The Benefits of building barrier-free: a contingent valuation of accessibilty as an attribute of housing

Estimating the social benefits of barrier-free building has always required indirect solutions, such as calculating the savings in social services, hospitalisation or adaptations made possible by the increase in accessibility. This research uses the Contingent Valuation Method to gain a direct appraisal of the benefits from barrier-free housing. When comparing two similar dwellings, with the only difference being their accessibility conditions, the 1,007 randomly chosen households that answered the direct survey would pay, on average 12.5 per cent more for being barrier-free. None of the different appraisals made on accessibility costs reaches 5 per cent. This confirms the social profitability of building without barriers and shows the potential size of the private market for those housing developers that meet the demand. Accessibility is a general concern, an economic good or attribute that most households value, irrespective of the physical conditions of their members.

Reproducibility of free-breathing cardiovascular magnetic resonance coronary angiography.

OBJECTIVE: Contemporary free-breathing non contrast enhanced cardiovascular magnetic resonance angiography (CMRA) was qualitatively and quantitatively evaluated to ascertain the reproducibility of the method for coronary artery luminal dimension measurements. SUBJECTS AND METHODS: Twenty-two healthy volunteers (mean age 32 +/- 7 years, 12 males) without coronary artery disease were imaged at 2 centers (1 each in Europe and North America) using navigator-gated and corrected SSFP CMRA on a commercial whole body 1.5T System. Repeat images of right (RCA, n = 21), left anterior descending (LAD, n = 14) and left circumflex (LCX, n = 14) coronary arteries were obtained in separate sessions using identical scan protocol and imaging parameters. True visible vessel length, signal-to-noise (SNR), contrast-to-noise ratios (CNR) and the average luminal diameter over the first 4 cm of the vessel were measured. Intra-observer, inter-observer and inter-scan reproducibility of coronary artery luminal diameter were determined using Pearson's correlation, Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: CNR, SNR and the mean length of the RCA, LAD and LCX imaged for original and repeat scans were not significantly different (all p > 0.30). There was a high degree of intra-observer, inter-observer and inter-scan agreements for RCA, LAD and LCX luminal diameter respectively on Bland-Altman and ICC analysis (ICC's for RCA: 0.98. 0.98 and 0.86; LAD: 0.89, 0.89 and 0.63; LCX: 0.95, 0.94 and 0.79). CONCLUSION: In a 2-center study, we demonstrate that free-breathing 3D SSFP CMRA can visualize long continuous segments of coronary vessels with highly reproducible measurements of luminal diameter.

Measuring intergenerational earnings mobility in Spain: a selection-bias-free approach

This paper analyses intergenerational earnings mobility in Spain correcting for different selection biases. We address the co-residence selection problem by combining information from two samples and using the two-sample two-stage least square estimator. We find a small decrease in elasticity when we move to younger cohorts. Furthermore, we find a higher correlation in the case of daughters than in the case of sons; however, when we consider the employment selection in the case of daughters, by adopting a Heckman-type correction method, the diference between sons and daughters disappears. By decomposing the sources of earnings elasticity across generations, we find that the correlation between child's and father's occupation is the most important component. Finally, quantile regressions estimates show that the influence of the father's earnings is greater when we move to the lower tail of the offspring's earnings distribution, especially in the case of daughters' earnings.

Die Inguinal-Hernienplastik nach Lichtenstein: Eine einfache und komplikationsarme Technik, besonders geeignet für die Tageschirurgie [The Lichtenstein inguinal hernia-plasty: a simple and complication-free technique, especially suited for ambulatory surgery].

A consecutive series of 353 patients who underwent Lichtenstein mesh repair for inguinal hernia from the 1st of July 1994 to the 30th of July 1995 were studied. We analysed our indication, technique, complications, follow-up and outcome. Special consideration was given to the advantages and acceptance of day-case surgery. Our results suggest that the Lichtenstein repair should be considered as a new standard procedure, especially outside of hernia centres.

Double-oblique free-breathing high resolution three-dimensional coronary magnetic resonance angiography.

OBJECTIVES: The goal of the present study was to develop a strategy for three-dimensional (3D) volume acquisition along the major axes of the coronary arteries. BACKGROUND: For high-resolution 3D free-breathing coronary magnetic resonance angiography (MRA), coverage of the coronary artery tree may be limited due to excessive measurement times associated with large volume acquisitions. Planning the 3D volume along the major axis of the coronary vessels may help to overcome such limitations. METHODS: Fifteen healthy adult volunteers and seven patients with X-ray angiographically confirmed coronary artery disease underwent free-breathing navigator-gated and corrected 3D coronary MRA. For an accurate volume targeting of the high resolution scans, a three-point planscan software tool was applied. RESULTS: The average length of contiguously visualized left main and left anterior descending coronary artery was 81.8 +/- 13.9 mm in the healthy volunteers and 76.2 +/- 16.5 mm in the patients (p = NS). For the right coronary artery, a total length of 111.7 +/- 27.7 mm was found in the healthy volunteers and 79.3 +/- 4.6 mm in the patients (p = NS). Comparing coronary MRA and X-ray angiography, a good agreement of anatomy and pathology was found in the patients. CONCLUSIONS: Double-oblique submillimeter free-breathing coronary MRA allows depiction of extensive parts of the native coronary arteries. The results obtained in patients suggest that the method has the potential to be applied in broader prospective multicenter studies where coronary MRA is compared with X-ray angiography.

A parameter-free approach for solving combinatorial optimization problems through biased randomization of efficient heuristics

This paper discusses the use of probabilistic or randomized algorithms for solving combinatorial optimization problems. Our approach employs non-uniform probability distributions to add a biased random behavior to classical heuristics so a large set of alternative good solutions can be quickly obtained in a natural way and without complex conguration processes. This procedure is especially useful in problems where properties such as non-smoothness or non-convexity lead to a highly irregular solution space, for which the traditional optimization methods, both of exact and approximate nature, may fail to reach their full potential. The results obtained are promising enough to suggest that randomizing classical heuristics is a powerful method that can be successfully applied in a variety of cases.

Free-breathing inner-volume black-blood imaging of the human heart using two-dimensionally selective local excitation at 3 T.

Black-blood fast spin-echo imaging is a powerful technique for the evaluation of cardiac anatomy. To avoid fold-over artifacts, using a sufficiently large field of view in phase-encoding direction is mandatory. The related oversampling affects scanning time and respiratory chest motion artifacts are commonly observed. The excitation of a volume that exclusively includes the heart without its surrounding structures may help to improve scan efficiency and minimize motion artifacts. Therefore, and by building on previously reported inner-volume approach, the combination of a black-blood fast spin-echo sequence with a two-dimensionally selective radiofrequency pulse is proposed for selective "local excitation" small field of view imaging of the heart. This local excitation technique has been developed, implemented, and tested in phantoms and in vivo. With this method, small field of view imaging of a user-specified region in the human thorax is feasible, scanning becomes more time efficient, motion artifacts can be minimized, and additional flexibility in the choice of imaging parameters can be exploited.

Comparison between computational alanine scanning and per-residue binding free energy decomposition for protein-protein association using MM-GBSA: application to the TCR-p-MHC complex.

Recognition by the T-cell receptor (TCR) of immunogenic peptides (p) presented by Class I major histocompatibility complexes (MHC) is the key event in the immune response against virus-infected cells or tumor cells. A study of the 2C TCR/SIYR/H-2K(b) system using a computational alanine scanning and a much faster binding free energy decomposition based on the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) method is presented. The results show that the TCR-p-MHC binding free energy decomposition using this approach and including entropic terms provides a detailed and reliable description of the interactions between the molecules at an atomistic level. Comparison of the decomposition results with experimentally determined activity differences for alanine mutants yields a correlation of 0.67 when the entropy is neglected and 0.72 when the entropy is taken into account. Similarly, comparison of experimental activities with variations in binding free energies determined by computational alanine scanning yields correlations of 0.72 and 0.74 when the entropy is neglected or taken into account, respectively. Some key interactions for the TCR-p-MHC binding are analyzed and some possible side chains replacements are proposed in the context of TCR protein engineering. In addition, a comparison of the two theoretical approaches for estimating the role of each side chain in the complexation is given, and a new ad hoc approach to decompose the vibrational entropy term into atomic contributions, the linear decomposition of the vibrational entropy (LDVE), is introduced. The latter allows the rapid calculation of the entropic contribution of interesting side chains to the binding. This new method is based on the idea that the most important contributions to the vibrational entropy of a molecule originate from residues that contribute most to the vibrational amplitude of the normal modes. The LDVE approach is shown to provide results very similar to those of the exact but highly computationally demanding method.

Assessment of total energy expenditure in free-living patients with cystic fibrosis.

The increase in resting energy expenditure (REE) reported in patients with cystic fibrosis (CF) does not necessarily imply an increase in total energy expenditure (TEE). In this study REE was assessed with open-circuit indirect calorimetry, and free-living 24-hour TEE with the heart rate method. Thirteen patients with CF, aged 8 to 24 years, with adequate nutritional status and moderately decreased pulmonary function, were studied. They were compared with 13 healthy control subjects matched for gender, age, height, and nutritional status. Resting energy expenditure was higher in patients with CF (1512 +/- 88 kcal/day) than in control subjects (1339 +/- 76 kcal/day; p less than 0.01), whereas free-living 24-hour TEE (2345 +/- 127 kcal/day and 2358 +/- 256 kcal/day, respectively) and net mechanical work efficiency of walking on a treadmill (20.4 +/- 0.7% and 19.8 +/- 0.6%, respectively) were similar. Respiratory quotient was higher in patients with CF than in control subjects at rest (0.834 +/- 0.009 vs 0.797 +/- 0.008; p less than 0.05), and tended to remain so during physical exercise, indicating a higher contribution of carbohydrate oxidation to energy expenditure. We conclude that in free living conditions, patients with CF can compensate for their increase in REE by a reduction in spontaneous physical activities or other yet undefined mechanisms.

Sensitive headspace gas chromatography analysis of free and conjugated 1-methoxy-2-propanol in urine

Glycol ethers still continue to be a workplace hazard due to their important use on an industrial scale. Currently, chronic occupational exposures to low levels of xenobiotics become increasingly relevant. Thus, sensitive analytical methods for detecting biomarkers of exposure are of interest in the field of occupational exposure assessment. 1-Methoxy-2-propanol (1M2P) is one of the dominant glycol ethers and the unmetabolized urinary fraction has been identified to be a good biological indicator of exposure. An existing analytical method including a solid-phase extraction and derivatization before GC/FID analysis is available but presents some disadvantages. We present here an alternative method for the determination of urinary 1M2P based on the headspace gas chromatography technique. We determined the 1M2P values by the direct headspace method for 47 samples that had previously been assayed by the solid-phase extraction and derivatization gas chromatography procedure. An inter-method comparison based on a Bland-Altman analysis showed that both techniques can be used interchangeably. The alternative method showed a tenfold lower limit of detection (0.1 mg/L) as well as good accuracy and precision which were determined by several urinary 1M2P analyses carried out on a series of urine samples obtained from a human volunteer study. The within- and between-run precisions were generally about 10%, which corresponds to the usual injection variability. We observed that the differences between the results obtained with both methods are not clinically relevant in comparison to the current biological exposure index of urinary 1M2P. Accordingly, the headspace gas chromatography technique turned out to be a more sensitive, accurate, and simple method for the determination of urinary 1M2P.[Authors]

Self-Navigation with Compressed Sensing for 2D Translational Motion Correction in Free-Breathing Coronary MRI: A Feasibility Study.

PURPOSE: Respiratory motion correction remains a challenge in coronary magnetic resonance imaging (MRI) and current techniques, such as navigator gating, suffer from sub-optimal scan efficiency and ease-of-use. To overcome these limitations, an image-based self-navigation technique is proposed that uses "sub-images" and compressed sensing (CS) to obtain translational motion correction in 2D. The method was preliminarily implemented as a 2D technique and tested for feasibility for targeted coronary imaging. METHODS: During a 2D segmented radial k-space data acquisition, heavily undersampled sub-images were reconstructed from the readouts collected during each cardiac cycle. These sub-images may then be used for respiratory self-navigation. Alternatively, a CS reconstruction may be used to create these sub-images, so as to partially compensate for the heavy undersampling. Both approaches were quantitatively assessed using simulations and in vivo studies, and the resulting self-navigation strategies were then compared to conventional navigator gating. RESULTS: Sub-images reconstructed using CS showed a lower artifact level than sub-images reconstructed without CS. As a result, the final image quality was significantly better when using CS-assisted self-navigation as opposed to the non-CS approach. Moreover, while both self-navigation techniques led to a 69% scan time reduction (as compared to navigator gating), there was no significant difference in image quality between the CS-assisted self-navigation technique and conventional navigator gating, despite the significant decrease in scan time. CONCLUSIONS: CS-assisted self-navigation using 2D translational motion correction demonstrated feasibility of producing coronary MRA data with image quality comparable to that obtained with conventional navigator gating, and does so without the use of additional acquisitions or motion modeling, while still allowing for 100% scan efficiency and an improved ease-of-use. In conclusion, compressed sensing may become a critical adjunct for 2D translational motion correction in free-breathing cardiac imaging with high spatial resolution. An expansion to modern 3D approaches is now warranted.

ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.

BACKGROUND Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. METHODS Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). RESULTS Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. CONCLUSION Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.

Surgery for incarcerated hernia: short-term outcome with or without mesh.

BACKGROUND: Incarcerated hernias represent about 5-15 % of all operated hernias. Tension-free mesh is the preferred technique for elective surgery due to low recurrence rates. There is however currently no consensus on the use of mesh for the treatment of incarcerated hernias, especially in case of bowel resection. AIM: The aims of this study were (i) to report our current practice for the treatment of incarcerated hernias, (ii) to identify risk factors for postoperative complications, and (iii) to assess the safety of mesh placement in potentially infected surgical fields. METHODS: This retrospective study included 166 consecutive patients who underwent emergency surgery for incarcerated hernia between January 2007 and January 2012 in two university hospitals. Demographics, surgical details, and short-term outcome were collected. Univariate analysis was employed to identify risk factors for overall, infectious, and major complications. RESULTS: Eighty-four patients (50.6 %) presented inguinal hernias, 43 femoral (25.9 %), 37 umbilical hernias (22.3 %), and 2 mixed hernias (1.2 %), respectively. Mesh was placed in 64 patients (38.5 %), including 5 patients with concomitant bowel resection. Overall morbidity occurred in 56 patients (32.7 %), and 8 patients (4.8 %) developed surgical site infections (SSI). Univariate risk factors for overall complications were ASA grade 3/4 (P = 0.03), diabetes (P = 0.05), cardiopathy (P = 0.001), aspirin use (P = 0.023), and bowel resection (P = 0.001) which was also the only identified risk factor for SSI (P = 0.03). In multivariate analysis, only bowel incarceration was associated with a higher rate of major morbidity (OR = 14.04; P = 0.01). CONCLUSION: Morbidity after surgery for incarcerated hernia remains high and depends on comorbidities and surgical presentation. The use of mesh could become current practice even in case of bowel resection.

Assessment of myocardial edema and area-at-risk in acute myocardial infarction by CMR: Evaluation of a novel T2-mapping method

Objectives. The goal of this study is to evaluate a T2-mapping sequence by: (i) measuring the reproducibility intra- and inter-observer variability in healthy volunteers in two separate scanning session with a T2 reference phantom; (2) measuring the mean T2 relaxation times by T2-mapping in infarcted myocardium in patients with subacute MI and compare it with patient's the gold standard X-ray coronary angiography and healthy volunteers results. Background. Myocardial edema is a consequence of an inflammation of the tissue, as seen in myocardial infarct (MI). It can be visualized by cardiovascular magnetic resonance (CMR) imaging using the T2 relaxation time. T2-mapping is a quantitative methodology that has the potential to address the limitation of the conventional T2-weighted (T2W) imaging. Methods. The T2-mapping protocol used for all MRI scans consisted in a radial gradient echo acquisition with a lung-liver navigator for free-breathing acquisition and affine image registration. Mid-basal short axis slices were acquired.T2-maps analyses: 2 observers semi- automatically segmented the left ventricle in 6 segments accordingly to the AHA standards. 8 healthy volunteers (age: 27 ± 4 years; 62.5% male) were scanned in 2 separate sessions. 17 patients (age : 61.9 ± 13.9 years; 82.4% male) with subacute STEMI (70.6%) and NSTEMI underwent a T2-mapping scanning session. Results. In healthy volunteers, the mean inter- and intra-observer variability over the entire short axis slice (segment 1 to 6) was 0.1 ms (95% confidence interval (CI): -0.4 to 0.5, p = 0.62) and 0.2 ms (95% CI: -2.8 to 3.2, p = 0.94, respectively. T2 relaxation time measurements with and without the correction of the phantom yielded an average difference of 3.0 ± 1.1 % and 3.1 ± 2.1 % (p = 0.828), respectively. In patients, the inter-observer variability in the entire short axis slice (S1-S6), was 0.3 ms (95% CI: -1.8 to 2.4, p = 0.85). Edema location as determined through the T2-mapping and the coronary artery occlusion as determined on X-ray coronary angiography correlated in 78.6%, but only in 60% in apical infarcts. All except one of the maximal T2 values in infarct patients were greater than the upper limit of the 95% confidence interval for normal myocardium. Conclusions. The T2-mapping methodology is accurate in detecting infarcted, i.e. edematous tissue in patients with subacute infarcts. This study further demonstrated that this T2-mapping technique is reproducible and robust enough to be used on a segmental basis for edema detection without the need of a phantom to yield a T2 correction factor. This new quantitative T2-mapping technique is promising and is likely to allow for serial follow-up studies in patients to improve our knowledge on infarct pathophysiology, on infarct healing, and for the assessment of novel treatment strategies for acute infarctions.

Effects of smoking and physical exercise on platelet free cytosolic calcium in healthy normotensive volunteers.

Platelet free cytosolic calcium (PFCC) was measured in 21 healthy volunteers before and after cigarette smoking or physical exercise. The aim was to investigate whether acute blood pressure changes and increases in circulating levels of catecholamines and vasopressin modify PFCC. PFCC was determined using the Quin-2 method. Following cigarette smoking, significant increases in blood pressure, heart rate, plasma epinephrine (35 +/- 18 pg/ml before versus 51 +/- 31 pg/ml after smoking, P less than 0.05, mean +/- s.d.) and vasopressin levels (0.8 +/- 0.3 pg/ml before and 4.2 +/- 4.1 pg/ml after smoking, P less than 0.001) were observed. However, despite these acute hormonal and hemodynamic changes, PFCC remained stable at 156 +/- 55 nmol/l prior to the study and 157 +/- 29 nmol/l and 156 +/- 38 nmol/l at 20 and 80 min post-smoking, respectively. Acute physical exercise led to an increase in heart rate and systolic blood pressure but to a decrease in diastolic pressure. Moreover, a marked increase in plasma norepinephrine levels was observed after exercise (213 +/- 71 pg/ml before versus 747 +/- 501 pg/ml after exercise, P +/- 0.001). Again, PFCC was stable at 185 +/- 56 nmol/l at baseline versus 188 +/- 51 nmol/l at 20 min and 155 +/- 26 nmol/l at 80 min after exercise. These results therefore demonstrate that PFCC is not influenced acutely either by blood pressure increases, or by elevations in circulating catecholamine and vasopressin concentrations.