Teacher Perceptions of Small High Schools

This research brief uses data from the School District of Philadelphia teacher survey to assess teacher perceptions of small and large neighborhood high schools

The ship in the sky

The sky’s grumbling. Layers of gray grinding above me the way teeth grind, angry and wanting, all nap long. Two boom-clap bangs and my eyes snap open to clouds thick as clay, metal-sheet lightening and thunder thumping close and heavy as fists. I grab the stone floor and I’m watching and listening, listening and watching and I’m hearing yelling and it’s my own heart yelling, and I realize this ain’t dreaming. This ain’t dreaming. I ease myself near the rock ledge, hanging there like a loose tooth when the ground rips apart, it clear splits thirty feet in front of me right through the Joneses' veggie patch. My gut leaps to my throat. Would be an awesome sight if it weren’t so terrifying. Air and water and fire and earth dancing into one, blasting the ground inches from the Joneses’ farmhouse splitting their flagpole, my eardrums just about splitting in the roar. I clasp on tight. Next thing, my legs are falling from my body, or my body’s falling from the rock and we’re sinking together, sliding down. Then silence. Earth shattering silence. A venomous pause. Nothing moves, not even my lungs. I grab at the ledge hanging, waiting, watching. Come on Bill. Get out of the house. Get the Missus and get the fuck out. The elements are hovering, brewing a soup so thick and dark a rich thick and dark soup. Triple decker boom and I’m rolling to the spine of the rock as it tilts and digs its feet in, crushing or protecting, as the sky breaks open with rain belting down. I crank my head towards the farmhouse and it’s sinking. Come on Bill and Betty. As the sky belts the earth belts my skull belts on the back of that blasted crushing protecting rock, the ground sinking further under the weight from above and rock falling, consciousness too, and then I’m dreaming of everything

The Role of β-synuclein in the Pathological Mechanisms of Dementia with Lewy Bodies

Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia following Alzheimer’s disease (AD). DLB neuropathology is characterised by Lewy bodies (LBs) and Lewy neurites (LNs) resulting from the modification and aggregation of α-synuclein. The presence of small pre-synaptic accumulations of α-synuclein lead to structural synaptic alterations that may precede neuronal demise. Family member β-synuclein does not readily aggregate and has been shown to prevent α-synuclein aggregation in vitro and in vivo and regional changes in β-synuclein levels has been observed in the brains of DLB patients. α-synuclein pathology is found in the limbic and cortical regions of the DLB brain producing fluctuating cognitive impairment, visual hallucinations and extrapyramidal motor disturbances. In order to examine whether regional changes in β-synuclein influence the course of DLB, examination of protein levels of α-synuclein and β-synuclein in the frontal cortex, occipital cortex and hippocampus of patients with DLB and age-matched controls was performed. Evidence is provided here for a neuronal increase of β-synuclein within the frontal cortex and a decrease in occipital cortex of DLB patients, both regions see similar levels of oligomeric α-synuclein. Further examination of key pre-synaptic SNARE proteins reveal an increase of VAMP2 in the frontal cortex and a decrease of VAMP2 and SNAP25 in the occipital cortex. Autophagy markers LC3-II and p62 were also increased in the frontal cortex where an increase in β-synuclein was identified in DLB brains and in vitro overexpression of β-synuclein attenuates the autophagy flux. Collectively, this data suggests that β-synuclein changes in the DLB cortex are regionally distinct and the possibility that β-synuclein may exacerbate neuronal dysfunction by influencing protein degradation pathways, cannot be excluded. This data highlights the possibility of a dual role for β-synuclein that may be both protective and antagonistic, advocating caution when considering the use of β-synuclein as a potential therapeutic.BRACE, Northcott Devon Medical Foundation and University of Plymout

Are interventions to reduce the impact of arsenic contamination of groundwater on human health in developing countries effective? A systematic review

BackgroundWithin developing countries, groundwater provides an alternative drinking source to polluted surface water. However, the presence of arsenic in some groundwater sources has resulted in chronic worldwide poisoning. The aim of this review was to determine the effectiveness of field-based technologies for the removal of arsenic from groundwater in developing countries.MethodsA structured search strategy was conducted in a range of databases. Titles, abstracts and full texts were screened using pre-defined inclusion criteria. Included studies were quality appraised prior to data extraction. The primary outcome was the percentage of effluent water samples meeting WHO guidelines for arsenic concentrations (≤0.01 mg/L). Secondary outcomes included: (a) arsenic concentrations in effluent water samples meeting the national guideline limit (≤0.05 mg/L), (b) arsenic concentrations in human tissue, and (c) knowledge and attitudes related to the interventions.ResultsFifty-one reports, evaluating 50 different technologies, were included. Sixty-seven percent (n = 34) of studies were conducted in Bangladesh. Fifty of the included reports were appraised as ‘weak’, with one ‘strong’ report of a randomised-controlled trial.In summary, the effectiveness of the oxidation and filtration interventions is poor, while the evidence for coagulation, co-precipitation and filtration, subterranean and membrane and electrolytic methods is mixed. Evidence regarding adsorption and zero valent iron interventions is more persuasive with most results suggesting good evidence of effectiveness (i.e. ≥95% of samples with arsenic concentrations ≤0.01 mg/L). In particular, activated alumina and sono/three-kolshi/gagri/pitcher filters have ≥95% of samples meeting national guidelines. Disappointingly, only one study reports excellent evidence of effectiveness: BRAC (2000) for activated alumina (i.e. ≥95% of samples with arsenic concentrations ≤0.01 mg/L).The success of each technology was highly dependent on context, especially their acceptability to users, a sense of ownership and expectations of women’s roles in society.ConclusionsMost studies were poorly conducted and reported. Consequently, although some technologies met national guidelines, the evidence-base for decision-making regarding arsenic mitigation technologies at household- and community-level is weak. To improve this situation, primary research needs to be commissioned with adequate sample sizes, testing the impact of key contextual factors, using valid tools for analysis, and meeting standards for completeness of reporting

Protocol for studying cough frequency in people with pulmonary tuberculosis.

INTRODUCTION: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed

Sustainability of locally driven centres for those affected by dementia: a protocol for the get real with meeting centres realist evaluation

INTRODUCTION: Improving support for people with early to moderate dementia to live at home in their communities is a global public health goal. Community adult social care is not robust in many parts of the UK, however, with the pandemic increasing pressure on services for this population. Community-led interventions can play a key role in supporting people postdiagnosis, helping delay decline, but many interventions struggle to sustain beyond 1-2 years. Meeting Centres (MCs) are one such intervention, which many UK community groups find attractive and achievable. However, it is not understood how these communities can ensure they are putting in place strategies that will help them sustain in the longer term, beyond start-up phase. METHODS AND ANALYSIS: This realist evaluation aims to understand the factors affecting sustainability of MCs in rural areas and learn lessons from MCs that have sustained beyond 3 years. Data will be collected using mixed methods: interviews and group discussions with stakeholders involved at every level in three case study locations in England and Wales, analysed with Soft Systems modelling; a Discrete Choice Experiment exploring what people across the UK value and are willing to pay for MCs, analysed with regression modelling. All data will be synthesised using a Realist logic of analysis to build a theoretical model of how, why, for whom, in what contexts and to what extent MCs can be successfully implemented for the long term. ETHICS AND DISSEMINATION: As participants may lack capacity for informed consent, favourable ethical opinion was received from a Health Research Authority research ethics committee. Resulting recommendations will be of interest to stakeholders including those commissioning, planning, running, supporting or attending MCs, as well as policy-makers and healthcare professionals. Knowledge will be shared with emerging MCs to help accelerate scale up of this intervention

Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy

INTRODUCTION: Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20-25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. METHODS: We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58-2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48-1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01). CONCLUSIONS: KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy

Therapeutic target-site variability in α1-antitrypsin characterized at high resolution

The intrinsic propensity of [alpha]1-antitrypsin to undergo conformational transitions from its metastable native state to hyperstable forms provides a motive force for its antiprotease function. However, aberrant conformational change can also occur via an intermolecular linkage that results in polymerization. This has both loss-of-function and gain-of-function effects that lead to deficiency of the protein in human circulation, emphysema and hepatic cirrhosis. One of the most promising therapeutic strategies being developed to treat this disease targets small molecules to an allosteric site in the [alpha]1-antitrypsin molecule. Partial filling of this site impedes polymerization without abolishing function. Drug development can be improved by optimizing data on the structure and dynamics of this site. A new 1.8 Å resolution structure of [alpha]1-antitrypsin demonstrates structural variability within this site, with associated fluctuations in its upper and lower entrance grooves and ligand-binding characteristics around the innermost stable enclosed hydrophobic recess. These data will allow a broader selection of chemotypes and derivatives to be tested in silico and in vitro when screening and developing compounds to modulate conformational change to block the pathological mechanism while preserving function