10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostatespecific antigen (PSA) testing remains uncertain. METHODS We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P = 0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P = 0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P = 0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.) a bs tr ac

CRISPR-Cas9 System for Intervening Duchenne Muscular Dystrophy in Mice Models: A Meta-Analysis

Objective This meta-analysis aims to summarize the current literature on CRISPR-Cas9 system as a potential therapeutic tool against Duchenne muscular dystrophy. Background Duchenne muscular dystrophy (DMD) is a fatal monogenic disorder with limited treatment options that affect 1 in 5,000 boys. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has been increasingly studied as a potential gene editing intervention against DMD with accumulating supportive evidence in in-vitro, ex-vivo, and in-vivo experiments. Method A meta-analysis of peer reviewed, experimental in-vivo studies on CRISPR-Cas9 system as a gene therapy against DMD were conducted. PubMed and EMBASE databases were utilized for the electronic search of the current literature on August 2020. The primary outcomes were (1) restoration of dystrophin expression measured by Western blots and (2) immunohistochemistry as well as (3) change in specific force of skeletal muscles in mice models of DMD after the intervention. The meta-analysis utilized random-intercept logistic regression model, maximum-likelihood estimator for tau2, logit transformation, and normal approximation confidence interval for individual studies. Results Seventeen and eleven studies were identified for the qualitative and quantitative meta-analyses, respectively. Both systemic and intramuscular administrations of CRISPR-Cas9 system partially restored dystrophin expression and skeletal muscle function with little heterogeneity between available studies. Conclusion Current literature supports that CRISPR-Cas9 system is a viable intervention against DMD, substantiated by the post-intervention improvements in dystrophin expression and skeletal muscle strengths. Further studies on refining CRISPR-Cas9 delivery system and studies with higher sample size are warranted

Use of Markers Observed in the Spoken Language Lexical Corpora of Children in Kannada Language

Abstract Research in the area of child language thrives on the availability of naturalistic language data. However, Indian endeavours are meagre and confined to the language data acquired by the Speech -Language Pathologists which is limited to the purview of their study. The present study is part of a post-doctoral work carried out at All India Institute of Speech and Hearing (AIISH). The study established a spoken language lexical corpus of children between the ages of 6 and 8 in Kannada language. The language data of 240 children, living in the city of Mysore was collected through description of standardised pictures, story narration and narration of daily activities of the child. The present paper looks into the use of markers by children while highlighting the need to encourage further research in the field of child language

Journal of International Academic Research for Multidisciplinary Editorial Board __________________________________________________________________________________________ ITEM-BASED COLLABORATIVE FILTERING RECOMMENDER SYSTEM

ABSTRACT: Recommendation algorithms are best known for their use on e-commerce Web sites, where they use input about a customer's interests to generate a list of recommended items. Many applications use only the items that customers purchase and explicitly rate to represent their interests, but they can also use other attributes, including items viewed, demographic data, subject interests, and favourite artists. Collaborative filtering is one of the most important technologies in electronic commerce. With the development of recommender systems, the magnitudes of users and items grow rapidly, resulted in the extreme sparsity of user rating data set. Traditional similarity measure methods work poor in this situation, make the quality of recommendation system decreased dramatically. Poor quality is one major challenge in collaborative filtering recommender systems. Sparsity of users' ratings is the major reason causing the poor quality. To address these issues we have explored item-based collaborative filtering techniques. Item based techniques first analyze the user-item matrix to identify relationships between different items, and then use these relationships to indirectly compute recommendations for users. This approach predicts item ratings that users have not rated, and then uses Pearson correlation similarity measurement to find the target items' neighbors, lastly produces the recommendations. The experiments are made on a common data set using different recommender algorithms. The results show that the proposed approach can improve the accuracy of the collaborative filtering recommender system