduction from baseline also predicted outcome: adjusted HR 0.80 (0.65-0.97) for Δ = -4, HR 0.98 (0.80-1.20) for Δ = -3, HR 0.92 (0.78-1.08) for Δ = -2, and HR 0.99 (0.89-1.10) for Δ = -1 compared with no HbA 1c change (Δ = 0). A large initial HbA 1c reduction and achievement of low HbA 1c levels within 6 months after metformin initiation are associated with a lower risk of cardiovascular events and death in patients with type 2 diabetes. © 2017 by the American Diabetes Association.

Effect on the structural, DC resistivity and magnetic properties of Zr and Cu co-SubstitutedNi0.5Zn0.5Fe2O4using sol-gel auto-combustion method

NASA Astrophysics Data System (ADS)

Jalaiah, K.; Vijaya Babu, K.; Chandra mouli, K.; Subba Rao, P. S. V.

2018-04-01

The Zr and Cu co-substituted Ni0.5Zn0.5Fe2O4 ferrite nanoparticles have been synthesized by the sol-gel auto combustion method. The XRD patterns confirmed single phase cubic spinel structure for present ferrite systems. The substitution of co-dopants in the spinel structure initially decreases the lattice parameter from x = 0.00 to 0.08 and thereafter increases and the same tendency reflecting in cell volume. The DC resistivity was initially increased later followed the decreasing trend; however the drift mobility of all ferrite samples appears to be in opposite phenomenon to DC resistivity. The saturation magnetization and net magnetic moments of all ferrite samples are decreasing with increasing dopant concentration. The coercive field and Y-K angles are increased with dopant concentration. The initial permeability of all samples is decreased with increasing dopant concentration. The Q-Factor for all samples shows the narrow frequency band with increasing frequency.

Screening for violence risk factors identifies young adults at risk for return emergency department visit for injury.

PubMed

Hankin, Abigail; Wei, Stanley; Foreman, Juron; Houry, Debra

2014-08-01

Homicide is the second leading cause of death among youth aged 15-24. Prior cross-sectional studies, in non-healthcare settings, have reported exposure to community violence, peer behavior, and delinquency as risk factors for violent injury. However, longitudinal cohort studies have not been performed to evaluate the temporal or predictive relationship between these risk factors and emergency department (ED) visits for injuries among at-risk youth. The objective was to assess whether self-reported exposure to violence risk factors in young adults can be used to predict future ED visits for injuries over a 1-year period. This prospective cohort study was performed in the ED of a Southeastern US Level I trauma center. Eligible participants were patients aged 18-24, presenting for any chief complaint. We excluded patients if they were critically ill, incarcerated, or could not read English. Initial recruitment occurred over a 6-month period, by a research assistant in the ED for 3-5 days per week, with shifts scheduled such that they included weekends and weekdays, over the hours from 8AM-8PM. At the time of initial contact in the ED, patients were asked to complete a written questionnaire, consisting of previously validated instruments measuring the following risk factors: a) aggression, b) perceived likelihood of violence, c) recent violent behavior, d) peer behavior, e) community exposure to violence, and f) positive future outlook. At 12 months following the initial ED visit, the participants' medical records were reviewed to identify any subsequent ED visits for injury-related complaints. We analyzed data with chi-square and logistic regression analyses. Three hundred thirty-two patients were approached, of whom 300 patients consented. Participants' average age was 21.1 years, with 60.1% female, 86.0% African American. After controlling for participant gender, ethnicity, or injury complaint at time of first visit, return visits for injuries were significantly associated with: hostile/aggressive feelings (Odds ratio (OR) 3.5, 95% Confidence interval (CI): 1.3, 9.8), self-reported perceived likelihood of violence (OR 10.1, 95% CI: 2.5, 40.6), and peer group violence (OR 6.7, 95% CI: 2.0, 22.3). A brief survey of risk factors for violence is predictive of increased probability of a return visit to the ED for injury. These findings identify a potentially important tool for primary prevention of violent injuries among at-risk youth seen in the ED for trauma-related and non-traumatic complaints.

Control of skeletal muscle perfusion at the onset of dynamic exercise

NASA Technical Reports Server (NTRS)

Delp, M. D.

1999-01-01

At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

Incidence and risk factors of herpes zoster among hiv-positive patients in the german competence network for HIV/AIDS (KompNet): a cohort study analysis.

PubMed

Jansen, Klaus; Haastert, Burkhard; Michalik, Claudia; Guignard, Adrienne; Esser, Stefan; Dupke, Stephan; Plettenberg, Andreas; Skaletz-Rorowski, Adriane; Brockmeyer, Norbert H

2013-08-10

HIV infection is a risk factor for the development of Herpes zoster (HZ) and its complications. Prior to antiretroviral therapy (ART), HZ incidence in HIV-infected individuals ranged from 2.9-5.1/100 person-years. There is limited evidence for the impact of ART on HZ occurrence among HIV-infected adults. We analysed the incidence of, and risk factors for, HZ in a large cohort of German HIV-positive patients. The study population was taken from the German KompNet cohort, a nationwide multicenter HIV cohort study. The study population was defined by age (≥ 18 years), year of first positive HIV diagnosis, CD4 values ± 6 months from HIV diagnosis (t0), and month of HZ diagnosis. Incidences were estimated using a Poisson distribution, and uni- and multivariate Cox proportional Hazard ratio (HR) regression models were fitted to identify risk factors for developing an initial HZ episode. Independent variables were sex, age at HIV diagnosis, route of HIV transmission, ART status, CD4 count before HZ episode, immunosuppressive medication, and mode of data documentation (retrospective or prospective). HZ incidence in the overall study population was 1.2/100 person-years. In a subset of patients for that we were able to examine risk factors the following was observed: We examined 3,757 individuals whose mean age at t0 was 38 years. Of those individuals, 96% were diagnosed with HIV in 1996 or later, with a mean observation time of 5.8 years. HZ episodes (n = 362) were recorded in 326 patients (8.7%), resulting in annual HZ incidences of 1.7/100 person-years overall, and 1.6/100 person-years for initial HZ cases. The main risk factors associated with an initial HZ episode were: not partaking in ART compared with an ART regimen containing a non-nucleoside reverse-transcriptase inhibitor (HR 0.530, p < 0.001) or a protease inhibitor (HR 0.624, p = 0.004); and lower CD4 count by 100 cells/μl (HR 0.918, p=0.001). HZ incidence was 4-11-fold higher than in non HIV-infected individuals, but in our study HZ incidences were lower than in previous studies relating to HIV-positive patients. We showed that ART is an important protective factor for HZ episodes.

What are the critical success factors for team training in health care?

PubMed

Salas, Eduardo; Almeida, Sandra A; Salisbury, Mary; King, Heidi; Lazzara, Elizabeth H; Lyons, Rebecca; Wilson, Katherine A; Almeida, Paula A; McQuillan, Robert

2009-08-01

Ineffective communication among medical teams is a leading cause of preventable patient harm throughout the health care system. A growing body of literature indicates that medical teamwork improves the quality, safety, and cost-effectiveness of health care delivery, and expectations for teamwork in health care have increased. Yet few health care professions' curricula include teamwork training, and few medical practices integrate teamwork principles. Because of this knowledge gap, growing numbers of health care systems are requiring staff to participate in formal teamwork training programs. Seven evidence-based, practical, systematic success factors for preparing, implementing, and sustaining a team training and performance improvement initiative were identified. Each success factor is accompanied by tips for deployment and a real-world example of application. (1) Align team training objectives and safety aims with organizational goals, (2) provide organizational support for the team training initiative, (3) get frontline care leaders on board, (4) prepare the environment and trainees for team training, (5) determine required resources and time commitment and ensure their availability, (6) facilitate application of trained teamwork skills on the job; and (7) measure the effectiveness of the team training program. Although decades of research in other high-risk organizations have clearly demonstrated that properly designed team training programs can improve team performance, success is highly dependent on organizational factors such as leadership support, learning climate, and commitment to data-driven change. Before engaging in a teamwork training initiative, health care organizations should have a clear understanding of these factors and the strategies for their establishment.

Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin.

PubMed

Wilson, Fiona A; Orellana, Renán A; Suryawan, Agus; Nguyen, Hanh V; Jeyapalan, Asumthia S; Frank, Jason; Davis, Teresa A

2008-07-01

Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7-10 days of pST (150 microg x kg(-1) x day(-1)) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 microU/ml), 2) fed control (25 microU/ml), and 3) fed pST-treated (50 microU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1.eIF4E complex association and increased active eIF4E.eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation.

Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin

PubMed Central

Wilson, Fiona A.; Orellana, Renán A.; Suryawan, Agus; Nguyen, Hanh V.; Jeyapalan, Asumthia S.; Frank, Jason; Davis, Teresa A.

2008-01-01

Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7–10 days of pST (150 μg·kg−1·day−1) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 μU/ml), 2) fed control (25 μU/ml), and 3) fed pST-treated (50 μU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1·eIF4E complex association and increased active eIF4E·eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation. PMID:18460595

Late effects of radiation on the lumbar spinal cord of guinea pigs: Re-treatment tolerance

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

Mason, K.A.; Withers, H.R.; Chiang, Chi-Shiun

Using a guinea pig model of lumbar myelopathy, various factors affecting the tolerance of spinal cord to irradiation were assessed: (a) extent of initial injury; (b) time interval between priming and test doses; and (c) animal age at the time of initial radiation treatment. A 3 cm section of lumbar spinal cord of guinea pigs was irradiated with fractionated doses of 4.5 Gy gamma rays given as 9 fractions per week. Guinea pigs were primed with 9 x 4.5 Gy in 7 days which is 60% of the ED[sub 50] for a continuous course of treatment. After 28 or 40more » weeks, animal were retreated with 6-14 fractions of 4.5 Gy. Animals were observed for 2 years following the priming dose and both the incidence and latency of myelopathy recorded. Young adult guinea pigs (8 wk old) showed both a decreased radiation tolerance and latency compared to old individuals (40 wk old). At 28 or 40 wk after 9 x 4.5 Gy, only about 8% of the initial injury was remembered in young adult guinea pigs. The amount of residual injury was dependent on the initial damage as a proportion of the tolerance dose. The spinal cord shows a greater capacity for long-term recovery than generally appreciated and re-treatment doses clinically prescribed may be lower than necessary. 8 refs., 3 figs., 2 tabs.« less

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Localization of TFIIB binding regions using serial analysis of chromatin occupancy

PubMed Central

Yochum, Gregory S; Rajaraman, Veena; Cleland, Ryan; McWeeney, Shannon

2007-01-01

Background: RNA Polymerase II (RNAP II) is recruited to core promoters by the pre-initiation complex (PIC) of general transcription factors. Within the PIC, transcription factor for RNA polymerase IIB (TFIIB) determines the start site of transcription. TFIIB binding has not been localized, genome-wide, in metazoans. Serial analysis of chromatin occupancy (SACO) is an unbiased methodology used to empirically identify transcription factor binding regions. In this report, we use TFIIB and SACO to localize TFIIB binding regions across the rat genome. Results: A sample of the TFIIB SACO library was sequenced and 12,968 TFIIB genomic signature tags (GSTs) were assigned to the rat genome. GSTs are 20–22 base pair fragments that are derived from TFIIB bound chromatin. TFIIB localized to both non-protein coding and protein-coding loci. For 21% of the 1783 protein-coding genes in this sample of the SACO library, TFIIB binding mapped near the characterized 5' promoter that is upstream of the transcription start site (TSS). However, internal TFIIB binding positions were identified in 57% of the 1783 protein-coding genes. Internal positions are defined as those within an inclusive region greater than 2.5 kb downstream from the 5' TSS and 2.5 kb upstream from the transcription stop. We demonstrate that both TFIIB and TFIID (an additional component of PICs) bound to internal regions using chromatin immunoprecipitation (ChIP). The 5' cap of transcripts associated with internal TFIIB binding positions were identified using a cap-trapping assay. The 5' TSSs for internal transcripts were confirmed by primer extension. Additionally, an analysis of the functional annotation of mouse 3 (FANTOM3) databases indicates that internally initiated transcripts identified by TFIIB SACO in rat are conserved in mouse. Conclusion: Our findings that TFIIB binding is not restricted to the 5' upstream region indicates that the propensity for PIC to contribute to transcript diversity is far greater than previously appreciated. PMID:17997859

A Dual Interaction Between the 5'- and 3'-Ends of the Melon Necrotic Spot Virus (MNSV) RNA Genome Is Required for Efficient Cap-Independent Translation.

PubMed

Miras, Manuel; Rodríguez-Hernández, Ana M; Romero-López, Cristina; Berzal-Herranz, Alfredo; Colchero, Jaime; Aranda, Miguel A; Truniger, Verónica

2018-01-01

In eukaryotes, the formation of a 5'-cap and 3'-poly(A) dependent protein-protein bridge is required for translation of its mRNAs. In contrast, several plant virus RNA genomes lack both of these mRNA features, but instead have a 3'-CITE (for cap-independent translation enhancer), a RNA element present in their 3'-untranslated region that recruits translation initiation factors and is able to control its cap-independent translation. For several 3'-CITEs, direct RNA-RNA long-distance interactions based on sequence complementarity between the 5'- and 3'-ends are required for efficient translation, as they bring the translation initiation factors bound to the 3'-CITE to the 5'-end. For the carmovirus melon necrotic spot virus (MNSV), a 3'-CITE has been identified, and the presence of its 5'-end in cis has been shown to be required for its activity. Here, we analyze the secondary structure of the 5'-end of the MNSV RNA genome and identify two highly conserved nucleotide sequence stretches that are complementary to the apical loop of its 3'-CITE. In in vivo cap-independent translation assays with mutant constructs, by disrupting and restoring sequence complementarity, we show that the interaction between the 3'-CITE and at least one complementary sequence in the 5'-end is essential for virus RNA translation, although efficient virus translation and multiplication requires both connections. The complementary sequence stretches are invariant in all MNSV isolates, suggesting that the dual 5'-3' RNA:RNA interactions are required for optimal MNSV cap-independent translation and multiplication.

Ten year experience with antiretroviral treatment in Cambodia: Trends in patient characteristics and treatment outcomes.

PubMed

Lay, Phirum; An, Sokkab; Soeung, Sunpiseth; Srey, Pich Sovannary; Thai, Sopheak; Lynen, Lutgarde; Griensven, Johan van

2017-01-01

Although HIV disease stage at ART initiation critically determines ART outcomes, few reports have longitudinally monitored this within Asia. Using prospectively collected data from a large ART program at Sihanouk Hospital Center of Hope in Cambodia, we report on the change in patient characteristics and outcomes over a ten-year period. We conducted a retrospective analysis including all adults (≥ 18 years old) starting ART from March 2003-March 2013 in a non-governmental hospital in Phnom Penh, Cambodia. The cumulative incidence of death, lost to follow-up (LTFU), attrition (death or LTFU) and first line treatment failure were calculated using Kaplan-Meier methods. Independent risk factors for these outcomes were determined using Cox regression modeling. Over the ten-year period, 3581 patients initiated ART with a median follow-up time of 4.8 years (IQR 2.8-7.2). The median age was 35 years (IQR 30-41), 54% were female. The median CD4 count at ART initiation increased from 22 cells/μL (IQR 4-129) in 2003 to 218 (IQR 57-302) in 2013. Over the 10 year period, a total of 282 (7.9%) individuals died and 433 (12.1%) were defined LTFU. Program attrition (died or LTFU) was 11.1% (95% CI: 10.1%- 12.4%) at one year, 16.3% (95% CI: 15.1%-17.6%) at three years, 19.8% (95% CI: 18.5%-21.2%) at five years and 23.3% (95% CI: 21.6-25.1) at ten years. Male sex and low baseline body mass index (BMI) were associated with increased attrition. Factors independently associated with mortality included a low baseline CD4 count, older age, male sex, low baseline BMI and hepatitis B co-infection. Individuals aged above 40 years old had an increased risk of mortality but were less likely to LTFU. There were a total of 137 individuals with first line ART failure starting second line treatment. The probability of first line failure was estimated at 2.8% (95% CI: 2.3%-3.4%) at 3 years, 4.6% (95% CI: 3.9%-5.5%) at 5 years and 7.8% (95% CI 4.8%-12.5%) at ten years of ART. The probability was particularly high in the first few program years. A lower risk was observed among individuals starting ART during the 2006-2008 period. Factors independently associated with an increased risk of treatment failure included ART-experience, NVP-based ART and a baseline CD4 count below 200 cells/μL. Overall program outcomes were fair, and generally compare well to other reports from the region. Despite gradually earlier initiation of ART over the ten year period, ART is still initiated at too low CD4 count levels, warranting increased efforts for early HIV diagnosis and enrolment/retention into HIV care. Tailored strategies for poor prognostic groups (older age, male, low BMI) should be designed and evaluated.

Molecular alignment and orientation with a hybrid Raman scattering technique

NASA Astrophysics Data System (ADS)

Bustard, Philip J.; Lausten, R.; Sussman, Benjamin J.

2012-11-01

We demonstrate a scheme for the preparation of molecular alignment and angular momentum orientation using a hybrid combination of two limits of Raman scattering. First a weak, impulsive pump pulse initializes the system via the nonresonant dynamic Stark effect. Then, having overcome the influence of the vacuum fluctuations, an amplification pulse selectively enhances the initial coherences by transient stimulated Raman scattering, generating alignment and angular momentum orientation of molecular hydrogen. The amplitude and phase of the resulting coherent dynamics are experimentally probed, indicating an amplification factor of 4.5. An analytic theory is developed to model the dynamics.

[Risk of arrhythmia and domestic low-voltage electrical injury].

PubMed

Claudet, I; Maréchal, C; Debuisson, C; Salanne, S

2010-04-01

Analysis of domestic low-voltage (220-240 V) electrical injury in children admitted to a pediatric emergency department to illustrate the low risk of initial or delayed risk of arrhythmia. Retrospective study between 2001 and 2008 analyzing all children aged less than 15 years admitted for a low-voltage electrical injury. The data collected were age, sex, time and circumstances of the accident, time and day of admission, transport modalities, presence of risk factors for arrhythmia (transthoracic current, wet skin, tetany, loss of consciousness or neurological symptoms, and initial EKG abnormalities), injuries, EKG, muscular and/or cardiac enzyme values, progression and complications. For statistical analysis, data were entered in Microsoft Excel tables. Analysis was done with StatView5.1 (SAS Institute) and Epi Info 6.04fr (VF, ENSP epiconcept). In the descriptive analysis, the data are presented as mean values with SD, median and range. Forty-eight children were included. The mean annual number of admissions was equal to 6 (range, 3-12). The mean age was 6.2 + or - 4.3 years (median, 4.6 years). There was a male predominance: the overall sex ratio was 1.5, i.e., 3 before the age of 2 and 2.6 before the age of 10. The electrical injury occurred after contact with a wire or a connected cord or after the introduction of a metallic object in a wall socket. Ten children had risk factors of arrhythmia (mainly wet skin or thoracic pain). Twenty-nine children suffered from burns to the extremities (digits and hands, 70 %). At admission, 45 children had an EKG performed. The initial EKG was considered abnormal in 8 cases showing: sinusal tachycardia (n=4), incomplete right bundle branch block (n=4), and V(1) negative T waves (n=1). The EKG normalized within the first 12h. Hospitalization for cardiac monitoring was required for 18 children. No delayed arrhythmia occurred. In a mean time of 3.5h after the accident, a troponin dosage was given to 15 children and was normal in all cases. One child developed rhabdomyolysis and evolved without needing dialysis. After a low-voltage electrical injury, initial arrhythmia is not frequent, with often a nonspecific and transitory EKG expression; delayed arrhythmia is very rare. Children presenting to the emergency department after such an electrical accident, who are asymptomatic, without any risk factors for arrhythmia (wet skin, tetany, vertical pathway of the current, preexistent cardiological conditions, loss of consciousness) and with a normal initial EKG do not require cardiac monitoring. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Injuries and Illnesses of Vietnam War POWs Revisited: IV. Air Force Risk Factors

DTIC Science & Technology

2017-03-22

predominantly aviators imprisoned in North Vietnam. Statistical analyses were performed using SPSS version 19. Pearson correlations were obtained...Repatriated Prisoner of War Initial Medical Evaluation Forms. Department of Defense. Washington, D.C. 5. IBM Corporation (2010). IBM SPSS Statistics for

Iterative initial condition reconstruction

NASA Astrophysics Data System (ADS)

Schmittfull, Marcel; Baldauf, Tobias; Zaldarriaga, Matias

2017-07-01

Motivated by recent developments in perturbative calculations of the nonlinear evolution of large-scale structure, we present an iterative algorithm to reconstruct the initial conditions in a given volume starting from the dark matter distribution in real space. In our algorithm, objects are first moved back iteratively along estimated potential gradients, with a progressively reduced smoothing scale, until a nearly uniform catalog is obtained. The linear initial density is then estimated as the divergence of the cumulative displacement, with an optional second-order correction. This algorithm should undo nonlinear effects up to one-loop order, including the higher-order infrared resummation piece. We test the method using dark matter simulations in real space. At redshift z =0 , we find that after eight iterations the reconstructed density is more than 95% correlated with the initial density at k ≤0.35 h Mpc-1 . The reconstruction also reduces the power in the difference between reconstructed and initial fields by more than 2 orders of magnitude at k ≤0.2 h Mpc-1 , and it extends the range of scales where the full broadband shape of the power spectrum matches linear theory by a factor of 2-3. As a specific application, we consider measurements of the baryonic acoustic oscillation (BAO) scale that can be improved by reducing the degradation effects of large-scale flows. In our idealized dark matter simulations, the method improves the BAO signal-to-noise ratio by a factor of 2.7 at z =0 and by a factor of 2.5 at z =0.6 , improving standard BAO reconstruction by 70% at z =0 and 30% at z =0.6 , and matching the optimal BAO signal and signal-to-noise ratio of the linear density in the same volume. For BAO, the iterative nature of the reconstruction is the most important aspect.

Void forming pyrolytic carbon coating process

DOEpatents

Beatty, Ronald L.; Cook, Jackie L.

2000-01-01

A pyrolytic carbon coated nuclear fuel particle and method of making it. The fuel particle has a core composed of a refractory compound of an actinide metal. The pyrolytic carbon coating surrounds the core so as to provide a void volume therebetween. The coating has an initial density of no greater than 1.45 grams/cm.sup.3 and an anisotropy factor than 3.0 and a final density upon heat treatment above about 2000.degree. C. of greater than 1.7 grams/cm.sup.3 and an anisotropy factor greater than 5.

Extended Mortality and Chronic Kidney Disease After Septic Acute Kidney Injury.

PubMed

Chua, Horng-Ruey; Wong, Weng-Kin; Ong, Venetia Huiling; Agrawal, Dipika; Vathsala, Anantharaman; Tay, Hui-Ming; Mukhopadhyay, Amartya

2018-01-01

To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns ( reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT ( P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively ( P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression ( P = .001). Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.

Response Surface Methodology for Design of Porous Hollow Sphere Thermal Insulator

NASA Astrophysics Data System (ADS)

Shohani, Nazanin; Pourmahdian, Saeed; Shirkavand Hadavand, Behzad

2017-11-01

In this study, response surface method is used for synthesizing polystyrene (PS) as sacrificial templates and optimizing the particle size. Three factors of initiator, stabilizer concentration and also stirring rate were selected as variable factors. Then, three different concentration of tetraethyl orthosilicate (TEOS) added to reaction media and core-shell structure with PS core and silica shell was developed. Finally, core-shell structure was changed to hollow silica sphere for using as thermal insulator. We observed that increased initiator concentration caused to larger PS particles, increase the stirring rate caused the smaller PS and also with increased the stabilizer concentration obtained that particle size decrease then after 2.5% began to increase. Also the optimum amount of TEOS was found.

Structure of a human cap-dependent 48S translation pre-initiation complex

PubMed Central

Eliseev, Boris; Yeramala, Lahari; Leitner, Alexander; Karuppasamy, Manikandan; Raimondeau, Etienne; Huard, Karine; Alkalaeva, Elena; Aebersold, Ruedi

2018-01-01

Abstract Eukaryotic translation initiation is tightly regulated, requiring a set of conserved initiation factors (eIFs). Translation of a capped mRNA depends on the trimeric eIF4F complex and eIF4B to load the mRNA onto the 43S pre-initiation complex comprising 40S and initiation factors 1, 1A, 2, 3 and 5 as well as initiator-tRNA. Binding of the mRNA is followed by mRNA scanning in the 48S pre-initiation complex, until a start codon is recognised. Here, we use a reconstituted system to prepare human 48S complexes assembled on capped mRNA in the presence of eIF4B and eIF4F. The highly purified h-48S complexes are used for cross-linking/mass spectrometry, revealing the protein interaction network in this complex. We report the electron cryo-microscopy structure of the h-48S complex at 6.3 Å resolution. While the majority of eIF4B and eIF4F appear to be flexible with respect to the ribosome, additional density is detected at the entrance of the 40S mRNA channel which we attribute to the RNA-recognition motif of eIF4B. The eight core subunits of eIF3 are bound at the 40S solvent-exposed side, as well as the subunits eIF3d, eIF3b and eIF3i. elF2 and initiator-tRNA bound to the start codon are present at the 40S intersubunit side. This cryo-EM structure represents a molecular snap-shot revealing the h-48S complex following start codon recognition. PMID:29401259

Motivational and Skills, Social, and Self-Management Predictors of College Outcomes: Constructing the Student Readiness Inventory

ERIC Educational Resources Information Center

Le, Huy; Casillas, Alex; Robbins, Steven B.; Langley, Ronelle

2005-01-01

The authors used a rational-empirical approach to construct the Student Readiness Inventory, measuring psychosocial and academic-related skill factors found to predict two important college outcomes, academic performance and retention, in a recent meta-analysis. The initial item pool was administered to 5,970 first-year college students and high…

ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability.

PubMed

Wang, Shenghao; Tang, Li; Lin, Junyu; Shen, Zhongliang; Yao, Yikun; Wang, Wei; Tao, Shuai; Gu, Chenjian; Ma, Jie; Xie, Youhua; Liu, Yanfeng

2017-10-07

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5 + ) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5 - ) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

The small molecule '1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate' and its derivatives regulate global protein synthesis by inactivating eukaryotic translation initiation factor 2-alpha.

PubMed

Hong, Mi-Na; Nam, Ky-Youb; Kim, Kyung Kon; Kim, So-Young; Kim, InKi

2016-05-01

By environmental stresses, cells can initiate a signaling pathway in which eukaryotic translation initiation factor 2-alpha (eIF2-α) is involved to regulate the response. Phosphorylation of eIF2-α results in the reduction of overall protein neogenesis, which allows cells to conserve resources and to reprogram energy usage for effective stress control. To investigate the role of eIF2-α in cell stress responses, we conducted a viability-based compound screen under endoplasmic reticulum (ER) stress condition, and identified 1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate (AMC-01) and its derivatives as eIF2-α-inactivating chemical. Molecular characterization of this signaling pathway revealed that AMC-01 induced inactivation of eIF2-α by phosphorylating serine residue 51 in a dose- and time-dependent manner, while the negative control compounds did not affect eIF2-α phosphorylation. In contrast with ER stress induction by thapsigargin, phosphorylation of eIF2-α persisted for the duration of incubation with AMC-01. By pathway analysis, AMC-01 clearly induced the activation of protein kinase RNA-activated (PKR) kinase and nuclear factor-κB (NF-κB), whereas it did not modulate the activity of PERK or heme-regulated inhibitor (HRI). Finally, we could detect a lower protein translation rate in cells incubated with AMC-01, establishing AMC-01 as a potent chemical probe that can regulate eIF2-α activity. We suggest from these data that AMC-01 and its derivative compounds can be used as chemical probes in future studies of the role of eIF2-α in protein synthesis-related cell physiology.

Physical Risk Factors for a Medial Elbow Injury in Junior Baseball Players: A Prospective Cohort Study of 353 Players.

PubMed

Sakata, Jun; Nakamura, Emi; Suzukawa, Makoto; Akaike, Atsushi; Shimizu, Kuniaki

2017-01-01

The physical risk factors for a medial elbow injury in junior baseball players are unknown. To identify the risk factors for an initial medial elbow injury in junior baseball players. Case-control study; Level of evidence, 3. Junior baseball players (aged 6-12 years) without a history of elbow pain underwent a clinical assessment, ultrasonography, and physical function measurements before the baseball season started. Bilateral passive range of motion (ROM) of elbow extension and flexion, external rotation (ER) and internal rotation (IR) of the shoulder, and ER and IR of the hip were measured. IR and ER strength of the shoulder and scapular muscles were measured on both sides. The thoracic kyphosis angle was measured with participants in a relaxed standing position. Before these examinations, every participant completed a questionnaire regarding his or her age, sex, total years of baseball played, position in baseball, number of balls thrown, and episodes of pain during throwing. After the initial test session, each participant was followed up for 12 months to assess for the occurrence of a new injury. Multiple regression analysis was used to identify the risk factors for a medial elbow injury. Seventy-eight players (22.1%) sustained a medial elbow injury. Age ≥9 years (odds ratio [OR], 2.708; 95% CI, 1.224-5.990), pitcher position (OR, 2.620; 95% CI, 1.389-4.941), >100 throws per day (OR, 1.936; 95% CI, 1.072-3.497), thoracic kyphosis angle ≥30° (OR, 2.501; 95% CI, 1.381-4.531), and elbow extension deficit ≥5° (OR, 1.973; 95% CI, 1.022-3.809) were significantly associated with a medial elbow injury. The incidence of an initial medial elbow injury was 22.1%. Age, number of throws per day, thoracic kyphosis angle, and elbow extension deficit are newly discovered risk factors related to physical function. Improvement of the posture and early detection of a silent elbow extension deficit may prevent a medial elbow injury.

[Predictive factors of contamination in a blood culture with bacterial growth in an Emergency Department].

PubMed

Hernández-Bou, S; Trenchs Sainz de la Maza, V; Esquivel Ojeda, J N; Gené Giralt, A; Luaces Cubells, C

2015-06-01

The aim of this study is to identify predictive factors of bacterial contamination in positive blood cultures (BC) collected in an emergency department. A prospective, observational and analytical study was conducted on febrile children aged on to 36 months, who had no risk factors of bacterial infection, and had a BC collected in the Emergency Department between November 2011 and October 2013 in which bacterial growth was detected. The potential BC contamination predicting factors analysed were: maximum temperature, time to positivity, initial Gram stain result, white blood cell count, absolute neutrophil count, band count, and C-reactive protein (CRP). Bacteria grew in 169 BC. Thirty (17.8%) were finally considered true positives and 139 (82.2%) false positives. All potential BC contamination predicting factors analysed, except maximum temperature, showed significant differences between true positives and false positives. CRP value, time to positivity, and initial Gram stain result are the best predictors of false positives in BC. The positive predictive values of a CRP value≤30mg/L, BC time to positivity≥16h, and initial Gram stain suggestive of a contaminant in predicting a FP, are 95.1, 96.9 and 97.5%, respectively. When all 3 conditions are applied, their positive predictive value is 100%. Four (8.3%) patients with a false positive BC and discharged to home were revaluated in the Emergency Department. The majority of BC obtained in the Emergency Department that showed positive were finally considered false positives. Initial Gram stain, time to positivity, and CRP results are valuable diagnostic tests in distinguishing between true positives and false positives in BC. The early detection of false positives will allow minimising their negative consequences. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Impact of creatine kinase correction on the predictive value of S-100B after mild traumatic brain injury.

PubMed

Bazarian, Jeffrey J; Beck, Christopher; Blyth, Brian; von Ahsen, Nicolas; Hasselblatt, Martin

2006-01-01

To validate a correction factor for the extracranial release of the astroglial protein, S-100B, based on concomitant creatine kinase (CK) levels. The CK- S-100B relationship in non-head injured marathon runners was used to derive a correction factor for the extracranial release of S-100B. This factor was then applied to a separate cohort of 96 mild traumatic brain injury (TBI) patients in whom both CK and S-100B levels were measured. Corrected S-100B was compared to uncorrected S-100B for the prediction of initial head CT, three-month headache and three-month post concussive syndrome (PCS). Corrected S-100B resulted in a statistically significant improvement in the prediction of 3-month headache (area under curve [AUC] 0.46 vs 0.52, p=0.02), but not PCS or initial head CT. Using a cutoff that maximizes sensitivity (> or = 90%), corrected S-100B improved the prediction of initial head CT scan (negative predictive value from 75% [95% CI, 2.6%, 67.0%] to 96% [95% CI: 83.5%, 99.8%]). Although S-100B is overall poorly predictive of outcome, a correction factor using CK is a valid means of accounting for extracranial release. By increasing the proportion of mild TBI patients correctly categorized as low risk for abnormal head CT, CK-corrected S100-B can further reduce the number of unnecessary brain CT scans performed after this injury.

Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model.

PubMed

Kim, Joong-Hyun; Oh, Se Heang; Min, Hyun Ki; Lee, Jin Ho

2018-01-01

Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ∼80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 115-125, 2018. © 2017 Wiley Periodicals, Inc.

Implementation factors affecting the large-scale deployment of digital health and well-being technologies: A qualitative study of the initial phases of the 'Living-It-Up' programme.

PubMed

Agbakoba, Ruth; McGee-Lennon, Marilyn; Bouamrane, Matt-Mouley; Watson, Nicholas; Mair, Frances S

2016-12-01

Little is known about the factors which facilitate or impede the large-scale deployment of health and well-being consumer technologies. The Living-It-Up project is a large-scale digital intervention led by NHS 24, aiming to transform health and well-being services delivery throughout Scotland. We conducted a qualitative study of the factors affecting the implementation and deployment of the Living-It-Up services. We collected a range of data during the initial phase of deployment, including semi-structured interviews (N = 6); participant observation sessions (N = 5) and meetings with key stakeholders (N = 3). We used the Normalisation Process Theory as an explanatory framework to interpret the social processes at play during the initial phases of deployment.Initial findings illustrate that it is clear - and perhaps not surprising - that the size and diversity of the Living-It-Up consortium made implementation processes more complex within a 'multi-stakeholder' environment. To overcome these barriers, there is a need to clearly define roles, tasks and responsibilities among the consortium partners. Furthermore, varying levels of expectations and requirements, as well as diverse cultures and ways of working, must be effectively managed. Factors which facilitated implementation included extensive stakeholder engagement, such as co-design activities, which can contribute to an increased 'buy-in' from users in the long term. An important lesson from the Living-It-Up initiative is that attempting to co-design innovative digital services, but at the same time, recruiting large numbers of users is likely to generate conflicting implementation priorities which hinder - or at least substantially slow down - the effective rollout of services at scale.The deployment of Living-It-Up services is ongoing, but our results to date suggest that - in order to be successful - the roll-out of digital health and well-being technologies at scale requires a delicate and pragmatic trade-off between co-design activities, the development of innovative services and the efforts allocated to widespread marketing and recruitment initiatives. © The Author(s) 2015.

Field evaluation of support practice (P-factor) for stone walls to control soil erosion in an arid area (Northern Jordan)

NASA Astrophysics Data System (ADS)

Gharaibeh, Mamoun; Albalasmeh, Ammar

2017-04-01

Stone walls have been adopted for long time to control water erosion in many Mediterranean countries. In soil erosion equations, the support practice factor (P-factor) for stone walls has not been fully studied or rarely taken into account especially in semi-arid and arid regions. Field studies were conducted to evaluate the efficiency of traditional stone walls and to quantify soil erosion in six sites in north and northeastern Jordan. Initial estimates using the Universal Soil Loss Equation (USLE) showed that rainfall erosion was reduced by 65% in areas where stone walls are present. Annual soil loss ranged from 5 to 15 t yr-1. The mean annual soil loss in the absence of stone walls ranged from 10-60 t ha-1 with an average value of 35 t ha-1. Interpolating the slope of thickness of A horizon provided an average initial estimate of 0.3 for P value.

eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control

PubMed Central

Jennings, Martin D.; Kershaw, Christopher J.; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P.; Costello, Joseph L.; Donaldson, Ian J.; Zhou, Yu; Pavitt, Graham D.

2016-01-01

In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. PMID:27458202

eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

PubMed

Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

2016-11-16

In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Growth inhibition of Microcystis aeruginosa by white-rot fungus Lopharia spadicea.

PubMed

Wang, Q; Su, M; Zhu, W; Li, X; Jia, Y; Guo, P; Chen, Z; Jiang, W; Tian, X

2010-01-01

Harmful cyanobacterial blooms cause water deterioration and threaten human health. It is necessary to remove harmful cyanobacteria with useful methods. A bio-treatment may be one of the best ways to do this. A strain of specific white-rot fungus, Lopharia spadicea, with algicidal ability was isolated. Its algicidal ability on algae under various conditions was determined using three main influence factors: initial chlorophyll-a content, initial pH, and algal cell mixture. The result showed that the chlorophyll-a content of Microcystis aeruginosa FACHB-912, Oocystis borgei FACHB-1108, and Microcystis flos-aquae FACHB-1028 decreased from 798+/-13, 756+/-40, and 773+/-24 microg/L to 0 within 39 h. L. spadicea could also remove more than 95% chlorophyll-a when initial chlorophyll-a content increased from 397+/-13 to 2,132+/-4 microg/L. Moreover, the strain has great removal ability under a broad initial pH range of 5.5 to 9.5. The chlorophyll-a content of the three algal strain mixtures decreased from about 672+/-23 microg/L to 0 within 45 h. After superoxide dismutase (SOD) and malondialdehyde (MAD) were assessed in a co-culture of L. spadicea, it was observed that an increase in MAD content was correlated with the decrease in chlorophyll-a content of M. aeruginosa FACHB-912. This result suggested that the algae was not only greatly inhibited but also severely damaged by the fungus.

Refinement and initial validation of a multidimensional composite scale for use in assessing acute postoperative pain in cats.

PubMed

Brondani, Juliana Tabarelli; Luna, Stelio Pacca Loureiro; Padovani, Carlos Roberto

2011-02-01

To refine and test construct validity and reliability of a composite pain scale for use in assessing acute postoperative pain in cats undergoing ovariohysterectomy. 40 cats that underwent ovariohysterectomy in a previous study. In a previous randomized, double-blind, placebo-controlled study, a composite pain scale was developed to assess postoperative pain in cats that received a placebo or an analgesic (tramadol, vedaprofen, or tramadol-vedaprofen combination). In the present study, the scale was refined via item analysis (distribution frequency and occurrence), a nonparametric ANOVA, and item-to-total score correlation. Construct validity was assessed via factor analysis and known-groups discrimination, and reliability was measured by assessing internal consistency. Respiratory rate and respiratory pattern were rejected after item analysis. Factor analysis resulted in 5 dimensions (F1 [psychomotor change], posture, comfort, activity, mental status, and miscellaneous behaviors; F2 [protection of wound area], reaction to palpation of the surgical wound and palpation of the abdomen and flank; F3 [physiologic variables], systolic arterial blood pressure and appetite; F4 [vocal expression of pain], vocalization; and F5 [heart rate]). Internal consistency was excellent for the overall scale and for F1, F2, and F3; very good for F4; and unacceptable for F5. Except for heart rate, the identified factors and scale total score could be used to detect differences between the analgesic and placebo groups and differences among the analgesic treatments. Results provided initial evidence of construct validity and reliability of a multidimensional composite tool for use in assessing acute postoperative pain in cats undergoing ovariohysterectomy.

The psychological impact of terrorism: an epidemiologic study of posttraumatic stress disorder and associated factors in victims of the 1995-1996 bombings in France.

PubMed

Verger, Pierre; Dab, William; Lamping, Donna L; Loze, Jean-Yves; Deschaseaux-Voinet, Céline; Abenhaim, Lucien; Rouillon, Frédéric

2004-08-01

A wave of bombings struck France in 1995 and 1996, killing 12 people and injuring more than 200. The authors conducted follow-up evaluations with the victims in 1998 to determine the prevalence of and factors associated with posttraumatic stress disorder (PTSD). Victims directly exposed to the bombings (N=228) were recruited into a retrospective, cross-sectional study. Computer-assisted telephone interviews were conducted to evaluate PTSD, per DSM-IV criteria, and to assess health status before the attack, initial injury severity and perceived threat at the time of attack, and psychological symptoms, cosmetic impairment, hearing problems, and health service use at the time of the follow-up evaluation. Factors associated with PTSD were investigated with univariate logistic regression followed by multiple logistic regression analyses. A total of 196 respondents (86%) participated in the study. Of these, 19% had severe initial physical injuries (hospitalization exceeding 1 week). Problems reported at the follow-up evaluation included attack-related hearing problems (51%), cosmetic impairment (33%), and PTSD (31%) (95% confidence interval=24.5%-37.5%). Results of logistic regression analyses indicated that the risk of PTSD was significantly higher among women (odds ratio=2.54), participants age 35-54 (odds ratio=2.83), and those who had severe initial injuries (odds ratio=2.79) or cosmetic impairment (odds ratio=2.74) or who perceived substantial threat during the attack (odds ratio=3.99). The high prevalence of PTSD 2.6 years on average after a terrorist attack emphasizes the need for improved health services to address the intermediate and long-term consequences of terrorism.

Promotional effects of CO2 laser on neoplastic lesions in hamsters

NASA Astrophysics Data System (ADS)

Kingsbury, Jeffrey S.; Margarone, Joseph E., III; Satchidanand, S.; Liebow, Charles

1991-06-01

Surgical incision may have promotional effects on neoplastic lesions, possibly through release of tissue growth factors (e.g., EGF, FGF(beta) , IGF, TGF(alpha) ). The CO2 laser may precipitate altered release of these factors. To test this, .5 cm laser, and scalpel incisions were made into fields treated by application of .5% DMBA in acetone, 3 times a week for 6 weeks (group 1) and 12 weeks (group 2). DMBA is a complete carcinogen (initiator and promoter). At 6 weeks, chemically, but not histologically, definable premalignant lesions are seen. Treatment for 12 weeks causes histologic neoplasia which can be graded with T-N-M classification. For both groups, the surgical sites were examined clinically and histologically 4 weeks post-op in a blind fashion. Standard criteria were utilized for defining neoplasia. For group 1, 3 out of 6 laser treated animals developed large exophytic squamous cell carcinomas, but no lesions developed in 12 contralateral, 3 control and 3 scalpel treated pouches. For group 2, 12 of 16 laser treated animals developed tumor with mean grade of 1.75 and mean size of 7.4 mm, 5 of 6 scalpel treated animals developed tumor with mean grade of 1.83 and mean size of 3.6 mm and 3 of 6 control animals developed tumor with mean grade of 1.00 and mean size of 1.5 mm. By the Student 't' test on the binomial distribution lasers cause significant promotion (p < .01). These results suggest that laser surgery may have earlier and more profound promotional effects than scalpel on initiated cells relative to tumor size in the vicinity of the wound site by increased release of growth factors.

Does menopausal hormone therapy reduce myocardial infarction risk if initiated early after menopause? A population-based case-control study.

PubMed

Carrasquilla, Germán D; Berglund, Anita; Gigante, Bruna; Landgren, Britt-Marie; de Faire, Ulf; Hallqvist, Johan; Leander, Karin

2015-06-01

This study aims to assess whether the timing of menopausal hormone therapy initiation in relation to onset of menopause and hormone therapy duration is associated with myocardial infarction risk. This study was based on the Stockholm Heart Epidemiology Program, a population-based case-control study including 347 postmenopausal women who had experienced a nonfatal myocardial infarction and 499 female control individuals matched for age and residential area. Odds ratios (with 95% CIs) for myocardial infarction were calculated using logistic regression. Early initiation of hormone therapy (within 10 y of onset of menopause or before age 60 y), compared with never use, was associated with an odds ratio of 0.87 (95% CI, 0.58-1.30) after adjustments for lifestyle factors, body mass index, and socioeconomic status. For late initiation of hormone therapy, the corresponding odds ratio was 0.97 (95% CI, 0.53-1.76). For hormone therapy duration of 5 years or more, compared with never use, the adjusted odds ratio was 0.64 (95% CI, 0.35-1.18). For hormone therapy duration of less than 5 years, the odds ratio was 0.97 (95% CI, 0.63-1.48). Neither the timing of hormone therapy initiation nor the duration of therapy is significantly associated with myocardial infarction risk.

Eukaryotic Translation Initiation Factor 4E Availability Controls the Switch between Cap-Dependent and Internal Ribosomal Entry Site-Mediated Translation†

PubMed Central

Svitkin, Yuri V.; Herdy, Barbara; Costa-Mattioli, Mauro; Gingras, Anne-Claude; Raught, Brian; Sonenberg, Nahum

2005-01-01

Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5′ end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation initiation bypasses the requirement for the cap and eIF4E and occurs on viral and cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we demonstrate that eIF4E availability plays a critical role in the switch from cap-dependent to IRES-mediated translation in picornavirus-infected cells. When both capped and IRES-containing mRNAs are present (as in intact cells or in vitro translation extracts), a decrease in the amount of eIF4E associated with the eIF4F complex elicits a striking increase in IRES-mediated viral mRNA translation. This effect is not observed in translation extracts depleted of capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for translation. These data explain numerous reported observations where viral mRNAs are preferentially translated during infection. PMID:16287867

Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation.

PubMed

Svitkin, Yuri V; Herdy, Barbara; Costa-Mattioli, Mauro; Gingras, Anne-Claude; Raught, Brian; Sonenberg, Nahum

2005-12-01

Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5' end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation initiation bypasses the requirement for the cap and eIF4E and occurs on viral and cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we demonstrate that eIF4E availability plays a critical role in the switch from cap-dependent to IRES-mediated translation in picornavirus-infected cells. When both capped and IRES-containing mRNAs are present (as in intact cells or in vitro translation extracts), a decrease in the amount of eIF4E associated with the eIF4F complex elicits a striking increase in IRES-mediated viral mRNA translation. This effect is not observed in translation extracts depleted of capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for translation. These data explain numerous reported observations where viral mRNAs are preferentially translated during infection.

Factors associated with initiation and exclusive breastfeeding at hospital discharge: late preterm compared to 37 week gestation mother and infant cohort.

PubMed

Ayton, Jennifer; Hansen, Emily; Quinn, Stephen; Nelson, Mark

2012-11-26

To investigate and examine the factors associated with initiation of, and exclusive breastfeeding at hospital discharge of, late preterm (34 0/7 - 36 6/7 weeks) compared to 37 week gestation (37 0/7 - 37 6/7 week) mother and baby pairs. A retrospective population-based cohort study using a Perinatal National Minimum Data Set and clinical medical records review, at the Royal Hobart Hospital, Tasmania, Australia in 2006. Late preterm and 37 week gestation infants had low rates of initiation of breastfeeding within one hour of birth, 31 (21.1%) and 61 (41.5%) respectively. After multiple regression analysis, late preterm infants were less likely to initiate breastfeeding within one hour of birth (OR 0.3 95% CI 0.1, 0.7 p = 0.009) and were less likely to be discharged exclusively breastfeeding from hospital (OR 0.4 95% CI 0.1, 1.0 p = 0.04) compared to 37 week gestation infants. A late preterm birth is predictive of breastfeeding failure, with late preterm infants at greater risk of not initiating breastfeeding and/or exclusively breastfeeding at hospital discharge, compared with those infants born at 37 weeks gestation. Stratifying breastfeeding outcomes by gestational age groups may help to identify those sub-populations at greatest risk of premature cessation of breastfeeding.

Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability

PubMed Central

Seal, Ruth; Temperley, Richard; Wilusz, Jeffrey; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M. A.

2005-01-01

PARN, a poly(A)-specific ribonuclease, binds the 5′ cap-structure of mRNA and initiates deadenylation-dependent decay. Eukaryotic initiation factor 4E (eIF4E) also binds to the cap structure, an interaction that is critical for initiating cap-dependent translation. The stability of various mRNA transcripts in human cell lines is reduced under conditions of serum starvation as determined by both functional and chemical half-lives. Serum starvation also leads to enhanced cap association by PARN. In contrast, the 5′ cap occupancy by eIF4E decreases under serum-deprivation, as does the translation of reporter transcripts. Further, we show that PARN is a phosphoprotein and that this modification can be modulated by serum status. Taken together, these data are consistent with a natural competition existing at the 5′ cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications. These phosphorylation-induced changes in the interplay of PARN and eIF4E may determine whether the mRNA is translated or decayed. PMID:15653638

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.

PubMed

Amable, Paola Romina; Carias, Rosana Bizon Vieira; Teixeira, Marcus Vinicius Telles; da Cruz Pacheco, Italo; Corrêa do Amaral, Ronaldo José Farias; Granjeiro, José Mauro; Borojevic, Radovan

2013-06-07

Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 10(6) to 1.9 × 10(6) platelets/μl). Platelets were highly purified, because only <0.3% from the initial red blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF. Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool from different donors with high reproducibility. These findings support the use of PRP in therapies aiming for tissue regeneration, and its content characterization will allow us to understand and improve the clinical outcomes.

iron phase control during pressure leaching at elevated temperature

NASA Astrophysics Data System (ADS)

Fleuriault, Camille

Iron is a common contaminant encountered in most metal recovery operations, and particularly hydrometallurgical processes. For example, the Hematite Process uses autoclaves to precipitate iron oxide out of the leaching solution, while other metals are solubilized for further hydrometallurgical processing. In some cases, Basic Iron Sulfate (BIS) forms in place of hematite. The presence of BIS is unwanted in the autoclave discharge because it diminishes recovery and causes environmental matters. The focus of this master thesis is on the various iron phases forming during the pressure oxidation of sulfates. Artificial leaching solutions were produced from CuSO4, FeSO4 and H2SO4 in an attempt to recreate the matrix composition and conditions used for copper sulfides autoclaving. The following factors were investigated in order to determine which conditions hinder the formation of BIS: initial free acidity (5 -- 98 g/L), initial copper concentration (12.7 -- 63.5 g/L), initial iron concentration (16.7 -- 30.7 g/L) and initial iron oxidation state. There were three solid species formed in the autoclave: hematite, BIS and hydronium jarosite. The results show that free acid is the main factor influencing the composition of the residue. At an initial concentration of 22.3 g/L iron and no copper added, the upper limit for iron oxide formation is 41 g/L H2SO4. The increase of BIS content in the residue is not gradual and occurs over a change of a few grams per liter around the aforementioned limit. Increasing copper sulfate concentration in the solution hinders the formation of BIS. At 63.5g/L copper, the upper free acidity limit is increased to 61g/L. This effect seems to be related to the buffering action of copper sulfate, decreasing the overall acid concentration and thus extending the stability range of hematite. The effect of varying iron concentration on the precipitate chemistry is unclear. At high iron levels, the only noticeable effect was the inhibition of jarosite. The results were reported within a Cu-Fe-S ternary system and modeled. The modeling confirmed the experimental observations with the exception that increasing iron concentrations seem to promote BIS stability.

Improved cellulase production by Botryosphaeria rhodina from OPEFB at low level moisture condition through statistical optimization.

PubMed

Bahrin, E K; Ibrahim, M F; Abd Razak, M N; Abd-Aziz, S; Shah, U K Md; Alitheen, N; Salleh, M Md

2012-01-01

The response surface method was applied in this study to improve cellulase production from oil palm empty fruit bunch (OPEFB) by Botryosphaeria rhodina. An experimental design based on a two-level factorial was employed to screen the significant environmental factors for cellulase production. The locally isolated fungus Botryosphaeria rhodina was cultivated on OPEFB under solid-state fermentation (SSF). From the analysis of variance (ANOVA), the initial moisture content, amount of substrate, and initial pH of nutrient supplied in the SSF system significantly influenced cellulase production. Then the optimization of the variables was done using the response surface method according to central composite design (CCD). Botryosphaeria rhodina exhibited its best performance with a high predicted value of FPase enzyme production (17.95 U/g) when the initial moisture content was at 24.32%, initial pH of nutrient was 5.96, and 3.98 g of substrate was present. The statistical optimization from actual experiment resulted in a significant increment of FPase production from 3.26 to 17.91 U/g (5.49-fold). High cellulase production at low moisture content is a very rare condition for fungi cultured in solid-state fermentation.

A search for structurally similar cellular internal ribosome entry sites

PubMed Central

Baird, Stephen D.; Lewis, Stephen M.; Turcotte, Marcel; Holcik, Martin

2007-01-01

Internal ribosome entry sites (IRES) allow ribosomes to be recruited to mRNA in a cap-independent manner. Some viruses that impair cap-dependent translation initiation utilize IRES to ensure that the viral RNA will efficiently compete for the translation machinery. IRES are also employed for the translation of a subset of cellular messages during conditions that inhibit cap-dependent translation initiation. IRES from viruses like Hepatitis C and Classical Swine Fever virus share a similar structure/function without sharing primary sequence similarity. Of the cellular IRES structures derived so far, none were shown to share an overall structural similarity. Therefore, we undertook a genome-wide search of human 5′UTRs (untranslated regions) with an empirically derived structure of the IRES from the key inhibitor of apoptosis, X-linked inhibitor of apoptosis protein (XIAP), to identify novel IRES that share structure/function similarity. Three of the top matches identified by this search that exhibit IRES activity are the 5′UTRs of Aquaporin 4, ELG1 and NF-kappaB repressing factor (NRF). The structures of AQP4 and ELG1 IRES have limited similarity to the XIAP IRES; however, they share trans-acting factors that bind the XIAP IRES. We therefore propose that cellular IRES are not defined by overall structure, as viral IRES, but are instead dependent upon short motifs and trans-acting factors for their function. PMID:17591613

Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics.

PubMed

Carbon, Maren; Kapoor, Sandeep; Sheridan, Eva; Al-Jadiri, Aseel; Azzo, Sally; Sarkaria, Tania; Kane, John M; Saito, Ema; Correll, Christoph U

2015-09-01

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Inhibitors and facilitators of willingness to participate (WTP) in an HIV vaccine trial: construction and initial validation of the Inhibitors and Facilitators of Willingness to Participate Scale (WPS) among women at risk for HIV infection.

PubMed

Fincham, Dylan; Kagee, Ashraf; Swartz, Leslie

2010-04-01

A psychometric scale assessing inhibitors and facilitators of willingness to participate (WTP) in an HIV vaccine trial has not yet been developed. This study aimed to construct and derive the exploratory factor structure of such a scale. The 35-item Inhibitors and Facilitators of Willingness to Participate Scale (WPS) was developed and administered to a convenience sample of 264 Black females between the ages of 16 and 49 years living in an urban-informal settlement near Cape Town. The subscales of the WPS demonstrated good internal consistency with Cronbach's alpha coefficients ranging between 0.69 and 0.82. A principal components exploratory factor analysis revealed the presence of five latent factors. The factors, which accounted for 45.93% of the variance in WTP, were (1) personal costs, (2) safety and convenience, (3) stigmatisation, (4) personal gains and (5) social approval and trust. Against the backdrop of the study limitations, these results provide initial support for the reliability and construct validity of the WPS among the most eligible trial participants in the Western Cape of South Africa.

Managing variability in decision making in swine growing-finishing units.

PubMed

Agostini, Piero da Silva; Manzanilla, Edgar Garcia; de Blas, Carlos; Fahey, Alan G; da Silva, Caio Abercio; Gasa, Josep

2015-01-01

Analysis of data collected from pig farms may be useful to understand factors affecting pig health and productive performance. However, obtaining these data and drawing conclusions from them can be done at different levels and presents several challenges. In the present study, information from 688 batches of growing-finishing (GF) pigs (average initial and final body weight of 19.1 and 108.5 kg respectively) from 404 GF farms integrated in 7 companies was obtained between July 2008 and July 2010 in Spain by survey. Management and facility factors associated with feed conversion ratio (FCR) and mortality were studied by multiple linear regression analysis in each single company (A to G) and in an overall database (OD). Factors studied were geographic location of the farm, trimester the pigs entered the farm, breed of sire and sex segregation in pens (BREGENSEG), use of circovirus vaccine, number of origins the pigs were obtained from, age of the farm, percentage of slatted floor, type of feeder, drinker and ventilation, number of phases and form of feed, antibiotic administration system, water source, and number and initial weight of pigs. In two or more companies studied and/or in OD, the trimester when pigs were placed in the farm, BREGENSEG, number of origins of the pigs, age of the farm and initial body weight were factors associated with FCR. Regarding mortality, trimester of placement, number of origins of the pigs, water source in the farm, number of pigs placed and the initial body weight were relevant factors. Age of the farm, antibiotic administration system, and water source were only provided by some of the studied companies and were not included in the OD model, however, when analyzed in particular companies these three variables had an important effect and may be variables of interest in companies that do not record them. Analysing data collected from farms at different levels helps better understand factors associated with productive performance of pig herds. Out of the studied factors trimester of placement and number of origins of the pigs were the most relevant factors associated with FCR and mortality.

Outcome and prognostic factors in a French cohort of patients with myositis-associated interstitial lung disease.

PubMed

Obert, Julie; Freynet, Olivia; Nunes, Hilario; Brillet, Pierre-Yves; Miyara, Makoto; Dhote, Robin; Valeyre, Dominique; Naccache, Jean-Marc

2016-12-01

Interstitial lung disease (ILD) is a common form of extramuscular involvement in patients with polymyositis/dermatomyositis and is associated with poor prognosis. This study was designed to describe the long-term outcome of myositis-associated ILD. This retrospective observational study was conducted in 48 consecutive patients. Two groups defined according to outcome were compared to determine prognostic factors: a "severe" group (vital capacity [VC] < 50 % or carbon monoxide transfer factor [TLCO] < 35 % or death or lung transplantation) and a "nonsevere" group (other patients). The study population comprised 31 women and 17 men with a median age of 49.5 ± 13.6 years. Mean PFT results at the onset of ILD were 56.9 ± 23.1 % pred. for VC and 42.1 ± 16.6 % pred. for TLCO. Median (range) follow-up was 65 (2-204) months. Three patients (6.4 %) died. At last follow-up, 19 patients were classified in the "severe" group and 27 patients were classified in the "nonsevere" group. Two patients lost to follow-up after less than 12 months were excluded from this analysis. Multivariate analysis identified two independent prognostic factors: VC at onset of ILD [OR 0.95 (95 % CI 0.90-0.99)] and myopathic changes on electromyography [OR 5.76 (95 % CI 1.10-30.3)]. Patients treated in our pulmonology department for myositis-associated ILD had severe initial PFT results but a low mortality rate. Independent prognostic factors at presentation were initial VC and myopathic changes on electromyography. This study highlights the need for studies focusing on the correlation between muscle and lung pathogenic mechanisms.

Nonsurgical acute traumatic subdural hematoma: what is the risk?

PubMed

Bajsarowicz, Paul; Prakash, Ipshita; Lamoureux, Julie; Saluja, Rajeet Singh; Feyz, Mitra; Maleki, Mohammad; Marcoux, Judith

2015-11-01

The Brain Trauma Foundation has published guidelines on the surgical management of traumatic subdural hematoma (SDH). However, no data exist on the proportion of patients with SDH that can be selected for conservative management and what is the outcome of these patients. The goals of this study were as follows: 1) to establish what proportion of patients are initially treated conservatively; 2) to determine what proportion of patients will deteriorate and require surgical evacuation; and 3) to identify risk factors associated with deterioration and delayed surgery. All cases of acute traumatic SDH (869 when inclusion criteria were met) presenting over a 4-year period were reviewed. For all conservatively treated SDH, the proportion of delayed surgical intervention and the Glasgow Outcome Scale score were taken as outcome measures. Multiple factors were compared between patients who required delayed surgery and patients without surgery. Of the 869 patients with acute traumatic SDH, 646 (74.3%) were initially treated conservatively. A good outcome was achieved in 76.7% of the patients. Only 6.5% eventually required delayed surgery, and the median delay for surgery was 9.5 days. Factors associated with deterioration were as follows: 1) thicker SDH (p<0.001); 2) greater midline shift (p<0.001); 3) location at the convexity (p=0.001); 4) alcohol abuse (p=0.0260); and 5) history of falls (p=0.018). There was no significant difference in regard to age, sex, Glasgow Coma Scale score, Injury Severity Score, abnormal coagulation, use of blood thinners, and presence of cerebral atrophy or white matter disease. The majority of patients with SDH are treated conservatively. Of those, only 6.5% later required surgery, for raised intracranial pressure or SDH progression. Patients at risk can be identified and followed more carefully.

Symptomatic Patients without Epidemiological Indicators of HIV Have a High Risk of Missed Diagnosis: A Multi-Centre Cross Sectional Study.

PubMed

Brännström, Johanna; Svedhem, Veronica; Marrone, Gaetano; Andersson, Örjan; Azimi, Farshad; Blaxhult, Anders; Sönnerborg, Anders

2016-01-01

One quarter of HIV-1 positive individuals in Sweden present for care with HIV or AIDS associated conditions without an HIV test (missed presentations) and 16% report neglect of such symptoms. The objective of this study was to identify risk factors for these missed opportunities of HIV-1 diagnosis. A national study, recruiting 409 newly diagnosed HIV-1 infected adults over a 2.5-year period, was performed. Logistic regression models tested the relationship between missed presentation and patient's neglect versus socio-demographic and behavioural risk factors. Additionally the initiator of the HIV test was assessed. The odds for a missed presentation was lower for migrants (from East Europe, Asia, and Pacific (East): OR 0.4 (0.2-0.8); Sub-Saharan Africa (SSA): 0.3 (0.2-0.6); other: 0.5 (0.2-1.0)), compared to patients born in Sweden, just as symptoms neglected by the patient (East (0.3 (0.1-1.0); SSA (0.4 (0.2-0.8)). The latter was also lower for men who have sex with men (0.5 (0.2-1.0)), compared to patients infected heterosexually. Patients infected in the East, with present/previous substance use or a previous negative HIV test were more likely to take the initiative to test on their own, whereas those >50 years and with a previously missed presentation had significantly reduced odds, p<0.05. Individuals without epidemiological indicators of HIV are more likely to have a history of missed presentations, to neglect symptoms and are less prone to take an initiative to test for HIV themselves. It is important to further implement testing to include all patients with symptoms and conditions indicative of HIV.

Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study.

PubMed

Jayasekara, Harindra; Reece, Jeanette C; Buchanan, Daniel D; Rosty, Christophe; Dashti, S Ghazaleh; Ait Ouakrim, Driss; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Giles, Graham G; Ahnen, Dennis J; Lowery, Jan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Parry, Susan; Jenkins, Mark A; Win, Aung Ko

2016-09-01

Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC. © 2016 UICC.

Inactivation of the Radiation-Resistant Spoilage Bacterium Micrococcus radiodurans

PubMed Central

Duggan, D. E.; Anderson, A. W.; Elliker, P. R.

1963-01-01

A simplified technique permitting the pipetting of raw puréed meats for quantitative bacteriological study is described for use in determining survival of these non-sporing bacteria, which are exceptionally resistant to radiation. Survival curves, using gamma radiation as the sterilizing agent, were determined in raw beef with four strains of Micrococcus radiodurans. Survival curves of the R1 strain in other meat substrates showed that survival was significantly greater in raw beef and raw chicken than in raw fish or in cooked beef. Resistance was lowest in the buffer. Cells grown in broth (an artificial growth medium) and resuspended in beef did not differ in resistance from cells that had been grown and irradiated in beef. Survival rate was statistically independent of the initial cell concentration, even though there appeared to be a correlation between lower death rate and lower initial cell concentrations. The initial viable count of this culture of the domesticated R1 strain in beef was reduced by a factor of about 10-5 by 3.0 megarad, and 4.0 megarad reduced the initial count by a factor of more than 10-9. Data suggest that M. radiodurans R1 is more resistant to radiation than spore-forming spoilage bacteria for which inactivation rates have been published. PMID:14063780

Incidence and risk factors of severe adverse events with nevirapine-based antiretroviral therapy in HIV-infected women. MTCT-Plus program, Abidjan, Côte d'Ivoire

PubMed Central

2010-01-01

Background In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women. Methods All HIV-infected women who initiated nevirapine-containing regimen in the MTCT-Plus operational program in Abidjan, Côte d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs. Results From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm3 (IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm3 and women with a CD4 cell count ≤250 cells/mm3 (8.3% vs. 9.9%, Log-rank test: p = 0.75). In a multivariate proportional hazard model, neither CD4 cell count >250 cells/mm3 at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs. Conclusion CD4 cell count >250 cells/mm3 was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity. PMID:20576111

Reproductive Factors and Incidence of Heart Failure Hospitalization in the Women’s Health Initiative

PubMed Central

Hall, Philip S.; Nah, Gregory; Howard, Barbara V.; Lewis, Cora E.; Allison, Matthew A.; Sarto, Gloria E.; Waring, Molly E.; Jacobson, Lisette T.; Manson, JoAnn E.; Klein, Liviu; Parikh, Nisha I.

2017-01-01

BACKGROUND Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF). OBJECTIVES This study examined the association between key reproductive factors and the incidence of HF. METHODS Women from a cohort of the Women’s Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration [time from menarche to menopause]) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models. RESULTS Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval [CI]: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52). CONCLUSIONS In postmenopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies. PMID:28521890

Loss to follow-up trends in HIV-positive patients receiving antiretroviral treatment in Asia from 2003 to 2013

PubMed Central

De La Mata, Nicole L.; Ly, Penh Sun; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Choi, Jun Yong; Ross, Jeremy; Law, Matthew G.; Ng, Oon Tek

2017-01-01

Introduction Over time there has been substantial improvement in antiretroviral treatment (ART) programmes, including expansion of services and increased patient engagement. We describe time trends in, and factors associated with, loss to follow-up (LTFU) in HIV-positive patients receiving ART in Asia. Methods Analysis included HIV-positive adults initiating ART in 2003-2013 at seven ART programmes in Asia. Patients LTFU had not attended the clinic for ≥180 days, had not died or transferred to another clinic. Patients were censored at recent clinic visit, follow-up to January 2014. We used cumulative incidence to compare LTFU and mortality between years of ART initiation. Factors associated with LTFU were evaluated using a competing risks regression model, adjusted for clinical site. Results A total of 8,305 patients were included. There were 743 patients LTFU and 352 deaths over 26,217 person-years (pys), a crude LTFU and mortality rate of 2.83 (2.64-3.05) per 100 pys and 1.34 (1.21-1.49) per 100 pys, respectively. At 24 months, the cumulative LTFU incidence increased from 4.3%(2.9-6.1%) in 2003-05 to 8.1%(7.1-9.2%) in 2006-09, then decreased to 6.7%(5.9-7.5%) in 2010-13. Concurrently, the cumulative mortality incidence decreased from 6.2%(4.5-8.2%) in 2003-05 to 3.3%(2.8-3.9%) in 2010-13. The risk of LTFU reduced in 2010-13 compared to 2006-09 (adjusted subhazard ratio=0.73, 0.69-0.99). Conclusions LTFU rates in HIV-positive patients receiving ART in our clinical sites have varied by the year of ART initiation, with rates declining in recent years while mortality rates have remained stable. Further increases in site-level resources are likely to contribute to additional reductions in LTFU for patients initiating in subsequent years. PMID:28129256

IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.

PubMed

Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko

2016-03-31

Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells. Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV. IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.

Using impedance cardiography to detect subclinical cardiovascular disease in women with multiple risk factors: a pilot study.

PubMed

Demarzo, Arthur P

2009-01-01

Early detection of cardiovascular disease (CVD) could initiate appropriate treatment and prevent progression. This study used impedance cardiography (ICG) waveform analysis with postural change to detect functional CVD in women older than 40 years with no history of CVD and >or=2 of the following risk factors: cigarette smoking, poor diet, physical inactivity, central adiposity, family history of premature CVD, hypertension, and dyslipidemia. A study group of 32 women underwent ICG in standing and supine positions. An age-matched control group had 20 women with an active lifestyle, no risk factors, and no history of CVD. All women in the control group had normal ICG data. All women in the study group had some abnormal ICG data, with 28 (87.5%) having multiple ICG abnormalities. ICG data indicated that 13 (40.6%) had ventricular dysfunction, 14 (43.8%) had high vascular resistive load, and 30 (93.8%) had elevated vascular pulsatile load. The data suggest that subclinical CVD, detectable by ICG, is prevalent in women older than 40 years with multiple risk factors. Abnormal ICG results could expedite the initiation of customized treatment as part of a preventive approach to CVD. (c) 2009 Wiley Periodicals, Inc.

Provider-Initiated Patient Satisfaction Reporting Yields Improved Physician Ratings Relative to Online Rating Websites.

PubMed

Ricciardi, Benjamin F; Waddell, Brad S; Nodzo, Scott R; Lange, Jeffrey; Nocon, Allina A; Amundsen, Spencer; Tarity, T David; McLawhorn, Alexander S

2017-09-01

Recently, providers have begun to publicly report the results of patient satisfaction surveys from their practices. However, these outcomes have never been compared with the findings of commercial online physician rating websites. The goals of the current study were to (1) compare overall patient satisfaction ratings for orthopedic surgeons derived from provider-based third-party surveys with existing commercial physician rating websites and (2) determine the association between patient ratings and provider characteristics. The authors identified 12 institutions that provided publicly available patient satisfaction outcomes derived from third-party surveys for their orthopedic surgeons as of August 2016. Orthopedic surgeons at these institutions were eligible for inclusion (N=340 surgeons). Provider characteristics were recorded from publicly available data. Four high-traffic commercial online physician rating websites were identified: Healthgrades.com, UCompareHealthCare.com, Vitals.com, and RateMDs.com. For each surgeon, overall ratings (on a scale of 1-5), total number of ratings, and percentage of negative ratings were compared between provider-initiated internal ratings and each commercial online website. Associations between baseline factors and overall physician ratings and negative ratings were assessed. Provider-initiated internal patient satisfaction ratings showed a greater number of overall patient ratings, higher overall patient satisfaction ratings, and a lower percentage of negative comments compared with commercial online physician rating websites. A greater number of years in practice had a weak association with lower internal ratings, and an academic practice setting and a location in the Northeast were protective factors for negative physician ratings. Compared with commercial online physician rating websites, provider-initiated patient satisfaction ratings of orthopedic surgeons appear to be more favorable, with greater numbers of responses. [Orthopedics. 2017; 40(5):304-310.]. Copyright 2017, SLACK Incorporated.

Motor power factor controller with a reduced voltage starter

NASA Technical Reports Server (NTRS)

Nola, F. J. (Inventor)

1981-01-01

A power factor type motor controller is disclosed in which the conventional power factor constant voltage command signal is replaced during a starting interval with a graduated control voltage. This continuation-impart of a pending patent application (Serial No. 199, 765: Three Phase Factor Controller) provides a means for modifying the operation of the system for a motor start-up interval of 5 to 30 second. Using a ramp generators, an initial ramp-like signal replaces a constant power factor signal supplied by a potentiometer. The ramp-like signal is applied to a 15 terminal where it is summed with an operating power factor signal from phase detectors in order to obtain a control signal for ultimately controlling SCR devices. The SCR devices are turned on at an advancing rate with time responsive to the combination signal described rather than simply a function of a ramp-like signal alone.

75 FR 13082 - Listing Endangered and Threatened Species; Initiation of 5-Year Reviews for 27 Evolutionarily...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

... steelhead. Under this policy, a DPS of steelhead must be discrete from other conspecific populations, and it must be significant to its taxon. A group of organisms is discrete if it is ``markedly separated from... behavioral factors.'' Under the DPS Policy, if a population group is determined to be discrete, the agency...

Who Gets Jobs? Initial Labour Market Experiences of York Graduates. Working Paper.

ERIC Educational Resources Information Center

Grayson, J. Paul

As part of a study which is following college graduates for 5 years, a survey of 2,264 graduates of York University (Ontario, Canada) who received B.A. degrees in 1995-96 shows that within 3 months of graduation, 54 percent of those seeking full-time employment had achieved this objective. The factors considered included background…

Perennial grasses reduce woody plant seedlings...on mixed conifer fuel-break

Treesearch

Harry E. Schimke Lisle R. Green Danny Heavilin

1970-01-01

After initial clearing, parts of a fuelbreak on the Stanislaus Nationd Forest, central California, were planted to perennial grasses; other parts were not. After 5 years, a comparison between adjacent seeded sand unseeded strips shows that the perernnials had reduced the number of woody plant seedlings by a factor of 8, height of seedlings by 50 percent, and amount of...

The Frontier Fields: Survey Design and Initial Results

NASA Astrophysics Data System (ADS)

Lotz, J. M.; Koekemoer, A.; Coe, D.; Grogin, N.; Capak, P.; Mack, J.; Anderson, J.; Avila, R.; Barker, E. A.; Borncamp, D.; Brammer, G.; Durbin, M.; Gunning, H.; Hilbert, B.; Jenkner, H.; Khandrika, H.; Levay, Z.; Lucas, R. A.; MacKenty, J.; Ogaz, S.; Porterfield, B.; Reid, N.; Robberto, M.; Royle, P.; Smith, L. J.; Storrie-Lombardi, L. J.; Sunnquist, B.; Surace, J.; Taylor, D. C.; Williams, R.; Bullock, J.; Dickinson, M.; Finkelstein, S.; Natarajan, P.; Richard, J.; Robertson, B.; Tumlinson, J.; Zitrin, A.; Flanagan, K.; Sembach, K.; Soifer, B. T.; Mountain, M.

2017-03-01

What are the faintest distant galaxies we can see with the Hubble Space Telescope (HST) now, before the launch of the James Webb Space Telescope? This is the challenge taken up by the Frontier Fields, a Director’s discretionary time campaign with HST and the Spitzer Space Telescope to see deeper into the universe than ever before. The Frontier Fields combines the power of HST and Spitzer with the natural gravitational telescopes of massive high-magnification clusters of galaxies to produce the deepest observations of clusters and their lensed galaxies ever obtained. Six clusters—Abell 2744, MACSJ0416.1-2403, MACSJ0717.5+3745, MACSJ1149.5+2223, Abell S1063, and Abell 370—have been targeted by the HST ACS/WFC and WFC3/IR cameras with coordinated parallel fields for over 840 HST orbits. The parallel fields are the second-deepest observations thus far by HST with 5σ point-source depths of ˜29th ABmag. Galaxies behind the clusters experience typical magnification factors of a few, with small regions magnified by factors of 10-100. Therefore, the Frontier Field cluster HST images achieve intrinsic depths of ˜30-33 mag over very small volumes. Spitzer has obtained over 1000 hr of Director’s discretionary imaging of the Frontier Field cluster and parallels in IRAC 3.6 and 4.5 μm bands to 5σ point-source depths of ˜26.5, 26.0 ABmag. We demonstrate the exceptional sensitivity of the HST Frontier Field images to faint high-redshift galaxies, and review the initial results related to the primary science goals.

Do parental education and income matter? A nationwide register-based study on HPV vaccine uptake in the school-based immunisation programme in Norway

PubMed Central

Feiring, Berit; Laake, Ida; Molden, Tor; Cappelen, Inger; Håberg, Siri E; Magnus, Per; Steingrímsdóttir, Ólöf Anna; Strand, Bjørn Heine; Stålcrantz, Jeanette; Trogstad, Lill

2015-01-01

Objective Vaccine against human papillomavirus (HPV) has been offered free of charge to all 12-year-old girls in Norway since 2009. Nevertheless, the uptake of HPV vaccine is lower than for other childhood vaccines. The aim of this study was to examine whether parental education and income are associated with initiation and completion of HPV vaccination. Design Nationwide register-based study. Setting Publicly funded childhood immunisation programme in Norway. Participants 91 405 girls born between 1997 and 1999 and registered in the Norwegian Central Population Registry were offered HPV vaccine during the first 3 programme years. Of these, 84 139 had complete information on all variables and were included in the study. Measurements Information on HPV-vaccination status was obtained from the Norwegian Immunisation Registry. Data on socioeconomic factors were extracted from Statistics Norway. Risk differences (RDs) and CIs were estimated with Poisson regression. Results In the study sample, 78.3% received at least one dose of HPV vaccine and 73.6% received all three doses. High maternal education was significantly associated with lower probability of initiating HPV vaccination (multivariable RD=−5.5% (95% CI −7.0% to −4.0%) for highest compared with lowest education level). In contrast, high maternal income was significantly associated with higher probability of initiating vaccination (multivariable RD=10.1% (95% CI 9.0% to 11.3%) for highest compared with lowest quintile). Paternal education and income showed similar, but weaker, associations. The negative association between education and initiation was only seen for incomes below the median value. Conclusions In spite of the presumably equal access to HPV vaccine in Norway, we found socioeconomic disparities in vaccine uptake. More studies are needed to explain the underlying factors responsible for the observed socioeconomic differences. Insight into these factors is necessary to target information and increase vaccination coverage to ultimately reduce HPV-related disease across socioeconomic barriers. PMID:25991445

Characterization of 5' end of human thromboxane receptor gene. Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets.

PubMed

D'Angelo, D D; Davis, M G; Houser, W A; Eubank, J J; Ritchie, M E; Dorn, G W

1995-09-01

Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction. To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene. The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA. A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site. The thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells. Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment. Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site. These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements. These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells.

Patient initiation and persistence with allergen immunotherapy.

PubMed

Anolik, Robert; Schwartz, Ann Marie; Sajjan, Shiva; Allen-Ramey, Felicia

2014-07-01

Allergen immunotherapy (AIT) is advised for patients with allergic rhinitis who remain symptomatic despite the use of pharmacotherapy and allergen avoidance. Several factors influence the decision to initiate and complete the AIT regimen. To evaluate patient initiation and persistence with subcutaneous and sublingual immunotherapies (SCIT and SLIT) according to physician recommendation. A retrospective review of electronic health records of patients with allergic rhinitis for whom AIT was recommended was conducted in a large private allergy practice in Pennsylvania. Of 8,790 patients advised to consider AIT, 36.2% initiated AIT (57% adults, 43% children); 78% chose SCIT and 22% chose SLIT drops. Election of AIT was significantly associated with select comorbidities, specifically chronic sinusitis (8.1% for AIT vs 10% for no AIT), allergic conjunctivitis (12.5% for AIT vs 18.5% for no AIT), and asthma (33.8% for AIT vs 37.4% for no AIT; P < .05). Choice of SCIT vs SLIT drops was significantly associated with older age, female sex, select comorbidities, and more allergy medications at initiation (P < .05). Of adults, 30.2% completed at least 3 years of recommended treatment. Median time on treatment was longer for adults on SCIT vs SLIT drops (3 vs 1.6 years). Similarly, 35.4% of children completed treatment, with a longer median time on treatment for SCIT (4.7 years) vs SLIT drops (3.5 years). A minority of patients initiated AIT according to allergist recommendation and a subset of these patients completed therapy. AIT might be an underused option that could benefit patients unable to manage allergic rhinitis symptoms by other means. clinicaltrials.gov Identifier: NCT01549340. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Exercise to Countereact Loss of Bone and Muscle During Androgen Deprivation Therapy in Men with Prostate Cancer

DTIC Science & Technology

2007-05-01

increases 5- to 10-fold after the initiation of ADT14 and that the relative risk of osteoporotic fracture is increased by 30% to 300%.15-17 In 31 men...of bone turnover; serum sex hormones; physical functional performance; quality of life, and risk factors for cardiovascular disease (blood lipids...hormone binding globulin; physical functional performance; and quality of life. Local project support will enable additional assessments of risk factors

[Adherence to patients antidepressant treatment and the factors associated of non-compiance].

PubMed

Párraga Martínez, Ignacio; López-Torres Hidalgo, Jesús; del Campo del Campo, José M; Villena Ferrer, Alejandro; Morena Rayo, Susana; Escobar Rabadán, Francisco

2014-01-01

To know the adherence to treatment in patients who initiate antidepressant drugs and to analyze the determinant factors of non-compliance, so much clinical as sociodemographic. Prospective longitudinal observational study. Primary Health Care and Mental Health Surgeries of three Castilla-La Mancha Areas. 185 adults patients who were started in antidepressant treatment were evaluated. Treatment adherence (test Haynes-Sackett, test Morisky-Green, count of tablets and MEMS), adverse effects, intensity of depressive symptoms, sociodemographic characteristics and other characteristics related to antidepressants or participants. After 6months of beginning antidepressing treatment, 46.9% (95%IC: 36.5-57.3) showed an inadequate fulfilment by pill count method and 28.6% (95%IC: 19.1-38.0) with Morisky-Green's questionnaire. To 15 days the lack of adherence was 48.5% (95%IC: 40.6-56.4) and of 33.5% (95%IC: 26.1-41.0). The 38.4% (95%IC: 31.1-45.7) demonstrated some side effect during the follow-up. Using proportional risk model of Cox the variables related to compliance were: younger age, level of instruction lower than secondary studies, free medicines for pensioner, no psychotherapeutic treatment, consume a fewer antidepressants drugs and a frequency ≤ 3 visits to the family doctor 3 months previous to the study. The non-compliance of antidepressant treatment in primary care is high from the first weeks after initiating it. The conditioning factors are related to sociodemographic characteristics and other patient characteristics as type of financing of pharmaceutical benefit and frequentness at primary care. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

The potential effects of pH and buffering capacity on dental erosion.

PubMed

Owens, Barry M

2007-01-01

Soft drink pH (initial pH) has been shown to be a causative factor--but not necessarily the primary initiating factor--of dental erosion. The titratable acidity or buffering capacity has been acknowledged as playing a significant role in the etiology of these lesions. This in vitro study sought to evaluate five different soft drinks (Coca-Cola Classic, Diet Coke, Gatorade sports drink, Red Bull high-energy drink, Starbucks Frappucino coffee drink) and tap water (control) in terms of initial pH and buffering capacity. Initial pH was measured in triplicate for the six beverages. The buffering capacity of each beverage was assessed by measuring the weight (in grams) of 0.10 M sodium hydroxide necessary for titration to pH levels of 5.0, 6.0, 7.0, and 8.3. Coca-Cola Classic produced the lowest mean pH, while Starbucks Frappucino produced the highest pH of any of the drinks except for tap water. Based on statistical analysis using ANOVA and Fisher's post hoc tests at a P < 0.05 level of significance, Red Bull had the highest mean buffering capacity (indicating the strongest potential for erosion of enamel), followed by Gatorade, Coca-Cola Classic, Diet Coke, and Starbucks Frappucino.

Evidence for cumulative temperature as an initiating and terminating factor in downstream migratory behavior of Atlantic salmon (Salmo salar) smolts

USGS Publications Warehouse

Zydlewski, G.B.; Haro, A.; McCormick, S.D.

2005-01-01

Temperature control of Atlantic salmon (Salmo salar) smolt migration was tested using a novel technique allowing nearly continuous monitoring of behavior with complete control over environmental conditions. Parr and presmolts were implanted with passive integrated transponder tags, placed in simulated streams, and monitored for upstream and downstream movements. Beginning 18 April, temperature was increased 1??C every third day (advanced), fourth day (ambient), and tenth day (delayed). Smolt downstream movements were initially low, peaked in mid-May, and subsequently declined under all conditions. Parr downstream movements were significantly lower than those of smolts in all treatments (0.8 ?? 0.5 movement??day-1 versus 26.5 ?? 4.5 movements??day-1, mean ?? SE) and showed no increase. At delayed temperatures, smolts sustained downstream movements through July; those under ambient and advanced conditions ceased activity by mid-June. Initiation and termination of downstream movements occurred at significantly different temperatures but at the same number of degree-days in all treatments. Physiological changes associated with smolting (gill Na+,K +-ATPase activity and plasma thyroxine) were coincident with behavioral changes. This is the first evidence of a behavioral component to the smolt window. We found that temperature experience over time is more relevant to initiation and termination of downstream movement than a temperature threshold. ?? 2005 NRC Canada.

Timing and adequate attendance of antenatal care visits among women in Ethiopia.

PubMed

Yaya, Sanni; Bishwajit, Ghose; Ekholuenetale, Michael; Shah, Vaibhav; Kadio, Bernard; Udenigwe, Ogochukwu

2017-01-01

Although ANC services are increasingly available to women in low and middle-income countries, their inadequate use persists. This suggests a misalignment between aims of the services and maternal beliefs and circumstances. Owing to the dearth of studies examining the timing and adequacy of content of care, this current study aims to investigate the timing and frequency of ANC visits in Ethiopia. Data was obtained from the nationally representative 2011 Ethiopian Demographic and Health Survey (EDHS) which used a two-stage cluster sampling design to provide estimates for the health and demographic variables of interest for the country. Our study focused on a sample of 10,896 women with history of at least one childbirth event. Percentages of timing and adequacy of ANC visits were conducted across the levels of selected factors. Variables which were associated at 5% significance level were examined in the multivariable logistic regression model for association between timing and frequency of ANC visits and the explanatory variables while controlling for covariates. Furthermore, we presented the approach to estimate marginal effects involving covariate-adjusted logistic regression with corresponding 95%CI of delayed initiation of ANC visits and inadequate ANC attendance. The method used involved predicted probabilities added up to a weighted average showing the covariate distribution in the population. Results indicate that 66.3% of women did not use ANC at first trimester and 22.3% had ANC less than 4 visits. The results of this study were unique in that the association between delayed ANC visits and adequacy of ANC visits were examined using multivariable logistic model and the marginal effects using predicted probabilities. Results revealed that older age interval has higher odds of inadequate ANC visits. More so, type of place of residence was associated with delayed initiation of ANC visits, with rural women having the higher odds of delayed initiation of ANC visits (OR = 1.65; 95%CI: 1.26-2.18). However, rural women had 44% reduction in the odds of having inadequate ANC visits. In addition, multi-parity showed higher odds of delayed initiation of ANC visit when compared to the primigravida (OR = 2.20; 95%CI: 1.07-2.69). On the contrary, there was 36% reduction in the odds of multigravida having inadequate ANC visits when compared to the women who were primigravida. There were higher odds of inadequacy in ANC visits among women who engaged in sales/business, agriculture, skilled manual and other jobs when compared to women who currently do not work, after adjusting for covariates. From the predictive margins, assuming the distribution of all covariates remained the same among respondents, but everyone was aged 15-19 years, we would expect 71.8% delayed initiation of ANC visit. If everyone was aged 20-24years, 73.4%; 25-29years, 66.5%; 30-34years, 64.8%; 35-39years, 65.6%; 40-44years, 59.6% and 45-49years, we would expect 70.1% delayed initiation of ANC visit. If instead the distribution of age was as observed and for other covariates remained the same among respondents, but no respondent lived in the rural, we would expect about 61.4% delayed initiation of ANC visit; if however, everyone lived in the rural, and we would expect 71.6% delayed initiation in ANC visit. Model III revealed the predictive margins of all factors examined for delayed initiation for ANC visits, while Model IV presented the predictive marginal effects of the determinants of adequacy of ANC visits. The precise mechanism by which these factors affect ANC visits remain blurred at best. There may be factors on the demand side like the women's empowerment, financial support of the husband, knowledge of ANC visits in the context of timing, frequency and the expectations of ANC visits might be mediating the effects through the factors found associated in this study. Supply side factors like the quality of ANC services, skilled staff, and geographic location of the health centers also mediate their effects through the highlighted factors. Irrespective of the knowledge about the precise mechanism of action, policy makers could focus on improving women's empowerment, improving women's education, reducing wealth inequity and facilitating improved utilization of ANC through modifications on the supply side factors such as geographic location and focus on hard to reach women.

Effect of cell density and HLA-DR incompatibility on T-cell proliferation and forkhead box P3 expression in human mixed lymphocyte reaction.

PubMed

Song, E Y; Han, S; Yang, B; Morris, G P; Bui, J D

2015-04-01

The proliferation rates of human T cells in vitro are affected by some factors such as initial T-cell number, dose of stimulating cells, and duration of culture. The transcription factor forkhead box P3 (FoxP3) has been used to identify regulatory T cells in humans and is thought to correlate with tolerance to allogeneic organ transplant. Thus, it is important to optimize conditions to expand FoxP3 cell proliferation to improve engraftment of allogeneic organ transplants. We studied proliferative responses and FoxP3 expression in divided T cells with the use of flow cytometric analysis of Ki-67 in culture of different concentrations of responding cells (6 × 10(6), 4 × 10(6), 2 × 10(6), 1 × 10(6), and 0.5 × 10(6)cells/mL), different types of stimulating cells (lymphocytes and low density cells), and different numbers of HLA mismatches. The proportion of CD3(+) cells, CD4(+)CD25(+) cells, and CD4(+)CD25(+)FoxP3(+) cells among mononuclear cells were highest at initial cell concentration of 2 × 10(6) responder cells/mL with lymphocytes as stimulators at day-5 mixed lymphocyte reaction (MLR). They were highest at a concentration of 4 × 10(6) responder cells/mL with low density cells as stimulators. The recovery (%), proportion of CD3(+) cells, CD4(+)CD25(+) cells, and CD4(+)CD25(+)FoxP3(+) cells with 2 HLA-DR incompatibility were significantly higher than those of 1 HLA-DR incompatibility at day-5 MLR. Initial cell concentration and HLA-DR incompatibility can affect the generation of FoxP3+ T cells in human MLR. These factors could be considered for efficient generation of Tregs for clinical trials in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmaceutic factors affecting pediatric compliance.

PubMed

Mattar, M E; Markello, J; Yaffe, S J

1975-01-01

Evaluation of treatment given at home was studied in children with otitis media who were seen in an outpatient clinic. Full compliance was present in only 5% of the initial 100 patients (Study A). Practical factors limiting their compliance included inadequate dispensing of medication at drug stores, 15%; incorrect therapy schedule, 36%; early termination, 37%; spilled medicine, 7%; therapy shared, 5%. Because of these findings, a plan was implemented (Study B) in which hospital pharmacy personnel gave patient families verbal and written instructions for administering medications that were dispensed, together with a calibrated measuring device and a calendar to record doses taken. Full compliance was raised to 51% in this pilot group (of 33 patients) as compared with 8.5% in 20 concurrent controls who went to neighborhood drug stores. The importance of detailed therapy instructions is stressed. The potential role of the pharmacist in improving compliance is demonstrated.

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics.

PubMed

Rossetti, Luca; Digiuni, Maurizio; Montesano, Giovanni; Giovanni, Montesano; Centofanti, Marco; Fea, Antonio M; Iester, Michele; Frezzotti, Paolo; Figus, Michele; Ferreras, Antonio; Oddone, Francesco; Tanga, Lucia; Rolle, Teresa; Battaglino, Valentina; Posarelli, Chiara; Motolese, Ilaria; Mittica, Pietro; Bagaglia, Simone Alex; Menicacci, Cristina; De Cilla', Stefano; Autelitano, Alessandro; Fogagnolo, Paolo

2015-01-01

To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder ('controls'). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°. Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.

Translation of 5′ leaders is pervasive in genes resistant to eIF2 repression

PubMed Central

Fahey, Ciara; Kenny, Elaine M; Terenin, Ilya M; Dmitriev, Sergey E; Cormican, Paul; Morris, Derek W; Shatsky, Ivan N; Baranov, Pavel V

2015-01-01

Eukaryotic cells rapidly reduce protein synthesis in response to various stress conditions. This can be achieved by the phosphorylation-mediated inactivation of a key translation initiation factor, eukaryotic initiation factor 2 (eIF2). However, the persistent translation of certain mRNAs is required for deployment of an adequate stress response. We carried out ribosome profiling of cultured human cells under conditions of severe stress induced with sodium arsenite. Although this led to a 5.4-fold general translational repression, the protein coding open reading frames (ORFs) of certain individual mRNAs exhibited resistance to the inhibition. Nearly all resistant transcripts possess at least one efficiently translated upstream open reading frame (uORF) that represses translation of the main coding ORF under normal conditions. Site-specific mutagenesis of two identified stress resistant mRNAs (PPP1R15B and IFRD1) demonstrated that a single uORF is sufficient for eIF2-mediated translation control in both cases. Phylogenetic analysis suggests that at least two regulatory uORFs (namely, in SLC35A4 and MIEF1) encode functional protein products. DOI: http://dx.doi.org/10.7554/eLife.03971.001 PMID:25621764

Early Mortality in Adults Initiating Antiretroviral Therapy (ART) in Low- and Middle-Income Countries (LMIC): A Systematic Review and Meta-Analysis

PubMed Central

Gupta, Amita; Nadkarni, Girish; Yang, Wei-Teng; Chandrasekhar, Aditya; Gupte, Nikhil; Bisson, Gregory P.; Hosseinipour, Mina; Gummadi, Naveen

2011-01-01

Background We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known. Methods and Findings Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3–55 months and 11–192 cells/mm3, respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%–27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11–0.24) versus 0.11 (95% CI 0.10–0.13) for Asia, and 0.07 (95% CI 0.007–0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%–44%), wasting (5%–53%), advanced HIV (20%–37%), and chronic diarrhea (10%–25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA. Conclusions Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed. PMID:22220193

Early mortality in adults initiating antiretroviral therapy (ART) in low- and middle-income countries (LMIC): a systematic review and meta-analysis.

PubMed

Gupta, Amita; Nadkarni, Girish; Yang, Wei-Teng; Chandrasekhar, Aditya; Gupte, Nikhil; Bisson, Gregory P; Hosseinipour, Mina; Gummadi, Naveen

2011-01-01

We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known. Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3-55 months and 11-192 cells/mm(3), respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%-27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11-0.24) versus 0.11 (95% CI 0.10-0.13) for Asia, and 0.07 (95% CI 0.007-0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%-44%), wasting (5%-53%), advanced HIV (20%-37%), and chronic diarrhea (10%-25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA. Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed.

Risk of Unsuccessful Noninvasive Ventilation for Acute Respiratory Failure in Heterogeneous Neuromuscular Diseases: A Retrospective Study.

PubMed

Kataoka, Hiroshi; Nanaura, Hitoki; Kinugawa, Kaoru; Uchihara, Yuto; Ohara, Hiroya; Eura, Nobuyuki; Syobatake, Ryogo; Sawa, Nobuhiro; Takao, Kiriyama; Sugie, Kazuma; Ueno, Satoshi

2017-02-20

If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV) in patients with acute respiratory failure (ARF), the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF among patients who receive continuous NIV support, patients who are switched from NIV to invasive ventilation, and patients in whom NIV is discontinued. Endpoints were evaluated 24 and 72 hours after the initiation of NIV. After 24 hours, all but 1 patient with amyotrophic lateral sclerosis (ALS) received continuous NIV support. 72 hours later, 5 patients were switched from NIV to invasive ventilation, and 5 patients continued to receive NIV support. 72 hours after the initiation of NIV, the proportion of patients with a diagnosis of ALS differed significantly among the three groups (P=0.039). NIV may be attempted to manage acute fatal respiratory failure associated with neuromuscular diseases, but clinicians should carefully manage the clinical course in patients with ALS.

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

PubMed

Krige, Jake E J; Kotze, Urda K; Distiller, Greg; Shaw, John M; Bornman, Philippus C

2009-10-01

Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Images of smokers and willingness to smoke among African American pre-adolescents: an application of the prototype/willingness model of adolescent health risk behavior to smoking initiation.

PubMed

Gerrard, Meg; Gibbons, Frederick X; Stock, Michelle L; Lune, Linda S Vande; Cleveland, Michael J

2005-06-01

This study used the prototype/willingness model of adolescent health risk behavior to examine factors related to onset of smoking. Two waves of data were collected from a panel of 742 African American children (mean age=10.5 at Wave 1) and their primary caregivers. Measures included cognitions outlined by the prototype model as well as self-reports of smoking by the parent and child. Structural equation modeling revealed a pattern consistent with expectations generated by the prototype model. The relation between contextual, familial, and dispositional factors-including neighborhood risk, parental smoking, and children's academic orientation-and the initiation of smoking at Wave 2, two years later, was mediated by the children's cognitions. Primary among these cognitions were the children's images of smokers and children's willingness to smoke. Smoking cognitions mediate the impact of important distal factors (such as context, family environment, and disposition) on the onset of smoking in children. Perhaps more important, it is possible to predict onset of smoking in African American children as young as age 10 by assessing the cognitive factors suggested by the prototype model.

Risk Factors Influencing Smoking Behavior: A Turkish Twin Study

PubMed Central

Öncel, Sevgi Yurt; Dick, Danielle M.; Maes, Hermine H.; Alıev, Fazil

2015-01-01

Aim In this study, we introduce the first twin study in Turkey, focusing on smoking behavior, and laying the foundation to register all twins born in Turkey for research purposes. Using Turkish twins will contribute to our understanding of health problems in the context of cultural differences. Materials and methods We assessed 309 twin pairs (339 males and 279 females) aged between 15 and 45 years living in the Kırıkkale and Ankara regions of Turkey, and administered a health and lifestyle interview that included questions about smoking status and smoking history. We analyzed the data using descriptive statistics, t-tests, chi-square tests, and bivariate and multivariate clustered logistic regression. In addition, we fit bivariate Structural Equation Models (SEM) to determine contributions of latent genetic and environmental factors to smoking outcomes in this sample. Results One hundred seventy-eight participants (28.8%) were identified as smokers, smoking every day for a month or longer, of whom 79.2% were males and 20.8% were females. Mean values for number of cigarettes per day and the Fagerstrom Test of Nicotine Dependence (FTND; Fagerstrom, 1978) score were higher in males than in females, and age of onset was earlier in males. There was a significant positive correlation between the FTND score and number of cigarettes smoked per day, and a significant negative correlation between both variables and age at onset of smoking. Our study showed that gender, presence of a smoking twin in the family, age, alcohol use, marital status, daily sports activities, and feeling moody all played a significant role in smoking behavior among twins. The twin analysis suggested that 79.5% of the liability to FTND was influenced by genetic factors and 20.5% by unique environment, while familial resemblance for smoking initiation was best explained by common environmental factors. Conclusions Marked differences in the prevalence of smoking behavior in men versus women were observed for the Turkish population. Genetic analyses showed that common environmental factors primarily contributed to smoking initiation, while genetic factors explained a greater proportion of variance in liability to nicotine dependence. Our study shows higher heritability estimate of the FTND scores and higher shared environmental influence on smoking initiation for both males and females than reported in previous studies. PMID:25431287

A possible reason behind the initial formation of pentagonal dodecahedron cavities in sI-methane hydrate nucleation: A DFT study

NASA Astrophysics Data System (ADS)

Mondal, Sukanta; Goswami, Tamal; Jana, Gourhari; Misra, Anirban; Chattaraj, Pratim Kumar

2018-01-01

In this letter, a possible reason behind selective host-guest organization in the initial stage of sI methane hydrate nucleation is provided, through density functional theory based calculations. In doing so, we have connected earlier experimental and theoretical observations on the structure and energetics of sI methane hydrate to our findings. Geometry and relative stability of small (H2O)5 and (H2O)6 clusters, presence of CH4 guest, integrity and cavity radius of (H2O)20 and (H2O)24, as well as the weak van der Waals type of forces, particularly dispersion interaction, are major factors responsible for initial formation of methane encapsulated dodecahedron cavity over tetrakaidecahedron.

Success factors for strategic change initiatives: a qualitative study of healthcare administrators' perspectives.

PubMed

Kash, Bita Arbab; Spaulding, Aaron; Johnson, Christopher E; Gamm, Larry

2014-01-01

Success factors related to the implementation of change initiatives are well documented and discussed in the management literature, but they are seldom studied in healthcare organizations engaged in multiple strategic change initiatives. The purpose of this study was to identify key success factors related to implementation of change initiatives based on rich qualitative data gathered from health leader interviews at two large health systems implementing multiple change initiatives. In-depth personal interviews with 61 healthcare leaders in the two large systems were conducted and inductive qualitative analysis was employed to identify success factors associated with 13 change initiatives. Results from this analysis were compared to success factors identified in the literature, and generalizations were drawn that add significantly to the management literature, especially to that in the healthcare sector. Ten specific success factors were identified for the implementation of change initiatives. The top three success factors were (1) culture and values, (2) business processes, and (3) people and engagement. Two of the identified success factors are unique to the healthcare sector and not found in the literature on change models: service quality and client satisfaction (ranked fourth of 10) and access to information (ranked ninth). Results demonstrate the importance of human resource functions, alignment of culture and values with change, and business processes that facilitate effective communication and access to information to achieve many change initiatives. The responses also suggest opportunities for leaders of healthcare organizations to more formally recognize the degree to which various change initiatives are dependent on one another.

A vaccine composed of a hypothetical protein and the eukaryotic initiation factor 5a from Leishmania braziliensis cross-protection against Leishmania amazonensis infection.

PubMed

Duarte, Mariana Costa; Lage, Daniela Pagliara; Martins, Vívian Tamietti; Costa, Lourena Emanuele; Carvalho, Ana Maria Ravena Severino; Ludolf, Fernanda; Santos, Thaís Teodoro de Oliveira; Vale, Danniele Luciana; Roatt, Bruno Mendes; Menezes-Souza, Daniel; Fernandes, Ana Paula; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antonio Ferraz

2017-02-01

In the present study, two proteins cloned from Leishmania braziliensis species, a hypothetical protein (LbHyp) and the eukaryotic initiation factor 5a (EiF5a), were evaluated to protect BALB/c mice against L. amazonensis infection. The animals were immunized with the antigens, either separately or in combination, using saponin as an immune adjuvant in both cases. Spleen cells from vaccinated and later infected mice produced significantly higher levels of protein and parasite-specific IFN-γ, IL-12, and GM-CSF, in addition to low levels of IL-4 and IL-10. Evaluating the parasite load by means of a limiting dilution technique and quantitative Real-Time PCR, vaccinated animals presented significant reductions in the parasite load in both infected tissues and organs, as well as lower footpad swelling, when compared to the control (saline and saponin) groups. The best results regarding the protection of the animals were achieved when the combined vaccine was administered into the animals. Protection was associated with an IFN-γ production against parasite antigens, which was mediated by both CD4 + and CD8 + T cells and correlated with antileishmanial nitrite production. In conclusion, data from the present study show that this polyprotein vaccine, which combines two L. braziliensis proteins, can induce protection against L. amazonensis infection. Copyright © 2016 Elsevier GmbH. All rights reserved.

Steroidogenic factor-1 (SF-1, NR5A1) and human disease

PubMed Central

Ferraz-de-Souza, Bruno; Lin, Lin; Achermann, John C.

2011-01-01

Steroidogenic factor-1 (SF-1, Ad4BP, encoded by NR5A1) is a key regulator of adrenal and reproductive development and function. Based upon the features found in Nr5a1 null mice, initial attempts to identify SF-1 changes in humans focused on those rare individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis and Müllerian structures. Although alterations affecting DNA-binding of SF-1 were found in two such cases, disruption of SF-1 is not commonly found in patients with adrenal failure. In contrast, it is emerging that variations in SF-1 can be found in association with a range of human reproductive phenotypes such as 46,XY disorders of sex development (DSD), hypospadias, anorchia, male factor infertility, or primary ovarian insufficiency in women. Overexpression or overactivity of SF-1 is also reported in some adrenal tumors or endometriosis. Therefore, the clinical spectrum of phenotypes associated with variations in SF-1 is expanding and the importance of this nuclear receptor in human endocrine disease is now firmly established. PMID:21078366

Quality factor and dose equivalent investigations aboard the Soviet Space Station Mir

NASA Astrophysics Data System (ADS)

Bouisset, P.; Nguyen, V. D.; Parmentier, N.; Akatov, Ia. A.; Arkhangel'Skii, V. V.; Vorozhtsov, A. S.; Petrov, V. M.; Kovalev, E. E.; Siegrist, M.

1992-07-01

Since Dec 1988, date of the French-Soviet joint space mission 'ARAGATZ', the CIRCE device, had recorded dose equivalent and quality factor values inside the Mir station (380-410 km, 51.5 deg). After the initial gas filling two years ago, the low pressure tissue equivalent proportional counter is still in good working conditions. Some results of three periods are presented. The average dose equivalent rates measured are respectively 0.6, 0.8 and 0.6 mSv/day with a quality factor equal to 1.9. Some detailed measurements show the increasing of the dose equivalent rates through the SAA and near polar horns. The real time determination of the quality factors allows to point out high linear energy transfer events with quality factors in the range 10-20.

Correlates of early versus later initiation into sex work in two Mexico-U.S. border cities.

PubMed

Loza, Oralia; Strathdee, Steffanie A; Lozada, Remedios; Staines, Hugo; Ojeda, Victoria D; Martínez, Gustavo A; Amaro, Hortensia; Patterson, Thomas L

2010-01-01

To examine correlates of early initiation into sex work in two Mexico-U.S. border cities. Female sex workers (FSWs) >/=18 years without known HIV infection living in Tijuana and Ciudad Juarez who had recent unprotected sex with clients underwent baseline interviews. Correlates of initiation into sex work before age 18 were identified with logistic regression. Of 920 FSWs interviewed in Tijuana (N=474) and Ciudad Juarez (N=446), 9.8% (N=90) were early initiators (<18 years) into sex work. Median age of entry into sex work was 26 years (range: 6-58). After adjusting for age, compared to older initiators, early initiators were more likely to use inhalants (21.1% vs. 9.6%, p=.002), initiate sex work to pay for alcohol (36.7% vs. 18.4%, p < .001), report abuse as a child (42.2% vs. 18.7%, p<.0001), and they were less likely to be migrants (47.8% vs. 62.3%, p=.02). Factors independently associated with early initiation included inhalant use (adjOR=2.39), initiating sex work to pay for alcohol (adjOR=1.88) and history of child abuse (adjOR=2.92). Factors associated with later initiation included less education (adjOR=0.43 per 5-year increase), migration (adjOR=0.47), and initiating sex work for better pay (adjOR=0.44) or to support children (adjOR=0.03). Different pathways for entering sex work are apparent among younger versus older females in the Mexico-U.S. border region. Among girls, interventions are needed to prevent inhalant use and child abuse and to offer coping skills; among older initiators, income-generating strategies, childcare, and services for migrants may help to delay or prevent entry into sex work. Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.

Correlates of Early versus Later Initiation into Sex Work in Two Mexico–U.S. Border Cities

PubMed Central

Loza, Oralia; Strathdee, Steffanie A.; Lozada, Remedios; Staines, Hugo; Ojeda, Victoria D.; Martínez, Gustavo A.; Amaro, Hortensia; Patterson, Thomas L.

2009-01-01

Purpose To examine correlates of early initiation into sex work in two Mexico–U.S. border cities. Methods Female sex workers (FSWs) ≥18 years without known HIV infection living in Tijuana and Ciudad Juarez who had recent unprotected sex with clients underwent baseline interviews. Correlates of initiation into sex work before age 18 were identified with logistic regression. Results Of 920 FSWs interviewed in Tijuana (N=474) and Ciudad Juarez (N=446), 9.8% (N=90) were early initiators (<18 years) into sex work. Median age of entry into sex work was 26 years (range: 6–58). After adjusting for age, compared to older initiators, early initiators were more likely to use inhalants (21.1% vs 9.6%, p=0.002), initiate sex work to pay for alcohol (36.7% vs 18.4%, p<.001), report abuse as a child (42.2% vs 18.7%, p<.0001), and they were less likely to be migrants (47.8% vs 62.3%, p=0.02). Factors independently associated with early initiation included inhalant use (adjOR=2.39), initiating sex work to pay for alcohol (adjOR=1.88) and history of child abuse (adjOR=2.92). Factors associated with later initiation included less education (adjOR=0.43 per 5-year increase), migration (adjOR=0.47), and initiating sex work for better pay (adjOR=0.44) or to support children (adjOR=0.03). Conclusions Different pathways for entering sex work are apparent among younger versus older females in the Mexico–U.S. border region. Among girls, interventions are needed to prevent inhalant use and child abuse and to offer coping skills; among older initiators, income-generating strategies, childcare, and services for migrants may help to delay or prevent entry into sex work. PMID:20123256

Altered Gene Expression Patterns During the Initiation and Promotion Stages of Neonatally Diethylstilbestrol-Induced Hyperplasia/Dysplasia/Neoplasia in the Hamster Uterus

PubMed Central

Hendry, William J.; Hariri, Hussam Y.; Alwis, Imala D.; Gunewardena, Sumedha S.; Hendry, Isabel R.

2014-01-01

Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: 1) immunoblot analyses and 2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and 3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: 1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and 2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Particularly interesting changes included members in the functional categories of nuclear receptors (progesterone receptor), cell-cell interactions (E-cadherin, connexins), cytokine action (IRF-1, Stat5A), growth factor action (IRS-1), extracellular matrix component (tenascin-C), transcription factors (Nrf2, Sp1), and multi-functional nuclear protein (SAFB1). PMID:25242112

Structures of transcription pre-initiation complex with TFIIH and Mediator.

PubMed

Schilbach, S; Hantsche, M; Tegunov, D; Dienemann, C; Wigge, C; Urlaub, H; Cramer, P

2017-11-09

For the initiation of transcription, RNA polymerase II (Pol II) assembles with general transcription factors on promoter DNA to form the pre-initiation complex (PIC). Here we report cryo-electron microscopy structures of the Saccharomyces cerevisiae PIC and PIC-core Mediator complex at nominal resolutions of 4.7 Å and 5.8 Å, respectively. The structures reveal transcription factor IIH (TFIIH), and suggest how the core and kinase TFIIH modules function in the opening of promoter DNA and the phosphorylation of Pol II, respectively. The TFIIH core subunit Ssl2 (a homologue of human XPB) is positioned on downstream DNA by the 'E-bridge' helix in TFIIE, consistent with TFIIE-stimulated DNA opening. The TFIIH kinase module subunit Tfb3 (MAT1 in human) anchors the kinase Kin28 (CDK7), which is mobile in the PIC but preferentially located between the Mediator hook and shoulder in the PIC-core Mediator complex. Open spaces between the Mediator head and middle modules may allow access of the kinase to its substrate, the C-terminal domain of Pol II.

Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2

PubMed Central

Aguilar-Valles, Argel; Matta-Camacho, Edna; Khoutorsky, Arkady; Gkogkas, Christos; Nader, Karim

2015-01-01

Exacerbated mRNA translation during brain development has been linked to autism spectrum disorders (ASDs). Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-inhibitory neurotransmission and ASD-like behaviors. Inhibition of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 reverses the autistic phenotypes in several ASD mouse models. Importantly, these receptors control synaptic physiology via activation of mRNA translation. We investigated the potential reversal of autistic-like phenotypes in Eif4ebp2−/− mice by using antagonists of mGluR1 (JNJ16259685) or mGluR5 (fenobam). Augmented hippocampal mGluR-induced long-term depression (LTD; or chemically induced mGluR-LTD) in Eif4ebp2−/− mice was rescued by mGluR1 or mGluR5 antagonists. While rescue by mGluR5 inhibition occurs through the blockade of a protein synthesis-dependent component of LTD, normalization by mGluR1 antagonists requires the activation of protein synthesis. Synaptically induced LTD was deficient in Eif4ebp2−/− mice, and this deficit was not rescued by group I mGluR antagonists. Furthermore, a single dose of mGluR1 (0.3 mg/kg) or mGluR5 (3 mg/kg) antagonists in vivo reversed the deficits in social interaction and repetitive behaviors (marble burying) in Eif4ebp2−/− mice. Our results demonstrate that Eif4ebp2−/− mice serve as a relevant model to test potential therapies for ASD symptoms. In addition, we provide substantive evidence that the inhibition of mGluR1/mGluR5 is an effective treatment for physiological and behavioral alterations caused by exacerbated mRNA translation initiation. SIGNIFICANCE STATEMENT Exacerbated mRNA translation during brain development is associated with several autism spectrum disorders (ASDs). We recently demonstrated that the deletion of a negative regulator of mRNA translation initiation, the eukaryotic initiation factor 4E-binding protein 2, leads to ASD-like behaviors and increased excitatory synaptic activity. Here we demonstrated that autistic behavioral and electrophysiological phenotypes can be treated in adult mice with antagonists of group I metabotropic glutamate receptors (mGluRs), which have been previously used in other ASD models (i.e., fragile X syndrome). These findings support the use of group I mGluR antagonists as a potential therapy that extends to autism models involving exacerbated mRNA translation initiation. PMID:26245973

Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2.

PubMed

Aguilar-Valles, Argel; Matta-Camacho, Edna; Khoutorsky, Arkady; Gkogkas, Christos; Nader, Karim; Lacaille, Jean-Claude; Sonenberg, Nahum

2015-08-05

Exacerbated mRNA translation during brain development has been linked to autism spectrum disorders (ASDs). Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-inhibitory neurotransmission and ASD-like behaviors. Inhibition of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 reverses the autistic phenotypes in several ASD mouse models. Importantly, these receptors control synaptic physiology via activation of mRNA translation. We investigated the potential reversal of autistic-like phenotypes in Eif4ebp2(-/-) mice by using antagonists of mGluR1 (JNJ16259685) or mGluR5 (fenobam). Augmented hippocampal mGluR-induced long-term depression (LTD; or chemically induced mGluR-LTD) in Eif4ebp2(-/-) mice was rescued by mGluR1 or mGluR5 antagonists. While rescue by mGluR5 inhibition occurs through the blockade of a protein synthesis-dependent component of LTD, normalization by mGluR1 antagonists requires the activation of protein synthesis. Synaptically induced LTD was deficient in Eif4ebp2(-/-) mice, and this deficit was not rescued by group I mGluR antagonists. Furthermore, a single dose of mGluR1 (0.3 mg/kg) or mGluR5 (3 mg/kg) antagonists in vivo reversed the deficits in social interaction and repetitive behaviors (marble burying) in Eif4ebp2(-/-) mice. Our results demonstrate that Eif4ebp2(-/-) mice serve as a relevant model to test potential therapies for ASD symptoms. In addition, we provide substantive evidence that the inhibition of mGluR1/mGluR5 is an effective treatment for physiological and behavioral alterations caused by exacerbated mRNA translation initiation. Exacerbated mRNA translation during brain development is associated with several autism spectrum disorders (ASDs). We recently demonstrated that the deletion of a negative regulator of mRNA translation initiation, the eukaryotic initiation factor 4E-binding protein 2, leads to ASD-like behaviors and increased excitatory synaptic activity. Here we demonstrated that autistic behavioral and electrophysiological phenotypes can be treated in adult mice with antagonists of group I metabotropic glutamate receptors (mGluRs), which have been previously used in other ASD models (i.e., fragile X syndrome). These findings support the use of group I mGluR antagonists as a potential therapy that extends to autism models involving exacerbated mRNA translation initiation. Copyright © 2015 the authors 0270-6474/15/3511126-08$15.00/0.

[Recovery in aphasia (Part 1)].

PubMed

Hojo, K; Watanabe, S; Tasaki, H; Sato, T; Metoki, H; Saito, M

1985-08-01

In order to elucidate the factors which have an influence on the prognosis of aphasia, a correlation was studied in 76 right-handed aphasic patients between recovery rates and various factors: i.e. aphasia type, age, educational level, time between onset of aphasia and institution of therapy and initial severity. Initial evaluations on Standard Language Test of Aphasia (SLTA) were obtained within 5 months after the cerebrovascular accident and reevaluations were obtained 3 months after the initial evaluation. Recovery rates were determined by comparing scores of these 2 tests in order to coincide with clinical impression. The results obtained were as follows: Aphasia type: The highest recovery rates were seen in conduction aphasics, followed by amnestic, Wernicke, and Broca aphasics. Global aphasics had significantly lower recovery rates. It was suggested that anarthria in Broca's aphasia and jargon in Wernicke's aphasia had a significant ratarding effect on recovery rates. Age: Age and recovery rates showed a significant negative correlation: younger patients recovered better, and this trend was remarkable in Wernicke aphasics but not Broca aphasics. Education: Patients with more education tended to improve more, and this trend was most remarkable in amnestic aphasics. Time between onset of aphasia and institution of therapy: Time elapsed from onset and recovery rates showed a significant negative correlation; recovery rates decreased as the time interval from onset increased. Initial severity: Correlation between the initial severity of aphasia, measured by the initial SLTA scores and recovery rates was very high; severily affected aphasics recovered to a lesser extent than mildly affected ones and this trend was remarkable in Wernicke and Broca aphasics.

Risk factors for lower limb injuries during initial naval training: a prospective study.

PubMed

Bonanno, Daniel R; Munteanu, S E; Murley, G S; Landorf, K B; Menz, H B

2018-04-06

This study aimed to identify risk factors associated with the development of common lower limb injuries during initial defence training in naval recruits who were enrolled in a randomised trial. Three-hundred and six naval recruits were randomly allocated flat insoles (n=153) or foot orthoses (n=153) while undertaking 11 weeks of initial training. Participant characteristics (including anthropometrics, general health, physical activity, fitness and foot characteristics) were collected at the baseline assessment and injuries were documented prospectively. Injury was defined as the combined incidence of participants with medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain throughout the 11 weeks of training. A discriminant function analysis was used to explore the ability of baseline measures to predict injury. Overall, 67 (21.9%) participants developed an injury. Discriminant function analysis revealed that participants who sustained an injury were slightly younger (mean 21.4±SD 4.1 vs 22.5±5.0 years) and were less likely to be allocated to the foot orthosis group (40% vs 53%) compared with those who remained uninjured. The accuracy of these baseline variables to predict injury was moderate (78.1%). Lower limb injury was not accurately predicted from health questionnaires, fitness results and clinical assessments in naval recruits undertaking initial defence training. However, although not reaching statistical significance, the use of foot orthoses may be protective against common lower limb injuries. ACTRN12615000024549; Post-results. © 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.

Predicting response to physiotherapy treatment for musculoskeletal shoulder pain: protocol for a longitudinal cohort study

PubMed Central

2013-01-01

Background Shoulder pain affects all ages, with a lifetime prevalence of one in three. The most effective treatment is not known. Physiotherapy is often recommended as the first choice of treatment. At present, it is not possible to identify, from the initial physiotherapy assessment, which factors predict the outcome of physiotherapy for patients with shoulder pain. The primary objective of this study is to identify which patient characteristics and baseline measures, typically assessed at the first physiotherapy appointment, are related to the functional outcome of shoulder pain 6 weeks and 6 months after starting physiotherapy treatment. Methods/Design Participants with musculoskeletal shoulder pain of any duration will be recruited from participating physiotherapy departments. For this longitudinal cohort study, the participants care pathway, including physiotherapy treatment will be therapist determined. Potential prognostic variables will be collected from participants during their first physiotherapy appointment and will include demographic details, lifestyle, psychosocial factors, shoulder symptoms, general health, clinical examination, activity limitations and participation restrictions. Outcome measures (Shoulder Pain and Disability Index, Quick Disability of the Arm, Shoulder and Hand, and Global Impression of Change) will be collected by postal self-report questionnaires 6 weeks and 6 months after commencing physiotherapy. Details of attendance and treatment will be collected by the treating physiotherapist. Participants will be asked to complete an exercise dairy. An initial exploratory analysis will assess the relationship between potential prognostic factors at baseline and outcome using univariate statistical tests. Those factors significant at the 5% level will be further considered as prognostic factors using a general linear model. It is estimated that 780 subjects will provide more than 90% power to detect an effect size of less than 0.25 adjusted for other variables which have a co-efficient of determination (R-squared) with the outcome of up to 0.5. Assuming a 22% loss to follow up at 6 months, 1000 participants will initially be recruited. Discussion This study may offer service users and providers with guidance to help identify whether or not physiotherapy is likely to be of benefit. Clinicians may have some direction as to what key factors indicate a patient’s likely response to physiotherapy. PMID:23800352

Risk factors for venous port migration in a single institute in Taiwan.

PubMed

Fan, Wen-Chieh; Wu, Cheng-Han; Tsai, Ming-Ju; Tsai, Ying-Ming; Chang, Hsu-Liang; Hung, Jen-Yu; Chen, Pei-Huan; Yang, Chih-Jen

2014-01-14

An implantable port device provides an easily accessible central route for long-term chemotherapy. Venous catheter migration is one of the rare complications of venous port implantation. It can lead to side effects such as pain in the neck, shoulder, or ear, venous thrombosis, and even life-threatening neurologic problems. To date, there are few published studies that discuss such complications. This retrospective study of venous port implantation in a single center, a Taiwan hospital, was conducted from January 2011 to March 2013. Venous port migration was recorded along with demographic and characteristics of the patients. Of 298 patients with an implantable import device, venous port migration had occurred in seven, an incidence rate of 2.3%. All seven were male and had received the Bard port Fr 6.6 which had smaller size than TYCO port Fr 7.5 and is made of silicon. Significantly, migration occurred in male patients (P = 0.0006) and in those with lung cancer (P = 0.004). Multivariable logistic regression analysis revealed that lung cancer was a significant risk factor for port migration (odds ratio: 11.59; P = 0.0059). The migration rate of the Bard port Fr 6.6 was 6.7%. The median time between initial venous port implantation and port migration was 35.4 days (range, 7 to 135 days) and 71.4% (5/7) of patients had port migration within 30 days after initial port implantation. Male sex and lung cancer are risk factors for venous port migration. The type of venous port is also an important risk factor.

Barriers to access to treatment for mothers with postpartum depression in primary health care centers: a predictive model1

PubMed Central

Martínez, Pablo; Vöhringer, Paul A.; Rojas, Graciela

2016-01-01

Objective to develop a predictive model to evaluate the factors that modify the access to treatment for Postpartum Depression (PPD). Methods prospective study with mothers who participated in the monitoring of child health in primary care centers. For the initial assessment and during 3 months, it was considered: sociodemographic data, gyneco-obstetric data, data on the services provided, depressive symptoms according to the Edinburgh Postpartum Depression Scale (EPDS) and quality of life according to the Short Form-36 Health Status Questionnaire (SF-36). The diagnosis of depression was made based on MINI. Mothers diagnosed with PPD in the initial evaluation, were followed-up. Results a statistical model was constructed to determine the factors that prevented access to treatment, which consisted of: item 2 of EPDS (OR 0.43, 95%CI: 0.20-0.93) and item 5 (OR 0.48, 95%CI: 0.21-1.09), and previous history of depression treatment (OR 0.26, 95%CI: 0.61-1.06). Area under the ROC curve for the model=0.79; p-value for the Hosmer-Lemershow=0.73. Conclusion it was elaborated a simple, well standardized and accurate profile, which advises that nurses should pay attention to those mothers diagnosed with PPD, presenting low/no anhedonia (item 2 of EPDS), scarce/no panic/fear (item 5 of EPDS), and no history of depression, as it is likely that these women do not initiate treatment. PMID:27027674

Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.

PubMed

Kim, Soo-Jeong; Cheong, June-Won; Min, Yoo Hong; Choi, Young Jin; Lee, Dong-Gun; Lee, Je-Hwan; Yang, Deok-Hwan; Lee, Sang Min; Kim, Sung-Hyun; Kim, Yang Soo; Kwak, Jae-Yong; Park, Jinny; Kim, Jin Young; Kim, Hoon-Gu; Kim, Byung Soo; Ryoo, Hun-Mo; Jang, Jun Ho; Kim, Min Kyoung; Kang, Hye Jin; Cho, In Sung; Mun, Yeung Chul; Jo, Deog-Yeon; Kim, Ho Young; Park, Byeong-Bae; Kim, Jin Seok

2014-01-01

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa.

PubMed

Asiimwe, Stephen B; Kanyesigye, Michael; Bwana, Bosco; Okello, Samson; Muyindike, Winnie

2016-02-01

In sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up. In a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05. Data from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4% had CD4+ T-cell counts <100 cells/μL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9% (established cumulative mortality = 2.3%, loss to follow-up = 24.6%), 5.6% were transferred to other service providers, and 67.5% were retained in care. A diagnosis of Kaposi's sarcoma (hazard ratio (HR) = 3.3, 95% CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95% CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95% CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95% CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10%; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status. Among HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

Child, family, and neighborhood associations with parent and peer interactive play during early childhood.

PubMed

Kenney, Mary Kay

2012-04-01

To examine national patterns of peer and parent interactive play opportunities that enhance early learning/socialization. Bivariate and multivariable analyses of cross-sectional data on 22,797 children aged 1-5 years from the National Survey of Children's Health 2007 were performed to determine the child, family, and neighborhood factors associated with four parent-initiated activities. Outcomes measures included time (days/week) children spent: participating in peer play; being read to; sung to/told stories; and taken on family outings. Covariates included race/ethnicity, poverty, TV watching, childcare, child and maternal physical and mental health, family factors (structure, size, language, stress, education), and neighborhood factors (amenities, support, physical condition, safety). According to adjusted regression models, minority children from lower income, non-English-speaking households with limited education, poorer maternal health and greater parenting stress were read to/told stories less than children without these characteristics, while neighborhood factors exerted less influence. In contrast, significant reductions in days/week of peer play were associated with unsupportive neighborhoods and those with the poorest physical conditions and limited amenities. Likewise, reductions in outings were associated with fewer neighborhood amenities. The findings of this study indicate that a variety of child, family, and neighborhood factors are associated with parent-initiated behaviors such as reading, storytelling, peer interactive play, and family outings. Appropriate evidence-based home visiting interventions targeting child health, parenting skills, early childhood education, and social services in at-risk communities would appear to be appropriate vehicles for addressing such parent-initiated play activities that have the potential to enhance development.

Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

PubMed

Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

2016-01-01

Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism.

PubMed

Bongers-Schokking, Jacoba J; de Muinck Keizer-Schrama, Sabine M P F

2005-12-01

To evaluate the influence of initial and postinitial treatment factors on cognitive, psychomotor, and psychological outcome in schoolchildren with congenital hypothyroidism (CH). We studied 45 patients (19 with severe CH and 26 with mild CH) and 37 control children by correlating initial and postinitial treatment factors (free thyroxine and thyroid-stimulating hormone [TSH] concentrations, and the percentage of overtreatment and undertreatment periods) with the results of neuropsychological tests and behavior (as reported on the Teacher Report Form [TRF]). The global IQ of the children with CH was comparable to that of the controls; visuomotor and verbal scores were lower, and total TRF scores were higher. Ethnic group, previous development, and overtreatment predicted IQ and verbal scores, with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated. As initial treatment was less satisfactory, total TRF scores were higher. Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields. Overtreatment may advance cognitive development in 5-1/2- to 7-year-olds. Suboptimal initial treatment may lead to behavioral problems. We recommend that TSH concentrations be maintained within the normal range in patients with CH.

Ethylene-responsive element-binding factor 5, ERF5, is involved in chitin-induced innate immunity response.

PubMed

Son, Geon Hui; Wan, Jinrong; Kim, Hye Jin; Nguyen, Xuan Canh; Chung, Woo Sik; Hong, Jong Chan; Stacey, Gary

2012-01-01

Our recent work demonstrated that chitin treatment modulated the expression of 118 transcription factor (TF) genes in Arabidopsis. To investigate the potential roles of these TF in chitin signaling and plant defense, we initiated an interaction study among these TF proteins, as well as two chitin-activated mitogen-activated protein kinases (MPK3 and MPK6), using a yeast two-hybrid system. This study revealed interactions among the following proteins: three ethylene-responsive element-binding factors (ERF), five WRKY transcription factors, one scarecrow-like (SCL), and the two MPK, in addition to many other interactions, reflecting a complex TF interaction network. Most of these interactions were subsequently validated by other methods, such as pull-down and in planta bimolecular fluorescence complementation assays. The key node ERF5 was shown to interact with multiple proteins in the network, such as ERF6, ERF8, and SCL13, as well as MPK3 and MPK6. Interestingly, ERF5 appeared to negatively regulate chitin signaling and plant defense against the fungal pathogen Alternaria brassicicola and positively regulate salicylic acid signaling and plant defense against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Therefore, ERF5 may play an important role in plant innate immunity, likely through coordinating chitin and other defense pathways in plants in response to different pathogens.

The impact of baseline hemoglobin A1c levels prior to initiation of pump therapy on long-term metabolic control.

PubMed

Pinhas-Hamiel, Orit; Tzadok, Michal; Hirsh, Galit; Boyko, Valentina; Graph-Barel, Chana; Lerner-Geva, Liat; Reichman, Brian

2010-07-01

This study was done to identify factors influencing long-term metabolic control in youth with type 1 diabetes mellitus (T1DM) treated with an insulin pump. Data were obtained from retrospective chart review of 113 patients (52 males) with T1DM treated with an insulin pump for up to 7 years. Their mean +/- SD age at diagnosis of T1DM was 9.7 +/- 5.1 years, and that at pump therapy initiation was 13.8 +/- 6.1 years. Linear trends and changes in hemoglobin A1c (HbA1c) levels following pump insertion were evaluated according to gender, metabolic control prior to initiation of pump therapy, time from diagnosis of diabetes until pump therapy, age at initiation, and the duration of pump treatment. Mean HbA1c levels of patients with good baseline metabolic control (HbA1c level 9%) control groups (8.1 +/- 0.9% and 8.2 +/- 1.1%, respectively; P < 0.001). However, with time a significant trend for increasing HbA1c level was demonstrated in the group with good metabolic control (P value for trend = 0.004). HbA1c levels of patients with poor baseline metabolic control decreased significantly immediately after pump initiation (9.4 +/- 1.6% vs. 8.0 +/- 1.2%, P = 0.0001) and thereafter remained stable (P value for trend = 0.54). In the multivariable analyses, baseline HbA1c level

Skin and soft-tissue infections: Factors associated with mortality and re-admissions.

PubMed

Macía-Rodríguez, Cristina; Alende-Castro, Vanesa; Vazquez-Ledo, Lourdes; Novo-Veleiro, Ignacio; González-Quintela, Arturo

2017-02-01

Skin and soft-tissue infections (SSTIs) are common and are linked to a wide variety of clinical conditions. Few studies have analysed the factors associated with mortality and re-admissions in medical patients with SSTIs. Accordingly, this study sought to describe the clinical and microbiological characteristics of patients diagnosed with SSTIs, and identify mortality and re-admission related factors. A total of 308 patients were included in the study. Clinical, socio-demographic and microbiological characteristics were collected. Univariate and logistic regression multivariate analyses were performed in order to identify factors associated with mortality and re-admission. The bacteria responsible were identified in 95 (30.8%) patients, with gram-positive bacteria being isolated in 67.4% and gram-negative in 55.8% of cases. Multi-resistant bacteria were frequent (39%), and the initial empirical treatment proved inadequate in 25.3% of all cases. In-hospital mortality was 14.9%; the related variables were heart failure (OR=5.96; 95%CI: 1.93-18.47), chronic renal disease (OR=6.04; 95%CI: 1.80-20.22), necrotic infection (OR=4.33; 95%CI: 1.26-14.95), and inadequate empirical treatment (OR=44.74; 95%CI: 5.40-370.73). Six-month mortality was 8%, with the main related factors being chronic renal disease (OR: 3.03; 95%CI: 1.06-8.66), and a Barthel Index score of under 20 (OR: 3.62; 95%CI: 1.17-11.21). Re-admission was necessary in 26.3% of cases, with the readmission-related variables being male gender (OR: 2.12; 95%CI: 1.14-3.94), peripheral vascular disease (OR: 3.05; 95%CI: 1.25-7.41), and an age-adjusted Charlson Comorbidity Index score of over 3 (OR: 3.27; 95%CI: 1.40-7.63). Clinical variables such as heart failure, chronic renal disease, peripheral vascular disease, and necrotic infection could help identify high-risk patients. The main factor associated with higher mortality was inadequate initial empirical treatment. Physicians should consider gram-negative, and even extended-spectrum beta-lactamase-producing bacteria when assigning initial empirical treatment for SSTIs, especially in healthcare-associated cases. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Factors associated with difficulty achieving initial control with crotalidae polyvalent immune fab antivenom in snakebite patients.

PubMed

Yin, Shan; Kokko, Jamie; Lavonas, Eric; Mlynarchek, Sara; Bogdan, Greg; Schaeffer, Tammi

2011-01-01

The prescribing information for Crotalidae Fab antivenom (FabAV) instructs clinicians to administer FabAV until initial control of the envenomation syndrome is achieved. Risk factors for difficulty achieving initial control are not known. The study aim was to identify factors present before administration of antivenom associated with difficulty achieving initial control. The authors conducted a retrospective study of all patients presenting to any one of 17 centers and receiving FabAV from 2002 to 2004. Demographic and historical information, as well as data about nine specific venom effects, were collected prior to the administration of antivenom. An expert panel used standard criteria to determine if initial control was achieved. The patient group that had difficulty achieving initial control was compared to the group that achieved initial control, and adjusted odds ratios were calculated using stepwise logistic regression. A total of 247 patients were included in the final analysis. The majority of patients were envenomated on the upper extremity and were young males. A total of 203 patients (82.2%) achieved initial control. In univariate analysis, thrombocytopenia, bleeding, neurologic effects, and a severe bite were significantly associated with difficulty achieving initial control. After logistic regression, the presence of neurologic effects and thrombocytopenia remained significantly associated with difficulty achieving initial control. When both factors were present, the patient was 13.8 times more likely to have difficulty achieving initial control. A number of factors were present before the administration of FabAV that were independently associated with difficulty achieving initial control of the envenomation syndrome. Predicting which patients will have difficulty achieving initial control has important ramifications for patient disposition and may provide insight into the mechanisms for lack of antivenom efficacy. © 2010 by the Society for Academic Emergency Medicine.

TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes

PubMed Central

Ryu, Jihye

2017-01-01

Transmembrane 4 L six family member 5 (TM4SF5) can form tetraspanin-enriched microdomains (TERMs) on the cell's surface. TERMs contain protein-protein complexes comprised of tetraspanins, growth factor receptors, and integrins. These complexes regulate communication between extracellular and intracellular spaces to control diverse cellular functions. TM4SF5 influences the epithelial-mesenchymal transition (EMT), aberrant multilayer cellular growth, drug resistance, enhanced migration and invasion, circulation through the bloodstream, tumor-initiation property, metastasis, and muscle development in zebrafish. Here, current data on TM4SF5's roles in the development of fibrotic phenotypes are reviewed. TM4SF5 is induced by transforming growth factor β1 (TGFβ1) signaling via a collaboration with epidermal growth factor receptor (EGFR) activation. TM4SF5, by itself or in concert with other receptors, transduces signals intracellularly. In hepatocytes, TM4SF5 expression regulates cell cycle progression, migration, and expression of extracellular matrix components. In CCl4-treated mice, TM4SF5, α-smooth muscle actin (α-SMA), and collagen I expression are observed together along the fibrotic septa regions of the liver. These fibrotic phenotypes are diminished by anti-TM4SF5 reagents, such as a specific small compound [TSAHC, 4′-(p-toluenesulfonylamido)-4-hydroxychalcone] or a chimeric antibody. This review discusses the antifibrotic strategies that target TM4SF5 and its associated protein networks that regulate the intracellular signaling necessary for fibrotic functions of hepatocytes. PMID:28458469

Differential uptake of recent Papanicolaou testing by HPV vaccination status among young women in the United States, 2008-2013.

PubMed

Sauer, Ann Goding; Jemal, Ahmedin; Simard, Edgar P; Fedewa, Stacey A

2015-08-01

A positive association between recent Papanicolaou (Pap) test uptake and initiation of HPV vaccination among U.S. women has been reported. However, it is unknown whether recent Pap testing by HPV vaccination status varies by race/ethnicity. Discerning racial/ethnic variations is important given the higher prevalence of HPV types other than 16 and 18 in some racial/ethnic groups. We assessed whether uptake of recent Pap testing differed among women aged 21-30 years who had not initiated the HPV vaccination series versus those who had and whether this pattern differed by sociodemographic factors. 2008, 2010, and 2013 National Health Interview Survey data were used to generate weighted prevalence estimates and 95% confidence intervals (CIs) (n=7095). Adjusted predicted marginal models were used to generate adjusted prevalence ratios (aPRs) to assess the relationship between recent Pap test uptake and HPV vaccination series initiation by race/ethnicity. The uptake of recent Pap testing among those who had not initiated the HPV vaccination series was significantly lower (81.0%) compared to those who had initiated vaccination (90.5%) (aPR=0.93, 95% CI: 0.90-0.96). This finding was consistent across most sociodemographic factors, though not statistically significant for Blacks, Hispanics, those with lower levels of education, or those with higher levels of income. Young women who had not initiated HPV vaccination were less likely to have had a recent Pap test compared to women who had initiated vaccination. Concerted efforts are needed to increase uptake of recommended cervical cancer screening and HPV vaccination among young women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Weed species composition and distribution pattern in the maize crop under the influence of edaphic factors and farming practices: A case study from Mardan, Pakistan.

PubMed

Ahmad, Zeeshan; Khan, Shujaul Mulk; Abd Allah, Elsayed Fathi; Alqarawi, Abdulaziz Abdullah; Hashem, Abeer

2016-11-01

Weeds are unwanted plant species growing in ordinary environment. In nature there are a total of 8000 weed species out of which 250 are important for agriculture world. The present study was carried out on weed species composition and distribution pattern with special reference to edaphic factor and farming practices in maize crop of District Mardan during the months of August and September, 2014. Quadrates methods were used to assess weed species distribution in relation to edaphic factor and farming practices. Phytosociological attributes such as frequency, relative frequency, density, relative density and Importance Values were measured by placing 9 quadrates (1 × 1 m 2 ) randomly in each field. Initial results showed that the study area has 29 diverse weed species belonging to 27 genera and 15 families distributed in 585 quadrats. Presence and absence data sheet of 29 weed species and 65 fields were analyzed through PC-ORD version 5. Cluster and Two Way Cluster Analyses initiated four different weed communities with significant indicator species and with respect to underlying environmental variables using data attribute plots. Canonical Correspondence Analyses (CCA) of CANOCO software version 4.5 was used to assess the environmental gradients of weed species. It is concluded that among all the edaphic factors the strongest variables were higher concentration of potassium, organic matter and sandy nature of soil. CCA plots of both weed species and sampled fields based on questionnaire data concluded the farming practices such as application of fertilizers, irrigation and chemical spray were the main factors in determination of weed communities.

Defects in tRNA processing and nuclear export induce GCN4 translation independently of phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2.

PubMed

Qiu, H; Hu, C; Anderson, J; Björk, G R; Sarkar, S; Hopper, A K; Hinnebusch, A G

2000-04-01

Induction of GCN4 translation in amino acid-starved cells involves the inhibition of initiator tRNA(Met) binding to eukaryotic translation initiation factor 2 (eIF2) in response to eIF2 phosphorylation by protein kinase GCN2. It was shown previously that GCN4 translation could be induced independently of GCN2 by overexpressing a mutant tRNA(AAC)(Val) (tRNA(Val*)) or the RNA component of RNase MRP encoded by NME1. Here we show that overexpression of the tRNA pseudouridine 55 synthase encoded by PUS4 also leads to translational derepression of GCN4 (Gcd(-) phenotype) independently of eIF2 phosphorylation. Surprisingly, the Gcd(-) phenotype of high-copy-number PUS4 (hcPUS4) did not require PUS4 enzymatic activity, and several lines of evidence indicate that PUS4 overexpression did not diminish functional initiator tRNA(Met) levels. The presence of hcPUS4 or hcNME1 led to the accumulation of certain tRNA precursors, and their Gcd(-) phenotypes were reversed by overexpressing the RNA component of RNase P (RPR1), responsible for 5'-end processing of all tRNAs. Consistently, overexpression of a mutant pre-tRNA(Tyr) that cannot be processed by RNase P had a Gcd(-) phenotype. Interestingly, the Gcd(-) phenotype of hcPUS4 also was reversed by overexpressing LOS1, required for efficient nuclear export of tRNA, and los1Delta cells have a Gcd(-) phenotype. Overproduced PUS4 appears to impede 5'-end processing or export of certain tRNAs in the nucleus in a manner remedied by increased expression of RNase P or LOS1, respectively. The mutant tRNA(Val*) showed nuclear accumulation in otherwise wild-type cells, suggesting a defect in export to the cytoplasm. We propose that yeast contains a nuclear surveillance system that perceives defects in processing or export of tRNA and evokes a reduction in translation initiation at the step of initiator tRNA(Met) binding to the ribosome.

Defects in tRNA Processing and Nuclear Export Induce GCN4 Translation Independently of Phosphorylation of the α Subunit of Eukaryotic Translation Initiation Factor 2

PubMed Central

Qiu, Hongfang; Hu, Cuihua; Anderson, James; Björk, Glenn R.; Sarkar, Srimonti; Hopper, Anita K.; Hinnebusch, Alan G.

2000-01-01

Induction of GCN4 translation in amino acid-starved cells involves the inhibition of initiator tRNAMet binding to eukaryotic translation initiation factor 2 (eIF2) in response to eIF2 phosphorylation by protein kinase GCN2. It was shown previously that GCN4 translation could be induced independently of GCN2 by overexpressing a mutant tRNAAACVal (tRNAVal*) or the RNA component of RNase MRP encoded by NME1. Here we show that overexpression of the tRNA pseudouridine 55 synthase encoded by PUS4 also leads to translational derepression of GCN4 (Gcd− phenotype) independently of eIF2 phosphorylation. Surprisingly, the Gcd− phenotype of high-copy-number PUS4 (hcPUS4) did not require PUS4 enzymatic activity, and several lines of evidence indicate that PUS4 overexpression did not diminish functional initiator tRNAMet levels. The presence of hcPUS4 or hcNME1 led to the accumulation of certain tRNA precursors, and their Gcd− phenotypes were reversed by overexpressing the RNA component of RNase P (RPR1), responsible for 5′-end processing of all tRNAs. Consistently, overexpression of a mutant pre-tRNATyr that cannot be processed by RNase P had a Gcd− phenotype. Interestingly, the Gcd− phenotype of hcPUS4 also was reversed by overexpressing LOS1, required for efficient nuclear export of tRNA, and los1Δ cells have a Gcd− phenotype. Overproduced PUS4 appears to impede 5′-end processing or export of certain tRNAs in the nucleus in a manner remedied by increased expression of RNase P or LOS1, respectively. The mutant tRNAVal* showed nuclear accumulation in otherwise wild-type cells, suggesting a defect in export to the cytoplasm. We propose that yeast contains a nuclear surveillance system that perceives defects in processing or export of tRNA and evokes a reduction in translation initiation at the step of initiator tRNAMet binding to the ribosome. PMID:10713174

Molecular analysis of the human SLC13A4 sulfate transporter gene promoter

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

Jefferis, J.; Rakoczy, J.; School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland

2013-03-29

Highlights: ► Basal promoter activity of SLC13A4 −57 to −192 nt upstream of transcription initiation site. ► Human SLC13A4 5′-flanking region has conserved motifs with other placental species. ► Putative NFY, SP1 and KLF7 motifs in SLC13A4 5′-flanking region enhance transcription. -- Abstract: The human solute linked carrier (SLC) 13A4 gene is primarily expressed in the placenta where it is proposed to mediate the transport of nutrient sulfate from mother to fetus. The molecular mechanisms involved in the regulation of SLC13A4 expression remain unknown. To investigate the regulation of SLC13A4 gene expression, we analysed the transcriptional activity of the humanmore » SLC13A4 5′-flanking region in the JEG-3 placental cell line using luciferase reporter assays. Basal transcriptional activity was identified in the region −57 to −192 nucleotides upstream of the SLC13A4 transcription initiation site. Mutational analysis of the minimal promoter region identified Nuclear factor Y (NFY), Specificity protein 1 (SP1) and Krüppel like factor 7 (KLF7) motifs which conferred positive transcriptional activity, as well as Zinc finger protein of the cerebellum 2 (ZIC2) and helix–loop–helix protein 1 (HEN1) motifs that repressed transcription. The conserved NFY, SP1, KLF7, ZIC2 and HEN1 motifs in the SLC13A4 promoter of placental species but not in non-placental species, suggests a potential role for these putative transcriptional factor binding motifs in the physiological control of SLC13A4 mRNA expression.« less

State, Foreign Operations, and Related Programs: FY2009 Appropriations

DTIC Science & Technology

2008-08-21

upgrades, and to include several factors (including political, security, social environment, and best ways to engage local populations) in designing...demonstrated a strong commitment to political, economic, and social reforms. The President initially promised $5 billion annually by FY2006...services, including Cantonese , Ukrainian, Tibetan, Portuguese to Africa, Romanian, and Kazakh, as well as broadcasts in Hindi, Russian, English

Foreign Aid to Education: Recent U.S. Initiatives--Background, Risks, and Prospects

ERIC Educational Resources Information Center

Heyneman, Stephen P.

2005-01-01

The Millennium Challenge Account (MCA) is a commitment of the United States to raise its grant aid by a factor of 50% over the next 3 years and will result in a $5 billion annual increase over current foreign aid levels. Many other countries and multinational development assistance agencies will be asked to help co-finance this new account, and…

Unique Challenges to Preventing Perinatal HIV Transmission among Hispanic Women in California: Results of a Needs Assessment

ERIC Educational Resources Information Center

Kropp, Rhonda Y.; Montgomery, Elizabeth T.; Hill, David W.; Ruiz, Juan D.; Maldonado, Yvonne A.

2005-01-01

To identify rates and factors associated with timely prenatal care (PNC) initiation, HIV test counseling, test offering, and test offer acceptance, we conducted a semistructured survey of a convenience sample of pregnant/recently delivered Hispanic women (n = 453, 418 with analyzable data) in four California counties in 2000. Only 68.4% and 43.5%…

Effects of listricity on near field ground motions: the kinematic case

NASA Astrophysics Data System (ADS)

Passone, Luca; Mai, P. Martin

2016-04-01

Listric faults are defined as curved faults in which the dip decreases with depth, resulting in a concave upwards shape. Previous works show that breaking the symmetry of faults affects rupture dynamics and near field ground motions (e.g. Oglesby et al., 1998; Nielsen, 1998; Oglesby et al., 2000b; O'Connell et al. 2007). In recent years listric faults have been associated with devastating events, such as the 2008 Mw 7.9 Wenchuan earthquake that caused almost 150 billion of damage, and the 1999 Mw 7.6 Chi- Chi earthquake that caused 10 billion worth of damage, each of them responsible also for tens of thousands of injured and dead. We focus on quantifying near field ground motions as a function of initial dip, style (normal or reverse) and a listricity. To construct a listric profile for the simulations we use an exponential function (Wang et al., 2009) that approximates the dip angle for a certain depth as a function of the depth itself, the initial dip angle and a listricity factor. We then generate an ensemble of source models, with initial dip ranging from 10 to 90 degrees and a listricity factor from 5 to 20. Finally, heterogeneous slip distributions are created for a magnitude Mw 6.8 earthquake. Choosing different hypocenter locations and rupture velocities, we construct a range of kinematic source models that are resolved on both the listric and planar-fault geometry. We then compute the near-source seismic wavefield within a uniform isotropic medium using a generalized 3D finite-difference method. The listric and planar simulations are then compared, and their differences quantified. Initial results show a secondary directivity effect once the listricity factor exceeds 10 for the larger initial dip faults, thus inducing a change in the azimuthal angle with respect of the epicenter where peak ground motions are experienced. At the same time, overall PGV values are decreased, more so for geometries with higher listricity factors. With the knowledge acquired, a ground motion reduction factor can be applied to ground motion prediction equations when the fault is considered to be listric and hazard maps should re-adjusted to cater for the relocation of peak ground motions due to directivity effects.

Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A

PubMed Central

Virgili, Geneviève; Frank, Filipp; Feoktistova, Kateryna; Sawicki, Maxime; Sonenberg, Nahum; Fraser, Christopher S.; Nagar, Bhushan

2013-01-01

Summary Death-associated protein 5 (DAP5/p97) is a homolog of the eukaryotic initiation factor 4G (eIF4G) that promotes the IRES-driven translation of multiple cellular mRNAs. Central to its function is the middle domain (MIF4G), which recruits the RNA helicase eIF4A. The middle domain of eIF4G consists of tandem HEAT repeats that coalesce to form a solenoid-type structure. Here, we report the crystal structure of the DAP5 MIF4G domain. Its overall fold is very similar to that of eIF4G, however, significant conformational variations impart distinct surface properties that could explain the observed differences in IRES binding between the two proteins. Interestingly, quantitative analysis of the DAP5-eIF4A interaction using isothermal titration calorimetry reveals a 10-fold lower affinity than with the eIF4G-eIF4A interaction that appears to affect their ability to stimulate eIF4A RNA unwinding activity in vitro. This difference in stability of the complex may have functional implications in selecting the mode of translation initiation. PMID:23478064

Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases.

PubMed

Bonin, Lucie; Pedreiro, Cécile; Moret, Stéphanie; Chene, Gautier; Gaucherand, Pascal; Lamblin, Géry

2017-01-01

We sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort. For this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure. Between February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%. In this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Protein arginine methyltransferase 5 is an essential component of the hypoxia-inducible factor 1 signaling pathway

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

Lim, Ji-Hong; Choi, Yong-Joon; Cho, Chung-Hyun

2012-02-10

Highlights: Black-Right-Pointing-Pointer HIF-1{alpha} is expressed PRMT5-dependently in hypoxic cancer cells. Black-Right-Pointing-Pointer The HIF-1 regulation of hypoxia-induced genes is attenuated in PRMT5-knocked-down cells. Black-Right-Pointing-Pointer The de novo synthesis of HIF-1{alpha} depends on PRMT5. Black-Right-Pointing-Pointer PRMT5 is involved in the HIF-1{alpha} translation initiated by 5 Prime UTR of HIF-1{alpha} mRNA. -- Abstract: Protein arginine methyltransferase 5 (PRMT5) is an enzyme that transfers one or two methyl groups to the arginine residues of histones or non-histone proteins, and that plays critical roles in cellular processes as diverse as receptor signaling and gene expression. Furthermore, PRMT5 is highly expressed in tumors, where it maymore » be associated with tumor growth. Although much research has been conducted on PRMT5, little is known regarding its role in adaption to hypoxia. As hypoxia-inducible factor 1 (HIF-1) is a key player in hypoxic response, we examined the possible involvement of PRMT5 in the HIF-1 signaling pathway. Of the siRNAs targeting PRMT1-8, only PRMT5 siRNA attenuated the hypoxic induction of HIF-1{alpha} in A549 cells, and this result was reproducible in all three cancer cell lines examined. PRMT5 knock-down also repressed the promoter activities and the transcript levels of HIF-1-governed genes. Mechanistically, de novo synthesis of HIF-1{alpha} protein was reduced in PRMT5-knocked-down A549 cells, and this was rescued by PRMT5 restoration. In contrast, HIF-1{alpha} transcription, RNA processing, and protein stability were unaffected by PRMT5 knock-down. Furthermore, PRMT5 was found to be essential for the HIF-1{alpha} translation initiated by the 5 Prime UTR of HIF-1{alpha} mRNA. Given our results and previous reports, we believe that PRMT5 probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF-1 activation.« less

Salvage Radiosurgery for Brain Metastases: Prognostic Factors to Consider in Patient Selection

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

Kurtz, Goldie; Zadeh, Gelareh; Gingras-Hill, Geneviève

2014-01-01

Purpose: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. Methods and Materials: This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate andmore » multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. Results: There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI] = 4.9-7.6). Median OS was 11.7 months (95% CI = 8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI = 18.4-26.8). On MVA, age (P=.01; hazard ratio [HR] = 1.04; 95% CI = 1.01-1.07), extracranial disease control (P=.004; HR = 0.46; 95% CI = 0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR = 2.46; 95% CI = 1.47-4.09) were predictive of OS. Conclusions: This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.« less

RNA Initiation with Dinucleoside Monophosphates during Transcription of Bacteriophage T4 DNA with RNA Polymerase of Escherichia coli

PubMed Central

Hoffman, David J.; Niyogi, Salil K.

1973-01-01

The effects of dinucleoside monophosphates on the transcription of phage T4 DNA by E. coli RNA polymerase have been examined at various concentrations of the sigma subunit and extremely low concentration of ribonucleoside triphosphate. The following conclusions were reached: (i) Labeled specific dinucleoside monophosphates are incorporated as chain initiators. (ii) When the ratio of sigma factor to core enzyme is small, there is a general stimulation by most 5′-guanosyl dinucleoside monophosphates. (iii) When the ratio is increased or holoenzyme is present, ApU, CpA, UpA, and GpU are the most effective stimulators. (iv) At high concentrations of sigma factor, only certain adenosine-containing dinucleoside monophosphates (ApU, CpA, UpA, and ApA) stimulate the reaction. (v) Competition hybridization studies indicate that the RNAs stimulated by dinucleoside monophosphates (ApU, CpA, UpA, and GpU) are of the T4 “early” type. (vi) Studies involving both combinations of stimulatory dinucleoside monophosphates and competitive effects of these compounds on chain initiation by ATP and GTP suggest that the stimulatory dinucleoside monophosphates act as chain initiators and may recognize part of a continuous sequence in a promoter region. Studies based on the incorporation of 3H-labeled stimulatory dinucleoside monophosphates support the above conclusions. PMID:4568732

Controlled breathing with or without peppermint aromatherapy for postoperative nausea and/or vomiting symptom relief: a randomized controlled trial.

PubMed

Sites, Debra S; Johnson, Nancy T; Miller, Jacqueline A; Torbush, Pauline H; Hardin, Janis S; Knowles, Susan S; Nance, Jennifer; Fox, Tara H; Tart, Rebecca Creech

2014-02-01

With little scientific evidence to support use of aromatherapy for postoperative nausea and/or vomiting (PONV) symptoms, this study evaluated controlled breathing with peppermint aromatherapy (AR) and controlled breathing alone (CB) for PONV relief. A single blind randomized control trial design was used. On initial PONV complaint, symptomatic subjects received either CB (n = 16) or AR (n = 26) intervention based on randomization at enrollment. A second treatment was repeated at 5 minutes if indicated. Final assessment occurred 10 minutes post initial treatment. Rescue medication was offered for persistent symptoms. Among eligible subjects, PONV incidence was 21.4% (42/196). Gender was the only risk factor contributing to PONV symptoms (P = .0024). Though not statistically significant, CB was more efficacious than AR, 62.5% versus 57.7%, respectively. CB can be initiated without delay as an alternative to prescribed antiemetics. Data also support use of peppermint AR in conjunction with CB for PONV relief. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

The influence of total solids content and initial pH on batch biohydrogen production by solid substrate fermentation of agroindustrial wastes.

PubMed

Robledo-Narváez, Paula N; Muñoz-Páez, Karla M; Poggi-Varaldo, Hector M; Ríos-Leal, Elvira; Calva-Calva, Graciano; Ortega-Clemente, L Alfredo; Rinderknecht-Seijas, Noemí; Estrada-Vázquez, Carlos; Ponce-Noyola, M Teresa; Salazar-Montoya, J Alfredo

2013-10-15

Hydrogen is a valuable clean energy source, and its production by biological processes is attractive and environmentally sound and friendly. In México 5 million tons/yr of agroindustrial wastes are generated; these residues are rich in fermentable organic matter that can be used for hydrogen production. On the other hand, batch, intermittently vented, solid substrate fermentation of organic waste has attracted interest in the last 10 years. Thus the objective of our work was to determine the effect of initial total solids content and initial pH on H2 production in batch fermentation of a substrate that consisted of a mixture of sugarcane bagasse, pineapple peelings, and waste activated sludge. The experiment was a response surface based on 2(2) factorial with central and axial points with initial TS (15-35%) and initial pH (6.5-7.5) as factors. Fermentation was carried out at 35 °C, with intermittent venting of minireactors and periodic flushing with inert N2 gas. Up to 5 cycles of H2 production were observed; the best treatment in our work showed cumulative H2 productions (ca. 3 mmol H2/gds) with 18% and 6.65 initial TS and pH, respectively. There was a significant effect of TS on production of hydrogen, the latter decreased with initial TS increase from 18% onwards. Cumulative H2 productions achieved in this work were higher than those reported for organic fraction of municipal solid waste (OFMSW) and mixtures of OFMSW and fruit peels waste from fruit juice industry, using the same process. Specific energetic potential due to H2 in our work was attractive and fell in the high side of the range of reported results in the open literature. Batch dark fermentation of agrowastes as practiced in our work could be useful for future biorefineries that generate biohydrogen as a first step and could influence the management of this type of agricultural wastes in México and other countries and regions as well. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does the circadian pattern for acute cardiac events presentation vary with fasting?

PubMed

Al Suwaidi, J; Bener, A; Gehani, A A; Behair, S; Al Mohanadi, D; Salam, A; Al Binali, H A

2006-01-01

Over one billion Muslims fast worldwide during the month of Ramadan. The impact of fasting on circadian presentation with acute cardiac events is unknown. To determine if fasting has any effect on the circadian presentation of acute cardiac events. A prospective study in a general hospital. Patients with acute coronary events were divided into two groups based on the history of fasting. Information about age, gender, cardiovascular risk factor profiles and outcome was collected. The relationship of time of presentation of initial symptoms with fasting was evaluated using Student's t-test, Mann-Whitney U-test and chi2 analysis. Of the 1019 patients hospitalized during the study period, 162 were fasting. Although, fasting patients were more likely to present to the emergency department in the time periods 5-6 AM (10.5% vs 6.3%) and 11 PM (11.1% vs 7.1%) and were less likely to present in the time periods 1-2 PM (3.7% vs 7.2%) and 5-6 PM (3.7% vs 7.0%); these differences were not statistically significant. Fasting patients were less likely to have their symptoms start between 5 and 8 AM (11.1% vs 19.4%) and more likely to have symptoms between 5 and 6 PM (11.1% vs 6.0%) and 3 and 4 AM (11.1% vs 6.9%). These differences for time of initial symptoms were statistically significant (P=0.002). Exogenous factors associated with fasting, namely, the changes in food intake and/or sleep timings, affect the circadian rhythm and influence the timing of presentation of acute coronary events.

Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population

PubMed Central

Park, Woo Ri; Oh, Tae Keun

2013-01-01

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 µIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH. PMID:24265525

Cochlear Pericytes Are Capable of Reversibly Decreasing Capillary Diameter In Vivo After Tumor Necrosis Factor Exposure.

PubMed

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Strupp, Michael; Canis, Martin

2017-12-01

The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis. Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane. Vessel diameter at sites of pericyte somas and downstream controls were quantified by specialized software. Values were obtained before treatment, after first treatment with tumor necrosis factor or placebo and after second treatment with etanercept or placebo. Overall, 199 pericytes in 12 animals were visualized. After initial treatment with TNF, a significant decrease in vessel diameter at sites of pericyte somas (3.6 ±4.3%, n = 141) compared with placebo and downstream controls was observed. After initial treatment with TNF, the application of etanercept caused a significant increase (3.3 ±5.5%, n = 59) in vessel diameter at the sites of pericyte somata compared with placebo and downstream controls. We have been able to show that cochlear pericytes are capable of reducing capillary diameter after exposition to TNF. Moreover, the reduction in capillary diameter observed after the application of TNF is revertible after neutralization of tumor necrosis factor by the application of etanercept. It seems that contraction of cochlear pericytes contributes to the regulation of cochlear blood flow.

Factors affecting return to oral intake in inpatient rehabilitation after acquired brain injury.

PubMed

Kjaersgaard, Annette; Nielsen, Lars Hedemann; Sjölund, Bengt H

2015-01-01

To extend previous observations by investigating if differences exist in time to initiation or to recovery of total oral intake in patients with acquired brain injury assessed by either Facial-Oral Tract Therapy (F.O.T.T.) or Fibreoptic Endoscopic Evaluation of Swallowing (FEES) and to investigate whether other factors influence these outcomes. Randomized controlled trial. One hundred and nineteen patients with dysphagia in inpatient neurorehabilitation were randomized. The main outcome was time to maximum on the Functional Oral Intake Scale. There was no difference in time to initiation or recovery of total oral intake using F.O.T.T. or FEES. Oral intake was initiated for 42% on admission and 92% at discharge; 2.5% of the patients were on total oral intake within 24 hours of admission and 37% at discharge. The likelihood of recovery to total oral intake before discharge was found to depend on age, Functional Independence Measure score, length of stay and number of dysphagia interventions. There was no significant difference in time to initiation and recovery of total oral intake before discharge, whether assessed by F.O.T.T. or FEES, indicating that an instrumental assessment is unnecessary for standard evaluation. Age, functional independence and length of stay had a significant influence.

Profile of referrals for early childhood developmental delay to ambulatory subspecialty clinics.

PubMed

Shevell, M I; Majnemer, A; Rosenbaum, P; Abrahamowicz, M

2001-09-01

The objective of this study was to determine the profile and pattern of referral to subspecialty clinics of young children with suspected developmental delay together with the factors prompting their referral. All children under 5 years of age referred to either developmental pediatrics or pediatric neurology clinics at a single tertiary hospital over an 18-month period were prospectively identified. Standardized demographic and referral information were collected at intake, final developmental delay subtype diagnosed was identified, and referring physicians were surveyed regarding factors prompting referral. A total of 224 children met study criteria. There was a marked male preponderance (166/224), especially among those with either cognitive or language delay. Two delay subtypes, global developmental delay and developmental language disorder, accounted for two thirds of the diagnoses made. For slightly more than one third of the children (75/224), the delay subtype diagnosed following specialty evaluation was different from that initially suspected by the referring physician. A mean delay of 15.5 months was observed for the cohort as a whole between initial parental concern and specialty assessment. For referring physicians, the major factor prompting referral was the severity of the observed delay. The most important aspects of the specialty evaluation according to referral sources were the identification of a possible etiology and confirmation of delay. A profile of referrals and the rationale thereof for a cohort of children with suspected developmental delay is presented that, although locale specific, has implications for service provision and training.

Polyamines and Hypusination Are Required for Ebolavirus Gene Expression and Replication

PubMed Central

Olsen, Michelle E.; Filone, Claire Marie; Rozelle, Dan; Mire, Chad E.; Agans, Krystle N.; Hensley, Lisa

2016-01-01

ABSTRACT Ebolavirus (EBOV) is an RNA virus that is known to cause severe hemorrhagic fever in humans and other primates. EBOV successfully enters and replicates in many cell types. This replication is dependent on the virus successfully coopting a number of cellular factors. Many of these factors are currently unidentified but represent potential targets for antiviral therapeutics. Here we show that cellular polyamines are critical for EBOV replication. We found that small-molecule inhibitors of polyamine synthesis block gene expression driven by the viral RNA-dependent RNA polymerase. Short hairpin RNA (shRNA) knockdown of the polyamine pathway enzyme spermidine synthase also resulted in reduced EBOV replication. These findings led us to further investigate spermidine, a polyamine that is essential for the hypusination of eukaryotic initiation factor 5A (eIF5A). Blocking the hypusination of eIF5A (and thereby inhibiting its function) inhibited both EBOV gene expression and viral replication. The mechanism appears to be due to the importance of hypusinated eIF5A for the accumulation of VP30, an essential component of the viral polymerase. The same reduction in hypusinated eIF5A did not alter the accumulation of other viral polymerase components. This action makes eIF5A function an important gate for proper EBOV polymerase assembly and function through the control of a single virus protein. PMID:27460797

Maternal Influences on Smoking Initiation among Urban Adolescent Girls

ERIC Educational Resources Information Center

Nichols, Tracy R.; Graber, Julia A.; Brooks-Gunn, Jeanne; Botvin, Gilbert J.

2004-01-01

This study examined associations between maternal social influences to smoke and girls' early smoking behaviors. Data were collected separately from 450 urban minority girls (65.7% Black, 21.5% Latina, and 12.8% other) and their mothers on smoking frequency as well as demographic and social factors hypothesized to promote smoking. Results showed…

TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

PubMed

Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

1994-09-01

We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation.

The School Counseling Program Implementation Survey: Initial Instrument Development and Exploratory Factor Analysis

ERIC Educational Resources Information Center

Clemens, Elysia V.; Carey, John C.; Harrington, Karen M.

2010-01-01

This article details the initial development of the School Counseling Program Implementation Survey and psychometric results including reliability and factor structure. An exploratory factor analysis revealed a three-factor model that accounted for 54% of the variance of the intercorrelation matrix and a two-factor model that accounted for 47% of…

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

PubMed Central

Damgaard, Christian Kroun; Lykke-Andersen, Jens

2011-01-01

The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post-transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 5′-terminal oligopyrimidine tracts (5′TOP). However, the responsible trans-factors and the mechanism by which they coregulate 5′TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 5′TOP mRNA regulation, which upon amino acid starvation assemble onto the 5′ end of 5′TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 5′TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5′TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment. PMID:21979918

5 CFR 847.912 - If an employee who elects to credit NAFI service under subpart H of this part elects a survivor...

Code of Federal Regulations, 2010 CFR

2010-01-01

... reduction under paragraph (a) of this section equals: (1) The difference in the present value of the initial..., divided by (2) The present value factor for the retiree's age (in full years) at the time of retirement. (c) The present value of the survivor annuity generated from the immediate annuity with credit for...

Expression of the Eukaryotic Translation Initiation Factors 4E and 2α in Non-Hodgkin’s Lymphomas

PubMed Central

Wang, Songtao; Rosenwald, Igor B.; Hutzler, Michael J.; Pihan, German A.; Savas, Lou; Chen, Jane-Jane; Woda, Bruce A.

1999-01-01

Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2α. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2α by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin’s lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt’s lymphomas). Strong expression of initiation factors 4E and 2α was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2α is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2α, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive follicles. A positive correlation was found between the expression of both initiation factors 4E and 2α and the Revised European-American Lymphoma behavior classification (P < 0.05). Thus, constitutively increased expression of initiation factors 4E and 2α may play an important role in the development of lymphomas and is correlated with their biological aggressiveness. PMID:10393856

Reducing Line Edge Roughness in Si and SiN through plasma etch chemistry optimization for photonic waveguide applications

NASA Astrophysics Data System (ADS)

Marchack, Nathan; Khater, Marwan; Orcutt, Jason; Chang, Josephine; Holmes, Steven; Barwicz, Tymon; Kamlapurkar, Swetha; Green, William; Engelmann, Sebastian

2017-03-01

The LER and LWR of subtractively patterned Si and SiN waveguides was calculated after each step in the process. It was found for Si waveguides that adjusting the ratio of CF4:CHF3 during the hard mask open step produced reductions in LER of 26 and 43% from the initial lithography for isolated waveguides patterned with partial and full etches, respectively. However for final LER values of 3.0 and 2.5 nm on fully etched Si waveguides, the corresponding optical loss measurements were indistinguishable. For SiN waveguides, introduction of C4H9F to the conventional CF4/CHF3 measurement was able to reduce the mask height budget by a factor of 5, while reducing LER from the initial lithography by 26%.

Undernutrition status and associated factors in under-5 children, in Tigray, Northern Ethiopia.

PubMed

Alemayehu, Mussie; Tinsae, Fitiwi; Haileslassie, Kiday; Seid, Oumer; Gebregziabher, Gebremedhin; Yebyo, Henock

2015-01-01

The aim of this study was to assess the nutritional status and associated factors in children <5 y in the Medebay Zana District, northern Ethiopia. A community-based cross-sectional study was conducted in the Medebay Zana District from September 8 to 29, 2013. A two-stage cluster-sampling technique was used to select 605 children age <5 y. Descriptive, binary, and multiple logistic regression analyses were performed. The results of this study demonstrated that the level of stunting was 56.6%, underweight 45.3%, and wasting 34.6%. Stunting was predicted by having mothers who attended high school (adjusted odds ratio [AOR], 0.75; 95% confidence interval [CI], 0.09-0.85), living in a household where providing priority food was given to the father (AOR, 4.32; 95% CI, 2.10-9.05), and water was taken from unprotected sources (AOR, 2.13; 95% CI, 1.09-4.14). In all children, initiation of breast-feeding within 1 to 3 h after birth (AOR, 4.06; 95% CI, 1.77-9.33), having mothers who could make financial decisions (AOR, 0.09; 95% CI, 0.02-0.51), and being breast-fed for 12 to 23 mo (AOR, 0.07; 95% CI, 0.01-0.40) were predictors of wasting. Moreover, in girls (AOR, 1.84; 95% CI, 1.25, 2.69), initiation of breast-feeding 6 h after birth (AOR, 12.94; 95% CI, 4.04-41.49) and having mothers who could make financial decisions (AOR, 0.33; 95% CI, 0.15-0.74) were predictors of being underweight. The undernutrition status among children <5 y was high. Children's age group, time initiation of breast-feeding, child's sex, source of water, parents' educational status, type of food used for starting of complementary feeding, and mothers' financial decision-making ability could have an influence in undernutrition of children in this age group. Copyright © 2015 Elsevier Inc. All rights reserved.

Paraplegia-quadriplegia Independently Increases All Percutaneous Nephrolithotomy Complications: A Comparative Study Using the Modified Clavien System.

PubMed

Danawala, Zeeshan A; Singh, Dinesh

2015-05-01

To investigate the perioperative complication rates for paraplegic-quadriplegic patients (PQPs) undergoing percutaneous nephrolithotomy (PCNL) as compared with non-PQPs using a standardized method of complication reporting via the Clavien system. Two hundred thirteen consecutive PCNLs performed by a single surgeon were analyzed. There were 31 and 115 patients separated into PQP and non-PQP groups, respectively. Data collection included demographic and clinical factors, as well as perioperative and delayed complications. Complications were organized by the Clavien grade. All- and initial-procedure complications were analyzed. The rate of adverse events for each Clavien grade was calculated, and statistical comparisons were made. The relationship between PQP and complication severity was investigated using univariate and multivariate analyses. There were 38 and 43 initial-procedure complications in the PQP and non-PQP groups, respectively. The rate of adverse events was higher across the spectrum of Clavien grades for the PQP group, specifically grade 1 (48.4% vs 20.2%; P = .002), grade 2 (22.6% vs 5.3%; P = .004), grade 3b (12.9% vs 2.6%; P = .038), grade 4a (6.5% vs 0%), and grade 4b (9.7% vs 1.8%; P = .066). Approximately 51.6% and 31.5% of PQPs and non-PQPs experienced ≥ 1 complications, respectively (odds ratio = 2.34; P = .05). Multivariate analysis demonstrated paraplegia or quadriplegia status to be an independent risk factor for the development of perioperative complications after adjusting for confounding factors (odds ratio = 2.91; P = .040). PCNL complication rates are higher in PQPs compared with non-PQPs. This study is one of the first in PCNL to use a standardized reporting system to highlight high-risk individuals within the stone population. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of a Discharge Pumped 13 nm Laser for Metrology of Projection Lithography Optics at the Manufacture-Site

DTIC Science & Technology

2003-09-14

nm @2,6,9#. In the particular case of Ar discharges the gain-length product for the 3p 1S0-3s 1P1 transition of Ne-like Ar at 46.9 nm has exceeded...The addition of the Al filter decreases the transmissivity in this window by a factor that increases from about 63 at 4.5 nm to about 6003 at 10 nm... factors including the smaller current and pinch radius, together with very good initial plasma symmetry and relatively short time duration of4-7 GONZALEZ

[A case-control study of factors associated with repeat teen pregnancy based on a sample from a university maternity hospital].

PubMed

Silva, Andréa de Albuquerque Arruda; Coutinho, Isabela C; Katz, Leila; Souza, Alex Sandro Rolland

2013-03-01

Repeat teen pregnancy is a frequent issue and is considered an aggravating factor for increased maternal and fetal morbidity and social problems. The aim of the study was to identify factors associated with repeat teen pregnancy. A case-control study was conducted in 90 postpartum adolescents with more than one pregnancy (cases) and 90 adult women with a history of only one pregnancy during adolescence (controls). Statistical analysis used hierarchical logistic regression with 5% significance. Early sexual initiation (< 15 years), early age at first pregnancy (< 16 years), not raising the children themselves, and low family income (< one minimum wage) were associated with repeat teenage pregnancy, while partner change was inversely associated. Repeat teen pregnancy was mainly associated with reproductive and socioeconomic factors. Partner change appeared as a protective factor. Measures should be adopted during the postpartum period of teenage mothers in order to avoid repeat pregnancy.

German "National Cancer Aid Monitoring" 2015-2019 - study protocol and initial results.

PubMed

Schneider, Sven; Görig, Tatiana; Schilling, Laura; Breitbart, Eckhard W; Greinert, Rüdiger; Diehl, Katharina

2017-09-01

The National Cancer Aid Monitoring of Tanning Bed Use (NCAM) project is a major German study that aims to observe the most significant risk factors for skin cancer: natural sunlight and artificial UV radiation. NCAM is a nationwide cross-sectional survey that will initially involve four rounds of data collection (so-called waves) between 2015 and 2018. Every year, a representative nationwide sample consisting of 3,000 individuals aged between 14 and 45 years will be surveyed. The cross-sectional survey will be complemented by a panel of n  =  450 current tanning bed users. The initial wave in 2015 shows an overall prevalence of tanning bed use of 29.5 %. Eleven percent of all participants had used a tanning bed within the past twelve months. Determinants of current tanning bed use included younger age, female gender, and full-time/part-time employment. The main motivations for tanning bed use reported were relaxation and increased attractiveness. NCAM is the first study worldwide to monitor skin cancer risk factors at one-year intervals using a large, nationally representative sample. Initial results indicate that, despite WHO warnings, millions of Germans use tanning beds, and that many of these users are adolescents despite legal restrictions aimed at preventing minors from using tanning beds. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting.

PubMed

Goldenberg, Shira M; Chettiar, Jill; Simo, Annick; Silverman, Jay G; Strathdee, Steffanie A; Montaner, Julio S G; Shannon, Kate

2014-01-01

To explore factors associated with early sex work initiation and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Baseline data (2010-2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. SWs completed a questionnaire and HIV/sexually transmitted infection testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs. Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian born [adjusted odds ratio (AOR): 6.8, 95% confidence interval (CI): 2.42 to 19.02], inject drugs (AOR: 1.6, 95% CI: 1.0 to 2.5), and to have worked for a manager (AOR: 2.22, 95% CI: 1.3 to 3.6) or been coerced into sex work (AOR: 2.3, 95% CI: 1.14 to 4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3 to 3.2) and prostitution arrests (AOR: 2.0, 95% CI: 1.3 to 3.2). Adolescent sex work initiation is concentrated among marginalized, drug, and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs.

Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting

PubMed Central

GOLDENBERG, Shira M.; CHETTIAR, Jill; SIMO, Annick; SILVERMAN, Jay G.; STRATHDEE, Steffanie A.; MONTANER, Julio; SHANNON, Kate

2014-01-01

Objectives To explore factors associated with early sex work initiation, and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Design Baseline data (2010–2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time-location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. Methods SWs completed a questionnaire and HIV/STI testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs. Results Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian-born (Adjusted Odds Ratio (AOR): 6.8, 95% Confidence Interval (CI): 2.42–19.02), inject drugs (AOR: 1.6, 95%CI: 1.0–2.5), and to have worked for a manager (AOR: 2.22, 95%CI: 1.3–3.6) or been coerced into sex work (AOR: 2.3, 95%CI: 1.14–4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3–3.2) and prostitution arrests (AOR: 2.0, 95%CI: 1.3–3.2). Conclusions Adolescent sex work initiation is concentrated among marginalized, drug and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs. PMID:23982660

Investigation of Cracks Found in Helicopter Longerons

NASA Technical Reports Server (NTRS)

Newman, John A.; Baughman, James M.; Wallace, Terryl A.

2009-01-01

Four cracked longerons, containing a total of eight cracks, were provided for study. Cracked regions were cut from the longerons. Load was applied to open the cracks, enabling crack surface examination. Examination revealed that crack propagation was driven by fatigue loading in all eight cases. Fatigue crack initiation appears to have occurred on the top edge of the longerons near geometric changes that affect component bending stiffness. Additionally, metallurigical analysis has revealed a local depletion in alloying elements in the crack initiation regions that may be a contributing factor. Fatigue crack propagation appeared to be initially driven by opening-mode loading, but at a crack length of approximately 0.5 inches (12.7 mm), there is evidence of mixed-mode crack loading. For the longest cracks studied, shear-mode displacements destroyed crack-surface features of interest over significant portions of the crack surfaces.

Investigation of Helicopter Longeron Cracks

NASA Technical Reports Server (NTRS)

Newman, John A.; Baughman, James; Wallace, Terryl A.

2009-01-01

Four cracked longerons, containing a total of eight cracks, were provided for study. Cracked regions were cut from the longerons. Load was applied to open the cracks, enabling crack surface examination. Examination revealed that crack propagation was driven by fatigue loading in all eight cases. Fatigue crack initiation appears to have occurred on the top edge of the longerons near geometric changes that affect component bending stiffness. Additionally, metallurgical analysis has revealed a local depletion in alloying elements in the crack initiation regions that may be a contributing factor. Fatigue crack propagation appeared to be initially driven by opening-mode loading, but at a crack length of approximately 0.5 inches (12.7 mm), there is evidence of mixed-mode crack loading. For the longest cracks studied, shear-mode displacements destroyed crack-surface features of interest over significant portions of the crack surfaces.

Genome-wide uniformity of human ‘open’ pre-initiation complexes

PubMed Central

Lai, William K.M.; Pugh, B. Franklin

2017-01-01

Transcription of protein-coding and noncoding DNA occurs pervasively throughout the mammalian genome. Their sites of initiation are generally inferred from transcript 5′ ends and are thought to be either locally dispersed or focused. How these two modes of initiation relate is unclear. Here, we apply permanganate treatment and chromatin immunoprecipitation (PIP-seq) of initiation factors to identify the precise location of melted DNA separately associated with the preinitiation complex (PIC) and the adjacent paused complex (PC). This approach revealed the two known modes of transcription initiation. However, in contrast to prevailing views, they co-occurred within the same promoter region: initiation originating from a focused PIC, and broad nucleosome-linked initiation. PIP-seq allowed transcriptional orientation of Pol II to be determined, which may be useful near promoters where sufficient sense/anti-sense transcript mapping information is lacking. PIP-seq detected divergently oriented Pol II at both coding and noncoding promoters, as well as at enhancers. Their occupancy levels were not necessarily coupled in the two orientations. DNA sequence and shape analysis of initiation complex sites suggest that both sequence and shape contribute to specificity, but in a context-restricted manner. That is, initiation sites have the locally “best” initiator (INR) sequence and/or shape. These findings reveal a common core to pervasive Pol II initiation throughout the human genome. PMID:27927716

Association of cartilage degeneration with four year weight gain– 3T MRI data from the Osteoarthritis Initiative

PubMed Central

Bucknor, Matthew D.; Nardo, Lorenzo; Joseph, Gabby B.; Alizai, Hamza; Srikhum, Waraporn; Nevitt, Michael C.; Lynch, John A.; McCulloch, Charles E.; Link, Thomas M.

2015-01-01

Objective To determine the effect of weight gain on progression of early knee morphologic abnormalities using magnetic resonance imaging (MRI) in a longitudinal study over 48 months. Design We studied the right knee of 100 subjects from the Osteoarthritis Initiative, selecting subjects aged ≥ 45 with osteoarthritis risk factors who demonstrated weight gain (minimum 5% increase in body mass index, BMI, n=50) or no change in weight (BMI change < 2%, n=50), frequency matched for age, gender, and baseline BMI. Baseline and 48 month knee MRI studies were scored for lesions using a modified whole organ MRI score (WORMS). Logistic regression models were used to compare the differences between the two groups. Results The odds of worsening maximum cartilage (11.3, 95%, CI 3.5–51.4) and meniscal WORMS (4.5, 95% CI 1.4–17.3) were significantly greater in the weight gain group compared to the no change group, in addition to the odds of worsening cartilage defects at the patella and average meniscal WORMS (p<0.05). Odds of worsening average bone marrow edema pattern (BMEP) were significantly greater for the weight gain group compared to the no change cohort (p<0.05). Conclusion Our study demonstrated that weight gain is strongly associated with increased progression of cartilage degeneration in middle-aged individuals with risk factors for osteoarthritis. PMID:25591445

Novel characteristics of the biological properties of the yeast Saccharomyces cerevisiae eukaryotic initiation factor 2A.

PubMed

Komar, Anton A; Gross, Stephane R; Barth-Baus, Diane; Strachan, Ryan; Hensold, Jack O; Goss Kinzy, Terri; Merrick, William C

2005-04-22

Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A genetically interacts with initiation factor eIF4E, suggesting that both proteins function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a severe slow growth phenotype, which correlated with the accumulation of 85% of the double mutant cells arrested at the G(2)/M border. These cells also exhibited a disorganized actin cytoskeleton and elevated actin levels, suggesting that eIF2A might be involved in controlling the expression of genes involved in morphogenic processes. Further insights into eIF2A function were gained from the studies of eIF2A distribution in ribosomal fractions obtained from either an eIF5BDelta (fun12Delta) strain or a eIF3b-ts (prt1-1) strain. It was found that the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain. We also found that eIF2A functions as a suppressor of Ure2p internal ribosome entry site-mediated translation in yeast cells. The regulation of expression from the URE2 internal ribosome entry site appears to be through the levels of eIF2A protein, which has been found to be inherently unstable with a half-life of approximately 17 min. It was hypothesized that this instability allows for translational control through the level of eIF2A protein in yeast cells.

Trends in baseline CD4 cell counts and risk factors for late antiretroviral therapy initiation among HIV-positive patients in Shanghai, a retrospective cross-sectional study.

PubMed

Sun, Jianjun; Liu, Li; Shen, Jiayin; Chen, Panpan; Lu, Hongzhou

2017-04-19

There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014. Late ART initiation was defined as a CD4 cell count <200 cells/mm 3 or having a clinical AIDS diagnosis prior to ART initiation. Trends in the median CD4 cell count at ART initiation and the proportion of late ART initiation by year were evaluated using Spearman's correlations and Chi-squared methods, respectively. We used a logistic regression model to analyze the risk factors for late ART initiation. The related factors collected in the multivariate model were the patient's age, gender, infection routes and marital status. A total of 3796 patients were analyzed in this study, with a median baseline CD4 cell count of 205 cells/mm 3 [interquartile range: 75-287]. The median CD4 cell counts of patients initiating ART late increased from 76 cells/mm 3 in 2008 to 103 cells/mm 3 in 2014 (p < 0.001), and the proportion of late ART initiation decreased from 80% to 45% (p < 0.001). The risk factors for late ART initiation were male gender, heterosexual transmission and older age (>30 years) (p < 0.001). Notable improvements were made in the median CD4 cell count at ART initiation and the proportion of late ART initiation from 2008 to 2014. However, persons with high risk of HIV exposure who are male, older even heterosexual orientation should be given more opportunities to receive frequently screening, earlier diagnoses and timely treatment.

Persistence and changes in bioavailability of dieldrin, DDE and heptachlor epoxide in earthworms over 45 years

USGS Publications Warehouse

Beyer, W. Nelson; Gale, Robert W.

2013-01-01

The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

Deep sequencing leads to the identification of eukaryotic translation initiation factor 5A as a key element in Rsv1-mediated lethal systemic hypersensitive response to Soybean mosaic virus infection in soybean.

PubMed

Chen, Hui; Adam Arsovski, Andrej; Yu, Kangfu; Wang, Aiming

2017-04-01

Rsv1, a single dominant resistance locus in soybean, confers extreme resistance to the majority of Soybean mosaic virus (SMV) strains, but is susceptible to the G7 strain. In Rsv1-genotype soybean, G7 infection provokes a lethal systemic hypersensitive response (LSHR), a delayed host defence response. The Rsv1-mediated LSHR signalling pathway remains largely unknown. In this study, we employed a genome-wide investigation to gain an insight into the molecular interplay between SMV G7 and Rsv1-genotype soybean. Small RNA (sRNA), degradome and transcriptome sequencing analyses were used to identify differentially expressed genes (DEGs) and microRNAs (DEMs) in response to G7 infection. A number of DEGs, DEMs and microRNA targets, and the interaction network of DEMs and their target mRNAs responsive to G7 infection, were identified. Knock-down of one of the identified DEGs, the eukaryotic translation initiation factor 5A (eIF5A), diminished the LSHR and enhanced viral accumulation, suggesting the essential role of eIF5A in the G7-induced, Rsv1-mediated LSHR signalling pathway. This work provides an in-depth genome-wide analysis of high-throughput sequencing data, and identifies multiple genes and microRNA signatures that are associated with the Rsv1-mediated LSHR. © 2016 HER MAJESTY THE QUEEN IN RIGHT OF CANADA MOLECULAR PLANT PATHOLOGY © 2016 BSPP AND JOHN WILEY & SONS LTD.

Sexual function of young women with myelomeningocele.

PubMed

Gamé, Xavier; Moscovici, Jacques; Guillotreau, Julien; Roumiguié, Mathieu; Rischmann, Pascal; Malavaud, Bernard

2014-06-01

To assess the sexual function of young women with spina bifida and myelomeningocele and to determine the factors influencing their sexual function. A postal cross-sectional study using a self-administered questionnaire was performed in 44 women, mean age 27.66 ± 5.89 years, with spina bifida and myelomeningocele. The questionnaire included the Brief Index of Sexual Functioning for Women and questions about voiding mode, urinary symptoms, socioeconomic status, education level, lifestyle, and partnership. In parallel, data were also collected from the paediatric surgery records of patients who returned the questionnaire. The response rate was 56.8% (25/44). All domains of female sexual function (thoughts/desires, arousal, frequency of sexual activity, receptivity/initiation, pleasure/orgasm, relationship satisfaction) were altered. Urinary incontinence was likely to be the main factor responsible for altered sexual function and was associated with lower thoughts/desires, arousal, and receptivity/initiation scores. Wearing pads also constituted a limitation to achieving intimacy. Young myelomeningocele women report poor sexual functioning. The presence of urinary incontinence is associated with lower thoughts/desire, arousal, and receptivity/initiation. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Postoperative Evaluation of Reduction Loss in Proximal Humeral Fractures: A Comparison of Plain Radiographs and Computed Tomography.

PubMed

Jia, Xiao-Yang; Chen, Yan-Xi; Qiang, Min-Fei; Zhang, Kun; Li, Hao-Bo; Jiang, Yu-Chen; Zhang, Yi-Jie

2017-05-01

To compare postoperative CT images with plain radiographs for measuring prognostic factors of reduction loss of fractures of the proximal part of the humerus. A total of 65 patients who sustained fractures of the proximal humerus treated with locking plates from June 2012 to October 2015 were retrospectively analyzed. There were 24 men and 41 women, with a mean age of 60.0 years (range, 22-76 years). According to the Neer classification system of proximal humeral fracture, there were 26 two-part, 27 three-part and 12 four-part fractures of the proximal part of the humerus, and all fractures were treated with open reduction and internal fixation (ORIF) using locked plating. All postoperative CT images and plain radiographs of the patients were obtained. Prognostic factors of the reduction loss were the change of neck shaft angle (NSA) and the change of humeral head height (HHH). The change of NSA and HHH were evaluated by the difference between postoperative initial and final follow-up measurement. Reduction loss was defined as the change ≥10° for NSA or ≥5 mm for HHH. The NSA and HHH were measured using plain radiographs and 3-D CT images, both initially and at final follow-up. The paired t-test was used for comparison of NSA, change of NSA, HHH, and change of HHH between two image modalities. The differences between two image modalities in the assessment of reduction loss were examined using the χ 2 -test (McNemar test). Intraclass correlation coefficients (ICC) were used to assess the intra-observer and inter-observer reliability. 3-D CT images (ICC range, 0.834-0.967) were more reliable in all parameters when compared with plain radiographs (ICC range, 0.598-0.915). Significant differences were found between the two image modalities in all parameters (plain radiographs: initial NSA = 133.6° ± 3.8°, final NSA = 130.0° ± 1.9°, initial HHH = 17.9 ± 0.9 mm, final HHH = 15.8 ± 1.5 mm; 3-D CT: initial NSA = 131.4° ± 3.4°, final NSA = 128.8° ± 1.7°, initial HHH = 16.8 ± 1.2 mm, final HHH = 14.5 ± 1.1 mm; all P < 0.05). In the assessment of reduction loss, the percentage was 16.9% (11/65) for the plain radiographs and 7.7% (5/65) for the 3-D CT scans (P < 0.05). For the 5 patients with reduction loss, which were observed by two imaging modalities, the mean Constant-Murley score was 61.0 ± 1.6. The patients with reduction loss, observed only in plain radiographs but not CT images, had good shoulder function (Constant-Murley score: 82.7 ± 1.0). Our data reveal that 3-D CT images are more reliable than plain radiographs in the assessment of the prognostic factors of reduction loss of fractures of the proximal part of the humerus with treatment of locking plates; this reliable CT technique can serve as an effective guideline for the subsequent clinical management of patients. © 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Combination phentermine and topiramate extended release in the management of obesity.

PubMed

Alfaris, Nasreen; Minnick, Alyssa M; Hopkins, Christina M; Berkowitz, Robert I; Wadden, Thomas A

2015-06-01

Losing ≥ 5% of initial weight improves quality of life and risk factors for cardiovascular disease (CVD) in obese individuals. Lifestyle modification, the cornerstone of weight reduction, may be complemented by pharmacotherapy. In 2012, the FDA approved the combination of phentermine and topiramate extended release (ER) for chronic weight management, as an adjunct to lifestyle modification. This review examines the safety and efficacy of phentermine-topiramate ER, as determined by randomized controlled trials (RCTs). A preliminary study confirmed the benefit of combining the two medications for improving weight loss and reducing adverse effects, as compared to using equivalent-dose monotherapy alone. Across RCTs, groups prescribed phentermine 15 mg/topiramate ER 92 mg lost an average of 10% of initial weight, ∼ 8% more than placebo and 2% more than phentermine 7.5 mg/topiramate 46 mg. Weight loss reduced the risk of developing type 2 diabetes and improved CVD risk factors. Phentermine-topiramate ER, however, was associated with increased heart rate, the clinical significance of which is being investigated in an FDA-required CVD outcomes study. The medication also must be used with caution in women of child-bearing age because of an increased risk to infants of oral cleft.

Platelet factor 4/heparin antibodies in blood bank donors.

PubMed

Hursting, Marcie J; Pai, Poulomi J; McCracken, Julianna E; Hwang, Fred; Suvarna, Shayela; Lokhnygina, Yuliya; Bandarenko, Nicholas; Arepally, Gowthami M

2010-11-01

Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing. Antibody was detected initially in 249 (6.6%; 95% confidence interval [CI], 5.8%-7.4%) of 3,795 donors and repeatedly in 163 (4.3%; 95% CI, 3.7%-5.0%) of 3,789 evaluable donors. "Unconfirmed" positives were mostly (93%) low positives (optical density [OD] = 0.40-0.59). Of 163 repeatedly positive samples, 116 (71.2%) were low positives, and 124 (76.1%) exhibited heparin-dependent binding. Predominant isotypes of intermediate to high seropositive samples (OD >0.6) were IgG (20/39 [51%]), IgM (9/39 [23%]), and indeterminate (10/39 [26%]). The marked background seroprevalence of PF4/heparin antibody (4.3%-6.6%) with the preponderance of low (and frequently nonreproducible) positives in blood donors suggests the need for further assay calibration, categorization of antibody level, and studies evaluating clinical relevance of "naturally occurring" PF4/heparin antibodies.

Attention-deficit/hyperactivity disorder Under Treatment Outcomes Research (AUTOR): a European observational study in pediatric subjects.

PubMed

Haynes, Virginia; Lopez-Romero, Pedro; Anand, Ernie

2015-12-01

The ADHD Under Treatment Observational Research (AUTOR) study was a European prospective, observational study that assessed factors associated with changes in ADHD severity, estimated change from baseline in quality of life (QoL), and characterized changes in ADHD symptoms over a 2-year period as a function of baseline treatment. The primary objective was to identify factors associated with worsening in ADHD severity during a 2-year follow-up period for subjects aged 6-17 years, who were receiving the same pharmacotherapy for 3-8 months before enrollment and had a Clinical Global Impression (CGI)-ADHD-Severity score of mild/lower and a CGI-ADHD-Improvement score of improved/very much improved. Multivariate logistic regression examined the association of factors with worsening in ADHD. Mixed-model repeated measures regression analyzed QoL in terms of change from baseline in CHIP-CE PRF scores. There were 704 subjects analyzed. Variables associated with worsening ADHD severity were parental occupation, poorer school outcomes, and use of psychoeducation; baseline treatment was not significant. Among the secondary objectives, initial use of atomoxetine (vs. stimulants) was associated with a significant improvement on the CHIP-CE PRF total score, with an adjusted treatment difference of -6.0 (95 % CI -7.9, -4.1) at 24 months. Additionally, the odds of stability (CGI-ADHD-S ≤ 3 over the 2-year period) were significantly lower for subjects initially responding to stimulants compared with atomoxetine (OR 0.5; 95 % CI 0.3, 0.8). ADHD symptom worsening was associated with initial use of psychoeducation, parental occupation, and poorer school outcomes. Response to initial treatment with atomoxetine was associated with improved QoL over 2 years.

The Frontier Fields: Survey Design and Initial Results

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

Lotz, J. M.; Koekemoer, A.; Grogin, N.

What are the faintest distant galaxies we can see with the Hubble Space Telescope ( HST ) now, before the launch of the James Webb Space Telescope ? This is the challenge taken up by the Frontier Fields, a Director’s discretionary time campaign with HST and the Spitzer Space Telescope to see deeper into the universe than ever before. The Frontier Fields combines the power of HST and Spitzer with the natural gravitational telescopes of massive high-magnification clusters of galaxies to produce the deepest observations of clusters and their lensed galaxies ever obtained. Six clusters—Abell 2744, MACSJ0416.1-2403, MACSJ0717.5+3745, MACSJ1149.5+2223, Abellmore » S1063, and Abell 370—have been targeted by the HST ACS/WFC and WFC3/IR cameras with coordinated parallel fields for over 840 HST orbits. The parallel fields are the second-deepest observations thus far by HST with 5 σ point-source depths of ∼29th ABmag. Galaxies behind the clusters experience typical magnification factors of a few, with small regions magnified by factors of 10–100. Therefore, the Frontier Field cluster HST images achieve intrinsic depths of ∼30–33 mag over very small volumes. Spitzer has obtained over 1000 hr of Director’s discretionary imaging of the Frontier Field cluster and parallels in IRAC 3.6 and 4.5 μ m bands to 5 σ point-source depths of ∼26.5, 26.0 ABmag. We demonstrate the exceptional sensitivity of the HST Frontier Field images to faint high-redshift galaxies, and review the initial results related to the primary science goals.« less

Reparable Inventory Reduction: Impacts on Air Force Fighter Aicraft Mission Capability.

DTIC Science & Technology

1999-09-01

operating just-in-time, there is less insurance (in the form of stocks) against these disruptions. Applying Lean Logistics approaches to all...impacts of initiatives such as these are isolated to the Air Force, and whether we can learn from the methods civilian companies use in handling...approx 84% service level Pipeline Stock (Q) 95.4 1.029555288 .3485+.5 Saftey Stock (SLQ) 16.92 Cost/Item Total Cost Rounding factor (K) 0.5 Total

Response surface method optimization of ectoine fermentation medium with moderate halophilic bacteria Halomonas sp. H02

NASA Astrophysics Data System (ADS)

Li, T. T.; Qu, A.; Yuan, X. N.; Tan, F. X.; Li, X. W.; Wang, T.; Zhang, L. H.

2017-07-01

Moderate halophilic bacteria are of halophilic bacteria whose suitable growth of NaCl is 5-10%. When the moderate halophilic bacteria response to high osmotic stress, the intracellular will synthesize small organic molecule compatible solutes. Ectoine, which is the major synthetic osmotic compatible solutes for moderate halophilic bacteria, can help microbial enzymes, nucleic acids and the whole cell resist to hypertonic, high temperature, freezing and other inverse environment. In order to increase the Ectoine production of Moderate halophilic bacteria Halomonas sp. H02, the Ectoine fermentation medium component was optimized by Plackett-Burman (PB) and Response Surface Methodology (RSM) based on the principle of non-complete equilibrium The results of PB experiments showed that the three main influencing factors of Moderate halophilic bacteria Halomonas sp. H02 synthesis Ectoine culture medium were C5H8NNaO4 concentration, NaCl concentration and initial pH. According to the center point of the steepest climbing experiment, the central combination design experiment was used to show that the model is consistent with the actual situation. The optimum combination of three influencing factors were C5H8NNaO4 41 g/L, NaCl 87.2 g/L and initial pH 5.9, and the predicted amount of Ectoine was 1835.8 mg/L, increased by 41.6%.

Piloting a multidisciplinary clinic for the management of non-alcoholic fatty liver disease: initial 5-year experience

PubMed Central

Cobbold, Jeremy F L; Raveendran, Sarrah; Peake, Christopher M; Anstee, Quentin M; Yee, Michael S; Thursz, Mark R

2013-01-01

Objective A multidisciplinary approach is advocated for the management of Non-Alcoholic Fatty Liver Disease (NAFLD), but few clinical data exist to support this. The objective of this study was to investigate the effectiveness of a multidisciplinary NAFLD clinic using surrogate markers of liver injury and cardiovascular risk. Design Retrospective survey of clinical practice. Setting The multidisciplinary NAFLD clinic in a secondary/tertiary care setting with hepatology, diabetology, dietetic and exercise therapy input: initial 5-years’ experience (2007–2012). Patients 180 patients with NAFLD but without hepatic comorbidities were followed up for a median of 19.5 (range 3–57) months. 52% had type 2 diabetes mellitus, 48% were Europoid Caucasian, 17% were South Asian. Interventions Multiple clinical interventions were employed including lifestyle (diet and exercise) advice, pharmacological intervention for cardiovascular risk factors, weight loss and exercise therapy. Main outcome measures Change in alanine aminotransferase (ALT), weight, HbA1c, lipid profile and blood pressure. Results Median ALT fell from 61 (12–270) U/l to 50 (11–221) U/l, −18%, p<0.001, and weight fell from 90.5 (42.7–175.0) kg to 87.3 (45.9–175.3) kg, −3.5%, p<0.001. There were significant improvements in total cholesterol overall, triglycerides (among dyslipidaemic patients), HbA1c (among diabetic patients) and systolic blood pressure (among hypertensive patients). 24% of patients achieved ≥7% weight loss during follow-up and 17% maintained this weight loss throughout. Conclusions Improvement in liver biochemistry and cardiovascular risk factors was seen in patients attending the multidisciplinary NAFLD clinic. Refinement of this approach is warranted in light of these data, novel therapies and a growing evidence base. PMID:28839736

Can We Predict Daily Adherence to Warfarin?

PubMed Central

Platt, Alec B.; Localio, A. Russell; Brensinger, Colleen M.; Cruess, Dean G.; Christie, Jason D.; Gross, Robert; Parker, Catherine S.; Price, Maureen; Metlay, Joshua P.; Cohen, Abigail; Newcomb, Craig W.; Strom, Brian L.; Laskin, Mitchell S.

2010-01-01

Background: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy. Methods: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin. Results: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence. Conclusions: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients. PMID:19903973

[Factors associated with compliance to the semi-recumbent position in the patient on mechanical ventilation: CAPCRI-Q questionnaire].

PubMed

Llauradó-Serra, M; Güell-Baró, R; Lobo-Cívico, A; Castanera-Duro, A; Pi-Guerrero, M; Piñol-Tena, A; Paños-Espinosa, C; Calpe-Damians, N; Olona, M; Sandiumenge, A; Jiménez-Herrera, M F

2015-01-01

To create a questionnaire (CAPCRI-Q) to determine the factors associated with the compliance of the semi-recumbent position in patients under mechanical ventilation. A closed questionnaire was created using a literature review and clinical practice. The initial version consisted of 61 items placed into 5 categories: patient factors, team and professionals factors, activity, educational and training factors, and equipment and resources. A Delphi method was used to prepare the questionnaire. Comprehension, relevance and importance of each item were evaluated, as well as the recommendations of experts. A qualitative pilot test with 9 healthcare professionals was performed, followed by a quantitative pilot test with 67 nurses from 6 intensive care units to test the internal consistency of the instrument. Three rounds with 15 experts were required to reach a consensus. The final version of the questionnaire consisted of 36 items enclosed in the same categories as the initial version. The internal consistency analysis showed values greater than 0.800 for each independent item, each category, and for the global questionnaire (0.873; 95%CI: 0.825-0.913). The analysis of the nurses' responses emphasised the importance of the patient factors, as well as organisational and infra-structural factors, for the compliance of the recommendation. The questionnaire created is reliable and appears to have content validity. The most influential factors for compliance are those related to the patient and the internal organisation. The results of the questionnaire can be used to evaluate the factors influencing the compliance and to establish improvement strategies. Copyright © 2015 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

Diabetes and Hypertension among Patients Receiving Antiretroviral Treatment Since 1998 in Senegal: Prevalence and Associated Factors

PubMed Central

Diouf, Assane; Cournil, Amandine; Ba-Fall, Khadidiatou; Ngom-Guèye, Ndèye Fatou; Eymard-Duvernay, Sabrina; Ndiaye, Ibrahima; Batista, Gilbert; Guèye, Papa Mandoumbé; Bâ, Pape Samba; Taverne, Bernard; Delaporte, Eric; Sow, Papa Salif

2012-01-01

Cardiovascular risk factors in people on antiretroviral treatment (ART) are poorly documented in resource-constrained settings. A cross-sectional study was conducted in 2009 to assess prevalence of diabetes and hypertension in a sample of 242 HIV-infected patients who had initiated ART between 1998 and 2002 in Dakar, Senegal (ANRS 1215 observational cohort). World Health Organization (WHO) criteria were applied to diagnose diabetes and hypertension. Multiple logistic regressions were used to identify factors associated with diabetes and hypertension. Patients had a median age of 46 years and had received ART for a median duration of about 9 years. 14.5% had diabetes and 28.1% had hypertension. Long duration of ART (≥119 months), older age, higher body mass index (BMI), and higher levels of total cholesterol were associated with higher risks of diabetes. Older age, higher BMI at ART initiation, and higher levels of triglycerides were associated with higher risk of hypertension. This study shows that diabetes and hypertension were frequent in these Senegalese HIV patients on ART. It confirms the association between duration of ART and diabetes and highlights the need to implement programs for prevention of cardiovascular risk factors in HIV patients from resource-constrained settings. PMID:24052880

Risk and Protective Factors for Early Substance Use Initiation: A Longitudinal Study of Mexican-Origin Youth

PubMed Central

Atherton, Olivia E.; Conger, Rand D.; Ferrer, Emilio; Robins, Richard W.

2015-01-01

Substance use initiation in adolescence is a critical issue, given its association with substance dependency and associated problems in adulthood. However, due to the dearth of fine-grained, longitudinal studies, the factors associated with early initiation are poorly understood, especially in minority youth. The present study examined substance use initiation in a sample of Mexican-origin youth (N=674) assessed annually from age 10 to 16. Using discrete-time survival analyses, we found that initiation escalated rapidly from late childhood to adolescence, and we identified a wide range of factors, from the individual to the cultural level of analysis, that significantly increased or decreased risk for early initiation. These findings have important implications for programs aimed at preventing early substance use by Mexican-origin youth. PMID:27990071

A 15-year retrospective analysis of prognostic factors in childhood bacterial meningitis.

PubMed

Wee, Liang Yi Justin; Tanugroho, Raymond Reinaldo; Thoon, Koh Cheng; Chong, Chia Yin; Choong, Chew Thye; Krishnamoorthy, Subramania; Maiwald, Matthias; Tee, Nancy Wen Sim; Tan, Natalie Woon Hui

2016-01-01

This retrospective chart review aimed to identify factors in childhood bacterial meningitis that predicted disease severity and long-term outcome. The study included 112 episodes of microbiologically confirmed bacterial meningitis in children aged three days to 15 years who were admitted to a Singapore hospital from 1998 to 2013. The mortality rate was 6%, and 44% required intensive care unit (ICU) admission. Predictive factors associated with ICU admission included pneumococcal meningitis, with an odds ratio (OR) of 5.2 and 95% confidence interval (CI) of 1.5-18.2, leukopenia (OR 5.6, 95% CI 1.7-17.9) and a cerebrospinal fluid (CSF):serum glucose ratio <0.25 (OR 4.5, 95% CI 1.4-14.4). An initial CSF white blood cell count >1000/mm(3) (OR 0.26, 95% CI 0.086-0.76) was negatively associated with ICU admission. Five years after meningitis, 32% had residual sequelae, and the associated prognostic factors were Haemophilus influenzae type b (Hib) meningitis (OR 29.5, 95% CI 2-429), seizures during their inpatient stay (OR 10.6, 95% CI 1.9-60.2) and septic shock (OR 8.4, 95% CI 1.1-62.1). As mortality was low in this bacterial meningitis study, ICU admission was used as a marker of disease severity. These findings underscore the importance of the pneumococcal and Hib meningitis vaccines. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Epidemiological Patterns of Initial and Subsequent Injuries in Collegiate Football Athletes.

PubMed

Williams, Jacob Z; Singichetti, Bhavna; Li, Hongmei; Xiang, Henry; Klingele, Kevin E; Yang, Jingzhen

2017-04-01

A body of epidemiological studies has examined football injuries and associated risk factors among collegiate athletes. However, few existing studies specifically analyzed injury risk in terms of initial or subsequent injuries. To determine athlete-exposures (AEs) and rates of initial and subsequent injury among collegiate football athletes. Descriptive epidemiological study. Injury and exposure data collected from collegiate football players from two Division I universities (2007-2011) were analyzed. Rate of initial injury was calculated as the number of initial injuries divided by the total number of AEs for initial injuries, while the rate for subsequent injury was calculated as the number of subsequent injuries divided by the total number of AEs for subsequent injury. Poisson regression was used to determine injury rate ratio (subsequent vs initial injury), with adjustment for other covariates. The total AEs during the study period were 67,564, resulting in an overall injury rate of 35.2 per 10,000 AEs. Rates for initial and subsequent injuries were 31.7 and 45.3 per 10,000 AEs, respectively, with a rate ratio (RR) of 1.4 for rate of subsequent injury vs rate of initial injury (95% CI, 1.1-1.9). Rate of injury appeared to increase with each successive injury. RR during games was 1.8 (95% CI, 1.1-3.0). The rate of subsequent injuries to the head, neck, and face was 10.9 per 10,000 AEs, nearly double the rate of initial injuries to the same sites (RR = 2.0; 95% CI, 1.1-3.5). For wide receivers, the rate of subsequent injuries was 2.2 times the rate of initial injuries (95% CI, 1.3-3.8), and for defensive linemen, the rate of subsequent injuries was 2.1 times the rate of initial injuries (95% CI, 1.1-3.9). The method used in this study allows for a more accurate determination of injury risk among football players who have already been injured at least once. Further research is warranted to better identify which specific factors contribute to this increased risk for subsequent injury.

Development and validation of a 21-item challenges to stopping smoking (CSS-21) scale

PubMed Central

Thomas, Dennis; Mackinnon, Andrew J; Bonevski, Billie; Abramson, Michael J; Taylor, Simone; Poole, Susan G; Weeks, Gregory R; Dooley, Michael J; George, Johnson

2016-01-01

Objective Identification of challenges associated with quitting and overcoming them may improve cessation outcomes. This study describes the development and initial validation of a scale for measuring challenges to stopping smoking. Methods The item pool was generated from empirical and theoretical literature and existing scales, expert opinion and interviews with smokers and ex-smokers. The questionnaire was administered to smokers and recent quitters who participated in a hospital-based smoking cessation trial. Exploratory factor analysis was performed to identify subscales in the questionnaire. Internal consistency, validity and robustness of the subscales were evaluated. Results Of a total of 182 participants with a mean age of 55 years (SD 12.8), 128 (70.3%) were current smokers and 54 (29.7%) ex-smokers. Factor analysis of the 21-item questionnaire resulted in a 2-factor solution representing items measuring intrinsic (9 items) and extrinsic (12 items) challenges. This structure was stable in various analyses and the 2 factors accounted for 50.7% of the total variance of the polychoric correlations between the items. Internal consistency (Cronbach's α) coefficients for the intrinsic and extrinsic subscales were 0.86 and 0.82, respectively. Compared with ex-smokers, current smokers had a higher mean score (±SD) for intrinsic (24.0±6.4 vs 20.5±7.4, p=0.002) and extrinsic subscales (22.3±7.5 vs 18.6±6.0, p=0.001). Conclusions Initial evaluation suggests that the 21-item challenges to stopping smoking scale is a valid and reliable instrument that can be used in research and clinical settings to assess challenges to stopping smoking. PMID:27033963

Delayed Treatment Acceleration in Patients with Rheumatoid Arthritis Who Have Inadequate Response to Initial Tumor Necrosis Factor Inhibitors: Data from the Corrona Registry

PubMed Central

Pappas, Dimitrios A.; Gerber, Robert A.; Litman, Heather J.; Gruben, David; Geier, Jamie; Hua, Winnie D.; Chen, Connie; Li, Youfu; Kremer, Joel M.; Andrews, John S.; Bourret, Jeffrey A.

2018-01-01

Background The implementation of treat-to-target principles in rheumatoid arthritis (RA) has not been fully investigated in patients with inadequate response to tumor necrosis factor (TNF) inhibitor treatment. Objectives To evaluate the prevalence of an inadequate response to initial TNF inhibitor treatment at 6 and 12 months among patients with RA in a real-world patient registry, as well as the delay in therapy adjustment and its impact on disease activity and patient-reported outcome (PRO) measures. Methods This analysis is based on data of patients with moderate or severe disease activity (Clinical Disease Activity Index [CDAI] score >10) who were included in the Consortium of Rheumatology Researchers of North America (Corrona) RA registry, a prospective, observational database. The patients had never received treatment with a biologic disease-modifying antirheumatic drug (DMARD) and had initiated treatment with a TNF inhibitor (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between October 2001 and December 2014. We evaluated treatment response (CDAI score ≤10), select PRO measures, and treatment changes at 6 months. Patients who had an inadequate response to TNF inhibitor therapy at 6 months and continued to use their initial TNF inhibitor were evaluated again at 12 months. Results This retrospective analysis included 2282 patients. At 6 months, 1732 (75.9%) of the patients continued to use their initial TNF inhibitor; of these, 803 (46.4%) patients had an inadequate response to treatment. Of the 803 patients who had an inadequate response at 6 months, 488 (60.8%) continued their initial treatment at 12 months. Of these 488 patients, 315 (64.5%) had an inadequate response at 12 months, and 173 (35.5%) had a response. Numerically greater improvements in all PRO measures were observed for patients who responded to therapy compared with patients with an inadequate response. Conclusions In this real-world analysis of data from the Corrona RA registry, a considerable proportion of patients with RA had an inadequate response to the initial TNF inhibitor therapy at 6 and 12 months. Many patients continued to have moderate or high disease activity, without accelerating treatment (eg, addition or increase in the dose of concurrent conventional synthetic DMARDs or a TNF inhibitor), contrary to treat-to-target principles, thus remaining at risk for accumulating joint damage and disability. PMID:29910846

Quantitative imaging reveals real-time Pou5f3–Nanog complexes driving dorsoventral mesendoderm patterning in zebrafish

PubMed Central

Perez-Camps, Mireia; Tian, Jing; Chng, Serene C; Sem, Kai Pin; Sudhaharan, Thankiah; Teh, Cathleen; Wachsmuth, Malte; Korzh, Vladimir; Ahmed, Sohail; Reversade, Bruno

2016-01-01

Formation of the three embryonic germ layers is a fundamental developmental process that initiates differentiation. How the zebrafish pluripotency factor Pou5f3 (homologous to mammalian Oct4) drives lineage commitment is unclear. Here, we introduce fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy to assess the formation of Pou5f3 complexes with other transcription factors in real-time in gastrulating zebrafish embryos. We show, at single-cell resolution in vivo, that Pou5f3 complexes with Nanog to pattern mesendoderm differentiation at the blastula stage. Later, during gastrulation, Sox32 restricts Pou5f3–Nanog complexes to the ventrolateral mesendoderm by binding Pou5f3 or Nanog in prospective dorsal endoderm. In the ventrolateral endoderm, the Elabela / Aplnr pathway limits Sox32 levels, allowing the formation of Pou5f3–Nanog complexes and the activation of downstream BMP signaling. This quantitative model shows that a balance in the spatiotemporal distribution of Pou5f3–Nanog complexes, modulated by Sox32, regulates mesendoderm specification along the dorsoventral axis. DOI: http://dx.doi.org/10.7554/eLife.11475.001 PMID:27684073

[Crisis unit at the general hospital: Determinants of further hospitalization].

PubMed

Norotte, C; Omnès, C; Crozier, C; Verlyck, C; Romanos, M

2017-10-01

The availability of short-stay beds for brief admission (less than 72hours) of crisis patients presenting to the emergency room is a model that has gained a growing interest because it allows time for developing alternatives to psychiatric hospitalization and favors a maintained functioning in the community. Still, the determinants influencing the disposition decision at discharge after crisis intervention remain largely unexplored. The primary objective of this study was to determine the factors predicting aftercare dispositions at crisis unit discharge: transfer for further hospitalization or return to the community. Secondary objectives included the description of clinical and socio-demographic characteristics of patients admitted to the crisis unit upon presentation to the emergency room. All patients (n=255) admitted to the short-stay unit of the emergency department of Rambouillet General Hospital during a one-year period were included in the study. Patient characteristics were collected in a retrospective manner from medical records: patterns of referral, acute stressors, presenting symptoms, initial patient demand, Diagnostic and Statistical Manual, 5th edition (DSM-5) disorders, psychiatric history, and socio-demographic characteristics were inferred. Logistic regression analysis was used to determine the factors associated with hospitalization decision upon crisis intervention at discharge. Following crisis intervention at the short-stay unit, 100 patients (39.2%) required further hospitalization and were transferred. Statistically significant factors associated with a higher probability of hospitalization (P<0.05) included the patient's initial wish to be hospitalized (OR=4.28), the presence of a comorbid disorder (OR=3.43), a referral by family or friends (OR=2.89), a history of psychiatric hospitalization (OR=2.71) and suicidal ideation on arrival in the emergency room (OR=2.26). Conversely, significant factors associated with a lower probability of hospitalization were the presence of a personality disorder (OR=0.31), a precipitating conflict situation (OR=0.41), age between 20 and 39 years (OR=0.42), being employed (OR=0.49). Our study confirms that clinical factors such as the presence of a personality disorder or the context of a precipitating conflict situation are predictive of a community return. Interestingly, it points out the importance of the patient's initial wish in the hospitalization decision. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

One-year weight losses in the Look AHEAD study: factors associated with success.

PubMed

Wadden, Thomas A; West, Delia S; Neiberg, Rebecca H; Wing, Rena R; Ryan, Donna H; Johnson, Karen C; Foreyt, John P; Hill, James O; Trence, Dace L; Vitolins, Mara Z

2009-04-01

This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self-reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population.

Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo

PubMed Central

Uprety, Bhawana; Sen, Rwik

2015-01-01

NuA4 (nucleosome acetyltransferase of H4) promotes transcriptional initiation of TFIID (a complex of TBP and TBP-associated factors [TAFs])-dependent ribosomal protein genes involved in ribosome biogenesis. However, it is not clearly understood how NuA4 regulates the transcription of ribosomal protein genes. Here, we show that NuA4 is recruited to the promoters of ribosomal protein genes, such as RPS5, RPL2B, and RPS11B, for TFIID recruitment to initiate transcription, and the recruitment of NuA4 to these promoters is impaired in the absence of its Eaf1p component. Intriguingly, impaired NuA4 recruitment in a Δeaf1 strain depletes recruitment of TFIID (a TAF-dependent form of TBP) but not the TAF-independent form of TBP to the promoters of ribosomal protein genes. However, in the absence of NuA4, SAGA (Spt-Ada-Gcn5-acetyltransferase) is involved in targeting the TAF-independent form of TBP to the promoters of ribosomal protein genes for transcriptional initiation. Thus, NuA4 plays an important role in targeting TFIID to the promoters of ribosomal protein genes for transcriptional initiation in vivo. Such a function is mediated via its targeted histone acetyltransferase activity. In the absence of NuA4, ribosomal protein genes lose TFIID dependency and become SAGA dependent for transcriptional initiation. Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions. PMID:26100014

Promoter-dependent and -independent activation of insulin-like growth factor binding protein-5 gene expression by prostaglandin E2 in primary rat osteoblasts

NASA Technical Reports Server (NTRS)

McCarthy, T. L.; Casinghino, S.; Mittanck, D. W.; Ji, C. H.; Centrella, M.; Rotwein, P.

1996-01-01

Insulin-like growth factor (IGF) action is mediated by high affinity cell surface IGF receptors and modulated by a family of secreted IGF binding proteins (IGFBPs). IGFBP-5, the most conserved of six IGFBPs characterized to date, uniquely potentiates the anabolic actions of IGF-I for skeletal cells. In osteoblasts, IGFBP-5 production is stimulated by prostaglandin E2 (PGE2), a local factor that mediates certain effects induced by parathyroid hormone, cytokines such as interleukin-1 and transforming growth factor-beta, and mechanical strain. In this study, we show that transcriptional and post-transcriptional events initiated by PGE2 collaborate to enhance IGFBP-5 gene expression in primary fetal rat osteoblast cultures. PGE2 treatment stimulated up to a 7-fold rise in steady-state levels of IGFBP-5 mRNA throughout 32 h of incubation. Analysis of nascent IGFBP-5 mRNA suggested that PGE2 had only a modest stimulatory effect on IGFBP-5 gene transcription, and transient transfection studies with IGFBP-5 promoter-reporter genes confirmed that PGE2 enhanced promoter activity by approximately 2-fold. Similar stimulatory effects were seen with forskolin. A DNA fragment with only 51 base pairs of the 5'-flanking sequence retained hormonal responsiveness, which may be mediated by a binding site for transcription factor AP-2 located at positions -44 to -36 in the proximal IGFBP-5 promoter. Incubation of osteoblasts with the mRNA transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole demonstrated that PGE2 enhanced IGFBP-5 mRNA stability by 2-fold, increasing the t1/2 from 9 to 18 h. The effects of PGE2 on steady-state IGFBP-5 transcripts were abrogated by preincubating cells with cycloheximide, indicating that the effects of PGE2 on both gene transcription and mRNA stability required ongoing protein synthesis. Therefore, both promoter-dependent and -independent pathways converge to enhance IGFBP-5 gene expression in response to PGE2 in osteoblasts.

Factors associated with inadequate work ability among women in the clothing industry.

PubMed

Augusto, Viviane Gontijo; Sampaio, Rosana Ferreira; Ferreira, Fabiane Ribeiro; Kirkwood, Renata Noce; César, Cibele Comini

2015-01-01

Work ability depends on a balance between individual resources and work demands. This study evaluated factors that are associated with inadequate work ability among workers in the clothing industry. We conducted a cross-sectional observational study of 306 workers in 40 small and medium-sized enterprises. We assessed work ability, individual resources, physical and psychosocial demands, and aspects of life outside work using a binary logistic regression model with hierarchical data entry. The mean work ability was 42.5 (SD=3.5); when adjusted for age, only 11% of the workers showed inadequate work ability. The final model revealed that smoking, high isometric physical load, and poor physical environmental conditions were the most significant predictors of inadequate work ability. Good working conditions and worker education must be implemented to eliminate factors that can be changed and that have a negative impact on work ability. These initiatives include anti-smoking measures, improved postures at work, and better physical environmental conditions.

A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.

PubMed Central

Méthot, N; Song, M S; Sonenberg, N

1996-01-01

The binding of mRNA to the ribosome is mediated by eukaryotic initiation factors eukaryotic initiation factor 4F (eIF4F), eIF4B, eIF4A, and eIF3, eIF4F binds to the mRNA cap structure and, in combination with eIF4B, is believed to unwind the secondary structure in the 5' untranslated region to facilitate ribosome binding. eIF3 associates with the 40S ribosomal subunit prior to mRNA binding. eIF4B copurifies with eIF3 and eIF4F through several purification steps, suggesting the involvement of a multisubunit complex during translation initiation. To understand the mechanism by which eIF4B promotes 40S ribosome binding to the mRNA, we studied its interactions with partner proteins by using a filter overlay (protein-protein [far Western]) assay and the two-hybrid system. In this report, we show that eIF4B self-associates and also interacts directly with the p170 subunit of eIF3. A region rich in aspartic acid, arginine, tyrosine, and glycine, termed the DRYG domain, is sufficient for self-association of eIF4B, both in vitro and in vivo, and for interaction with the p170 subunit of eIF3. These experiments suggest that eIF4B participates in mRNA-ribosome binding by acting as an intermediary between the mRNA and eIF3, via a direct interaction with the p170 subunit of eIF3. PMID:8816444

Multimode theory of plasmon excitation at a metal - photonic crystal interface

NASA Astrophysics Data System (ADS)

Kuznetsova, T. I.; Raspopov, N. A.

2017-12-01

Surface plasmon excitation at a photonic crystal - metal interface is studied taking into account multiple scattering of an initial light wave on a periodical crystal structure. The analysis is focused on calculating characteristics of the eigenwaves in a one-dimensional crystal, which comprise a set of harmonics with the wavevectors separated from each other by the value of the crystal lattice wavevector. Reflection from the crystal - metal interface binds the amplitudes of propagating and evanescent modes. Calculations show that for the dielectric characteristics of a synthetic opal and a substrate made of a real metal with a ruby laser radiation used as the initial wave, the fulfilment of plasmon resonance conditions leads to a local increase in the surface plasmon amplitude by a factor of 6.4 - 9 as compared to the average amplitude of the initial wave. As a rule, the effect can only be obtained for a single surface wave, all other waves being substantially weaker than the main plasmon. There is a specific case where the resonance condition holds for two modes simultaneously. In this case, two oppositely directed fluxes of equal intensity are generated at the interface. The resonance condition breaks at a small deviation of the incident angle of the initial wave θ from the normal direction (|θ| ⩾ 10-4 rad). In the latter case, the picture is asymmetric: at angles |θ| ⩾ 5 × 10-3 rad, only one plasmon remains intensive. The local density of electromagnetic energy at the photonic crystal - metal interface may exceed the corresponding value of the initial wave by a factor of 40 - 80.

Timeliness of lung cancer care in Victoria: a retrospective cohort study.

PubMed

Evans, Sue M; Earnest, Arul; Bower, Wendy; Senthuren, Meera; McLaughlin, Peta; Stirling, Rob

2016-02-01

To assess factors associated with second-line delays in the management of patients diagnosed with lung cancer. A retrospective cohort study, conducted in six public and two private Victorian hospitals, of 1417 patients aged 18 years or more who were diagnosed between July 2011 and October 2014 with an incident case of lung cancer identified by International Classification of Diseases, 10th revision codes (C34.0-C34.9, Z85.1, Z85.2) on the basis of either a clinical or pathological diagnosis. Time intervals between referral, diagnosis and initial definitive management. The median time from referral to diagnosis was 15 days (interquartile range [IQR], 5-36); from diagnosis to initial definitive management, 30 days (IQR, 6-84); and from referral to initial definitive management, 53 days (IQR, 25-106). Factors that were significantly associated with delay between referral and initial definitive management include declining or not being referred to palliative care (hazard ratio [HR], v patients referred for palliation, 0.73; 95% CI, 0.62-0.86; P < 0.001), and being treated in a public hospital (HR, v patients managed in a private hospital, 0.55; 95% CI, 0.48-0.64; P < 0.001). The median time from referral to initial definitive management in public and private hospitals was 61 days (IQR, 35-118) and 30 days (IQR, 13-76) respectively; 48% of patients in public hospitals waited longer than the British National Health Service target of a maximum 62 days between referral and first definitive treatment. There are significant delays at various stages of the patient journey after referral for initial definitive management. Having a greater understanding of these delays will enable strategies to be developed that improve the timeliness of care for patients with lung cancer.

Comparing the burden of illness of haemophilia between resource-constrained and unconstrained countries: the São Paulo-Toronto Hemophilia Study.

PubMed

Carneiro, J D A; Blanchette, V; Ozelo, M C; Antunes, S V; Villaca, P R; Young, N L; Castro, D; Brandão, L R; Carcao, M; Abad, A; Feldman, B M

2017-09-01

Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative. © 2017 John Wiley & Sons Ltd.

The untold stories of the speech gene, the FOXP2 cancer gene.

PubMed

Herrero, Maria Jesus; Gitton, Yorick

2018-01-01

FOXP2 encodes a transcription factor involved in speech and language acquisition. Growing evidence now suggests that dysregulated FOXP2 activity may also be instrumental in human oncogenesis, along the lines of other cardinal developmental transcription factors such as DLX5 and DLX6 [1-4]. Several FOXP familymembers are directly involved during cancer initiation, maintenance and progression in the adult [5-8]. This may comprise either a pro-oncogenic activity or a deficient tumor-suppressor role, depending upon cell types and associated signaling pathways. While FOXP2 is expressed in numerous cell types, its expression has been found to be down-regulated in breast cancer [9], hepatocellular carcinoma [8] and gastric cancer biopsies [10]. Conversely, overexpressed FOXP2 has been reported in multiple myelomas, MGUS (Monoclonal Gammopathy of Undetermined Significance), several subtypes of lymphomas [5,11], as well as in neuroblastomas [12] and ERG fusion-negative prostate cancers [13]. According to functional evidences reported in breast cancer [9] and survey of recent transcriptomic and proteomic analyses of different tumor biopsies, we postulate that FOXP2 dysregulation may play a main role throughout cancer initiation and progression. In some cancer conditions, FOXP2 levels are now considered as a critical diagnostic marker of neoplastic cells, and in many situations, they even bear strong prognostic value [5]. Whether FOXP2 may further become a therapeutic target is an actively explored lead. Knowledge reviewed here may help improve our understanding of FOXP2 roles during oncogenesis and provide cues for diagnostic, prognostic and therapeutic analyses.

The untold stories of the speech gene, the FOXP2 cancer gene

PubMed Central

2018-01-01

FOXP2 encodes a transcription factor involved in speech and language acquisition. Growing evidence now suggests that dysregulated FOXP2 activity may also be instrumental in human oncogenesis, along the lines of other cardinal developmental transcription factors such as DLX5 and DLX6 [1–4]. Several FOXP familymembers are directly involved during cancer initiation, maintenance and progression in the adult [5–8]. This may comprise either a pro-oncogenic activity or a deficient tumor-suppressor role, depending upon cell types and associated signaling pathways. While FOXP2 is expressed in numerous cell types, its expression has been found to be down-regulated in breast cancer [9], hepatocellular carcinoma [8] and gastric cancer biopsies [10]. Conversely, overexpressed FOXP2 has been reported in multiple myelomas, MGUS (Monoclonal Gammopathy of Undetermined Significance), several subtypes of lymphomas [5,11], as well as in neuroblastomas [12] and ERG fusion-negative prostate cancers [13]. According to functional evidences reported in breast cancer [9] and survey of recent transcriptomic and proteomic analyses of different tumor biopsies, we postulate that FOXP2 dysregulation may play a main role throughout cancer initiation and progression. In some cancer conditions, FOXP2 levels are now considered as a critical diagnostic marker of neoplastic cells, and in many situations, they even bear strong prognostic value [5]. Whether FOXP2 may further become a therapeutic target is an actively explored lead. Knowledge reviewed here may help improve our understanding of FOXP2 roles during oncogenesis and provide cues for diagnostic, prognostic and therapeutic analyses. PMID:29725501

Movement patterns and the medium-sized city. Tenants on the move in Gweru, Zimbabwe.

PubMed

Grant, M

1995-01-01

During 1965-79, urban growth rates accelerated and continued after Zimbabwe's independence in 1980. For 1960-80, the estimated urban growth rate was 5.6% as compared with the natural growth rate of 3.5% and urban growth rate of 5.0% to 8.1% for the period 1982-92. Gweru, Zimbabwe, had a population of 110,000 in 1990, and as the provincial capital it is an important destination for rural and interurban migrants. Between 1982 and 1990 there was a 4.9% growth rate, resulting in the municipal waiting list for housing to exceed 14,000 in mid-1990. In a large study on migration and rental shelter, 188 tenants were interviewed in high, low-medium density, and periurban areas of the city with the intent of tracing respondents and the nature of migration streams. Regarding origins and connections, only one-fifth of the migrants were born in Gweru, more than half were born in rural areas, and the rest in other urban areas. More than 90% still had rural homes. Two-thirds made rural home visits six times or less a year and one-fourth visited seven times a year to once a month. 40% of the migrants to Gweru originated in larger cities, 24% in smaller urban areas, and 36% in rural areas. 58% moved to high density areas, 34% to low-medium, and 8% to peri-urban areas. The dominant motive was the search for employment and direct transfers, thus economic factors dominated over social factors. Three groups were distinguished according to length of stay: 1) 5 years or less who lived mainly in high and low-medium density housing; 2) 6-15 years; and 3) more than 15 years who lived in low density and high density areas. Regarding the previous two migrations, two-thirds stayed at the previous place for 5 years of less. The reasons for migration were overcrowding, family, and employment. Within Gweru high mobility was typical: one-third initiated one step, 43% initiated two steps, and 27% initiated three steps. Lodgers were the most mobile since one-third were moving three times.

Heat Pre-Treatment of Beverages Wastewater on Hydrogen Production

NASA Astrophysics Data System (ADS)

Uyub, S. Z.; Mohd, N. S.; Ibrahim, S.

2017-06-01

At present, a large variety of alternative fuels have been investigated and hydrogen gas is considered as the possible solution for the future due to its unique characteristics. Through dark fermentation process, several factors were found to have significant impact on the hydrogen production either through process enhancement or inhibition and degradation rates or influencing parameters. This work was initiated to investigate the optimum conditions for heat pre-treatment and initial pH for the dark fermentative process under mesophilic condition using a central composite design and response surface methodology (RSM). Different heat treatment conditions and pH were performed on the seed sludge collected from the anaerobic digester of beverage wastewater treatment plant. Heat treatment of inoculum was optimized at different exposure times (30, 90, 120 min), temperatures (80, 90 and 100°C) and pH (4.5, 5.5, 6.5) in order to maximize the biohydrogen production and methanogens activity inhibition. It was found that the optimum heat pre-treatment condition and pH occurred at 100°C for 50 min and the pH of 6.00. At this optimum condition the hydrogen yield was 63.0476 ml H2/mol glucose (H2 Yield) and the COD removal efficiency was 90.87%. In conclusion, it can be hypothesized that different heat treatment conditions led to differences in the initial microbial communities (hydrogen producing bacteria) which resulted in the different hydrogen yields.

Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

PubMed Central

Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

2013-01-01

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612

Is Follow-Up Testing with the FilmArray Gastrointestinal Multiplex PCR Panel Necessary?

PubMed Central

Park, Sholhui; Hitchcock, Matthew M.; Gomez, Carlos A.

2017-01-01

ABSTRACT The FilmArray gastrointestinal (GI) panel (BioFire Diagnostics, Salt Lake City, UT) is a simple, sample-to-answer, on-demand, multiplex, nucleic acid amplification test for syndromic diagnosis of infectious gastroenteritis. The aim of this study was to measure the yield of follow-up testing with FilmArray GI panel within 4 weeks of an initial test. Consecutive adult and pediatric patients tested at an academic institution between August 2015 and June 2016 were included in this study. Of 145 follow-up tests in 106 unique patients with an initial negative result, 134 (92.4%) tests and 98 (92.5%) patients remained negative upon follow-up testing. Excluding targets that are not reported at this institution (Clostridium difficile, enteroaggregative Escherichia coli, enteropathogenic E. coli, and enterotoxigenic E. coli), 137 (94.5%) follow-up tests and 101 (95.3%) patients remained negative. Weekly conversion rates were not significantly different across the 4-week follow-up interval. No epidemiological or clinical factors were significantly associated with a negative to positive conversion. Of 80 follow-up tests in patients with an initial positive result, 43 (53.8%) remained positive for the same target, 34 (42.5%) were negative, and 3 were positive for a different target (3.8%). Follow-up testing with FilmArray GI panel within 4 weeks of a negative result rarely changed the initial result, and the follow-up test reverted to negative less than half the time after an initial positive result. In the absence of clinical or epidemiological evidence for a new infection, follow-up testing should be limited and FilmArray GI panel should not be used as a test of cure. PMID:28122874

A 67-Item Stress Resilience item bank showing high content validity was developed in a psychosomatic sample.

PubMed

Obbarius, Nina; Fischer, Felix; Obbarius, Alexander; Nolte, Sandra; Liegl, Gregor; Rose, Matthias

2018-04-10

To develop the first item bank to measure Stress Resilience (SR) in clinical populations. Qualitative item development resulted in an initial pool of 131 items covering a broad theoretical SR concept. These items were tested in n=521 patients at a psychosomatic outpatient clinic. Exploratory and Confirmatory Factor Analysis (CFA), as well as other state-of-the-art item analyses and IRT were used for item evaluation and calibration of the final item bank. Out of the initial item pool of 131 items, we excluded 64 items (54 factor loading <.5, 4 residual correlations >.3, 2 non-discriminative Item Response Curves, 4 Differential Item Functioning). The final set of 67 items indicated sufficient model fit in CFA and IRT analyses. Additionally, a 10-item short form with high measurement precision (SE≤.32 in a theta range between -1.8 and +1.5) was derived. Both the SR item bank and the SR short form were highly correlated with an existing static legacy tool (Connor-Davidson Resilience Scale). The final SR item bank and 10-item short form showed good psychometric properties. When further validated, they will be ready to be used within a framework of Computer-Adaptive Tests for a comprehensive assessment of the Stress-Construct. Copyright © 2018. Published by Elsevier Inc.

Enlistment Motivation and the Disposition of Army Applicants. Technical Report 74-5.

ERIC Educational Resources Information Center

Fisher, Allan H., Jr.; Harford, Margi R.

Objectives of the study were (1) to determine the structure of reasons that lead to the enlistment decision and (2) to isolate factors that lead some initial Army applicants to enlist in one of the other Services instead of the Army. This study involved the analysis and interpretation of data from an existing survey base--data from a sample of…

The impact of initial antibiotic treatment failure: Real-world insights in healthcare-associated or nosocomial pneumonia.

PubMed

Ryan, Kellie; Karve, Sudeep; Peeters, Pascale; Baelen, Elisa; Potter, Danielle; Rojas-Farreras, Sonia; Pascual, Esther; Rodríguez-Baño, Jesús

2018-05-06

To assess real-world treatment patterns and clinical outcomes associated with initial antibiotic therapy (IAT, antibiotics received ≤ 48 h post-initiation of antibiotic therapy), including level of IAT failure, and potential risk factors for IAT failure in healthcare-associated infections. Data were obtained from medical records of adult patients hospitalized with healthcare-associated pneumonia (HCAP) and nosocomial pneumonia (NP), including ventilator-associated pneumonia, from 1 July 2013 to 30 June 2014 in Brazil, France, Italy, Russia and Spain during the retrospective, observational study, RECOMMEND (NCT02364284; D4280R00005). Potential risk factors for IAT failure were explored using logistic regression analyses. Mean (standard deviation) age and Deyo-Charlson Comorbidity Score were 66.0 (16.2) years and 2.4 (2.4), respectively (N = 451). Most patients (62.5%) received monotherapy. Mean (standard deviation) duration of IAT was 8.8 (7.2) days. Multidrug-resistant (MDR) pathogens were identified in 52.4% of patients with ≥ 1 pathogen isolated (154/294). IAT failure was recorded in 72.5% of patients and was significantly associated with isolation of a MDR pathogen and country using multivariate analyses. Real-world data demonstrate the burden of HCAP/NP, with high rates of IAT failure. The association of IAT failure with MDR pathogens highlights the urgent need to understand and account for local prevalence of MDR pathogens when selecting IAT for the management of HCAP/NP. Copyright © 2018. Published by Elsevier Ltd.

Assurance of Myeloid Growth Factor Administration in an Infusion Center: Pilot Quality Improvement Initiative.

PubMed

Ramirez, Pamela Maree; Peterson, Barry; Holtshopple, Christine; Borja, Kristina; Torres, Vincent; Valdivia-Peppers, Lucille; Harriague, Julio; Joe, Melanie D

2017-12-01

Four incident reports involving missed doses of myeloid growth factors (MGFs) triggered the need for an outcome-driven initiative. From March 1, 2015, to February 29, 2016, at University of California Irvine Health Chao Infusion Center, 116 of 3,300 MGF doses were missed (3.52%), including pegfilgrastim, filgrastim, and sargramostim. We hypothesized that with the application of Lean Six Sigma methodology, we would achieve our primary objective of reducing the number of missed MGF doses to < 0.5%. This quality improvement initiative was conducted at Chao Infusion Center as part of a Lean Six Sigma Green Belt Certification Program. Therefore, Lean Six Sigma principles and tools were used throughout each phase of the project. Retrospective and prospective medical record reviews and data analyses were performed to evaluate the extent of the identified problem and impact of the process changes. Improvements included systems applications, practice changes, process modifications, and safety-net procedures. Preintervention, 24 missed doses (20.7%) required patient supportive care measures, resulting in increased hospital costs and decreased quality of care. Postintervention, from June 8, 2016, to August 7, 2016, zero of 489 MGF doses were missed after 2 months of intervention ( P < .001). Chao Infusion Center reduced missed doses from 3.52% to 0%, reaching the goal of < 0.5%. The establishment of simplified and standardized processes with safety checks for error prevention increased quality of care. Lean Six Sigma methodology can be applied by other institutions to produce positive outcomes and implement similar practice changes.

Risk factors for severe acute malnutrition in children below 5 y of age in India: a case-control study.

PubMed

Mishra, Kirtisudha; Kumar, Praveen; Basu, Srikanta; Rai, Kiran; Aneja, Satinder

2014-08-01

To determine the possible risk factors for severe acute malnutrition (SAM) in children below 5 y admitted in a hospital in north India. This case-control study was conducted in a medical college hospital in children below 5 y of age. All cases of SAM (diagnosed as per WHO definition) between 6 and 59 mo of age were compared with age-matched controls with weight for height above -2SD of WHO 2006 growth standards. Data regarding socio-demographic parameters, feeding practices and immunization were compared between the groups by univariable and multivariable logistic regression models. A total of 76 cases and 115 controls were enrolled. Among the 14 factors compared, maternal illiteracy, daily family income less than Rs. 200, large family size, lack of exclusive breast feeding in first 6 mo, bottle feeding, administration of pre-lacteals, deprivation of colostrum and incomplete immunization were significant risk factors for SAM. Regarding complementary feeding, it was the consistency, rather than the age of initiation, frequency and variety which showed a significant influence on occurrence of SAM. Multivariate analysis revealed that the risk of SAM was independently associated with 6 factors, namely, illiteracy among mothers, incomplete immunization, practice of bottle feeding, consistency of complementary feeding, deprivation of colostrum and receipt of pre-lacteals at birth. The present study identifies certain risk factors which need to be focused on during health planning and policy making related to children with SAM in India.

Prevalence and patterns of antidepressant switching amongst primary care patients in the UK.

PubMed

Mars, Becky; Heron, Jon; Gunnell, David; Martin, Richard M; Thomas, Kyla H; Kessler, David

2017-05-01

Non-response to antidepressant treatment is a substantial problem in primary care, and many patients with depression require additional second-line treatments. This study aimed to examine the prevalence and patterns of antidepressant switching in the UK, and identify associated demographic and clinical factors. Cohort analysis of antidepressant prescribing data from the Clinical Practice Research Datalink, a large, anonymised UK primary care database. The sample included 262,844 patients who initiated antidepressant therapy between 1 January 2005 and 31 June 2011. 9.3% of patients switched to a different antidepressant product, with most switches (60%) occurring within 8 weeks of the index date. The proportion switching was similar for selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants (9.3%, 9.8% and 9.2%, respectively). Most switches were to an SSRI (64.5%), and this was the preferred option regardless of initial antidepressant class. Factors predictive of switching included male gender, age, and history of self-harm and psychiatric illness. Over one in every 11 patients who initiates antidepressant therapy will switch medication, suggesting that initial antidepressant treatment has been unsatisfactory. Evidence to guide choice of second-line treatment for individual patients is currently limited. Additional research comparing different pharmacological and psychological second-line treatment strategies is required in order to inform guidelines and improve patient outcomes.

The value of initial cavitation to predict re-treatment with pulmonary tuberculosis.

PubMed

Huang, Qiusheng; Yin, Yongmei; Kuai, Shougang; Yan, Yan; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Pei, Hao; Wang, Jun

2016-05-06

Pulmonary cavitation is the classic hallmark of pulmonary tuberculosis (PTB) and is the site of very high mycobacterial burden associated with antimycobacterial drug resistance and treatment failure. The objective of this study was to investigate the relationship between re-treatment PTB and initial pulmonary cavitation coordinated with other clinical factors. We conducted a case-control study of 291 newly diagnosed cases of pulmonary TB in The Infectious Hospital of Wuxi from Dec 2009 to Dec 2011 with complete follow-up information until December 31st of 2014. 68 patients were followed-up with PTB re-treatment; the rest of the PTB patients (n = 223) had completed anti-TB treatment, and cured without re-treatment were selected as controls. The univariate analysis [hazard ratio (HR) 1.885, 95 % CI 1.170-3.035, P = 0.009] and the multivariable analysis (HR 2.242, 95 % CI 1.294-3.882, P = 0.004) demonstrated that the initial pulmonary cavitation was a prognostic predictor for TB re-treatment. Additionally, the re-treatment rates in PTB patients with cavitation and no-cavitation were 27.1 and 15.5 %, respectively, with significant difference (log-rank test; P = 0.010). Other factors, age of ≥60 and history of smoking, were also prognostic variables. Initial pulmonary cavitation of chest X-ray was a significant predictor for PTB re-treatment.

Water infiltration in prewetted porous media: dynamic capillary pressure and Green-Ampt modeling

NASA Astrophysics Data System (ADS)

Hsu, S.; Hilpert, M.

2013-12-01

Recently, an experimental study has shown that the modified Green-Ampt (GA) model, which accounts for a velocity-dependent capillary pressure, can describe water infiltration in dry sand columns better than the classical GA model. Studies have also shown that the initial water content of prewetted porous media affects the dynamic capillary pressure during infiltration. In this study, we performed a series of downward water infiltration experiments in prewetted sand columns for four different initial water contents: 0%, 3.3%, 6.5%, and 13.8%. We also used three different ponding heights: 10 cm, 20 cm, and 40 cm. As expected, an increase in ponding height resulted in a monotonic increase in cumulative infiltration. However, we found anomalous behavior, in that the cumulative infiltration did not monotonically decrease as the initial water content increased. When modeling the experiments with the modified GA approach, we linked this anomalous behavior to the reduction factor in the model for dynamic capillary pressure that is a function of initial water content.