The relationship context of nonmarital childbearing in the U.S.

Using Early Childhood Longitudinal Study-Birth Cohort data, we update estimates of cohabiting nonmarital births, examine factors associated with relationship context at birth, and assess racial/ethnic differences. We find that 52% of nonmarital births occur within cohabitations – an increase of 33% since the early 1990s. Blacks have shown the greatest increase in cohabiting births over time. We also find that the fertility histories of men and women have opposite influences on nonmarital childbearing. Furthermore, for Whites, a partner of a different race/ethnicity is associated with a higher risk of a nonmarital birth; for Blacks and Hispanics, the opposite is true.cohabitation, non-marital childbearing

SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND:Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. METHODS:This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. RESULTS:412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC < 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC < 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC < 50%, 10.0 months, P = 0.39, respectively). CONCLUSIONS:PD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies. Trial registration ClinicalTrials.gov, NCT02543476. Registered September 4, 2015

Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling

BACKGROUND: Abnormal proteostasis due to alterations in protein turnover has been postulated to play a central role in several neurodegenerative diseases. Therefore, the development of techniques to quantify protein turnover in the brain is critical for understanding the pathogenic mechanisms of these diseases. We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain. RESULTS: Cohorts of mice were pulse labeled with (13) C(6)-leucine and the brains were isolated after pre-determined time points. The extent of label incorporation was measured over time using mass spectrometry to measure the ratio of labeled to unlabeled apolipoprotein E (apoE) and amyloid β (Aβ). The fractional clearance rate (FCR) was then calculated by analyzing the time course of disappearance for the labeled protein species. To validate the technique, apoE clearance was measured in mice that overexpress the low-density lipoprotein receptor (LDLR). The FCR in these mice was 2.7-fold faster than wild-type mice. To demonstrate the potential of this technique for understanding the pathogenesis of neurodegenerative disease, we applied our SILK technique to determine the effect of ATP binding cassette A1 (ABCA1) on both apoE and Aβ clearance. ABCA1 had previously been shown to regulate both the amount of apoE in the brain, along with the extent of Aβ deposition, and represents a potential molecular target for lowering brain amyloid levels in Alzheimer's disease patients. The FCR of apoE was increased by 1.9- and 1.5-fold in mice that either lacked or overexpressed ABCA1, respectively. However, ABCA1 had no effect on the FCR of Aβ, suggesting that ABCA1 does not regulate Aβ metabolism in the brain. CONCLUSIONS: Our SILK strategy represents a straightforward, cost-effective, and efficient method to measure the clearance of proteins in the mouse brain. We expect that this technique will be applicable to the study of protein dynamics in the pathogenesis of several neurodegenerative diseases, and could aid in the evaluation of novel therapeutic agents

Structural and functional investigation of the cytoplasmic domain of the Fas death receptor

Activation of the transmembrane death receptor Fas (CD95/APO-1) by a membrane bound ligand (FasL/CD95L) activates the extrinsic pathway of apoptosis. Intracellular Fas death domains (DDs) are induced to oligomerise enabling binding to the adaptor protein FADD, thereby leading to the recruitment of procaspase 8 and other proteins to form the death inducing signalling complex (DISC).This thesis describes an investigation of the structure and function of the cytoplasmic Fas-DD. A model for the solution structure of the Fas-DD was published in 1996, it has since been reported that the death domain can form at least one other conformation when in complex with FADD. As a foundation to the work in this thesis, modern multidimensional NMR techniques have been used to solve the structure of the FasDD, to further probe the potential for alternative conformations. It has previously been reported that Fas can be phosphorylated at Tyr291, providing a platform for the recruitment of binding partners that can affect non-apoptotic signalling. The second part of this thesis details the development of an expressed protein ligation methodology to prepare a Tyr291 phosphorylated Fas DD to provide a basis for in vitro studies of the structural, dynamic and functional effects of phosphorylation. It is widely accepted that Fas is palmitoylated at Cys199 and recognised by the membrane cytoskeletal protein, ezrin. Fas palmitoylation is important for clathrinmediated internalisation of the DISC, and amplification of the caspase cascade. There are multiple reports detailing the binding of ezrin to Fas, but it is not clear whether this interaction occurs in a palmitoylation-dependent manner. Efforts to characterise an interaction between bacterially expressed intracellular Fas and ezrin proteins were carried out using a number of biophysical assays, described in the third part of this thesis. Building upon this, the fourth section explores the preparation of a palmitoylated Fas construct suitable for biophysical analysis by incubating recombinant Fas with palmitoyl-CoA

Of Herbicides and Humankind: Palmer\u27s Common Law Lessons

In 1982-83 a small group of Cape Breton landowners and two Indian chiefs, with wide-spread public support took the multi-national forest industry to court in Nova Scotia; and lost Their objective was to obtain an injunction to prevent the spraying of a dioxin-contaminated herbicide on forest plantations near their homes and properties and those of their neighbours The case raised important environmental law issues including the use of class actions, reliance upon common law causes of action, and the availability of injunctive remedies Most significantly, the case brought to the fore the question of how the judicial system should handle the deliberate release of toxic chemicals into the environment when uncertainty existed concerning the impact this activity would have. In this article the author provides background to the case and analyzes the Nova Scotia Supreme Court decision. He concludes that future plaintiffs in a similar position should win on existing legal theory. Finally, Professor Wildsmith suggests an alternative approach that judges could and should within an evolving common law system, take to adjust the burden of proof in cases concerning the use of toxic chemicals

An American Enforcement Model of Civil Process in a Canadian Landscape

One general perspective from which to view the Anglo-American legal system shared by Canada is that proposed by Charles Darwin to explain the origin and diversity of biologically distinct species. Darwin\u27s theory of evolution places emphasis upon the adjustment or adaptation over time of biological characteristics to environmental factors by the selection of genetically determined features enabling the most suited to their surroundings to better thrive - the so-called survival of the fittest .\u27 Law might usefully be thought of as bearing an analogous relationship to the social environment in which it exists and must operate. As this milieu for various reasons inevitably undergoes a process of change, a process dramatically popularized as the death of permanence by Alvin Toffler2 , so must the legal system in response adapt itself to the needs dictated by current conditions

Western Individualism and the Christian Community: Towards a Faithful Expressing of Church in the West

As evangelicals living in Canada, we are tasked with finding a way to faithfully live out the calling of the church in our North American context. Yet as we try to do this, we are regularly faced with the cultural reality of individualism and are often influenced by it in ways that we do not fully understand. This thesis will suggest that the integration of individualism in the Western evangelical church is having a detrimental effect on our ability to create or maintain Biblical community. This thesis will examine the issue of individualism as it relates to Christian community through interviews with 15 evangelical laypersons and pastors. This thesis will also employ secondary sources in the analysis of these interviews, engaging them in dialogue with some classic and contemporary theologians of the church.Master of Divinity (M.Div

The International Law of Pollution: Protecting the Global Environment in a World of Sovereign States

A good book must have focus. This may not be the only criteria for evaluating a book, but it is certainly a sine qua non. A scholarly work such as Professor Springer\u27s is a means of communicating ideas; the sharper its focus the clearer the message of its author and the better it and he communicates. When reading this book I wondered about its focus: was there a central unified objective? Having now completed the book, I can see that the author has painted us a useful, but blurred picture. He has not quite brought into focus his objective; much valuable information and many good ideas are obscured by the lack of a clear thesis. The book is not a repository or summing up of law; it does not provide reform or future-oriented suggestions; it does not argue for a particular point. What it does do is provide much interesting description on the theme of international pollution. But this is not the focus suggested by the author himself

Building a knowledge base for language teaching through translanguaging

The aim of the research reported on in this article was to explore the effects on student learning and performance of the use of two languages of instruction, viz. isiZulu and English, in a course on the teaching of isiZulu as an additional language at school level. The course was for third year BA students considering a language teaching career. The content of the course came from the Applied Linguistics field and had not been translated from English into isiZulu. In addition, the discipline content was taught by a non-isiZulu speaking applied linguistics lecturer who had recently joined a three-year major course in isiZulu but was not fluent. The course was team taught by the Applied Linguist and an isiZulu lecturer who made the content accessible to the students through translation of difficult terms and concepts into isiZulu. Students were free to use either language. The research questions focused on how the two languages interacted naturally within a translanguaging framework in order to scaffold learning, and whether and how the use of isiZulu would facilitate understanding of key disciplinary concepts when the terminology had not yet been developed. Class sessions were recorded and transcribed with informed consent. Instances of translanguaging were analyzed in terms of the functions they were fulfilling within a broad discourse analysis framework. Findings revealed that what began as planned and systematic code-switching became, over time, translanguaging. Students appreciated the affordance for meaningful engagement with the subject content as they found it easier to challenge the lecturers and to present their own points of view in isiZulu. The experience also created rich affordances for building an academic discourse in isiZulu. Finally, teaching on the course created learning experiences for the lecturers who increased their knowledge of the languages concerned and the subject content respectively.Keywords: applied linguistics; codeswitching; isiZulu; language learning; languages of learning and teaching (LoLTs); language scaffolding; tertiary level; translanguagin