No abstract

No abstract

Idiopathic pulmonary fibrosis is a chronic, progressive fibrotic disease with a poor prognosis. The balance between transforming growth factor β1 and bone morphogenetic protein (BMP) signaling plays an important role in tissue homeostasis, and alterations can result in pulmonary fibrosis. We hypothesized that multiple BMP accessory proteins may be responsible for maintaining this balance in the lung. Using the bleomycin mouse model for fibrosis, we examined an array of BMP accessory proteins for changes in mRNA expression. We report significant increases in mRNA expression of gremlin 1, noggin, follistatin, and follistatin-like 1 (Fstl1), and significant decreases in mRNA expression of chordin, kielin/chordin-like protein, nephroblastoma overexpressed gene, and BMP and activin membrane-bound inhibitor (BAMBI). Protein expression studies demonstrated increased levels of noggin, BAMBI, and FSTL1 in the lungs of bleomycin-treated mice and in the lungs of idiopathic pulmonary fibrosis patients. Furthermore, we demonstrated that transforming growth factor β stimulation resulted in increased expression of noggin, BAMBI, and FSTL1 in human small airway epithelial cells. These results provide the first evidence that multiple BMP accessory proteins are altered in fibrosis and may play a role in promoting fibrotic injury.

We detected a lower rate of clinicopathological discrepancy in critically ill patients than previously reported. Potential reasons for such findings include advances in diagnostic techniques and the use of a more robust definition to classify diagnostic discrepancies. Autopsy can still identify discrepancies in diagnosis even in patients who have undergone appropriate investigations. Prospective research is required to accurately define discrepancy rates in the critically ill population and to identify the patient subgroups in whom autopsy will continue to yield valuable information.

Accurate disease definitions are essential for clinical decisionmaking, trial enrolment, and mechanistic research. Since it was first recognized over four decades ago multiple attempts have been made to adequately define the acute respiratory distress syndrome (ARDS). However, up to half of the patients captured by definitions to date do not have the disease. This poor diagnostic accuracy may, in part, explain how over 200 randomized control trials have, with the exception of a low tidal volume ventilation strategy, failed to identify any mortality-reducing therapies. The recently published Berlin definition of ARDS was introduced to address the poor accuracy and shortcomings associated with previous models; however, a recent validation study found the diagnostic reliability of the Berlin definition to be no superior to its predecessor. In the absence of accurate, objectively validated criteria for diagnosing this condition, clinical trials will continue to include large numbers of patients without the disease.ARDS is a non-pneumonic, non-cardiogenic condition characterized by increased vascular permeability, pulmonary oedema, and severe arterial hypoxaemia-a clinical triad found in many critically ill patients. It is precipitated by both direct and indirect causes, resulting in a variable clinical pattern of presentation and progression. ARDS is frequently associated with other organ failures, resulting in both pulmonary and extra-pulmonary factors influencing mortality. Unlike most medical conditions, this complex syndrome does not yet benefit from an accessible in vivo reference standard (e.g. diagnosis of pulmonary embolism), or the existence of clear biomarkers (e.g. acute coronary syndrome). As a result, separating true 'lung injury' from other conditions, such as heart failure or pneumonia, which display similar clinical signs, is challenging.Although the reference standard has so far remained constant, lack of clarity about the clinical definition of ARDS has been problematic. Since 1967, when Ashbaugh and Petty first described the syndrome, there have been attempts to refine its definition. 1 Initially, Murray proposed a definition comprising four variables-chest X-ray (CXR) findings, Pa O 2 /FI O 2 ratio, positive end expiratory pressure (PEEP), and respiratory compliance. 2 The resultant lung injury score (LIS) predicts the need for prolonged mechanical ventilation and has good sensitivity and specificity (0.74 and 0.77, respectively) as a predictor of diffuse alveolar damage (DAD) at autopsy. 3 4 Despite this, the LIS has not entered routine practice, and a more pragmatic approach that targets ease of use has prevailed.In 1994, the American-European Consensus Conference (AECC) redefined ARDS using criteria based on hypoxaemia, CXR infiltrates, and absence of left atrial hypertension; abnormal lung mechanics were dropped as a criterion. The AECC authors also urged diagnostic caution 'in order to minimize the chance of including non-ARDS-related illnesses'. 3 Their criteria are accessible, were adopted ...

Reports the findings and conclusions of a study of five small businesses in the hotel and catering sector which had adopted national vocational qualifications (NVQs). Using an open system model, a comparative case study design and a range of data sources and methods of data collection within each organization, traces the preconditions, processes, outcomes and problems/issues associated with NVQ adoption and implementation. In a small business context, this is shown more likely to be successful where there is an existing training culture and infrastructure; where on‐the‐job training is positive, supportive and monitored; and where there is a senior management NVQ “champion” and an enthusiastic cadre of in‐house trainers and potential assessors. Shows that NVQs give a sharper focus to training activity, improve candidates’ perceived job satisfaction, morale and career prospects; enhance work flexibility and performance; and have a perceived, if hard‐to‐measure payoff in terms of business performance.

No abstract

Acute respiratory distress syndrome is one of the leading causes of death in critically ill patients. Recent advances in supportive care have led to a moderate improvement in mortality. In particular, a much lower mortality rate than expected was evident in the severest category of patients (requiring extracorporeal membrane oxygenation) in Australia during the recent H1N1 pandemic.Though improvements in supportive care may have provided some benefit, there remains an absence of effective biological agents that are necessary to achieve further incremental reduction in mortality. This article will review the evidence available for current treatment strategies and discuss future research directions that may eventually improve outcomes in this important global disease.