Can breathing gases be analyzed without a mouth mask? Proof-of-concept and concurrent validity of a newly developed design with a mask-less headset:Proof-of-concept and concurrent validity of a newly developed design with a mask-less headset

A portable headset has been developed to analyze breathing gases and establish the energetic workload of physically active workers. This proof-of-concept study aimed to investigate the following: (1) the validity of the headset compared to indirect calorimetry using a mouth mask; (2) the validity of the headset compared to the validity of oxygen consumption (V̇O2) estimated on the basis of heart rate; (3) the influence of wind on validity; and (4) user experiences of the headset. Fifteen subjects performed a submaximal cycling test twice, once with the headset, and once with a mouth mask and heartrate monitor. Concurrent validity of the headset was analyzed using an intraclass correlation coefficient (ICC). Across all phases, a good correlation between the headset and mouth mask was observed for V̇O2, carbon dioxide production (V̇CO2) and exhaled volume (V̇E) (ICC≥0.72). The headset tended to underestimate V̇O2, V̇CO2 and V̇E at low intensities and to overestimate it at higher intensities. The headset was more valid for estimating V̇O2 (ICC = 0.39) than estimates based on heart rate (ICC = 0.11) (n = 7). Wind flow caused an overestimation (md ≥ 18.4 ± 16.9%) and lowered the correlation of V̇O2 between the headset and the mouth mask to a moderate level (ICC = 0.48). The subjects preferred the headset over the mouth mask because it was more comfortable, did not hinder communication and had lower breathing resistance. The headset appears to be useable for monitoring development of the energetic workloads of physically active workers, being more valid than heart rate monitoring and more practical than indirect calorimetry with a mouth mask. Proof-of-concept was confirmed. Another design step and further validation studies are needed before implementation in the workplace

Four Design Criteria for Any Future Contractarian Theory of Business Ethics

This article assesses the quality of Integrative Social Contracts Theory (ISCT) as a social contract argument. For this purpose, it embarks on a comparative analysis of the use of the social contract model as a theory of political authority and as a theory of social justice. Building on this comparison, it then develops four criteria for any future contractarian theory of business ethics (CBE). To apply the social contract model properly to the domain of business ethics, it should be: (1) self-disciplined, i.e., not aspire results beyond what the contract model can realistically establish; (2) argumentative, i.e., it should seek to provide principles that are demonstrative results of the contractarian method; (3) task-directed, i.e., it should be clear what the social contract thought-experiment is intended to model; and (4) domain-specific, i.e., the contractarian choice situation should be tailored to the defining problems of business ethics

Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation:the minimal important difference obtained with anchor- and distribution-based method

Background: Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR. Methods: Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV1 31.1 (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen's effect size was used as distribution based method. Results: The estimated MID of the ESWT with the different anchors ranged from 186-199 s, 76-82% and 154-164 m. Using the distribution based method the MID was 144 s, 61% and 137 m. Conclusions: Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of 186-199 s, 76-82% or 154-164 m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions

The autonomy of the contracting partner. An argument for heuristic contractarian business ethics

Due to the domain characteristics of business ethics, a contractarian theory for business ethics will need to be essentially different from the contract model as it is applied to other domains. Much of the current criticism of contractarian business ethics (CBE) can be traced back to autonomy, one of its three boundary conditions. After explaining why autonomy is so important, this article considers the notion carefully vis à vis the contracting partners in the contractarian approaches in business ethics. Autonomy is too demanding a condition for the realm of CBE. But a less stringent version of the contract may be possible, a version which uses the contract as a heuristic device, which merely requires moral responsibility. Furthermore, it is argued that views of (human) agency and the moral subject should be made explicit in such a theory. © Springer 2006

Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Stereopure Lactam-Based HIV-1 Protease Inhibitors

In an effort to identify a new class of druglike HIV-1 protease inhibitors, four different stereopure beta-hydroxy gamma-lactam-containing inhibitors have been synthesized, biologically evaluated, and cocrystallized. The impact of the tether length of the central spacer (two or three carbons) was also investigated. A compound with a shorter tether and (3R,4S) absolute configuration exhibited high activity with a K-i of 2.1 nM and an EC50 of 0.64 mu M. Further optimization by decoration of the P1' side chain furnished an even more potent HIV-1 protease inhibitor (K-i = 0.8 nM, EC50 = 0.04 mu M). According to X-ray analysis, the new class of inhibitors did not fully succeed in forming two symmetric hydrogen bonds to the catalytic aspartates. The crystal structures of the complexes further explain the difference in potency between the shorter inhibitors (two-carbon spacer) and the longer inhibitors (three-carbon spacer)

More Evidence that Depressive Symptoms Predict Mortality in COPD Patients: Is Type D Personality an Alternative Explanation?

The present study attempted to replicate our previous finding that depressive symptoms are a risk factor for mortality in stable chronic obstructive pulmonary disease (COPD), but in a different population with a different measure of depressive symptoms. We further investigated whether type D personality is associated with mortality in patients with COPD and whether it explains any relationship observed between depressive symptoms and mortality. In 122 COPD patients, mean age 60.8 +/- 10.3 years, 52% female, and mean forced expiratory volume in 1 s (FEV(1)) 41.1 +/- 17.6%pred, we assessed body mass index, post bronchodilator FEV(1), exercise capacity, depressive symptoms with the Hospital Anxiety and Depression Scale, and type D with the Type D Scale. In the 7 years follow-up, 48 (39%) deaths occurred. The median survival time was 5.3 years. Depressive symptoms (hazard ratio = 1.07, 95% confidence intervals = 1.00-1.14) were an independent risk factor for mortality. Type D was not associated with mortality. We can rule out type D as an explanation for the relationship between depressive symptoms and mortality observed in this sample. However, ambiguity remains as to the interpretation of the value of depressive symptoms in predicting death

EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours

Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR-21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia