The influence of Teach For America on Algebra I student achievement

This non-experimental study examined the influence of an initiative that High Risk School District (pseudonym) implemented to offset the effect of low student academic performance in low performing-schools. The study attempted to answer the following research question: Does having a Teach For America (TFA) teacher have an influence on a student's Algebra I EOC score, independent of gender and race? Teach For America teachers were assigned to the district's most disenfranchised schools. Previous studies have revealed mixed results on TFA teachers' impact on student achievement. The researcher compared student performance on the Algebra I North Carolina End of Course test in High Risk Schools between TFA and non-TFA classrooms. To analyze the data, the responses were measured using the composite Algebra I EOC scores, and the explanatory variables of student gender (male or female), race (African-American, Hispanic and White) and teacher type (TFA or non-TFA) employing a hierarchical modeling procedure. After considering the nesting nature of students within different schools, the researcher used hierarchical linear modeling and found that students taught by TFA out-performed students taught by non-TFA students t (1956)= 3.23, p=.002. Students taught by TFA teachers for all subgroups White, Black and Hispanic out performed students taught by non-TFA teachers (all ps<.01). The results of this study demonstrate that TFA teachers assigned to Algebra I classes have a significant influence on increasing student achievement. The researcher discusses the limitations of these findings. Other studies have shown that TFA teachers, in comparison to regularly certified teachers, have a negative influence on achievement

DNA fragments of altered electrophoretic mobility in leukemia samples can arise from double-strand DNA breaks at nuclease hypersensitive sites of active genes

Chromosome translocations that disrupt or alter gene function have been implicated in the pathogenesis of a variety of malignancies. Therefore, identification of a translocation breakpoint has become a more important means by which to identify genes involved in cellular transformation. A common site of translocation in myeloid and lymphoid malignancies involves 11q23. One human protooncogene, ETS1, has been localized to this chromosomal segment, and several tumors with 11q23 translocations have been shown to have altered ETS1 DNA migration after restriction enzyme digestion. Two laboratories, however, have recently localized the 11q23 breakpoint region to a small region of DNA telomeric of the CD3 loci, a region at considerable distance from the ETS1 gene locus. Therefore, it is difficult to reconcile the studies that suggest altered migration of fragments associated with ETS1 and lack of a localization of the breakpoint to a region near the ETS1 gene. Recently, in our studies to characterize the promoter/enhancer region of the ETS1 protooncogene, we had the opportunity to analyze DNA from 18 patients with acute leukemia involving chromosome 11q23 aberrations. We were unable to demonstrate rearrangement of the ETS1 gene in this group, thus confirming that the 11q23 breakpoint does not involve ETS1 protooncogene. In one patient, however, a DNA break in the region of the ETS1 promoter was detected reproducibly. This DNA break was mapped to the major DNaseI hypersensitive site in the ETS1 promoter. Mapping from both sides of the break demonstrated that the break must have occurred during processing of the leukemic cells for DNA analysis. Therefore, artifactual DNA breaks can occur at nuclease-hypersensitive sites of active genes. These data suggest that previous reports of chromosomal translocations involving the ETS1 protooncogene may have resulted from DNA breaks at nuclease hypersensitive sites. This mechanism may account for sporadic case reports of altered restriction enzyme fragment migration involving genes that are not ultimately shown to be associated with the chromosome translocation being examined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30693/1/0000338.pd

Adalimumab for Treating Moderate-to-Severe Hidradenitis Suppurativa: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company’s submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company’s submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy

A scoping review found increasing examples of rapid qualitative evidence syntheses and no methodological guidance

Objectives: To identify existing methodological guidance for the conduct of rapid qualitative evidence syntheses, and examples of rapid qualitative evidence syntheses to describe the methods used. Study Design and Setting: We conducted a systematic scoping review. We searched MEDLINE, CINAHL, grey literature, including PROSPERO, with no date limits and solicited examples through experts and researchers in the field. Results: We found no methodological guidance to direct the conduct of rapid qualitative evidence synthesis, and 15 examples including 13 completed reviews and two protocols. Diverse methods to abbreviate the review process were followed, which largely mirror methods developed for rapid reviews of clinical effects. Abbreviated search strategies, including date and language restrictions, were common, as was the use of a single reviewer for screening, data extraction and quality appraisal. Descriptive approaches to synthesis, such as thematic synthesis, were more common than interpretive approaches, such as meta-ethnography. Conclusion: There is a need to develop and explore methods for the synthesis of qualitative research that balance the need for rapidity with rigour. In the meantime, providing details on the methods used, shortcuts made, and the implications of such methodological choices, together with collective sharing of innovations, becomes more important under increased time constraints

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus