Memory\u27s Future

Memory and the Future: Transnational Politics, Ethics and Society edited by Yifat Gutman, Adam D. Brown, and Amy Sodaro. (Houndmills, England: Palgrave Macmillan, 2010. Pp. 232. £50.

Israel Charny’s attack on the Journal of Genocide Research and its authors: a response

Israel Charny has published an article, “Holocaust Minimization, Anti-Israel Themes, and Antisemitism: Bias at the Journal of Genocide Research” (JGR) in the Journal for the Study of Antisemitism. His specific allegations are bundled together in a single sentence: “minimization of the Holocaust, delegitimization of the State of Israel, and repeat[ing] common themes of contemporary antisemitism”. We write as the authors of articles and contributors to the JGR attacked by Charny. His allegations are false and we reject them. This article shows how they are based on distortions, misquotations, and falsifications of our work

The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis

Background and Purpose Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis. Experimental Approach Secretion of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometry. Involvement of cancer cell-derived LPI on angiogenesis was tested in the in vivo chicken chorioallantoic membrane (CAM) assay along with the assessment of the effect of LPI on proliferation, network formation, and migration of neonatal and adult human endothelial colony-forming cells (ECFCs). Engagement of GPR55 was verified by using its pharmacological inhibitor CID16020046 and diminution of GPR55 expression by four different target-specific siRNAs. To study underlying signal transduction, Western blot analysis was performed. Key Results Ovarian carcinoma cell-derived LPI stimulated angiogenesis in the CAM assay. Applied LPI stimulated proliferation, network formation, and migration of neonatal ECFCs in vitro and angiogenesis in the in vivo CAM. The pharmacological GPR55 inhibitor CID16020046 inhibited LPI-stimulated ECFC proliferation, network formation and migration in vitro as well as ovarian carcinoma cell- and LPI-induced angiogenesis in vivo. Four target-specific siRNAs against GPR55 prevented these effects of LPI on angiogenesis. These pro-angiogenic effects of LPI were transduced by GPR55-dependent phosphorylation of ERK1/2 and p38 kinase. Conclusions and Implications We conclude that inhibiting the pro-angiogenic LPI/GPR55 pathway appears a promising target against angiogenesis in ovarian carcinoma

Archive of Darkness:William Kentridge's Black Box/Chambre Noire

Situating itself in histories of cinema and installation art, William Kentridge's Black Box/Chambre Noire (2005) raises questions about screens, exhibition space, site-specificity and spectatorship. Through his timely intervention in a debate on Germany’s colonial past, Kentridge’s postcolonial art has contributed to the recognition and remembrance of a forgotten, colonial genocide. This article argues that, by transposing his signature technique of drawings for projection onto a new set of media, Kentridge explores how and what we can know through cinematic projection in the white cube. In particular, his metaphor of the illuminated shadow enables him to animate archival fragments as shadows and silhouettes. By creating a multi-directional archive, Black Box enables an affective engagement with the spectres of colonialism and provides a forum for the calibration of moral questions around reparation, reconciliation and forgiveness

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.[Please see the Supplementary Note for acknowledgments.]This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.337

Learning at the bottom of the pyramid : Science, measurement, and policy in low-income countries

In this volume, a diverse group of authors discuss and analyse the scientific tensions in understanding learning among poor and marginalized populations in Low- and Middle-income countries (LMICs). Four broad areas are considered: how to define the BoP; how to measure and assess learning outcomes across diverse populations within a country; variations in learning across the life-span; and the implications for international education policy. Each of the 12 chapters is complemented by two commentaries, thus there are a total of 36 contributions. In the social sciences, learning is defined most commonly as a change – such as in knowledge, skills, attitudes, and values – based on experiences of some kind.Thus, schooling is not the same thing as learning. While schooling is usually designed to foster curriculum-based learning in classrooms, research increasingly demonstrates that much of what we presume is learned in school is not, and that a great deal of learning takes place outside of schools. There is a large and diverse empirical research base in the area of human learning. However, much of the available research is limited by constraints of various kinds. Most prominent among these is the limited ability to generalize from findings in one population or context to others. In Chapter 1, Schmelkes considers common elements to human learning, in and out of school, including important cultural variations that are large and often poorly understood. She concludes that much more should be done to improve educational policy and address such contextual issues. A second key priority is to determine what populations are meant by the phrase BoP. How do populations differ in LMICs – both across and within countries? As pointed out by Montoya in Chapter 2, there are at least six prominent dimensions through which populations at the BoP may be described in low-income countries, and each is important for considering the ways that young people can escape from persistent poverty. Building on the first two chapters, Crouch (Chapter 3) lays out a conceptual model, buttressed by data from international assessments, that describes how to flatten the learning pyramid to ensure more equitable learning outcomes for all by focusing on the poorest learners. Overall, these three chapters provide a framework for considering the nature and extent of BoP studies of learning. There are many critiques of the educational assessment enterprise, the beginning of which is sometimes attributed to the French psychometrician Alfred Binet. In order to support the expansion of public schooling in France, Binet famously created assessments through which he could predict which children would have the most difficulty in school. In this section, we consider contemporary approaches to learning assessments, with a specific focus on the socio-cultural determinants of who succeeds and who does not at the BoP. Kanjee, in Chapter 4, takes a broad perspective by reviewing the purposes of international assessment studies, suggesting that assessments have only limited impact on supporting BoP learning achievement. He concludes that assessments can better address the learning needs of poor and marginalized learners by reporting results through formative evaluations that can impact children before learning gaps widen. In Chapter 5, Willms describes a conceptual model for improved learning over the life-course, empirically supported by research in Uruguay among preschool children, and in Canada with young indigenous children. One of his findings is that in order to succeed in school, children need to learn to read with confidence during the primary grades, and use language to think critically, solve problems, and create new knowledge. He concludes that national and international assessments can serve to establish standards, assess the extent of inequalities among various subpopulations, and provide a framework for basic or theoretical research, but that there should be greater focus on changing classroom practice. One way to understand the inner workings of assessments and use them to promote learning at the BoP is provided by Vagh and Sharma (Chapter 6) in their action research project in Allahabad, India. This project sought to develop and evaluate a local language literacy and numeracy programme for children from low socioeconomic backgrounds in government school primary grades, using measurement and assessment to drive programme change. It highlights some of the strengths and challenges of localized assessments. Moreover, it suggests that assessments can be used by teachers to support early reading. Finally, in Chapter 7, Maddox asks a seminal question: To what extent are learning assessments able to identify and include individual and cultural differences, without reproducing relations of disadvantage? These issues are described in terms of test fairness and procedures for anticipating and removing sources of test bias. In a series of ethnographic studies, Maddox advises the reader to pay close attention to how assessments are carried out in situ, and how questions are interpreted by the person tested. Serious problems can and will ensue without such care in local contexts. Another approach to BoP issues is through a life-span perspective. How do measurement tools on learning and learning outcomes vary for young children, students in school, as well as among youth and adults? Three chapters in this section consider such age-related differences. Dowd and Pisani, in Chapter 8, have been deeply involved in the field of assessments of young children before they reach school age. Their chapter reviews the application of the International Development and Early Learning Assessment (IDELA) instrument to explore young children’s skills at the BoP and identify learning gaps in early academic, physical, and social-emotional development. Based on the broad findings from more than 20 LMICs, and closer analysis of particular contexts, the authors make that case that there is much variation in early childhood learning within countries, particularly between urban and rural contexts. They argue that national policies in support of early childhood need to be guided by disaggregated data in order to ensure that children at the BoP receive adequate support. In Chapter 9, Care, Robertson, and Ferido describe how well-designed assessments for school-aged children can provide individualized information that can support school-based learning. These assessments build on the skill levels that children bring to the classroom. Through what they term a ‘learning progression model’, they present data on children in the Philippines who are best able to learn from specifically guided instruction tailored to their particular skill level. They conclude that learning assessments can and should be inclusive of diverse groups within any larger target population. Finally, Oketch (Chapter 10) focuses on youth and adult learning in subSaharan African, pointing out that rapidly changing demographics and economies in the region require significantly greater attention. Further, the population of low-skilled youth is growing dramatically, even though more African children are going to school than ever before. This chapter describes the importance of technical and vocational education and training (TVET) and non-formal education as two known methodologies for directly providing instruction and learning outside of the classroom in support of out-of-school youth and adults. The problem remains, according to Oketch, that there is a paucity of research in this domain, and in particular among populations at the BoP. In Chapters 1–10, authors and commentators present multiple views on scientific definitions, measurement tools, and life-span approaches for understanding learning at the BoP. This final section of the volume considers the kinds of educational policy implications that need to be considered by both national and international decision-makers. Benavot (Chapter 11) raises a key issue in supporting learning at the BoP, notably the need to move beyond easily accessible measures of learning – namely, school-based surveys of a narrow range of learning outcomes at the primary and lower secondary level – and engage with the broader and more comprehensive learning agenda proposed in the SDGs. He points out that many of the UN goals contain diverse elements of learning, and the specific targets for each goal may vary a great deal across diverse populations. Further, he notes that many of the key markers of disadvantage in education (such as socio-economic status, SES) are very difficult to change. He concludes that a serious focus on learning at the BoP will require greater clarity of definitions, and a more deliberate approach to building evidence on how best to improve relevant learning outcomes for the disadvantaged. In Chapter 12, Van Damme provides a global policy perspective supported by the findings of the Organisation for Economic Co-operation and Development (OECD) international learning assessments. He asserts that international educational policies can only be inclusive and sustainable if those at the bottom of the social and educational pyramid benefit from them. To support this perspective, Van Damme presents findings that demonstrate how higher levels of economic growth are driven by more years of education and greater learning achievement within countries. By disaggregating data from the Programme for International Student Assessment (PISA) 2015 assessment, he reminds us that students with very low proficiency tend to drive down national averages (similar to the findings by Crouch in Chapter 3). He concludes that countries need to focus on raising average learning outcomes to desired national standards while at the same time narrowing the distribution of national learning outcomes

Pre-Micro RNA Signatures Delineate Stages of Endothelial Cell Transformation in Kaposi Sarcoma

MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma–associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline