A Cryptographic Solution to the Predefind Bound of Ciphertext Classes in KAC

In Cloud Computingsecure data sharing is an important functionality. Cloud computing is the storing of data online which is accessible from multiple and connected resources. It is the fastest growing field in computer world which serves various services to users. Using Cloud Storage, users can remotely store their data and enjoy the on-demand high quality applications and services. This paper attempts to show how data is shared among cloud users securely, efficiently, and flexibly. On cloud anyone can share data as much they want to i.e. only selected content can be shared. With cryptography users can share the data to others in safe way. So that user encrypts data and upload it on cloud server. The proposed algorithm uses a new cryptosystem that is called as Key Aggregate Cryptosystem (KAC)[1] which generates a single key for multiple files. In particular, it uses a public key encryption which releases aggregate key for set of secret keys. With this aggregate key others can decrypt ciphertext set and remaining encrypted files outside the set are remains confidential

Formulation and Evaluation of Ezetimibe Lyophilized Dry Emulsion Tablets

This article presents the development of lyophilized dry emulsion tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug Ezetimibe. Ezetimibe (EZT) is a lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients. Ezetimibe has a very low solubility and dissolution rate resulting in highly variable bioavailability, which is also in part due to extensive efflux by p-glycoprotein (P-Gp). Tablets were fabricated by freezedrying o/w emulsions of Ezetimibe. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol), as the water phase and Labrafac® as the oil phase under proper homogenization. In the present study friability, disintegration time, and in-vitro dissolutionof lyophilized dry emulsion tablets were done. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution studies revealed the enhanced dissolution rate of Ezetimibe from the lyophilized tablets compared to the plain drug. DSC studies proved presence of the drug in the amorphous form in the fabricated tablets. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia. Keywords: Ezetimibe, lyophilized dry emulsion tablet, and hyperlipidemia, freeze drying, Labrafac

Re-establishing Responsiveness in a Case of Refractory Metastatic Rectal Cancer with a Personalized de novo Combination Regimen

Introduction: Encyclopedic Tumor Analysis (ETA) is multi-analyte, molecular and functional interrogation to identify latent vulnerabilities in solid tumors which can then be targeted in organ- and label-agnostic combination treatment regimens.Case Presentation: We describe here a case of metastatic rectal cancer in a 61-year-old male who was progressed on all prior Standard of Care (SoC) treatment modalities including surgery, chemotherapy and radiotherapy. We addressed disease recurrence via personalized therapy guided by ETA which revealed characteristic molecular heterogeneity in primary and metastatic lesions in terms of single nucleotide variations (SNVs) and gene copy number variations (CNVs).  Notably, a novel TBL1XR1 (Exon1) – PIK3CA (Exon 2) gene fusion was identified in the tumor along with gene copy number gains in TERT, IGF-1R, MYC, FGFR1 and EGFR genes.Conclusion: ETA based molecular analysis with synchronous in vitro chemo-sensitivity profiling strategy helped to define de novo combinatorial therapy regimen of targeted and cytotoxic drugs which countered disease progression at each instance and led to the durable regression of primary as well as metastatic lesions

A Comparison of Three Drug Combinations for Sedation during Middle Ear Surgeries under Local Anesthesia: A Multicentric Randomized Double Blind Study

Background: During Middle Ear Surgeries (MES) done under Local Anesthesia (LA), patients may feel discomfort due to noise of suction, manipulation of instruments, positioning of head-neck and sometimes due to pain. A bloodless microscopic field is also essential to facilitate surgical exposure in MES. Various combinations of analgesics and sedatives have been tried to alleviate apprehension of the patients and improve microscopic field which may result into reduction in surgical time. In the present study, we have compared Dexmedetomedine (Dex) with Midazolam-Fentanyl (MF) and PentazocinePromethazine (PP) combinations for their sedoanalgesia, anxiolysis and other pharmacological effects when administered during MES, not lasting for more than 60 min. Material and Methods: Ninety American Society of American Society of Anesthesiologists (ASA) group I /II patients admitted in either of the three hospitals during May 2014 to January 2015 for MES under LA were randomly divided into three groups by an independent observer. Group D received intravenous bolus of Injection Dexmedetomidine 1 µg/ kg over 10 min. Group MF received Injection Midazolam 0.06 mg/ kg + Inj. Fentanyl 1 µg/ kg and Group PP received Injection Pentazocine 0.3 mg/kg + Injection Promethazine 0.5mg/kg given intravenously followed by LA before taking incision for the surgery. Need of a rescue sedoanalgesic dose of (Midazolam 0.01 mg/kg + Fentanyl 0.5 µg/kg) during the surgery was noted. All the patients received 500 ml of normal saline infusion till the end of the surgery. All surgeries were finished within 60 min. Vital parameters and Ramsay Sedation Score (RSS) of the patients were noted from the time of administration of sedative till the end of the surgery. Patient and surgeon satisfaction scores were recorded immediately after the surgery. Drug combinations of three groups were compared for their effectiveness, adverse effects and satisfaction scores in given doses. Children, mentally unstable patients, uncooperative patients, patients requesting general anesthesia, patients with known sensitivity to local anesthetic drug Lignocaine, and allergy to study drugs, pregnant and lactating females were excluded from the study. Results: RSS were satisfactory in Group D and Group MF but not in Group PP. Percentage of patients requiring rescue sedoanalgesic dose of (Midazolam 0.01 mg/kg + Fentanyl 0.5 µg/kg) was the highest (20%) in Group PP. It was the least in Group D. Intraoperative heart rate and mean arterial pressure in Group D were significantly lower than the baseline values and the corresponding values in Group MF and Group PP. Incidence of postoperative nausea was higher in Group PP. One patient in Group D had significant bradycardia with hypotension while one patient in Group MF got desaturated needing Oxygen therapy. Statistically significant number of patients from Group D had bloodless microscopic field compared to Group MF and Group PP. Surgeon satisfaction scores which showed statistically significant correlation with type of microscopic field were better in Group D. Patient satisfaction scores were better in Group D than Group MF and Group PP. Conclusion: Out of the sedoanalgesics tested, Dexmedetomidine was found to be the best drug for MES patients performed under local anaesthesia. It produced near bloodless microscopic surgical field with better surgeon and patient satisfaction

Development and validation of a multigene variant profiling assay to guide targeted and immuno therapy selection in solid tumors.

We present data on analytical validation of the multigene variant profiling assay (CellDx) to provide actionable indications for selection of targeted and immune checkpoint inhibitor (ICI) therapy in solid tumors. CellDx includes Next Generation Sequencing (NGS) profiling of gene variants in a targeted 452-gene panel as well as status of total Tumor Mutation Burden (TMB), Microsatellite instability (MSI), Mismatch Repair (MMR) and Programmed Cell Death-Ligand 1 (PD-L1) respectively. Validation parameters included accuracy, sensitivity, specificity and reproducibility for detection of Single Nucleotide Alterations (SNAs), Copy Number Alterations (CNAs), Insertions and Deletions (Indels), Gene fusions, MSI and PDL1. Cumulative analytical sensitivity and specificity of the assay were 99.03 (95% CI: 96.54-99.88) and 99.23% (95% CI: 98.54% - 99.65%) respectively with 99.20% overall Accuracy (95% CI: 98.57% - 99.60%) and 99.7% Precision based on evaluation of 116 reference samples. The clinical performance of CellDx was evaluated in a subsequent analysis of 299 clinical samples where 861 unique mutations were detected of which 791 were oncogenic and 47 were actionable. Indications in MMR, MSI and TMB for selection of ICI therapies were also detected in the clinical samples. The high specificity, sensitivity, accuracy and reproducibility of the CellDx assay is suitable for clinical application for guiding selection of targeted and immunotherapy agents in patients with solid organ tumors