Mechanistic modeling of generic orally inhaled drug products: A workshop summary report.

In silico mechanistic modeling approaches have been designed by various stakeholders with the goal of supporting development and approval of generic orally inhaled drug products in the United States. This review summarizes the presentations and panel discussion that comprised a workshop session concentrated on the use of in silico models to predict various outcomes following orally inhaled drug product administration, including the status of such models and how model credibility may be effectively established.

Combining 1,4-dihydroxy quininib with Bevacizumab/FOLFOX alters angiogenic and inflammatory secretions in ex vivo colorectal tumors.

Background: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality worldwide with one in every five patients diagnosed with metastatic CRC (mCRC). In mCRC cases, the 5-year survival rate remains at approximately 14%, reflecting the lack of effectiveness of currently available treatments such as the anti-VEGF targeting antibody Bevacizumab combined with the chemotherapy folinic acid, fluorouracil and oxaliplatin (FOLFOX). Approximately 60% of patients do not respond to this combined treatment.

The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation.

Background: Only 10-30% of oesophageal and rectal adenocarcinoma patients treated with neoadjuvant chemoradiotherapy have a complete pathological response. Inflammatory and angiogenic mediators in the tumour microenvironment (TME) may enable evasion of anti-tumour immune responses.

Methods: The TME influence on infiltrating dendritic cells (DCs) was modelled by treating immature monocyte-derived DCs with Tumour Conditioned Media (TCM) from distinct gastrointestinal sites, prior to LPS-induced maturation.

1,4-dihydroxy quininib attenuates growth of colorectal cancer cells and xenografts and regulates the TIE-2 signaling pathway in patient tumours.

Colorectal cancer (CRC) is the second leading cause of cancer associated deaths in developed countries. Cancer progression and metastatic spread is reliant on new blood vasculature, or angiogenesis. Tumour-related angiogenesis is regulated by pro- and anti-angiogenic factors secreted from malignant tissue in a stepwise process.

Working the 'wise' in speech and language therapy: Evidence-based practice, biopolitics and 'pastoral labour'.

This paper examines how power and knowledge are involved in the workings of speech and language therapy and in the work of speech and language therapists (SLTs). The paper draws on Foucault for its conceptual frame, with reference to his exposition of governmentality, biopolitics and pastoral power. Based on interviews with thirty-three SLTs in the UK, the findings show that evidence-based practice (EBP) is ever-present in speech and language therapy, despite its apparent absence; and that its power circulates in a multitude of ways.

Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial.

Background: Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate if inhaled furosemide relieves the air hunger component (uncomfortable urge to breathe) but not the sense of breathing work/effort of dyspnoea.

Nurses' experiences of managing patient deterioration following a post-registration education programme: A critical incident analysis study.

The aim of this study was to explore nurses' experiences assessing and managing deteriorating patients in practice following completion of a relevant post-registration education programme. Recognising the increasing acuity of ward patients, nurses are faced with patients who are at an increased risk of deterioration. Patients who are acutely ill or deteriorating often exhibit periods of physiological deterioration; however there is evidence illustrating that these clinical changes are frequently missed, misinterpreted or mismanaged in practice.

A Quininib Analogue and Cysteinyl Leukotriene Receptor Antagonist Inhibits Vascular Endothelial Growth Factor (VEGF)-independent Angiogenesis and Exerts an Additive Antiangiogenic Response with Bevacizumab.

Excess blood vessel growth contributes to the pathology of metastatic cancers and age-related retinopathies. Despite development of improved treatments, these conditions are associated with high economic costs and drug resistance. Bevacizumab (Avastin®), a monoclonal antibody against vascular endothelial growth factor (VEGF), is used clinically to treat certain types of metastatic cancers.

Preclinical validation of the small molecule drug quininib as a novel therapeutic for colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g.

Evaluation of Cysteinyl Leukotriene Signaling as a Therapeutic Target for Colorectal Cancer.

Colorectal cancer is the third most common cancer worldwide and is associated with significant morbidity and mortality. Current pharmacotherapy options include cytotoxic chemotherapy, anti-VEGF, and anti-EGFR targeting drugs, but these are limited by toxic side effects, limited responses and ultimately resistance. Cysteinyl leukotriene (CysLT) signaling regulates intestinal homeostasis with mounting evidence suggesting that CysLT signaling also plays a role in the pathogenesis of colorectal cancer.

Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis.

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization.

Identity and stammering: negotiating hesitation, side-stepping repetition, and sometimes avoiding deviation.

Individuals who experience speech dysfluency are often stigmatised because their speech acts differ from the communicative norm. This article is located in and seeks to further the identity debates in exploring how individuals who are subject to the intermittent emergence of a stigmatised characteristic manage this randomised personal discrediting in their identity work. Through a series of focus groups and semi-structured interviews participants grudgingly report their management approaches which include concealing, drafting in unwitting others, role-playing and segregating self from their stammer.