Artist's Statement: Warli Village Solar Trust

Artist’s Statement for the cover art of IJPS volume 8, issue 2: Warli Village Solar Trust, rice paste on parchment

Anxious/depressed symptoms are related to microstructural maturation of white matter in typically developing youths

AbstractThere are multiple recent reports of an association between anxious/depressed (A/D) symptomatology and the rate of cerebral cortical thickness maturation in typically developing youths. We investigated the degree to which anxious/depressed symptoms are tied to age-related microstructural changes in cerebral fiber pathways. The participants were part of the NIH MRI Study of Normal Brain Development. Child Behavior Checklist A/D scores and diffusion imaging were available for 175 youths (84 males, 91 females; 241 magnetic resonance imagings) at up to three visits. The participants ranged from 5.7 to 18.4 years of age at the time of the scan. Alignment of fractional anisotropy data was implemented using FSL/Tract-Based Spatial Statistics, and linear mixed model regression was carried out using SPSS. Child Behavior Checklist A/D was associated with the rate of microstructural development in several white matter pathways, including the bilateral anterior thalamic radiation, bilateral inferior longitudinal fasciculus, left superior longitudinal fasciculus, and right cingulum. Across these pathways, greater age-related fractional anisotropy increases were observed at lower levels of A/D. The results suggest that subclinical A/D symptoms are associated with the rate of microstructural development within several white matter pathways that have been implicated in affect regulation, as well as mood and anxiety psychopathology.</jats:p

First-Line Biological Agents Plus Chemotherapy in Older Patients with Metastatic Colorectal Cancer: A Retrospective Pooled Analysis

Artículo escrito por un elevado número de autores, sólo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMBackground Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older patients with mCRC is limited. Objective This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy. Methods This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours. All were studies of adults with advanced CRC who received first-line treatment with chemotherapy plus bevacizumab, cetuximab or panitumumab, stratified by age (≥ 65 vs. < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety. Results In total, 999 patients from five studies were included in the analysis: 480 (48%) were aged ≥ 65 years, and 519 (52%) were aged < 65 years. Median PFS did not differ significantly between patients aged ≥ 65 and < 65 years (9.9 vs. 9.4 months; hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.88–1.17). Median OS was significantly shorter in older than in younger patients (21.3 vs. 25.0 months; HR 1.21; 95% CI 1.04–1.41). There was no significant difference between older and younger patients in ORR (59 vs. 62%). Patients aged ≥ 65 years experienced significantly more treatment-related grade 3 or higher adverse events (61.67%) than did patients aged < 65 years (45.86%). Conclusions Biologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patientsThis study was funded by the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) collaborative group. All medical writing assistance was funded by the Spanish Cooperative TTD and Roche Farma S

Caretaker Expectations Regarding the Management of Pediatric Asthma Scale (CE)

Asthma, a very serious health condition in the United States, results in morbidity and mortality that disproportionately affect children living in inner-city areas. The National Cooperative Inner-City Asthma Study (NCICAS) examined a variety of factors related to pediatric asthma. The CE scale was developed in the NCICAS study and is designed to assess three psychological factors in caretakers of children with asthma (self-efficacy, outcome expectations, and response difficulty). The scale is provided here and background is available in: Holden, G., Wade, S., Mitchell, H., Ewart, C., Islam, S. (1998). Caretaker expectations and the management of pediatric asthma in the inner-city: A scale development study. Social Work Research, 22, 51-59. or from the lead author: [email protected] by grants UO1 A1-30751, A1-30752, A1-30756, A1-30772, A1-30773-01, A1-30777, A1-30779, A1-30780, NO1 A1-15105 from the National Institute of Allergy and Infectious Disease (National Institutes of Health, Bethesda, MD)

Significance of epitope spreading in the pathogenesis of pemphigus vulgaris and foliaceus

Os pênfigos são dermatoses bolhosas auto-imunes, em que há a produção de auto-anticorpos direcionados contra moléculas de adesão dos epitélios, levando à perda da coesão celular. A produção de auto-anticorpos ocorre quando os pacientes desenvolvem um desequilíbrio da resposta imune (quebra da tolerância imunológica), passando a reconhecer antígenos próprios. A resposta é geralmente direcionada contra um único epítopo alvo; entretanto, como conseqüência da resposta inflamatória do processo primário e do extenso dano tecidual ocasionado, pode haver exposição de componentes protéicos ocultos, levando à produção de diferentes auto-anticorpos. Assim, é possível que surja uma nova doença cutânea auto-imune, em decorrência do fenômeno intra ou intermolecular de epitope spreading. São revistos os principais conceitos desse fenômeno e sua ocorrência nas dermatoses bolhosas auto-imunes, com ênfase nos pênfigos, grupo de dermatoses bolhosas autoimunes mais prevalente no Brasil.Pemphigus comprises autoimmune blistering skin diseases in which autoantibodies directed against antigens (epithelial adhesion molecules) are found, leading to loss of cell cohesion. The production of autoantibodies occurs due to an immune imbalance (break of immune tolerance) driving to recognition of self- antigens. The response is usually directed against an exclusive target epitope; however, due to the inflammatory response and to the extensive tissue damage, it is possible that the exposure of hidden protein components leads to distinct autoantibody production. Hence, a new autoimmune disease may occur in consequence of an intra- or intermolecular epitope spreading phenomenon. The authors review the main concepts of this phenomenon, and its occurrence in autoimmune blistering diseases, with emphasis on pemphigus, the most prevalent disease of this group in our country

Prevalence of Comorbidities and Their Influence on Blood Pressure Goal Attainment in Geriatric Patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72595/1/j.1076-7460.2007.05543.x.pd

A Weighted Prognostic Covariate Adjustment Method for Efficient and Powerful Treatment Effect Inferences in Randomized Controlled Trials

A crucial task for a randomized controlled trial (RCT) is to specify a statistical method that can yield an efficient estimator and powerful test for the treatment effect. A novel and effective strategy to obtain efficient and powerful treatment effect inferences is to incorporate predictions from generative artificial intelligence (AI) algorithms into covariate adjustment for the regression analysis of a RCT. Training a generative AI algorithm on historical control data enables one to construct a digital twin generator (DTG) for RCT participants, which utilizes a participant's baseline covariates to generate a probability distribution for their potential control outcome. Summaries of the probability distribution from the DTG are highly predictive of the trial outcome, and adjusting for these features via regression can thus improve the quality of treatment effect inferences, while satisfying regulatory guidelines on statistical analyses, for a RCT. However, a critical assumption in this strategy is homoskedasticity, or constant variance of the outcome conditional on the covariates. In the case of heteroskedasticity, existing covariate adjustment methods yield inefficient estimators and underpowered tests. We propose to address heteroskedasticity via a weighted prognostic covariate adjustment methodology (Weighted PROCOVA) that adjusts for both the mean and variance of the regression model using information obtained from the DTG. We prove that our method yields unbiased treatment effect estimators, and demonstrate via comprehensive simulation studies and case studies from Alzheimer's disease that it can reduce the variance of the treatment effect estimator, maintain the Type I error rate, and increase the power of the test for the treatment effect from 80% to 85%~90% when the variances from the DTG can explain 5%~10% of the variation in the RCT participants' outcomes.Comment: 49 pages, 6 figures, 12 table

Fibrosis progression in chronic hepatitis C: Morphometric image analysis in the HALT-C trial

Computer-assisted morphometry can provide precise measurement of hepatic fibrosis on a continuous scale. Previous morphometric studies of large cohorts of patients with treatment refractory chronic hepatitis C have shown a mean increase in fibrosis of 30% to 58% in 1 year. The aim of the present study was to quantify fibrosis progression in biopsy specimens obtained over 1.5 to 5 years from three groups of patients with baseline bridging fibrosis or cirrhosis (Ishak stages 3-6) enrolled in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial. The main group of 346 lead-in nonresponders (viremic after 24 weeks of peginterferon-ribavirin therapy) had a mean fibrosis increase of 61% over pretreatment baseline after 2 years and 80% after 4 years. In contrast, the 78 breakthrough/relapse patients (undetectable serum hepatitis C virus RNA after 24 weeks of peginterferon-ribavirin and receiving antiviral therapy for 48 weeks) showed a mean increase in fibrosis of 48% when biopsied 36 months from pretreatment baseline but no further increase at 60 months. Finally, the 111 express patients with baseline biopsies following unsuccessful peginterferon-ribavirin outside the trial had significantly more baseline fibrosis than the others but an increase of only 21% after 21 months and a slight decrease at 45 months. Maintenance therapy with low-dose peginterferon had no effect on fibrosis changes in any of the groups. Conclusion: Morphometry demonstrated complex, nonlinear changes in fibrosis over time in this heterogeneous cohort of patients with interferon-refractory chronic hepatitis C. (H EPATOLOGY 2009.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64551/1/23211_ftp.pd