From \u27omics\u27 to complex disease: a systems biology approach to gene-environment interactions in cancer

Background Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. Hypothesis The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. Conclusion Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression

From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

<p>Abstract</p> <p>Background</p> <p>Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development.</p> <p>Hypothesis</p> <p>The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction.</p> <p>Conclusion</p> <p>Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and <it>in vitro/in vivo </it>translational research that more accurately reflects the complex process of tumor initiation and progression.</p

Clients\u27 Internal Representations of Their Therapists

Thirteen adults in long-term individual psychotherapy were interviewed regarding their internal representations (defined as bringing to awareness the internalized image ) of their therapists. Results indicated that in the context of a good therapeutic relationship, clients\u27 internal representations combined auditory, visual, and kinesthetic (i.e., felt presence) modalities; were triggered when clients thought about past or future sessions, or when distressed; occurred in diverse locations; and varied in frequency, duration, and intensity. Clients felt positively about their representations and used them to introspect or influence therapy within sessions, beyond sessions, or both. The frequency of, comfort with, and use of clients\u27 internal representations increased over the course of therapy, and the representations benefited the therapy and therapeutic relationship. Therapists tended not to take a deliberate role in creating clients\u27 internal representations, and few clients discussed their internal representations with their therapists

Sexual Attraction Toward Clients, Use of Supervision, and Prior Training: A Qualitative Study of Predoctoral Psychology Interns

Interviews were conducted with 13 predoctoral psychology interns about an experience of sexual attraction toward a client, use of supervision to address the sexual attraction, and prior training regarding sexual attraction. Results indicated that sexual attraction to clients consisted of physical and interpersonal aspects. Therapists believed they were more invested and attentive than usual to clients to whom they were sexually attracted, and they indicated that sexual attraction created distance, distraction, and loss of objectivity. In terms of supervision, only half of the participants disclosed their sexual attraction to supervisors, and supervisors seldom initiated the discussion. Furthermore, trainees found it helpful when supervisors normalized the sexual attraction and provided the opportunity to explore feelings in supervision. Finally, trainees believed their training programs did not adequately address therapist sexual attraction

Rubella immunity and serum perfluoroalkyl substances: Sex and analytic strategy

Background Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to child- hood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations. Objective To examine whether serum PFASs were associated with reduced immunity to rubella immu- nization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differ- ences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage. Methods We analyzed a nationally representative sample of individuals 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999–2000 and 2003–2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances. Results After exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size anal- yses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex. Conclusions These results support our earlier studies showing sex specific responses to PFASs and indi- cate the importance of thinking carefully about analytic strategies in population based toxi- cology research

Association between Depressive Symptoms and Metabolic Syndrome in Police Officers: Results from Two Cross-Sectional Studies

Policing is one of the most dangerous and stressful occupations and such stress can have deleterious effects on health. The purpose of this study was to examine the association between depressive symptoms and metabolic syndrome (MetSyn) in male and female police officers from two study populations, Buffalo, NY and Spokane, WA. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale. MetSyn was defined using the 2005 AHA/NHBLI guidelines. Analysis of covariance was used to describe differences in number of MetSyn components across depressive symptom categories. The number of MetSyn components increased significantly across categories of CES-D for Spokane men only (p-trend = 0.003). For each 5-unit increase in CES-D score, odds increased by 47.6% for having hypertriglyceridemia, by 51.8% for having hypertension, and by 56.7% for having glucose intolerance. Exploring this association is important since both are predictors of future chronic health problems and the results could be helpful in developing future gender-specific prevention and intervention efforts among police officers

Treatment compliance and effectiveness of a cognitive behavioural intervention for low back pain : a complier average causal effect approach to the BeST data set

Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance. Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment. Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation. Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance

Kate 2006 Winter

Each year, kate seeks to: explore ideas about normative gender, sex, and sexuality work against oppression and hierarchies of power in any and all forms serve as a voice for race and gender equity as well as queer positivity encourage the silent to speak and feel less afraid build a zine and community that we care about and trusthttps://digitalcommons.otterbein.edu/kate/1005/thumbnail.jp

AGT M235T Genotype/Anxiety Interaction and Gender in the HyperGEN Study

BACKGROUND. Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N=1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups. METHODOLOGY. The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style). PRINCIPAL FINDINGS. Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype. CONCLUSION/SIGNIFICANCE. The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.National Heart, Lung and Blood Institute (UT FC, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515

Multiwavelength observations of the EUV variable metal-rich white dwarf GD 394

We present new Hubble Space Telescope (HST) ultraviolet and ground-based optical observations of the hot, metal-rich white dwarf GD394. Extreme-ultraviolet (EUV) observations in 1992-1996 revealed a 1.15 d periodicity with a 25 per cent amplitude, hypothesized to be due to metals in a surface accretion spot. We obtained phase resolved HST/Space Telescope Imaging Spectrograph high resolution far-ultraviolet spectra of GD394 that sample the entire period, along with a large body of supplementary data. We find no evidence for an accretion spot, with the flux, accretion rate, and radial velocity of GD394 constant over the observed time-scales at ultraviolet and optical wavelengths. We speculate that the spot may have no longer been present when our observations were obtained, or that the EUV variability is being caused by an otherwise undetected evaporating planet. The atmospheric parameters obtained from separate fits to optical and ultraviolet spectra are inconsistent, as is found for multiple hot white dwarfs. We also detect non-photospheric, high ionisation absorption lines of multiple volatile elements, which could be evidence for a hot plasma cocoon surrounding the white dwarf.European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013 / ERC Grant) [320964]; Leverhulme Trust Research Project Grant; NASA [NAS 5-26555]; NASA through a Space Telescope Science Institute [13719]; W. M. Keck FoundationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]