Spotlight on ixazomib: Potential in the treatment of multiple myeloma

Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib

Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant

Jet event rates in deep inelastic ep scattering at HERA are investigated applying the modified JADE jet algorithm. The analysis uses data taken with the H1 detector in 1994 and 1995. The data are corrected for detector and hadronization effects and then compared with perturbative QCD predictions using next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2) is determined evaluating the jet event rates. Values of alpha_S(Q^2) are extracted in four different bins of the negative squared momentum transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the renormalization group equation to these several alpha_S(Q^2) values results in alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys. J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4

An RCT of dating matters:Effects on teen dating violence and relationship behaviors

Introduction Teen dating violence is a serious public health problem with few effective prevention strategies. This study examines whether the Dating Matters comprehensive prevention model, compared with a standard of care intervention, prevented negative relationship behaviors and promoted positive relationship behaviors. Study design This longitudinal, cluster-RCT compared the effectiveness of Dating Matters with standard of care across middle school. Standard of care was an evidence-based teen dating violence prevention curriculum (Safe Dates) implemented in eighth grade. Setting/participants Forty-six middle schools in high-risk urban neighborhoods in four U.S. cities were randomized. Schools lost to follow-up were replaced with new schools, which were independently randomized (71% school retention). Students were surveyed in fall and spring of sixth, seventh, and eighth grades (2012–2016). The analysis sample includes students from schools implementing Dating Matters or standard of care for >2 years who started sixth grade in the fall of 2012 or 2013 and had dated (N=2,349 students, mean age 12 years, 49% female, and 55% black, non-Hispanic, 28% Hispanic, 17% other). Intervention Dating Matters is a comprehensive, multicomponent prevention model including classroom-delivered programs for sixth to eighth graders, training for parents of sixth to eighth graders, educator training, a youth communications program, and local health department activities to assess capacity and track teen dating violence–related policy and data. Main outcome measures Self-reported teen dating violence perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills were examined as outcomes. Imputation and analyses were conducted in 2017. Results Latent panel models demonstrated significant program effects for three of four outcomes; Dating Matters students reported 8.43% lower teen dating violence perpetration, 9.78% lower teen dating violence victimization, and 5.52% lower use of negative conflict resolution strategies, on average across time points and cohorts, than standard of care students. There were no significant effects on positive relationship behaviors. Conclusions Dating Matters demonstrates comparative effectiveness, through middle school, for reducing unhealthy relationship behaviors, such as teen dating violence and use of negative conflict resolution strategies, relative to the standard of care intervention

Measurement of Leading Proton and Neutron Production in Deep Inelastic Scattering at HERA

Deep--inelastic scattering events with a leading baryon have been detected by the H1 experiment at HERA using a forward proton spectrometer and a forward neutron calorimeter. Semi--inclusive cross sections have been measured in the kinematic region 2 <= Q^2 <= 50 GeV^2, 6.10^-5 <= x <= 6.10^-3 and baryon p_T <= MeV, for events with a final state proton with energy 580 <= E' <= 740 GeV, or a neutron with energy E' >= 160 GeV. The measurements are used to test production models and factorization hypotheses. A Regge model of leading baryon production which consists of pion, pomeron and secondary reggeon exchanges gives an acceptable description of both semi-inclusive cross sections in the region 0.7 <= E'/E_p <= 0.9, where E_p is the proton beam energy. The leading neutron data are used to estimate for the first time the structure function of the pion at small Bjorken--x.Comment: 30 pages, 9 figures, 2 tables, submitted to Eur. Phys.

Reverse flow in academic mobility from core to periphery:Motivations of international faculty working in Kazakhstan

Through expanding flows of labor and knowledge on a global scale, academics are increasingly mobile as higher education institutions compete for talent that transcends borders. However, talent often flows from the periphery to the core as scholars seek out employment in recognized institutions of higher learning in developed economies. This study examines faculty mobility in a reverse direction: from the core to Kazakhstan, the largest country in Central Asia. What factors persuade faculty members to relocate to Kazakhstan for full-time employment? What types of individuals pursue this relocation? Through interviews with international faculty members based in Kazakhstan, the study identifies push factors that trigger departure from one’s previous country of residence: job market, unsatisfactory work conditions, age, and marital status. Alternatively, Kazakhstan attracts scholars via pull factors that include salary, sense of adventure, and the opportunity to build new institutions and programs as well as conduct research. Unlike previous studies that highlight boundaryless mobility and individual agency, this study reveals constraints that mediate international faculty mobility. Furthermore, salary plays a limited role as a pull factor particularly among early career academics who are seeking research opportunities and meaningful contributions in building new academic programs and institutions

My approach to superficial inflammatory dermatoses

Superficial inflammatory dermatoses are very common and comprise a wide, complex variety of clinical conditions. Accurate histological diagnosis, although it can sometimes be difficult to establish, is essential for clinical management. Knowledge of the microanatomy of the skin is important to recognise the variable histological patterns of inflammatory skin diseases. This article reviews the non-vesiculobullous/pustular inflammatory superficial dermatoses based on the compartmental microanatomy of the skin