Extending structures I: the level of groups

Let $H$ be a group and $E$ a set such that $H \subseteq E$. We shall describe and classify up to an isomorphism of groups that stabilizes $H$ the set of all group structures that can be defined on $E$ such that $H$ is a subgroup of $E$. A general product, which we call the unified product, is constructed such that both the crossed product and the bicrossed product of two groups are special cases of it. It is associated to $H$ and to a system $\bigl((S, 1_S,\ast), \triangleleft, \, \triangleright, \, f \bigl)$ called a group extending structure and we denote it by $H \ltimes S$. There exists a group structure on $E$ containing $H$ as a subgroup if and only if there exists an isomorphism of groups $(E, \cdot) \cong H \ltimes S$, for some group extending structure $\bigl((S, 1_S,\ast), \triangleleft, \, \triangleright, \, f \bigl)$. All such group structures on $E$ are classified up to an isomorphism of groups that stabilizes $H$ by a cohomological type set ${\mathcal K}^{2}_{\ltimes} (H, (S, 1_S))$. A Schreier type theorem is proved and an explicit example is given: it classifies up to an isomorphism that stabilizes $H$ all groups that contain $H$ as a subgroup of index 2.Comment: 17 pages; to appear in Algebras and Representation Theor

The Role of Pragmatics in Solving the Winograd Schema Challenge

Different aspects and approaches to commonsense reasoning have been investigated in order to provide solutions for the Winograd Schema Challenge (WSC). The vast complexities of natural language processing (parsing, assigning word sense, integrating context, pragmatics and world-knowledge, ...) give broad appeal to systems based on statistical analysis of corpora. However, solutions based purely on learning from corpora are not currently able to capture the semantics underlying the WSC - which was intended to provide problems whose solution requires knowledge and reasoning, rather than statistical analysis of superficial lexical features. In this paper we consider the WSC as a means for highlighting challenges in the field of commonsense reasoning more generally. We begin by discussing issues with current approaches to the WSC. Following this we outline some key challenges faced, in particular highlighting the importance of dealing with pragmatics. We then argue for an alternative approach which favours the use of knowledge bases where the deep semantics of the different interpretations of commonsense terms are formalised. Furthermore, we suggest using heuristic approaches based on pragmatics to determine appropriate configurations of both reasonable interpretations of terms and necessary assumptions about the world

Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.

BackgroundCabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts.Patients and methodsEligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily. After an initial 12-week cabozantinib treatment period, patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead-in stage was objective response rate (ORR) at week 12, and the primary endpoint of the randomized stage was progression-free survival (PFS).ResultsAmong the 41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a confirmed partial response (PR). The week 12 disease control rate (PR or SD) was 66% (Asian subgroup: 73%). Of patients with ≥1 post-baseline scan, 78% had tumor regression, with no apparent relationship to prior sorafenib therapy. Alpha-fetoprotein (AFP) response (>50% reduction from baseline) occurred in 9 of the 26 (35%) patients with elevated baseline AFP and ≥1 post-baseline measurement. Twenty-two patients with SD at week 12 were randomized. Median PFS after randomization was 2.5 months with cabozantinib and 1.4 months with placebo, although this difference was not statistically significant. Median PFS and overall survival from Day 1 in all patients were 5.2 and 11.5 months, respectively. The most common grade 3/4 adverse events, regardless of attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia (15%). Dose reductions were utilized in 59% of patients.ConclusionsCabozantinib has clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in AFP. Adverse events were managed with dose reductions.Trial registration numberNCT00940225

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System

Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Discourses of student orientation to medical education programs

Background: Although medical students’ initial orientation is an important point of transition in medical education, there is a paucity of literature on the subject and major variations in the ways that different institutions orient incoming medical students to their programs. Methods: We conducted a discourse analysis of medical education orientation in the literature and on data from a survey of peer institutions’ approaches to orientation. Results: These two discourses of orientation had clear similarities, in particular, the critical role of ceremony and symbols, and the focus on developing professionalism and physician identities. There were also differences between them, in particular, in the way that the discourse in the literature focused on the symbolic and professional aspects of orientation; something we have called ‘cultural orientation’. Meanwhile, those who were responsible for orientation in their own institutions tended to focus on the practical and social dimensions. Conclusion: By examining how orientation has been described and discussed, we identify three domains of orientation: cultural, social, and practical. These domains are relatively distinct in terms of the activities associated with them, and in terms of who is involved in organizing and running these activities. We also describe orientation as a liminal activity system on the threshold of medical school where incoming students initially cross into the profession. Interestingly, this state of ambiguity also extends to the scholarship of orientation with only some of its aspects attracting formal enquiry, even though there is a growing interest in transitions in medical education as a whole. We hope, therefore, that this study can help to legitimize enquiry into orientation in all its forms and that it can begin to situate the role of orientation more firmly within the firmament of medical education practice and research

Prisoners co-infected with tuberculosis and HIV: a systematic review.

INTRODUCTION: Almost from the beginning of the HIV epidemic in 1981, an association with tuberculosis (TB) was recognized. This association between HIV and TB co-infection has been particularly evident amongst prisoners. However, despite this, few studies of TB in prisons have stratified results by HIV status. Given the high prevalence of HIV-positive persons and TB-infected persons in prisons and the documented risk of TB in those infected with HIV, it is of interest to determine how co-infection varies amongst prison populations worldwide. For this reason we have undertaken a systematic review of studies of co-infected prisoners to determine the incidence and/or prevalence of HIV/TB co-infection in prisons, as well as outcomes in this group, measured as treatment success or death. METHODS: A literature search was undertaken using the online databases PubMed, Embase, IBSS, Scopus, Web of Science, Global Health and CINAHL Plus. No restrictions were set on language or publication date for article retrieval, with articles included if indexed up to 18 October 2015. A total of 1975 non-duplicate papers were identified. For treatment and outcome data all eligible papers were appraised for inclusion; for incidence/prevalence estimates papers published prior to 2000 were excluded from full text review. After full text appraisal, 46 papers were selected for inclusion in the review, 41 for incidence/prevalence estimates and nine for outcomes data, with four papers providing evidence for both outcomes and prevalence/incidence. RESULTS: Very few studies estimated the incidence of TB in HIV positive prisoners, with most simply reporting prevalence of co-infection. Co-infection is rarely explicitly measured, with studies simply reporting HIV status in prisoners with TB, or a cross-sectional survey of TB prevalence amongst prisoners with HIV. Estimates of co-infection prevalence ranged from 2.4 to 73.1% and relative risks for one, given the other, ranged from 2.0 to 10.75, although some studies reported no significant association between HIV and TB. Few studies provided a comparison with the risk of co-infection in the general population. CONCLUSIONS: Prisoners infected with HIV are at high risk of developing TB. However, the magnitude of risk varies between different prisons and countries. There is little evidence on treatment outcomes in co-infected prisoners, and the existing evidence is conflicting in regards to HIV status influence on prisoner treatment outcomes.PROSPERO Number: CRD42016034068

Accreting Millisecond X-Ray Pulsars

Accreting Millisecond X-Ray Pulsars (AMXPs) are astrophysical laboratories without parallel in the study of extreme physics. In this chapter we review the past fifteen years of discoveries in the field. We summarize the observations of the fifteen known AMXPs, with a particular emphasis on the multi-wavelength observations that have been carried out since the discovery of the first AMXP in 1998. We review accretion torque theory, the pulse formation process, and how AMXP observations have changed our view on the interaction of plasma and magnetic fields in strong gravity. We also explain how the AMXPs have deepened our understanding of the thermonuclear burst process, in particular the phenomenon of burst oscillations. We conclude with a discussion of the open problems that remain to be addressed in the future.Comment: Review to appear in "Timing neutron stars: pulsations, oscillations and explosions", T. Belloni, M. Mendez, C.M. Zhang Eds., ASSL, Springer; [revision with literature updated, several typos removed, 1 new AMXP added