Genetic Variants of Human Granzyme B Predict Transplant Outcomes after HLA Matched Unrelated Bone Marrow Transplantation for Myeloid Malignancies

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41–0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27–0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47–0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35–1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT

A brief history of news making in Russia

In this introductory article to our special issue on newsmaking in Russia, we provide a context for how the study of journalism evolved in Russia in contrast to Europe and the US. This brief historical overview helps make sense of the specific trajectory of journalism studies: from normative Cold War perspectives to a highly diverse and vibrant field that considers journalistic agency, the interplay of commercialisation and media control and the complexities of a rapidly changing media environment. The contributions to this special issue present nuanced approaches to self-censorship, the impact of digital technologies and political intervention

Developments in the Photonic Theory of Fluorescence

Conventional fluorescence commonly arises when excited molecules relax to their ground electronic state, and most of the surplus energy dissipates in the form of photon emission. The consolidation and full development of theory based on this concept has paved the way for the discovery of several mechanistic variants that can come into play with the involvement of laser input – most notably the phenomenon of multiphoton-induced fluorescence. However, other effects can become apparent when off-resonant laser input is applied during the lifetime of the initial excited state. Examples include a recently identified scheme for laser-controlled fluorescence. Other systems of interest are those in which fluorescence is emitted from a set of two or more coupled nanoemitters. This chapter develops a quantum theoretical outlook to identify and describe these processes, leading to a discussion of potential applications ranging from all-optical switching to the generation of optical vortices

Generalizations of the short pulse equation

We classify integrable scalar polynomial partial differential equations of second order generalizing the short pulse equation

Language development after cochlear implantation: an epigenetic model

Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic–phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent–child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child’s acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience

Micro-CT screening of old shell collections helps to understand the distribution of viviparity in the highly diversifed clausiliid clade of land snails

Current zoological research may benefit in many ways from the study of old collections of shells. These collections may provide materials for the verification of broad zoogeographical and ecological hypotheses on the reproduction of molluscs, as they include records from many areas where sampling is currently impossible or very difficult due to political circumstances. In the present paper we present data on viviparous and embryo-retention reproductive modes in clausiliid land snails (subfamily Phaedusinae) acquired from specimens collected since the nineteenth century in the Pontic, Hyrcanian, and East and Southeast Asian regions. X-ray imaging (micro-CT) enabled relatively quick screening of more than 1,000 individuals classified within 141 taxa, among which we discovered 205 shells containing embryos or eggs. Gravid individuals were found to belong to 55 species, representing, for some of these species, the first indication of brooding reproductive strategy

A comprehensive evaluation of cervical spine surgery outcomes

Aim: study of diagnostic value of different assessment scales to evaluate outcomes of surgeries in degenerative and post-injury deformities of cervical spine. Material and Methods. Between January and December 2015, 110 consecutive patients with degenerative and traumatic lesions of cervical spine were selected for surgery and results of treatment were followed. Preoperatively and 12 months postoperatively the patients filled in a questionnaire that included a VAS, Odom's scale, NDI, modified JOAand the Zung Depression Scale. To assess the results of the intervention, the concept of "effect size" was used. Distribution of different scores classified according to Odom's criteria as excellent/good and fair/poor. Results. All scores improved in all group of patients. For VAS, NDI and modified JOA scores the effect size was largest. NDI, JOAand ZDS seemed to correlate well with the classification of outcome by Odom. Conclusion. It is suggested many scales to assess the outcomes of the cervical spine surgery based on different criteria; nevertheless, there are no generally accepted and validated methods that can be used to analysis the outcome of cervical spine surgery. We conclude that investigated</p