Influence of Conserved and Hypervariable Genetic Markers on Genotyping Circulating Strains of Neisseria gonorrhoeae

Presently there is no vaccine against Neisseria gonorrhoeae and therefore accurate information on gonococcal transmission plays a crucial role for interventions designed to limit the spread of infections caused by this microorganism. We evaluated the impact of two different categories of genetic markers, (i) concatenated sequences of 10 housekeeping genes and (ii) hypervariable porB DNA sequences, on the genetic relatedness and subsequently on genotyping analysis of this human pathogen. Eighty gonococcal isolates from Canada, China, the US, Argentina, Venezuela and Chile, collected over different times, were analyzed. Our results show that the choice of genetic marker had a profound effect on the interpretation of genotyping results associated with N. gonorrhoeae. The concatenated sequences of the housekeeping genes preserved the genetic relatedness of closely related isolates, enabling detection of the predominant strains circulating within a community (Saskatchewan, Canada) over an extended period of time. In contrast, a genetic marker based on antigen gene, porB, may lead to a failure to detect these predominant circulating strains. Based on the analysis of the DNA sequences of the 10 housekeeping genes, we identified two major clonal complexes, CC33 and CC22, which comprised STs from China, and Argentina as well as two STs from Canada. Several minor clonal complexes were observed among isolates from Saskatchewan. eBURST analysis suggested that the majority of the tested gonococcal isolates from Saskatchewan, Canada were endemic, with only a couple of genotypes introduced

Adaptation of a Lay Health Advisor Model as a Recruitment and Retention Strategy in a Clinical Trial of College Student Smokers

This study describes and provides results from a process evaluation of a lay health advisor (LHA) model to enhance participation in a clinical trial of the effectiveness of motivational interviewing on smoking cessation in college fraternity and sorority members. The implementation of the model had two phases: (a) the selection and training of LHAs as liaisons between research staff and participants and (b) LHAs’ roles in recruitment and retention. Perceptions of the LHA model were explored using survey questionnaires. Trial participants (N = 118) and LHAs (N = 8) were generally satisfied with the model and identified LHAs as helpful to participation. Seventy-four percent of chapter members were screened and 73% of participants received three of the four motivational interviewing sessions. These results indicate the LHA model was well received and met the needs of the research project

Why a contextual approach to professional development?

One of the peculiarities of the literature on academic professional development with regard to teaching is its a-political nature. It pays insufficient attention to issues of equity, and to how privilege, geographical location, class and ethnicity influence the way that staff in higher education learn to teach. This is surprising, or paradoxical, given the strong world-wide concern for widening participation and student success in higher education. The approaches towards professional academic development have been dominated by literature from the global North, which does not take into account conditions in resource-constrained environments. We contend that literature from these Southern environments enrich the international body of literature. Thus there is a need for scholarly writing on learning to teach in higher education, which takes a specifically social, contextual and relational approach and which considers these within resource-rich as well as resource-constrained environments

Dendritic reidite from the Chesapeake Bay impact horizon, Ocean Drilling Program Site 1073 (offshore northeastern USA): A fingerprint of distal ejecta?

High-pressure minerals provide records of processes not normally preserved in Earth’s crust. Reidite, a quenchable polymorph of zircon, forms at pressures >20 GPa during shock compression. However, there is no broad consensus among empirical, experimental, and theoretical studies on the nature of the polymorphic transformation. Here we decipher a multistage history of reidite growth recorded in a zircon grain in distal impact ejecta (offshore northeastern United States) from the ca. 35 Ma Chesapeake Bay impact event which, remarkably, experienced near-complete conversion (89%) to reidite. The grain displays two distinctive reidite habits: (1) intersecting sets of planar lamellae that are dark in cathodoluminescence (CL); and (2) dendritic epitaxial overgrowths on the lamellae that are luminescent in CL. While the former is similar to that described in literature, the latter has not been previously reported. A two-stage growth model is proposed for reidite formation at >40 GPa in Chesapeake Bay impact ejecta: formation of lamellar reidite by shearing during shock compression, followed by dendrite growth, also at high pressure, via recrystallization. The dendritic reidite is interpreted to nucleate on lamellae and replace damaged zircon adjacent to lamellae, which may be amorphous ZrSiO4 or possibly an intermediate phase, all before quenching. These results provide new insights on the microstructural evolution of the highpressure polymorphic transformation over the microseconds-long interval of reidite stability during meteorite impact. Given the formation conditions, dendritic reidite may be a unique indicator of distal ejecta

Health-related quality of life in KEYNOTE-010 : a phase II/III study of pembrolizumab versus docetaxel in patients with previously treated advanced, programmed death ligand 1-expressing NSCLC

Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score >= 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m(2) every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Refining lunar impact chronology through high spatial resolution 40Ar/39Ar dating of impact melts

Quantitative constraints on the ages of melt-forming impact events on the Moon are based primarily on isotope geochronology of returned samples. However, interpreting the results of such studies can often be difficult because the provenance region of any sample returned from the lunar surface may have experienced multiple impact events over the course of billions of years of bombardment. We illustrate this problem with new laser microprobe 40Ar/39Ar data for two Apollo 17 impact melt breccias. Whereas one sample yields a straightforward result, indicating a single melt-forming event at ca. 3.83 Ga, data from the other sample document multiple impact melt–forming events between ca. 3.81 Ga and at least as young as ca. 3.27 Ga. Notably, published zircon U/Pb data indicate the existence of even older melt products in the same sample. The revelation of multiple impact events through 40Ar/39Ar geochronology is likely not to have been possible using standard incremental heating methods alone, demonstrating the complementarity of the laser microprobe technique. Evidence for 3.83 Ga to 3.81 Ga melt components in these samples reinforces emerging interpretations that Apollo 17 impact breccia samples include a significant component of ejecta from the Imbrium basin impact. Collectively, our results underscore the need to quantitatively resolve the ages of different melt generations from multiple samples to improve our current understanding of the lunar impact record, and to establish the absolute ages of important impact structures encountered during future exploration missions in the inner Solar System

Oncology providers' perspectives on endocrine therapy prescribing and management.

Adjuvant endocrine therapy (ET) can reduce the risk of recurrence among females with hormone receptor-positive breast cancer. Overall, initiation and adherence to ET are suboptimal, though reasons are not well described. The study's objective was to better understand ET decision making, prescribing, and patient management from oncology providers' perspectives. Using purposive sampling, we recruited oncology providers who saw five or more breast cancer patients per week (n=20). We conducted 30-45-minute telephone interviews, using a semistructured guide to elicit perspectives on ET use. We used thematic content analysis to systematically identify categories of meaning and double-coded transcripts using Atlas.ti. Providers recommend ET to all eligible patients except those with contraindications or other risk factors. Providers base their ET prescribing decisions on the patient's menopausal status, side effects, and comorbidities. ET is typically discussed multiple times: at the onset of breast cancer treatment and in more detail after other treatment completion. Providers felt that the associated recurrence risk reduction is the most compelling argument for patients during ET decision making. While providers rarely perceived noninitiation as a problem, nonadherence was prevalent, often due to unresolvable side effects. From the clinicians' perspectives, side effects from ET are the dominant factor in nonadherence. Efforts to improve adherence should focus on strategies to minimize side effects and ensure clinicians and patients are well informed regarding optimal side effect management. This finding has important implications for novel endocrine regimens that offer improved outcomes through longer duration or more intensive therapy