bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX
Authors: Coates Alan S , Millar Ewan KA , O'Toole Sandra A , Molloy Timothy J , Viale Giuseppe , Goldhirsch Aron , Regan Meredith M , Gelber Richard D , Sun Zhuoxin , Castiglione-Gertsch Monica , Gusterson Barry , Musgrove Elizabeth A , Sutherland Robert L 
Published: November 2012

Abstract
Introduction
The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown.

Methods
We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections.

Results
ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared.

Conclusions
Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression.

Trial registration
Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX).
Breast cancer risk assessment across the risk continuum: genetic and nongenetic risk factors contributing to differential model performance
Authors: Quante Anne S , Whittemore Alice S , Shriver Tom , Strauch Konstantin , Terry Mary B 
Published: November 2012

Abstract
Introduction
Clinicians use different breast cancer risk models for patients considered at average and above-average risk, based largely on their family histories and genetic factors. We used longitudinal cohort data from women whose breast cancer risks span the full spectrum to determine the genetic and nongenetic covariates that differentiate the performance of two commonly used models that include nongenetic factors - BCRAT, also called Gail model, generally used for patients with average risk and IBIS, also called Tyrer Cuzick model, generally used for patients with above-average risk.

Methods
We evaluated the performance of the BCRAT and IBIS models as currently applied in clinical settings for 10-year absolute risk of breast cancer, using prospective data from 1,857 women over a mean follow-up length of 8.1 years, of whom 83 developed cancer. This cohort spans the continuum of breast cancer risk, with some subjects at lower than average population risk. Therefore, the wide variation in individual risk makes it an interesting population to examine model performance across subgroups of women. For model calibration, we divided the cohort into quartiles of model-assigned risk and compared differences between assigned and observed risks using the Hosmer-Lemeshow (HL) chi-squared statistic. For model discrimination, we computed the area under the receiver operator curve (AUC) and the case risk percentiles (CRPs).

Results
The 10-year risks assigned by BCRAT and IBIS differed (range of difference 0.001 to 79.5). The mean BCRAT- and IBIS-assigned risks of 3.18% and 5.49%, respectively, were lower than the cohort's 10-year cumulative probability of developing breast cancer (6.25%; 95% confidence interval (CI) = 5.0 to 7.8%). Agreement between assigned and observed risks was better for IBIS (HL X42 = 7.2, P value 0.13) than BCRAT (HL X42 = 22.0, P value <0.001). The IBIS model also showed better discrimination (AUC = 69.5%, CI = 63.8% to 75.2%) than did the BCRAT model (AUC = 63.2%, CI = 57.6% to 68.9%). In almost all covariate-specific subgroups, BCRAT mean risks were significantly lower than the observed risks, while IBIS risks showed generally good agreement with observed risks, even in the subgroups of women considered at average risk (for example, no family history of breast cancer, BRCA1/2 mutation negative).

Conclusions
Models developed using extended family history and genetic data, such as the IBIS model, also perform well in women considered at average risk (for example, no family history of breast cancer, BRCA1/2 mutation negative). Extending such models to include additional nongenetic information may improve performance in women across the breast cancer risk continuum.
What clinicians need to know before assessing risk in sexual offenders
Authors: Darjee Rajan , Russell Katharine 
Published: November 2012

SummaryThis article covers what clinicians need to know before undertaking a risk assessment of a sexual offender. It discusses general information about sexual offenders (characteristics, aetiological models, recidivism rates and legal responses); the association between mental disorders and sexual offending; risk and protective factors; and risk assessment tools.
To scan or not to scan: neuroimaging in mild cognitive impairment and dementia
Authors: Sullivan Victoria , Majumdar Biswadeep , Richman Anna , Vinjamuri Sobhan 
Published: November 2012

SummaryThere is currently a huge variation in clinical practice as to whether patients being assessed for dementia undergo neuroimaging investigations. With an ageing population it is likely that there will be greater pressures on psychogeriatric services, so accurate assessment, diagnosis and prompt treatment will be required. This article will examine the evidence for the use of different neuroimaging techniques in the diagnosis of mild cognitive impairment and dementia.
Supervision: an issue for supervisors and supervisees
Authors: Wickham Jill Munro 
Published: November 2012

SummarySupervision, both managerial and clinical, is integral to all areas of practice in health and social care and arguably constitutes the most important aspect of our work. Through supervision, we demonstrate our own suitability and can offer others support in identifying strategies for improvement. It is surprising that many healthcare organisations either do not have a supervision policy or do little to monitor the effectiveness of the supervisory process. The aim of this brief article is to offer a starting point for thought, discussion and reading to motivate and encourage readers to improve their own supervisory practice as supervisor and supervisee.
ADHD with comorbid substance use disorder: review of treatment
Authors: Magon Rakesh , Müller Ulrich 
Published: November 2012

SummarySubstance use disorders are a frequent comorbidity in adult attention-deficit hyperactivity disorder (ADHD). This review discusses the relationship between adult ADHD and substance use disorder, including use of licit and illicit substances such as nicotine, alcohol, cocaine and cannabis. We discuss treatment studies in this area and provide a treatment algorithm to guide clinicians in the management of adult ADHD comorbid with different forms and severities of substance use disorder.
Preventive strategies in depression: gathering evidence for risk
factors and potential interventions
Authors: Berk Michael , Jacka Felice 
Published: November 2012

SummaryThis editorial critiques the recent literature concerning both vitamin D
deficiency in major depression and supplementation as a treatment strategy,
and contextualises it within a broader approach to the prevention of
depression, based on the recent evidence for lifestyle as a risk factor for
depression and anxiety.
Changes in diagnoses before admission to a specialist medium secure unit
Authors: Shetty Amrith , Jayawickrama Dilum , Taylor Pamela J. 
Published: November 2012

Aims and methodThere is evidence that changing diagnoses may be an important factor preceding homicide, but there is little literature on diagnostic antecedents to admission to specialist secure units after violent behaviour. Our aim was to establish the frequency of a history of changing diagnoses in patients in a UK specialist unit, and to explore the characteristics of these patients.ResultsIn total, 38 of 42 study participants had prior contact with psychiatric services. Just over 40% (16 of the 38) had had their diagnosis changed three or more times. All those who had major changes in their diagnosis had received a diagnosis of a psychotic illness at some point prior to the secure unit admission, but then had it withdrawn, only to be restored after prolonged assessment in the secure unit. Personality disorder and substance misuse comorbidity was common in this group; however, non-psychotic diagnoses were seen as more important than psychotic diagnoses by general services.Clinical implicationsChanges in diagnosis between first presentation to psychiatric services and admission to a medium-security unit were more common than would be expected from reports in the general literature. They are a testimony to the difficulties experienced by service providers in delivering a consistent service. This needs to be studied further.
E-learning package on the Mental Capacity Act 2005 for junior doctors and medical students
Authors: Schofield Zena , di Mambro Ben , Schofield Chris 
Published: November 2012

Aims and methodThe assessment of capacity is integral to all areas of medical practice; however, research has shown that doctors in many specialties have inadequate knowledge about both the Mental Capacity Act and the Mental Health Act. In this study, 39 trainee doctors and 49 fourth-year medical students completed an e-learning package, which included a pre- and post-evaluation of knowledge of the Mental Capacity Act and confidence in the use of this act.ResultsIn comparison to pre-intervention scores, trainee doctors and students displayed a statistically significant improvement in knowledge and subjective confidence.Clinical implicationsThe e-learning package is an effective educational tool for improving knowledge about the Mental Capacity Act for trainee doctors and could be included as part of induction training for all foundation doctors as well as being considered for use in the induction programme of other trainee doctors. It is an effective tool for educating clinical medical students about the Mental Capacity Act.
Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI
Authors: Stegger Lars , Martirosian Petros , Schwenzer Nina , Bisdas Sotirios , Kolb Armin , Pfannenberg Christina , Claussen Claus D , Pichler Bernd , Schick Fritz , Boss Andreas 
Published: November 2012

Background Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. Purpose To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. Material and Methods ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 × 128 and 192 × 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. Results Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51±9 and 51±7 mL/100 g/min for the 128 × 128 and 192 × 192 matrices (stand-alone MR, 57±2 and 55 ± 5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 × 192 matrix size ( P < 0.01), the relative signal change (δS) was significantly lower for the 192 × 192 matrix size ( P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. Conclusion ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.
Fixed flexion deformity and total knee arthroplasty
Authors: Su E. P. 
Published: November 2012

Fixed flexion deformities are common in osteoarthritic knees that are indicated for total knee arthroplasty. The lack of full extension at the knee results in a greater force of quadriceps contracture and energy expenditure. It also results in slower walking velocity and abnormal gait mechanics, overloading the contralateral limb. Residual flexion contractures after TKA have been associated with poorer functional scores and outcomes. Although some flexion contractures may resolve with time after surgery, a substantial percentage will become permanent. Therefore, it is essential to correct fixed flexion deformities at the time of TKA, and be vigilant in the post-operative course to maintain the correction. Surgical techniques to address pre-operative flexion contractures include: adequate bone resection, ligament releases, removal of posterior osteophytes, and posterior capsular releases. Post-operatively, extension can be maintained with focused physiotherapy, a specially modified continuous passive motion machine, a contralateral heel lift, and splinting.
Use of Romiplostim in a Hemodialysis Patient with Primary Immune Thrombocytopenia
Authors: Al-Jafar Hassan , Giagounidis Aristoteles , El-Rashaid Kamel , Al-Ali Masouma , Hakim Abbas A 
Published: November 2012

OBJECTIVE: To present the case of a patient with primary immune thrombocytopenia (ITP), renal impairment, and chronic hepatitis C virus (HCV) infection who was treated with platelet transfusions, intravenous immunoglobulin (IVIG), corticosteroids, eltrombopag, rituximab, and romiplostim in an attempt to raise platelet counts to a clinically acceptable level. CASE SUMMARY: A 71-year-old man with end-stage renal disease (ESRD) was on maintenance hemodialysis and had long-term diabetes mellitus, chronic obstructive pulmonary disease, and other comorbidities. He was admitted with epistaxis, severe thrombocytopenia, and a platelet count of 4 × 109/L. Platelet transfusions, treatment with IVIG, corticosteroids, eltrombopag, and rituximab resulted in transient and inadequate increases in platelet counts. Further bleeding manifestations, including epistaxis, melena, hematomas, and ecchymotic patches prompted treatment with blood product concentrates and a higher dose of eltrombopag, resulting in a further lack of clinical response. After 6 weeks of failed treatment attempts, initiation of weekly treatment with romiplostim 5 μg/kg resulted in rapid stabilization (within a week) of platelet counts in the range of 200 × 109/L. The patient was discharged, with subsequent dose adjustment of weekly romiplostim treatment to 2.5 μg/kg, continued hemodialysis, and a return to normal daily activities. DISCUSSION: The primary clinical concern in this elderly patient with multiple comorbidities was to lower the bleeding risk associated with consistent thrombocytopenia. Despite the lack of clinical data to support the efficacy and safety of romiplostim in patients with ITP and renal impairment, stimulation of platelet production with romiplostim was a reasonable approach in view of the bleeding risk and following nonresponse to treatment with corticosteroids, IVIG, eltrombopag, and rituximab. To our knowledge, this case represents the first successful use of romiplostim to manage primary ITP in the presence of ESRD and concurrent chronic HCV infection in a patient on hemodialysis. CONCLUSIONS: Romiplostim appears to be a viable option for treatment of ITP in a patient with ESRD and chronic HCV infection following nonresponse to treatment with corticosteroids, IVIG, eltrombopag, and rituximab.
Extended-Release Mesalamine Granules for Ulcerative Colitis
Authors: Love Bryan L , Miller April D 
Published: November 2012

OBJECTIVE: To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). DATA SOURCES: Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. DATA SYNTHESIS: The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. CONCLUSIONS: Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.
Competitive Effects of Mass Customization
Authors: Loginova Oksana 
Published: November 2012

Abstract
The existing theoretical literature on mass customization maintains that customization reduces product differentiation and intensifies price competition. In contrast, operations management studies argue that customization serves primarily to differentiate a company from its competitors. Interactive involvement of the customer in product design creates an affective relationship with the firm, relaxing price competition. This paper provides a model that incorporates consumer involvement to explain the phenomena described in the operations management literature.Two firms on the Hotelling line compete for a continuum of consumers with heterogeneous brand preferences. An exogenously given fraction of consumers is potentially interested in customization. Consumer benefits from customization are the rewards from a special shopping experience and the value of product customization (a better fitting product); these benefits are higher for consumers located closer to the customizing brand. When a consumer purchases a customized product, he/she incurs waiting costs. Each firm simultaneously decides whether to offer standard products, customized products, or both, and then engage in price competition. I show that customization increases product differentiation, leading to less intense price competition. Depending on the parameter values, in equilibrium either both firms offer customized products, one firm offers customized products and the other standard and customized products, or one firm offers customized products and the other standard products. I perform comparative statics analysis with respect to the fraction of consumers interested in customization, the waiting costs, and the fixed cost of customization.
Heterogeneity in Number and Type of Sexual Contacts in a Gay Urban Cohort
Authors: Romero-Severson Ethan O. , Alam Shah Jamal , Volz Erik M. , Koopman James S. 
Published: November 2012

Abstract
HIV transmission models include heterogeneous individuals with different sexual behaviors including contact rates, mixing patterns, and sexual practices. However, heterogeneity can also exist within individuals over time. In this paper we analyze a two year prospective cohort of 882 gay men with observations at six month intervals focusing on heterogeneity both within and between individuals in sexual contact rates and sexual roles. The total number of sexual contacts made over the course of the study (mean 1.55 per month) are highly variable between individuals (standard deviation 9.82 per month) as expected. At the individual level, contacts were also heterogeneous over time. For a homogeneous count process the variance should scale with the mean; however, at the individual level the variance scaled with the square root of the mean implying the presence of heterogeneity within individuals over time. We also observed a high level of movement between dichotomous sexual roles (insertive/receptive, protected/unprotected, anal/oral, and HIV status of partners). On average periods of exclusively unprotected sexual contacted lasted 16 months. Our results suggest that future HIV models should consider heterogeneities both between and within individuals in sexual contact rates and sexual roles.
Degradation of channelopsin-2 in the absence of retinal and degradation resistance in certain mutants
Authors: Ullrich Sybille , Gueta Ronnie , Nagel Georg 
Published: November 2012

Abstract
Channelrhodopsin-2 is a light-gated cation channel from the green alga Chlamydomonas reinhardtii. It is functional in animal cells and therefore widely used for light-activated depolarization, especially in neurons. To achieve a fully functional protein, the chromophore all-trans-retinal is needed. It has not been investigated whether or not the apoprotein is stable without its cofactor until now. Here we show that channelopsin-2 (Chop2, protein without bound retinal) is much more prone to degradation than channelrhodopsin-2 (protein with retinal). Constructs of Chop2 fused to yellow fluorescent protein (Chop2::YFP) in the absence and presence of retinal confirm this observation by exhibiting strongly differing fluorescence. We present mutants of Chop2 with highly increased stability in the absence of retinal. Substitution of threonine 159 with aromatic amino acids causes enhanced resistance to degradation in the absence of retinal, which is confirmed by fluorescence intensity, the increase in photocurrents on the addition of retinal to previously expressed protein, and Western blot analysis. Exchanging threonine 159 with cysteine, however, increases photocurrents due to better binding of retinal, without obvious stabilization against degradation of the retinal-free opsin. We also show that the light-activated hyperpolarizing chloride pump halorhodopsin from Natronomonas pharaonis (NpHR) is not prone to retinal-dependent degradation.