Assessing Reproducibility and Value in Genomic Signatures

Consider a genomic signature to be a set of genes whose measured expression is transformed into a prediction of an outcome of interest. Such signatures are the bases of a set of FDA-approved medical tests for predicting the risk of distal recurrence and differential survival in breast cancer patients [84, 83, 63]. The goal of these tests is to provide clinicians with an additional piece of prognostic information that may affect their decision making pertaining to the treatment of a breast cancer patient. As it stands, the tests based on these genomic signatures (MammaPrint, Oncotype DX, Prosigna) are not part of the standard of care for a patient, and there are many issues in the translation of these discoveries from bench to bedside that hinder their reliable use [24]. These issues range from insufficiently thorough validation [86], to technical errors or oversights [5,46], to outright retraction of results [75]. In addition to the lack of impact in clinical practice, the difficulty of translating these genomic discoveries represents uncertainty about the viability of clinical genomics in general. The vast majority of genetic quantities that are routinely evaluated for a patient were discovered and characterized prior to the era of high-throughput genomics, e.g. [28, 88, 77, 34, 51]. Although there have been one-off successes [89] and a wide range of candidate and pathway discoveries [85], the costs have been great relative to the payout in terms of widespread clinical use [14]. By examining issues at the point of translation, we can begin to provide a clearer picture of what is possible and realistic to accomplish in the clinic with the discoveries that we have from the high-thorughput era

HANU BASTI AN INNOVATIVE PROCEDURE IN HANU SANDHIGATA ROGA

Osteoarthritis, a form of arthritis is characterised by chronic degeneration of various hard and soft tissues around the joint. It can also affect the Temperomandibular joint and called as TMJ osteoarthritis. The non dental causes of oral pain closely related to Temperomandibular disorder. It affects both sexes with higher prevalance in women. Hanubasti a form of Bahya Sneha and Sveda, designed on the principle of Shirobasti. Here the word innovative is used because the SOP (standard operating procedure) of Hanubasti is unique and new. We have standardized the procedure and want to conduct large trial of the same. In this article, an attempt is made to describe the methods, indications and precautions of Hanubasti procedure based on the clinical experience and evidence based medicine (EBM).   &nbsp

Multi-study R-learner for Heterogeneous Treatment Effect Estimation

We propose a general class of algorithms for estimating heterogeneous treatment effects on multiple studies. Our approach, called the multi-study R-learner, generalizes the R-learner to account for between-study heterogeneity and achieves cross-study robustness of confounding adjustment. The multi-study R-learner is flexible in its ability to incorporate many machine learning techniques for estimating heterogeneous treatment effects, nuisance functions, and membership probabilities. We show that the multi-study R-learner treatment effect estimator is asymptotically normal within the series estimation framework. Moreover, we illustrate via realistic cancer data experiments that our approach results in lower estimation error than the R-learner as between-study heterogeneity increases

(E)-1-(4-Bromo­phen­yl)-3-(3,4,5-trimethoxy­phen­yl)prop-2-en-1-one1

In the title compound, C18H17BrO4, the dihedral angle between the 4-bromo­phenyl and 3,4,5-trimethoxy­phenyl rings is 44.18 (6)°. In the crystal structure, the mol­ecules are linked by C—H⋯O and C—H⋯π inter­actions

Recurrent Interstitial pregnancy: a new approach in diagnosis with MRI and management with systemic methotrexate along with intra foetal cardiac 10% potassium chloride

We present a case of recurrent interstitial pregnancy in a setting of recurrent pregnancy loss where we used a new modality in the diagnosis and treatment. The patient after diagnosis of interstitial pregnancy by Ultrasonography was very keen to continue her pregnancy so the diagnosis was confirmed with MRI imaging showing the “interstitial sign” that convinced her for termination. In this case presence of active foetal cardiac activity and high Serum βhCG (43000 mIU/ml), made medical management a difficult proposition. Then we conceived a hybrid combined medical management of intra-foetal cardiac 10% KCl and adjuvant systemic multi-dose MTX therapy. This resulted in resolution of ectopic and conserves her fertility

A RARE CASE OF PULMONARY ASPERGILLOMA

Pulmonary aspergilloma is unprecedented disorder affecting lung parenchyma in already existing cavity in healed pulmonary tuberculosis patients. Typically, it is resulting from Aspergillus fumigates leading to development of fungal ball. Common presenting complaints are Haemoptysis, Dyspnoea, Cough, Chest pain and Fever. We are reporting a case of Pulmonary aspergilloma a sequel of Pulmonary tuberculosis, has been recognized on basis of clinical findings, chest X-ray, CT thorax in which Fungal ball is seen in pre-existing cavity. It has been managed with antifungal drug Amphotericin B and Itraconazole. It must be differentiated from different clinical entity specifically Lung carcinoma on basis of relevant examination and research to treat successfully