Study of Network Security Using Cryptographic Techniques

In information security network security is one of the most important element because it is responsible for providing security to all information passed through network devices. Network Security refers to all hardware and software functions, characteristics, features, events, responsibility, measures, access control, and administrative and management strategy required to provide an acceptable level of protection & security for Hardware & Software and information in a network. merely one particular element underlies more of the protection mechanisms in use: Cryptographic technique hence focus is on this area Cryptography. It is an rising technology which is more important for network security

Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study

PURPOSE: In RE-MIND2 (NCT04697160), patient-level outcomes from the L-MIND study (NCT02399085) of tafasitamab plus lenalidomide were retrospectively compared with patient-level matched observational cohorts treated with National Cancer Care Network (NCCN)/European Society for Medical Oncology (ESMO)-listed systemic therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Data were collected from health records of eligible patients aged ≥18 years with histologically confirmed DLBCL who had received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients from L-MIND were matched with patients from the RE-MIND2 observational cohort using estimated propensity score-based 1:1 nearest-neighbor matching, balanced for nine covariates. The primary analysis compared tafasitamab plus lenalidomide with patients who received any systemic therapy for R/R DLBCL (pooled in one cohort) or bendamustine plus rituximab (BR) or rituximab plus gemcitabine and oxaliplatin (R-GemOx; as two distinct cohorts). The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and time-to-event outcomes. RESULTS: In RE-MIND2, 3,454 patients were enrolled from 200 sites in North America, Europe, and Asia-Pacific. Strictly matched pairs of patients consisted of tafasitamab plus lenalidomide versus systemic therapies pooled (n = 76 pairs), versus BR (n = 75 pairs), and versus R-GemOx (n = 74 pairs). Significantly prolonged OS was reported with tafasitamab plus lenalidomide versus systemic pooled therapies [hazard ratios (HR): 0.55; P = 0.0068], BR (HR: 0.42; P < 0.0001), and R-GemOx (HR: 0.47; P = 0.0003). CONCLUSIONS: RE-MIND2, a retrospective observational study, met its primary endpoint, demonstrating prolonged OS with tafasitamab plus lenalidomide versus BR and R-GemOx. See related commentary by Cherng and Westin, p. 3908

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a real-world lenalidomide monotherapy cohort in relapsed or refractory diffuse large B-cell lymphoma

Purpose: Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse largeB-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MINDto delineate the contribution of tafasitamab to the efficacy of the combination. Patients and Methods: Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide-treated patients (L-MIND). Key eligibility criteria were aligned with L-MIND. Estimated propensity score-based Nearest Neighbor 1:1 Matching methodology balanced the cohorts for nine prespecified prognostic baseline covariates.The primary endpointwas investigator-assessed best overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and overall survival (OS). Results: Data from 490 patients going through lenalidomide monotherapy were collected; 140 qualified for matching with the L-MIND cohort. The primary analysis included 76 patients from each cohort who received a lenalidomide starting dose of 25 mg/day. Cohort baseline covariates were comparable. A significantly better ORR of 67.1% (95% confidence interval, 55.4-77.5) was observed for the combination therapy versus 34.2% (23.7-46.0) for lenalidomide monotherapy [odds ratio, 3.89 (1.90-8.14); P < 0.0001]. HigherCR rates were achieved with combination therapy compared with lenalidomide monotherapy [39.5% (28.4-51.4) vs. 13.2% (6.5-22.9)]. Survival endpoints favored combination therapy. Lenalidomide monotherapy outcomes were similar to previously published data. Conclusions: RE-MIND enabled the estimation of the additional treatment effect achieved by combining tafasitamab with lenalidomide in patients with R/R DLBCL

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085

Characterization of the amorphous solid state using solvent vapour induced transformations

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Characterisation of the amorphous solid state using solvent vapour induced transitions

There is increasing awareness about the amorphous form or disordered structure of material. The amorphous state is studied widely, due to two reasons; first, it is encountered without choice during many processes (e.g. milling/micronization) and second due to its advantages over the crystalline form (e.g. solubility). The important aspect of the amorphous form is its metastability (tendency to transform into a thermodynamically stable crystalline form). The current studies on the amorphous solid state involve, i) quantifying the disorders in otherwise ordered crystalline structures; ii) identifying the conditions under which its transformation into an ordered crystalline form could be controlled and iii) stabilizing the amorphous form by formulating as a solid dispersion. The characterisation of the amorphous state is mainly based on thermal analytical techniques (DSC) to estimate glass transition temperature. Other techniques, which are used routinely to study the amorphous state, involve spectroscopy (XRPD, FT-Raman, FT-IR, and Terahertz), microcalorimetric analysis (Solution calorimetry) and vapour sorption analysis (DVS). The aim of the thesis was to identify the techniques to characterise the amorphous state under the controlled conditions of temperature and humidity. These techniques would then be used to identify the conditions for the zero molecular mobility in the amorphous model substances selected for the study. The heating rate dependence of the glass transition was studied for amorphous indometacin. These studies were then used to calculate the fragility or the strength parameter and the activation energy (of relaxation process) for the amorphous solid. These parameters can be used to compare the relative stability of the different glasses. The StepScan DSC could successfully distinguish the process of aging in the amorphous states of indometacin, nifedipine and lactose. It was also observed that below a certain temperature for each amorphous state the relaxation time became extremely high, this temperature could be correlated to the Kauzmann temperature (Tk). The various transitions induced in the amorphous state of indometacin and lactose due to RH ramp were studied using DVS, perfusion calorimetry and IGC. The correlation of transitions from DVS was based on changes in weight gain profile as compared to changes in power output signal from perfusion calorimetry and changes in retention volume and pressure drop by using IGC. For amorphous lactose a sequence of transitions viz. mobility onset, glass transition, collapse and crystallisation could be followed as the RH was ramped. It was possible to characterise each transition with respect to a critical RH (%cRH) required for its induction e.g. %cRHg and %cRHcry as %RH required to induce glass transition and crystallisation respectively. The values of %cRH obtained using different techniques matched with each other. In the case of amorphous indometacin, the preferential surface plasticisation effect of sorbed water was demonstrated using IGC. Although the glass transition could be observed on the surface of amorphous particle, no spontaneous crystallisation could be seen with the RH ramp. Using a serial ramp of alcohol pressure (e.g. methanol, ethanol and propanol) by perfusion calorimetry it was possible to demonstrate glass transition and crystallisation in amorphous indometacin; these transitions could be observed from the power out put signal obtained. The different values of critical solvent pressures obtained at different temperatures were used to estimate Tk for amorphous indometacin and lactose. NIR studies demonstrated changes in amorphous nifedipine for the storage at room temperature, which otherwise would have been missed while characterising by IGC, DVS and TAM. The various techniques used in this work could be used very effectively to study the amorphous state