Dependency of Adult Vocational Students Enrolled at Gordon Cooper Area Vocational-Technical School upon Financial Aid

Occupational and Adult Educatio

Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.

Altered metabolism in pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) contributes to the pathology of pulmonary hypertension (PH), but changes in substrate uptake and how substrates are utilized have not been fully characterized. We hypothesized stable isotope metabolomics would identify increased glucose, glutamine and fatty acid uptake and utilization in human PASMCs and PAECs from PH versus control specimens, and that TGF-β treatment would phenocopy these metabolic changes. We used 13C-labeled glucose, glutamine or a long-chain fatty acid mixture added to cell culture media, and mass spectrometry-based metabolomics to detect and quantify 13C-labeled metabolites. We found PH PASMCs had increased glucose uptake and utilization by glycolysis and the pentose shunt, but no changes in glutamine or fatty acid uptake or utilization. Diseased PAECs had increased proximate glycolysis pathway intermediates, less pentose shunt flux, increased anaplerosis from glutamine, and decreased fatty acid β-oxidation. TGF-β treatment increased glycolysis in PASMCs, but did not recapitulate the PAEC disease phenotype. In TGF-β-treated PASMCs, glucose, glutamine and fatty acids all contributed carbons to the TCA cycle. In conclusion, PASMCs and PAECs collected from PH subjects have significant changes in metabolite uptake and utilization, partially recapitulated by TGF-β treatment

Embedding Academic Literacies through Growing Student and Staff Communities

In the UK, HE practical writing support has not kept pace with advances in our understanding of how students learn to write in their disciplines or greater comprehension of the nature of these discourses they are acquiring. Current institutional provision can be still be characterized as fragmented offering generic, deficit focused, skills-based instruction, despite such approaches being theoretically discredited. One alternative means to develop academic literacies in more inclusive and nuanced ways is to embed this work at a disciplinary level; while long recommended this model is unusual in the UK. This paper reviews approaches to embedding academic literacies work and reports on our attempts to embed writing development work within a social science department through an extended action research project which aimed to increase student mastery of academic literacies within one department. We focused on building opportunities for engagement using Writing Exemplars, Retreats and Writing Circles. Key features of our work are identified that appear transferable and may further facilitate successful interdisciplinary collaborations

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study.

OBJECTIVE: Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome "resistance" in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. METHODS: Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. RESULTS: Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. CONCLUSIONS: Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment

Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury

Acute respiratory distress syndrome (ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A2AR-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A2AR agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e.g., with inhalative application of A2AR agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure

Expressions 1990

https://openspace.dmacc.edu/expressions/1012/thumbnail.jp

Role of the HSP90-Associated Cochaperone p23 in Enhancing Activity of the Androgen Receptor and Significance for Prostate Cancer

Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor. A key stage in AR signaling occurs in the cytoplasm, where unliganded receptor is associated with the heat shock protein (HSP)90 foldosome complex. p23, a key component of this complex, is best characterized as a cochaperone for HSP90 but also has HSP90-independent activity and has been re-ported as having differential effects on the activity of different steroid receptors. Here we report that p23 increases activity of the AR, and this appears to involve steps both in the cytoplasm (increasing ligand-binding capacity, possibly via direct interaction with AR) and the nucleus (en-hancing AR occupancy at target promoters). We show, for the first time, that AR and p23 can interact, perhaps directly, when HSP90 is not present in the same complex. The effects of p23 on AR activity are at least partly HSP90 independent because a mutant form of p23, unable to bind HSP90, nevertheless increases AR activity. In human prostate tumors, nuclear p23 was higher in malignant prostate cells compared with benign/normal cells, supporting the utility of p23 as a therapeutic target in prostate cancer. © 2012 by The Endocrine Society

The formalized framework for decision-making in child protection care orders : a cross-country analysis

Care orders within the child protection system are some of the most invasive interventions a state can make. This article examines the discretionary space governments set out for child protection workers when they prepare care orders. We analyse the formalized framework for these decisions in England, Finland, Norway and the United States. We focus on knowledge, timelines, how children and parents are involved and accountability. We find that Norway and Finland have highly de-regulated systems with wide discretionary space, whereas England and the United States are highly regulated systems with narrow discretionary space. The United States differentiates itself with relatively little parent and/or child involvement in decision-making. England and Finland do not have defined deadlines for terminating the process, and Norway has few directives on what information to collect. Such differences will influence the quality of decisions as well as the principles of the rule of law

Fatigue and vigilance in medical experts detecting breast cancer

An abundance of laboratory-based experiments has described a vigilance decrement of reducing accuracy to detect targets with time on task, but there are few real-world studies, none of which have previously controlled the environment to control for bias. We describe accuracy in clinical practice for 360 experts who examined >1 million women’s mammograms for signs of cancer, whilst controlling for potential biases. The vigilance decrement pattern was not observed. Instead, test accuracy improved over time, through a reduction in false alarms and an increase in speed, with no significant change in sensitivity. The multiple-decision model explains why experts miss targets in low prevalence settings through a change in decision threshold and search quit threshold and propose it should be adapted to explain these observed patterns of accuracy with time on task. What is typically thought of as standard and robust research findings in controlled laboratory settings may not directly apply to real-world environments and instead large, controlled studies in relevant environments are needed