Increase in mammography detected breast cancer over time at a community based regional cancer center: a longitudinal cohort study 1990–2005

Background: Coincident with the advent of mammography screening, breast carcinoma in situ has increased in the US population. Methods: We conducted a prospective cohort study of all women presenting with primary breast cancer, aged 21-94, and biopsy confirmed Stage 0-IV from 1990-2005 identified and tracked by our registry. Clinical presentation characteristics including age, race, TNM stage, family and pregnancy history, histologic type and method of detection by patient (PtD), physician (PhysD) or mammography (MgD) were chart abstracted at time of diagnosis. Cases with unknown or other method of detection (n = 84), or unusual cell types (n = 26) were removed (n = 6074). Results: From 1990 to 1998 the percentage of PtD and MgD cases was roughly equivalent. In 1999 the percentage of MgD cases increased to 56% and PtD dropped to 37%, a significant 20% differential, constant to 2005 (Pearson chi square = 120.99, p less than .001). Overall, percent TNM stage 0 (breast carcinoma in situ) cases increased after 1990, percent stage I and III cases declined, and stage II and IV cases remained constant (Pearson chi square = 218.36, p less than .001). Increase in MgD over time differed by age group with an 8.5% increase among women age 40-49 and 12% increase among women age 50-95. Women age 21-39 rarely had MgD BC. In forward stepwise logistic regression modeling, significant predictors of MgD BC by order of entry were TNM stage, age at diagnosis, diagnosis year, and race (chi square = 1867.56, p less than .001). Conclusion: In our cohort the relative proportion of mammography detected breast cancer increased over time with a higher increase among women age 50+ and an increase of breast carcinoma in situ exclusively among MgD cases. The increase among women currently targeted by mammography screening programs (age = 50) combined with an increase of breast carcinoma in situ most often detected by mammography screening indicates a possible incidence shift to lower stage breast cancer as a result of mammographic detection.Kaplan Research Fun

Competing Activities of Heterotrimeric G Proteins in Drosophila Wing Maturation

Drosophila genome encodes six alpha-subunits of heterotrimeric G proteins. The Gαs alpha-subunit is involved in the post-eclosion wing maturation, which consists of the epithelial-mesenchymal transition and cell death, accompanied by unfolding of the pupal wing into the firm adult flight organ. Here we show that another alpha-subunit Gαo can specifically antagonize the Gαs activities by competing for the Gβ13F/Gγ1 subunits of the heterotrimeric Gs protein complex. Loss of Gβ13F, Gγ1, or Gαs, but not any other G protein subunit, results in prevention of post-eclosion cell death and failure of the wing expansion. However, cell death prevention alone is not sufficient to induce the expansion defect, suggesting that the failure of epithelial-mesenchymal transition is key to the folded wing phenotypes. Overactivation of Gαs with cholera toxin mimics expression of constitutively activated Gαs and promotes wing blistering due to precocious cell death. In contrast, co-overexpression of Gβ13F and Gγ1 does not produce wing blistering, revealing the passive role of the Gβγ in the Gαs-mediated activation of apoptosis, but hinting at the possible function of Gβγ in the epithelial-mesenchymal transition. Our results provide a comprehensive functional analysis of the heterotrimeric G protein proteome in the late stages of Drosophila wing development

Using historical documentary methods to explore the history of occupational therapy

peer-reviewed.Introduction: Historical research can benefit health professions by providing a basis for understanding how current beliefs and practices developed over time. From an occupational therapy perspective, a need for deeper critical understandings of the profession has been identified; historical research can facilitate this process. Documentary research is a significant methodology in historical inquiry, but there is a dearth of guidance for occupational therapists wishing to employ this method. Method: A conceptual literature review was conducted to describe how to use documentary sources to understand the development of the profession, drawing on literature from the disciplines of history and occupational therapy. Results: The stages of historical documentary research are described: choosing a topic, sourcing and selecting evidence, and managing sources. How to consider the authenticity, credibility and representativeness of historical material is discussed. Various means to determine the meaning of historical evidence are considered, with chronological, thematic and theoretical approaches proposed. Conclusion: Methodological transparency is central to the process of historical documentary research. To enhance understanding of the quality of historical source material, adoption of the guidelines outlined is recommended. Adopting a clearly defined questioning perspective promotes more substantial conclusions and professional understandingspeer-reviewe

Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions

Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation

Violent Recidivism: A Long-Time Follow-Up Study of Mentally Disordered Offenders

Background: In this prospective study, mentally disordered perpetrators of severe violent and/or sexual crimes were followed through official registers for 59 (range 8 to 73) months. The relapse rate in criminality was assessed, compared between offenders sentenced to prison versus forensic psychiatric care, and the predictive ability of various risk factors (criminological, clinical, and of structured assessment instruments) was investigated. Method: One hundred perpetrators were consecutively assessed between 1998 and 2001 by a clinical battery of established instruments covering DSM-IV diagnoses, psychosocial background factors, and structured assessment instruments (HCR-20, PCL-R, and life-time aggression (LHA)). Follow-up data was collected from official registers for: (i) recidivistic crimes, (ii) crimes during ongoing sanction. Results: Twenty subjects relapsed in violent criminality during ongoing sanctions (n = 6) or after discharge/parole (n = 14). Individuals in forensic psychiatric care spent significantly more time at liberty after discharge compared to those in prison, but showed significantly fewer relapses. Criminological (age at first conviction), and clinical (conduct disorder and substance abuse/dependence) risk factors, as well as scores on structured assessment instruments, were moderately associated with violent recidivism. Logistic regression analyses showed that the predictive ability of criminological risk factors versus clinical risk factors combined with scores from assessment instruments was comparable, with each set of variables managing to correctly classify about 80% of all individuals, but the only predictors that remained significant in multiple models were criminological (age at first conviction, and a history of substance abuse among primary relatives). Conclusions: Only one in five relapsed into serious criminality, with significantly more relapses among subjects sentenced to prison as compared to forensic psychiatric care. Criminological risk factors tended to be the best predictors of violent relapses, while few synergies were seen when the risk factors were combined. Overall, the predictive validity of common risk factors for violent criminality was rather weak

Molecular Dynamics Analysis Reveals Structural Insights into Mechanism of Nicotine N-Demethylation Catalyzed by Tobacco Cytochrome P450 Mono-Oxygenase

CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND) activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys–trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase

Is Body Fat a Predictor of Race Time in Female Long-Distance Inline Skaters?

Purpose: The aim of this study was to evaluate predictor variables of race time in female ultra-endurance inliners in the longest inline race in Europe. Methods: We investigated the association between anthropometric and training characteristics and race time for 16 female ultraendurance inline skaters, at the longest inline marathon in Europe, the ‘Inline One-eleven’ over 111 km in Switzerland, using bi- and multivariate analysis. Results: The mean (SD) race time was 289.7 (54.6) min. The bivariate analysis showed that body height (r=0.61), length of leg (r=0.61), number of weekly inline skating training sessions (r=-0.51)and duration of each training unit (r=0.61) were significantly correlated with race time. Stepwise multiple regressions revealed that body height, duration of each training unit, and age were the best variables to predict race time. Conclusion: Race time in ultra-endurance inline races such as the ‘Inline One-eleven’ over 111 km might be predicted by the following equation (r2 = 0.65): Race time (min) = -691.62 + 521.71 (body height, m) + 0.58 (duration of each training unit, min) + 1.78 (age, yrs) for female ultra-endurance inline skaters

Normative values for the Foot Posture Index

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Values - reviewing the construct and drawing implications for values work in organisation and leadership. Kap. 2

I: H.Askeland, G. Espedal, B. Jelstad Løvaas & S. Sirris (Eds.), Understanding values work : Institutional perspectives in organizations and leadershipThis chapter outlines the trajectory of values, particularly within streams of organisational institutionalism, in order to analyse its application to values work in organisation and leadership. Conveying a frame for discussing values work, it aims at clarifying how to conceptualise the term values. Discussing classic and recent contributions, the chapter proposes seeing values as individual and collective conceptions of desirable trans-situational behaviours, objectives and ideals, serving to guide or valuate practice. Despite being an essential part of defining organisational institutionalism, and its sub-streams, values are seldom explicated. Utilising values in organisational and leadership research requires attention to their situatedness in contexts, and this chapter argues they are salient to organisations operating in pluralistic institutional environment. Studying values work, attention should be given to who and how such work is performed.publishedVersio