Cell Cycle of Normal and Psoriatic Epidermis In Vitro

Studies of growth kinetics of normal and psoriatic epidermal cells in vitro indicate that there is no significant difference in the rate of proliferation under these conditions. The data may also be compatible with the hypothesis that both kinds of cells replicate at similar rates in vivo and that earlier conclusions regarding the markedly shortened cell cycle in psoriasis were based on insufficient data regarding the size of the proliferative pool in normal steady state epidermis

EFFECTS OF METHOTREXATE ON PROLIFERATION OF HUMAN KERATINOCYTES IN VITRO

Normal human keratinocytes, propagated as epithelial outgrowths in vitro, were exposed to different concentrations of methotrexate (MTX) for different periods of time. After a 1-hr exposure, DNA synthesis was inhibited in a reversible manner. No change in the mitotic index was observed. After a 6-hr exposure, both DNA synthesis and mitosis were inhibited, again in a reversible fashion. Prolonged exposure (24 hr) resulted in irreversible mitotic inhibition even when followed by recovery periods of 168 hr. The effective concentrations of MTX in vitro were similar to those described previously in vivo

Relationships between two dimensions of employee perfectionism, postwork cognitive processing, and work day functioning

This daily diary study examined relations between two distinct perfectionism dimensions and work-related cognitions experienced by employees during evening leisure time. Drawing from perseverative cognitive processing theory, we hypothesized that perfectionistic concerns would be related to work-related worry and rumination during postwork evenings. In contrast, we hypothesized that a theoretically more adaptive perfectionist dimension (perfectionistic strivings) would be associated with positively valenced self-reflections about work across consecutive evenings. A sample of 148 full-time workers completed an initial survey, which included a trait perfectionism measure, reported their work-related cognitions across four consecutive evenings of a working week, rated their sleep quality immediately upon awakening on each subsequent morning, and their daily levels of emotional exhaustion and work engagement at the end of each work day. Results showed that perfectionistic concerns were indirectly negatively associated with sleep quality and work day functioning via the tendency to worry and ruminate about work. In contrast, perfectionistic strivings were indirectly positively associated with work day engagement via the propensity to experience positive thoughts about work during evening leisure time. The theoretical and practical implications of these findings are discussed

Ablation of Barrett's oesophagus: towards improved outcomes for oesophageal cancer?

This is the accepted version of the following article: Mayne, G. C., Bright, T., Hussey, D. J. and Watson, D. I. (2012), Ablation of Barrett's oesophagus: towards improved outcomes for oesophageal cancer?. ANZ Journal of Surgery, 82: 592–598, which has been published in final form at doi:10.1111/j.1445-2197.2012.06151.xBarrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. The management of Barrett’s oesophagus entails treating reflux symptoms with acid-suppressing medication or surgery (fundoplication). However neither form of anti-reflux therapy produces predictable regression, or prevents cancer development. Patients with Barrett’s oesophagus usually undergo endoscopic surveillance which aims to identify dysplastic changes or cancer at its earliest stage, when treatment outcomes should be better. Alternative endoscopic interventions are now available and are suggested for the treatment of early cancer, and prevention of progression of Barrett’s oesophagus to cancer. Such treatments could minimize the risks associated with oesophagectomy. The current status of these interventions is reviewed. Various endoscopic interventions have been described, but with long term outcomes uncertain, they remain somewhat controversial. Radiofrequency ablation (RFA) of dysplastic Barrett’s oesophagus might reduce the risk of cancer progression, although cancer development has been reported after this treatment. Endoscopic mucosal resection (EMR) allows a 1.5 to 2 cm diameter piece of oesophageal mucosa to be removed. This provides better pathology for diagnosis and staging, and if the lesion is confined to the mucosa and fully excised, EMR can be curative. The combination of EMR and RFA has been used for multifocal lesions, but long term outcomes are unknown. The new endoscopic interventions for Barrett’s oesophagus and early oesophageal cancer have potential to improve clinical outcomes, although evidence which confirms superiority over oesphagectomy is limited. Longer term outcome data and data from larger cohorts is required to confirm the appropriateness of these procedure

Robust metrics for assessing the performance of different verbal autopsy cause assignment methods in validation studies

<p>Abstract</p> <p>Background</p> <p>Verbal autopsy (VA) is an important method for obtaining cause of death information in settings without vital registration and medical certification of causes of death. An array of methods, including physician review and computer-automated methods, have been proposed and used. Choosing the best method for VA requires the appropriate metrics for assessing performance. Currently used metrics such as sensitivity, specificity, and cause-specific mortality fraction (CSMF) errors do not provide a robust basis for comparison.</p> <p>Methods</p> <p>We use simple simulations of populations with three causes of death to demonstrate that most metrics used in VA validation studies are extremely sensitive to the CSMF composition of the test dataset. Simulations also demonstrate that an inferior method can appear to have better performance than an alternative due strictly to the CSMF composition of the test set.</p> <p>Results</p> <p>VA methods need to be evaluated across a set of test datasets with widely varying CSMF compositions. We propose two metrics for assessing the performance of a proposed VA method. For assessing how well a method does at individual cause of death assignment, we recommend the average chance-corrected concordance across causes. This metric is insensitive to the CSMF composition of the test sets and corrects for the degree to which a method will get the cause correct due strictly to chance. For the evaluation of CSMF estimation, we propose CSMF accuracy. CSMF accuracy is defined as one minus the sum of all absolute CSMF errors across causes divided by the maximum total error. It is scaled from zero to one and can generalize a method's CSMF estimation capability regardless of the number of causes. Performance of a VA method for CSMF estimation by cause can be assessed by examining the relationship across test datasets between the estimated CSMF and the true CSMF.</p> <p>Conclusions</p> <p>With an increasing range of VA methods available, it will be critical to objectively assess their performance in assigning cause of death. Chance-corrected concordance and CSMF accuracy assessed across a large number of test datasets with widely varying CSMF composition provide a robust strategy for this assessment.</p