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1.  Prevalence and co-occurrence of addictive behaviors among former alternative high school youth 
Background and Aims
Recent work has studied multiple addictions using a matrix measure, which taps multiple addictions through single responses for each type.
Methods
The present study investigated use of a matrix measure approach among former alternative high school youth (average age = 19.8 years) at risk for addictions. Lifetime and last 30-day prevalence of one or more of 11 addictions reviewed in other work (Sussman, Lisha & Griffiths, 2011) was the primary focus (i.e., cigarettes, alcohol, other/hard drugs, eating, gambling, Internet, shopping, love, sex, exercise, and work). Also, the co-occurrence of two or more of these 11 addictive behaviors was investigated. Finally, the latent class structure of these addictions, and their associations with other measures, was examined.
Results
We found that ever and last 30-day prevalence of one or more of these addictions was 79.2% and 61.5%, respectively. Ever and last 30-day co-occurrence of two or more of these addictions was 61.5% and 37.7%, respectively. Latent Class Analysis suggested two groups: a generally Non-addicted Group (67.2% of the sample) and a “Work Hard, Play Hard”-addicted Group that was particularly invested in addiction to love, sex, exercise, the Internet, and work. Supplementary analyses suggested that the single-response type self-reports may be measuring the addictions they intend to measure.
Discussion and Conclusions
We suggest implications of these results for future studies and the development of prevention and treatment programs, though much more validation research is needed on the use of this type of measure.
doi:10.1556/JBA.3.2014.005
PMCID: PMC3969796
multiple addictions; prevalence; co-occurrence; latent class analysis; addiction groups; convergent validity
2.  Impaired conditioned fear response and startle reactivity in epinephrine deficient mice 
Behavioural pharmacology  2013;24(1):1-9.
Norepinephrine and epinephrine signaling is thought to facilitate cognitive processes related to emotional events and heightened arousal, however, the specific role of epinephrine in these processes is less known. To investigate the selective impact of epinephrine on arousal and fear-related memory retrieval, mice unable to synthesize epinephrine (phenylethanolamine N-methyltransferase knockout, PNMT-KO) were tested in context and cued fear conditioning. To assess the role of epinephrine in other cognitive and arousal-based behaviors these mice were also tested for acoustic startle, prepulse inhibition, novel object recognition and open field activity. Our results show that compared to wild-type (WT) mice, PNMT-KO mice displayed reduced context fear but normal cued fear. Mice exhibited normal memory performance in the short-term version of the novel object recognition task suggesting PNMT mice exhibit more selective memory effects on highly emotional and/or long term memories. Similarly, open field activity was unaffected by epinephrine deficiency, suggesting differences in freezing are not related to changes in overall anxiety or exploratory drive. Startle reactivity to acoustic pulses was reduced in PNMT-KO mice while prepulse inhibition was increased. These findings provide further evidence for a selective role of epinephrine in contextual fear learning, and support its potential role in acoustic startle.
doi:10.1097/FBP.0b013e32835cf408
PMCID: PMC3558035  PMID: 23268986
PNMT; epinephrine; conditioned fear; memory; acoustic startle; prepulse inhibition; arousal
3.  Expression of glucosylceramide synthase in invasive ductal breast cancer may be correlated with high estrogen receptor status and low HER-2 status 
Diagnostic Pathology  2014;9:22.
Abstract
Background and objectives
Breast cancer is one of the most common causes of cancer-related deaths in women worldwide. Studies on glucosylceramide synthase (GCS) activity suggest that this enzyme has a role in the development of multidrug resistance in many cancer cells. However, few studies have shown the expression of GCS in invasive ductal breast cancer and breast intraductal proliferative lesions.
Methods
In total, 196 samples from patients with invasive ductal breast cancer and 61 samples of breast intraductal proliferative lesions were collected. Immunohistochemical analyses were conducted to determine the expression of GCS and other related proteins.
Results
Expression of GCS was high in estrogen receptor (ER)-positive and HER-2 negative samples. In contrast, the expression of GCS in invasive ductal cancer was significantly lower than that in intraductal proliferative lesions.
Conclusion
Our data demonstrates a correlation between the expression of the GCS protein and ER-positive/HER-2 negative breast cancer. Furthermore, in contrast to previous reports, the expression of GCS protein was shown to be much higher in ductal carcinoma in-situ than that in invasive ductal cancer.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1559854430111589.
doi:10.1186/1746-1596-9-22
PMCID: PMC3976100  PMID: 24456584
Glucosylceramide synthase; Breast cancer; Multidrug resistance; ER; HER-2
4.  Long-Term Ovarian Cancer Survival Associated With Mutation in BRCA1 or BRCA2 
Background
Studies have suggested that the 5-year survival of women with ovarian cancer and a BRCA1 or BRCA2 mutation is better than expected. We sought to evaluate the impact of carrying a BRCA1 or BRCA2 mutation on long-term survival of women after a diagnosis of invasive ovarian cancer.
Methods
One thousand six hundred twenty-six unselected women diagnosed with invasive ovarian cancer in Ontario, Canada, or in Tampa, Florida, between 1995 and 2004 were followed for a mean of 6.9 years (range = 0.3 to 15.7 years). Mutation screening for BRCA1 and BRCA2 revealed mutations in 218 women (13.4%). Left-truncated survival analysis was conducted to estimate ovarian cancer–specific survival at various time points after diagnosis for women with and without mutations.
Results
In the 3-year period after diagnosis, the presence of a BRCA1 or BRCA2 mutation was associated with a better prognosis (adjusted hazard ratio = 0.68, 95% confidence interval [CI] = 0.48 to 0.98; P = .03), but at 10 years after diagnosis, the hazard ratio was 1.00 (95% CI = 0.83 to 1.22; P = .90). Among women with serous ovarian cancers, 27.4% of women who were BRCA1 mutation carriers, 27.7% of women who were BRCA2 carriers, and 27.1% of women who were noncarriers were alive at 12 years past diagnosis.
Conclusion
For women with invasive ovarian cancer, the short-term survival advantage of carrying a BRCA1 or BRCA2 mutation does not lead to a long-term survival benefit.
doi:10.1093/jnci/djs494
PMCID: PMC3611851  PMID: 23257159
5.  Evaluation of the Psychometric Properties of the Revised Inventory of the Dimensions of Emerging Adulthood (IDEA-R) in a Sample of Continuation High School Students 
Evaluation & the health professions  2012;10.1177/0163278712452664.
It is now presumed that youth do not move directly from adolescence to adulthood, but rather pass through a transitional period, “emerging adulthood.” The Revised Inventory of the Dimensions of Emerging Adulthood (IDEA-R) is a self-report instrument developed to examine the attributes of this period. “At-risk” youth appear to enter emerging adulthood developmental tasks at a slightly earlier age than general population youth. In the present study, a 21-item version of the IDEA was administered to a sample of 1676 “at-risk” continuation (alternative) high school students in Southern California. Principal component factor analysis with orthogonal rotation revealed three factors the authors labeled “Identity Exploration,” “Experimentation/Possibilities,” and “Independence.” Overall, the measure demonstrated high internal consistency. Construct validity analyses indicated that the measure was correlated with demographics, risk behaviors, and psychological measures. The authors conclude that the IDEA-R is a useful instrument for measuring emerging adulthood in at-risk populations.
doi:10.1177/0163278712452664
PMCID: PMC3796175  PMID: 22786874
emerging adulthood; continuation high school; at-risk youth; inventory of the dimensions of emerging adulthood (IDEA); psychometrics
6.  The Effects of Implementation Fidelity in the Towards No Drug Abuse Dissemination Trial 
Purpose
The current study examines the influence of contextual and provider-level factors on the implementation fidelity of a research-based substance abuse prevention program. Also, it investigates whether two provider-level factors, self-efficacy and beliefs about the value of the program, statistically moderate and mediate the effects of a provider training intervention on implementation fidelity.
Design/methodology/approach
Using generalized mixed-linear modeling, we examine relationships between program provider-, organizational, and community-level factors and implementation fidelity in a sample of 50 high school teachers from 43 high schools in 8 states across the U.S. Fidelity of implementation was assessed utilizing an observation procedure.
Findings
Implementation fidelity was negatively associated with the urbanicity of the community and the level of teachers’ beliefs about the value of the program, and positively predicted by the organizational capacity of the school. Comprehensive training significantly increased teachers’ self-efficacy, which resulted in an increase in implementation fidelity.
Research implications
School-based prevention program implementation is influenced by a variety of contextual factors occurring at multiple ecological levels. Future effectiveness and dissemination studies need to account for the complex nature of schools in analyses of implementation fidelity and outcomes.
Practical implications
Our findings suggest that both provider- and organizational-level factors are influential in promoting implementation fidelity. Before implementation begins, as well as throughout the implementation process, training and ongoing technical assistance should be conducted to increase teachers’ skills, self-efficacy, and comfort with prevention curricula.
Originality/value
The present study is one of the few to examine contextual and provider-level correlates of implementation fidelity and use mediation analyses to explore whether provider-level factors mediate the effects of a provider training intervention on implementation fidelity.
doi:10.1108/09654281311329231
PMCID: PMC3876420
7.  Tamoxifen and the Risk of Ovarian Cancer in BRCA1 Mutation Carriers 
Gynecologic oncology  2009;115(1):135-137.
Objective
BRCA1 mutation carriers have a high rate of both breast and ovarian cancer. Tamoxifen is a selective estrogen receptor modulator (SERM), which is used for the treatment of primary breast cancer and for the prevention of contralateral breast cancer. Our objective is to assess if tamoxifen treatment is associated with an increase in the subsequent risk of ovarian cancer among women with a BRCA1 mutation.
Methods
A matched case-control study was performed. Cases were 154 women with ovarian cancer and a previous history of breast cancer. Controls were 560 women with no ovarian cancer and a history of breast cancer. All cases and controls carry a deleterious BRCA1 mutation. Cases and controls were matched for year of birth, age at diagnosis of breast cancer and country of residence. The effect of tamoxifen treatment on the risk of subsequent ovarian cancer was estimated using conditional logistic regression.
Results
The unadjusted odds ratio for ovarian cancer, given previous tamoxifen treatment was 0.89 (95% CI 0.54–1.49, p = 0.66). After adjusting for other treatments, the odds ratio was 0.78 (95% CI 0.46–1.33, p = 0.36).
Conclusion
Tamoxifen treatment for breast cancer does not appear to increase the risk of ovarian cancer in BRCA1 mutation carriers.
doi:10.1016/j.ygyno.2009.06.012
PMCID: PMC3756313  PMID: 19577280
Ovarian cancer; Tamoxifen; BRCA1 mutation
8.  Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers 
Breast (Edinburgh, Scotland)  2010;19(6):479-483.
Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrolment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70–0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71–1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.
doi:10.1016/j.breast.2010.05.009
PMCID: PMC3756317  PMID: 20541936
BRCA1; BRCA2; Alcohol; Breast cancer; Case-control; Wine
10.  Association of Dll4/Notch and HIF-1a -VEGF Signaling in the Angiogenesis of Missed Abortion 
PLoS ONE  2013;8(8):e70667.
Background
Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion.
Methods
Women with missed abortion (n = 27) and healthy controls (n = 26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry.
Results
Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1.
Conclusions
The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.
doi:10.1371/journal.pone.0070667
PMCID: PMC3739820  PMID: 23950980
11.  N,N-Diethyl-4-[1-phenyl-3-(pyridin-2-yl)-4,5-di­hydro-1H-pyrazol-5-yl]aniline 
In the title mol­ecule, C24H26N4, the pyrazoline ring assumes an envelope conformation with the aniline-bearing C atom at the flap position. The benzene ring and the pyridine ring form with the pyrazoline ring dihedral angles of 4.53 (1) and 6.26 (1)°, respectively. In turn, the aniline group is nearly perpendicular to the pyrazoline ring [dihedral angle = 79.96 (1)°]. The ethyl groups of the di­ethyl­amine substituent are disordered over two sets of sites, with an occupancy ratio of 0.624 (8):0.376 (8).
doi:10.1107/S1600536813019879
PMCID: PMC3793803  PMID: 24109390
12.  Predicting Self-Initiated Marijuana Use Cessation among Youth at Continuation High Schools 
The current article reports a large scale study of the prediction of marijuana use cessation among individuals attending alternative high schools who were regular users at baseline. Based on the Triadic Influence Theory, predictors of marijuana use cessation at 1-year follow-up were organized by type of influence (e.g., interpersonal, cultural and attitudinal, and intrapersonal) and level of influence (e.g., distal and ultimate). Among the 522 students who were past 30-day marijuana users at baseline, quitting was defined as having not used marijuana in the last 30 days at 1-year follow-up (43% of baseline users). To account for the level of influence we employed a theory-based analytic strategy, hierarchical regression. In the final multivariate model, lower level of baseline marijuana use and less of a likelihood to endorse pro-drug-use myths remained predictors of marijuana use cessation 1-year later. Implications of these findings include the need to develop cessation programs that reduce psychological dependence on marijuana use, and correct cognitive misperceptions about drug use in order to help adolescents make decisions that lead to health-promoting behaviors.
doi:10.3389/fpsyt.2013.00069
PMCID: PMC3724123  PMID: 23898305
marijuana; cessation; adolescents; youth; cannabis; self-initiated; predictors
13.  One-year outcomes of a drug abuse prevention program for older teens and emerging adults: Evaluating a motivational interviewing booster component 
Health Psychology  2011;31(4):476-485.
Objective
The present study tested the efficacy of motivational interviewing-based booster sessions for Project Towards No Drug Abuse (TND), a 12-session school-based curriculum targeting youth at risk for drug abuse. In addition, generalization of effects to risky sexual behavior was assessed. The one-year outcomes evaluation of the project is presented.
Methods
A total of 24 schools were randomized to one of three conditions: Standard Care Control (SCC), TND classroom program only (TND-only), and TND plus Motivational Interviewing booster (TND+MI). A total of 1186 participants completed baseline and one-year follow-up surveys. Following the classroom program, youth in the TND+MI condition received up to three sessions of MI in person or by telephone. Effects were examined on 30-day cigarette, alcohol, marijuana, and hard drug use, as well as measures of risky sexual behavior (number of sex partners, condom use, having sex while using drugs or alcohol).
Results
Collapsed across the two program conditions, results showed significant reductions in alcohol, hard drug use, and cigarette smoking, relative to controls. These effects held for an overall substance use index. The MI booster component failed to achieve significant incremental effects above and beyond the TND classroom program. No effects were found on risky sexual behavior.
Conclusions
While the program effects of previous studies were replicated, the study failed to demonstrate that an adequately implemented MI booster was of incremental value at one-year follow-up.
doi:10.1037/a0025756
PMCID: PMC3276711  PMID: 21988096
one-year follow-up; drug prevention; continuation high schools; Motivational Interviewing; boosters
14.  The Risk of Breast Cancer in Women with a BRCA1 Mutation from North America and Poland 
Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, non-genetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.
doi:10.1002/ijc.26369
PMCID: PMC3334396  PMID: 21834074
BRCA1; breast cancer; penetrance
15.  Anhedonia Predicts Altered Processing of Happy Faces in Abstinent Cigarette Smokers 
Psychopharmacology  2012;222(2):343-351.
Rationale
Anhedonia—diminished capacity to experience pleasure—is associated with tobacco dependence and smoking cessation failure. However, the mechanisms linking anhedonia and smoking are unclear.
Objectives
This study examined whether trait anhedonia predicted cognitive processing of emotional faces during experimentally-manipulated acute tobacco deprivation in smokers. Because nicotine may offset reward processing deficits in anhedonia and these deficits may become expressed during abstinence, we hypothesized that anhedonia would predict diminished cognitive processing of happy (vs. neutral) facial expressions in nicotine deprived but not nondeprived states.
Methods
Smokers not attempting to quit (n=75; 10+cig/day) completed anhedonia questionnaires in a baseline session. Participants then attended two counterbalanced experimental sessions: one following 18-hours of tobacco abstinence and one after unrestricted smoking. At both sessions, they completed a computer-based measure of attentional interference induced by emotional facial expressions.
Results
The extent to which anhedonia predicted Happiness interference differed as a function of deprivation status (ps ≤ .04, ηp 2s > .06). Anhedonia predicted lower interference by happy (vs. neutral) faces in the deprived condition (r=−.28, p=.02) but not in the nondeprived condition (r=.08, p=.51). Analyses of a secondary measure of anhedonia found marginally-significant effects in the same direction.
Conclusions
These findings indicate that disrupted processing of positively-valenced social cues occurs upon abstinence in high-anhedonia individuals. This alteration may motivate reinstatement of smoking in order to remediate these deficits. More broadly, these results suggest that the neuropharmacological pathways affected by nicotine may underlie disrupted emotional processing in anhedonia—a prominent feature in several psychiatric disorders.
doi:10.1007/s00213-012-2649-5
PMCID: PMC3383908  PMID: 22311383
Anhedonia; Smoking; Nicotine Dependence; Nicotine Withdrawal; Emotional Processing; Facial expressions
16.  Oophorectomy after Menopause and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers 
Background
To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers.
Methods
We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates.
Results
The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ = −0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (P-trend < 0.0001) but not among BRCA2 (P-trend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause (OR = 0.52; 95%CI 0.40–0.66; P-trend < 0.0001) was greater than that associated with natural menopause (OR = 0.81; 95%CI 0.62–1.07; P-trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR = 0.13; 95%CI 0.02–0.54; P = 0.006).
Conclusions
These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and post-menopausal oophorectomy protect against breast cancer.
Impact
Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.
doi:10.1158/1055-9965.EPI-12-0201
PMCID: PMC3593267  PMID: 22564871
BRCA1; ovulatory cycles; breast cancer; oophorectomy
17.  The protective effect of geniposide on human neuroblastoma cells in the presence of formaldehyde 
Background
Formaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline.
Methods
In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored.
Results
Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment.
Conclusions
Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.
doi:10.1186/1472-6882-13-152
PMCID: PMC3702466  PMID: 23815892
Formaldehyde impairment; Geniposide; Neuroprotection
18.  Correction: Protein Tyrosine Phosphatase µ (PTP µ or PTPRM), a Negative Regulator of Proliferation and Invasion of Breast Cancer Cells, Is Associated with Disease Prognosis 
PLoS ONE  2013;8(6):10.1371/annotation/c8259769-10d5-4acf-be8e-ba24ff22a3e5.
doi:10.1371/annotation/c8259769-10d5-4acf-be8e-ba24ff22a3e5
PMCID: PMC3681986
19.  A Low Selenium Level Is Associated with Lung and Laryngeal Cancers 
PLoS ONE  2013;8(3):e59051.
Purpose
It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls.
Methods
We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype.
Results
Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers.
Conclusion
A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.
doi:10.1371/journal.pone.0059051
PMCID: PMC3596323  PMID: 23516596
20.  Associations between Posttraumatic Stress Disorder Symptom Clusters and Cigarette Smoking 
Understanding the relationship between Posttraumatic stress disorder (PTSD) and cigarette smoking has been difficult due to PTSD’s symptomatic heterogeneity. This study examined common and unique lifetime cross-sectional relationships between PTSD symptom clusters (Re-experiencing [intrusive thoughts and nightmares about the trauma], Avoidance [avoidance of trauma-associated memories or stimuli], Emotional Numbing [loss of interest, interpersonal detachment, restricted positive affect], and Hyperarousal [irritability, difficulty concentrating, hypervigilance, insomnia]) and three indicators of smoking behavior: (1) smoking status; (2) cigarettes per day; and (3) nicotine dependence. Participants were adult respondents in the National Epidemiologic Survey of Alcohol and Related Conditions with a trauma history (N=23,635). All four symptom clusters associated with each smoking outcome in single-predictor models (ps<.0001). In multivariate models including all of the symptom clusters as simultaneous predictors, Emotional Numbing was the only cluster to retain a significant association with lifetime smoking over and above the other clusters, demographics, and Axis-I comorbidity (OR=1.30, p<.01). While Avoidance uniquely associated with smoking status and nicotine dependence in multivariate models, these relations fellow below significance after adjusting for demographics and comorbidity. No clusters uniquely associated with cigarettes per day. Hyperarousal uniquely related with nicotine dependence over and above the other clusters, demographics, and Axis-I comorbidity (OR=1.51, p<.001). These results suggest that: (a) common variance across PTSD symptom clusters contribute to PTSD’s linkage with smoking in the American population; and (b) certain PTSD symptom clusters may uniquely associate with particular indicators of smoking behavior. These findings may clarify the underpinnings of PTSD-smoking comorbidity and inform smoking interventions for trauma-exposed individuals.
doi:10.1037/a0024328
PMCID: PMC3307596  PMID: 21688875
Posttraumatic Stress Disorder; Smoking; Comorbidity; Nicotine Dependence; Posttraumatic Stress Disorder Symptom Clusters
21.  Expression of c-myc and PCNA in Epstein-Barr virus-associated gastric carcinoma 
The aim of this study was to detect the expression of proliferatng cell nuclear antigen (PCNA) and c-myc in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), as well as the expression of EBV-encoded proteins in EBVaGC and their effect on carcinogenesis and the development of gastric cancer. The PCNA and c-myc protein levels were assessed by immunohistochemistry in 13 EBVaGC and 45 EBVnGC specimens. The expression of related genes of EBV, including EB nuclear antigen (NA)-1 and EBNA2 genes, latent membrane protein 1 (LMP1) and early genes BARF1 and BHRF1 were tested by reverse transcription-polymerase chain reaction (RT-PCR) and southern blotting. The PCNA labeling index (LI) of EBVaGCs, EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 49.3768±12.1832, 14.839±7.1847, 35.613±8.3831 and 24.2735±10.1332, respectively. The PCNA LI was significantly different between EBVaGC and EBVnGC of EBVaGC (t=4.686, P<0.01). The difference between EBVaGC and corresponding adjacent tissues of EBVaGC was also significant (t=8.805, P<0.01). The expression of c-myc protein was detected in 33 of 58 (55.39%) gastric carcinomas and in 21 of 58 (36.21%) adjacent tissues. There was a significant difference between the two groups (χ2=4.989, P<0.05). The expression of the c-myc protein was detected in 8 of 13 (61.54%) EBVaGCs and in 25 of 45 (55.56%) EBVnGCs. The difference between the two groups was not significant (χ2=0.147, P>0.05). EBNA1 mRNA was detected in all 13 EBVaGC cases, while EBNA2 and LMP1 mRNA was not detected in these cases. Of the 13 EBV-positive samples, 6 exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. c-myc expression did not correlate with the presence of EBV in EBVaGC. EBV infection may induce PCNA expression. The lack of EBNA2 and LMP1 protein expression in EBVaGC suggests that EBNA2 and LMP1 do not correlate with cell apoptosis and c-myc expression. Early genes BARF1 and BHRF1 may play an important role in the development and progression of gastric carcinomas by immortalizing epithelial cells.
doi:10.3892/etm.2013.972
PMCID: PMC3628757  PMID: 23599727
stomach neoplasm; Epstein-Barr virus; c-myc; proliferating cell nuclear antigen; reverse transcription-polymerase chain reaction; immunohistochemistry; progressive genes
22.  Can we update the Summary Hospital Mortality Index (SHMI) to make a useful measure of the quality of hospital care? An observational study 
BMJ Open  2013;3(1):e002018.
Objective
To advance methods for the estimation of hospital performance based upon mortality ratios.
Design
Observational study estimating trust performance in a year derived according to comparative standards from a 3-year period, accounting for patient-level case-mix and overdispersion (unexplained variability).
Participants
23 363 630 admissions to the English National Health Service (NHS) by NHS Trust.
Main outcome measures
Number of SDs (QUality and Outcomes Research Unit Measure, QUORUM banding) and comparative odds of hospital mortality difference from mean performance by trust compared for 2010/2011, 2008/2009 and 2009/2010, accounting for patient-level case-mix.
Results
The model was highly predictive of mortality (C statistic=0.93), and well calibrated by risk stratum. There was substantial overdispersion. No trusts were more than 3 SDs above the mean, and only one trust was more than 2 SDs above the mean for 2010/2011.
Conclusions
QUORUM is highly predictive of patient mortality in hospital or up to 30 days after admission. However, like the Summary Hospital Mortality Indicator (SHMI), QUORUM is subjected to considerable remaining legitimate but unexplained variation. It is unlikely that measures like QUORUM and SHMI will be useful beyond identifying a very small number of trusts as potential outliers.
doi:10.1136/bmjopen-2012-002018
PMCID: PMC3563139  PMID: 23370014
Public Health; Education & Training (See Medical Education & Training); Epidemiology
23.  Electrocorticography Links Human Temporoparietal Junction to Visual Perception 
Nature neuroscience  2012;15(7):957-959.
Electrical stimulation of visual cortex can produce a visual percept (phosphene). We electrically stimulated visual cortex in human patients implanted with subdural electrodes while recording from other brain sites. Across experimental manipulations, we found that phosphene perception occurred only if stimulation evoked high-frequency gamma oscillations in the temporoparietal junction (TPJ), a brain region associated with visual extinction and neglect. Electrical stimulation of TPJ modified detectability of low-contrast visual stimuli.
doi:10.1038/nn.3131
PMCID: PMC3386474  PMID: 22660480

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