Evaluation of tracheal stenosis: comparison between computed tomography virtual tracheobronchoscopy with multiplanar reformatting, flexible tracheofiberoscopy and intra-operative findings

The aim of the study was to evaluate and compare various helical CT display modes [virtual endoscopy (VE)] and multiplanar reformations (MPR), conventional flexible tracheobronchoscopy (FT) and intra-operative (IO) findings in patients with tracheal stenosis and to analyze the advantage of MPR and VE in diagnosis and treatment planning and in postoperative follow-up. Thirty-seven patients with tracheal stenosis underwent standard neck and chest CT followed by MPR and VE. Results were correlated with the results of FT and IO findings. Thirty-three of the 37 stenoses were correctly graded and measured adequately using VE. Complete correlation among CT, fiberoptic tracheoscopy, and surgery of stenosis grading, stenosis length and length of planned resection segment of the trachea was noted between 33 of 37 patients with tracheal stenosis. Correlation between VE and IO was noted in 35 of 37 patients and between FT and VE was noted in 33 of 37 patients with tracheal stenosis. The sensitivity of VE was 94–97%, specificity was 100% with comparison to IO findings. The sensitivity and accuracy of MPR was 86–89% and specificity was 100% with comparison to FT findings. The results of the study indicate that VE is an excellent, consistent, and objective technique. VE with MPR is very useful in diagnostic evaluation and treatment planning in patients with tracheal stenosis

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

On the relationship between the reversed hazard rate and elasticity

Despite hazard and reversed hazard rates sharing a number of similar aspects, reversed hazard functions are far less frequently used. Understanding their meaning is not a simple task. The aim of this paper is to expand the usefulness of the reversed hazard function by relating it to other well-known concepts broadly used in economics: (linear or cumulative) rates of increase and elasticity. This will make it possible (i) to improve our understanding of the consequences of using a particular distribution and, in certain cases, (ii) to introduce our hypotheses and knowledge about the random process in a more meaningful and intuitive way, thus providing a means to achieving distributions that would otherwise be hardly imaginable or justifiable

An Allosteric Mechanism for Switching between Parallel Tracks in Mammalian Sulfur Metabolism

Methionine (Met) is an essential amino acid that is needed for the synthesis of S-adenosylmethionine (AdoMet), the major biological methylating agent. Methionine used for AdoMet synthesis can be replenished via remethylation of homocysteine. Alternatively, homocysteine can be converted to cysteine via the transsulfuration pathway. Aberrations in methionine metabolism are associated with a number of complex diseases, including cancer, anemia, and neurodegenerative diseases. The concentration of methionine in blood and in organs is tightly regulated. Liver plays a key role in buffering blood methionine levels, and an interesting feature of its metabolism is that parallel tracks exist for the synthesis and utilization of AdoMet. To elucidate the molecular mechanism that controls metabolic fluxes in liver methionine metabolism, we have studied the dependencies of AdoMet concentration and methionine consumption rate on methionine concentration in native murine hepatocytes at physiologically relevant concentrations (40–400 µM). We find that both [AdoMet] and methionine consumption rates do not change gradually with an increase in [Met] but rise sharply (∼10-fold) in the narrow Met interval from 50 to 100 µM. Analysis of our experimental data using a mathematical model reveals that the sharp increase in [AdoMet] and the methionine consumption rate observed within the trigger zone are associated with metabolic switching from methionine conservation to disposal, regulated allosterically by switching between parallel pathways. This regulatory switch is triggered by [Met] and provides a mechanism for stabilization of methionine levels in blood over wide variations in dietary methionine intake

A Framework for Examining Social Stress and Susceptibility to Air Pollution in Respiratory Health

Objective: There is growing interest in disentangling the health effects of spatially clustered social and physical environmental exposures and in exploring potential synergies among them, with particular attention directed to the combined effects of psychosocial stress and air pollution. Both exposures may be elevated in lower-income urban communities, and it has been hypothesized that stress, which can influence immune function and susceptibility, may potentiate the effects of air pollution in respiratory disease onset and exacerbation. In this paper, we attempt to synthesize the relevant research from social and environmental epidemiology, toxicology, immunology, and exposure assessment to provide a useful framework for environmental health researchers aiming to investigate the health effects of environmental pollution in combination with social or psychological factors. Data synthesis: We review the existing epidemiologic and toxicologic evidence on synergistic effects of stress and pollution, and then describe the physiologic effects of stress and key issues related to measuring and evaluating stress as it relates to physical environmental exposures and susceptibility. Finally, we identify some of the major methodologic challenges ahead as we work toward disentangling the health effects of clustered social and physical exposures and accurately describing the interplay among these exposures. Conclusions: There is still tremendous work to be done toward understanding the combined and potentially synergistic health effects of stress and pollution. As this research proceeds, we recommend careful attention to the relative temporalities of stress and pollution exposures, to nonlinearities in their independent and combined effects, to physiologic pathways not elucidated by epidemiologic methods, and to the relative spatial distributions of social and physical exposures at multiple geographic scales

Socio-economic status and types of childhood injury in Alberta: a population based study

BACKGROUND: Childhood injury is the leading cause of mortality, morbidity and permanent disability in children in the developed world. This research examines relationships between socio-economic status (SES), demographics, and types of childhood injury in the province of Alberta, Canada. METHODS: Secondary analysis was performed using administrative health care data provided by Alberta Health and Wellness on all children, aged 0 to 17 years, who had injuries treated by a physician, either in a physician's office, outpatient department, emergency room and/or as a hospital inpatient, between April 1(st). 1995 to March 31(st). 1996. Thirteen types of childhood injury were assessed with respect to age, gender and urban/rural location using ICD9 codes, and were related to SES as determined by an individual level SES indicator, the payment status of the Alberta provincial health insurance plan. The relationships between gender, SES, rural/urban status and injury type were determined using logistic regression. RESULTS: Twenty-four percent of Alberta children had an injury treated by physician during the one year period. Peak injury rates occurred about ages 2 and 13–17 years. All injury types except poisoning were more common in males. Injuries were more frequent in urban Alberta and in urban children with lower SES (receiving health care premium assistance). Among the four most common types of injury (78.6% of the total), superficial wounds and open wounds were more common among children with lower SES, while fractures and dislocations/sprains/strains were more common among children receiving no premium assistance. CONCLUSION: These results show that childhood injury in Alberta is a major health concern especially among males, children living in urban centres, and those living on welfare or have Treaty status. Most types of injury were more frequent in children of lower SES. Analysis of the three types of the healthcare premium subsidy allowed a more comprehensive picture of childhood injury with children whose families are on welfare and those of Treaty status presenting more frequently for an injury-related physician's consultation than other children. This report also demonstrates that administrative health care data can be usefully employed to describe injury patterns in children

Patterns of alcohol drinking and its association with obesity: data from the third national health and nutrition examination survey, 1988–1994

BACKGROUND: Recent reports suggest that alcohol use may have a protective effect on obesity. This study explores association between obesity and alcohol consumption in the non-smoking U.S. adult population. METHODS: We analyzed data on a total of 8,236 respondents who participated in the Third National Health and Nutrition Examination Survey. Body mass index (weight-kg/height-m(2)) was derived from measured height and weight data and categorized into: normal weight, overweight, and obese. Alcohol consumption was measured using following measures: history of drinking, binge drinking, quantity of drinks/day, frequency of drinking, and average volume of drinks/week. RESULTS: Mean body mass index in this sample of non-smokers was 26.4 (95% CI: 26.1, 26.7). Approximately 46% of respondents were classified as current drinkers. Current drinkers had lower odds of obesity (Adjusted odds ratio = 0.73, 95% CI: 0.55, 0.97) as compared to non-drinkers. The odds of overweight and obesity were significantly greater among binge drinkers and those consuming four or more drinks/day. However, those who reported drinking one or two drinks per day had 0.46 (95% CI: 0.34, 0.62) and 0.59 (95% CI: 0.41, 0.86) times the odds of obesity, respectively. Similarly, the odds of obesity were significantly lower among those who reported drinking frequently and consuming less than five drinks per week. The association between overweight and other alcohol measures was less pronounced. CONCLUSION: The results suggest further exploring the possible role of moderate alcohol drinking in controlling body weight in adults

The influence of a consumer-wearable activity tracker on sedentary time and prolonged sedentary bouts: secondary analysis of a randomized controlled trial

Abstract Objective A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activity tracker to reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month randomized control trial where 800 employees from 13 organizations were assigned to control, activity tracker, or one of two activity tracker plus incentive groups designed to increase step count. The primary outcome was accelerometer measured moderate-to-vigorous physical activity. Results We conducted a secondary analysis on accelerometer measured daily ST and PSB bouts. A general linear mixed model was used to examine changes in ST and prolonged sedentary bouts, followed by between-group pairwise comparisons. Regression analyses were conducted to examine the association of changes in step counts with ST and PSB. The changes in ST and PSB were not statistically significant and not different between the groups (P < 0.05). Increases in step counts were concomitantly associated with decreases in ST and PSB, regardless of intervention (P < 0.05). Caution should be taken when considering consumer-wearable activity trackers as a means to reduce sedentary behavior. Trial registration NCT01855776 Registered: August 8, 201