Integrating new assessment strategies into mathematics classrooms: an exploratory study in Singapore primary and secondary schools

Educational researchers and practitioners have in recent years paid mounting attention to the importance of new assessment (or the so-called alternative assessment) strategies in Mathematics instruction to better reflect the new desired educational goals and shifted values in education. However, research is wanting in this area, particularly in Singapore's educational setting. This project seeks to investigate the influence of using new assessment strategies in Mathematics teaching and learning on students' achievements, in both the cognitive and affective domains, in our local school settings. A quasi-experimental study with about 15-20 teachers at primary and lower secondary levels will be carried out to assess the impact of using a variety of strategies (e.g., projects, journal writing, oral presentation, performance tasks, student self-assessment, classroom observation and interview, etc.) for three school semesters on students' learning. The project will also look into issues concerning how to use new assessment strategies effectively in classrooms in local schools. For this purpose, data will be collected from classroom observation, interviews with teachers and students, and questionnaire surveys. It is hoped that the project will provide research-based evidence and practical suggestions for promoting the effective use of alternative assessment in Singapore Mathematics classrooms. <br/

ESTUDO DA VIABILIDADE ECONÔMICA, FINANCEIRA E MERCADOLÓGICA DA IMPLANTAÇÃO DE UMA LIVRARIA NA CIDADE DE XANXERÊ, SC

O plano de negócios realizado tem como finalidade analisar a viabilidade econômica, financeira e mercadológica da implantação de uma livraria na cidade de Xanxerê, SC. O projeto é voltado para uma livraria que também disponha de espaço de cafeteria, a Dedo de Pó Livraria e Café. Nesse âmbito, foi realizada pesquisa de mercado com a população, estudo e análise da concorrência existente; as informações coletadas foram interpretadas por meio do plano e estratégias de marketing. A pesquisa viabilizou perceber a aceitação das pessoas com a abertura da livraria; no entanto, a realização do planejamento financeiro foi primordial para buscar os reais resultados do investimento. Foram estabelecidos três cenários a serem trabalhados, buscando confrontar os números obtidos nas projeções de vendas e compras com três situações diferentes de mercado, sendo uma favorável, outra mais próxima à realidade e uma situação desfavorável. Por meio da elaboração das ferramentas de controle financeiro como projeções de vendas, fluxos de caixa e indicadores financeiros foi possível comprovar a inviabilidade do plano de negócios proposto, considerando-se que a livraria não produz receita de vendas adequada para gerar margem capaz de cobrir seus custos totais, acarretando em prejuízo em todos os períodos e cenários explanados.Palavras-chave: Pesquisa. Livraria. Planejamento. Investimento

Predictors of Nonsentinel Nodal Involvement to Aid Intraoperative Decision Making in Breast Cancer Patients with Positive Sentinel Lymph Nodes

Background. Up to 60% of patients with a positive sentinel lymph node (SLN) have no additional nodal involvement and do not benefit from completion axillary lymph node dissection (ALND). We aim to identify factors predicting for non-SLN involvement and to validate the MSKCC nomogram and Tenon score in our population. Methods. Retrospective review was performed of 110 consecutive patients with positive SLNs who underwent ALND over an 8-year period. Results. Fifty patients (45%) had non-SLN involvement. Non-SLN involvement correlated positively with the number of positive SLNs (P = 0.04), macrometastasis (P = 0.01), and inversely with the total number of SLNs harvested (P = 0.03). The MSKCC nomogram and Tenon score both failed to perform as previously reported. Conclusions. The MSKCC nomogram and Tenon score have limited value in our practice. Instead, we identified three independent predictors, which are more relevant in guiding the intraoperative decision for ALND

Germline breast cancer susceptibility genes, tumor characteristics, and survival.

BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]). CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions

Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure

Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations.After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations.This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci

Homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita–like phenotypes

This research was originally published in Blood Online. Tummala, H., et al. (2018). "Homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita–like phenotypes." Blood 132(12): 1349-1353. Title. Blood. Prepublished Sept 20 2018; DOI https://doi.org/10.1182/blood-2018-03-837799Dyskeratosis congenita (DC) and its severe form, Hoyeraal-Hreidarsson syndrome (HHS), are rare and have life-threatening failure of hematopoiesis. Typically, DC patients present with disease features such as nail dystrophy, oral leukoplakia, and abnormal skin pigmentation along with peripheral pancytopenia and marrow hypoplasia with strong predisposition to cancer.1 In DC, hematopoietic failure occurs due to critical shortening of telomeres,2,3 which enhances the DNA damage response4,5 and leads to premature senescence of hematopoietic stem cellsMedical Research Council (grant MR/P018440/1), Bloodwise (grant 14032), and Children with Cancer UK (grant 2013/144)

A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias

Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the ‘discoverability’ of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes