Sizing the Depth and Width of Narrow Cracks in Real Parts by Laser-Spot Lock-In Thermography

We present a complete characterization of the width and depth of a very narrow fatigue crack developed in an Al-alloy dog bone plate using laser-spot lock-in thermography. Unlike visible micrographs, which show many surface scratches, the thermographic image clearly identifies the presence of a single crack about 1.5 mm long. Once detected, we focus a modulated laser beam close to the crack and we record the temperature amplitude. By fitting the numerical model to the temperature profile across the crack, we obtain both the width and depth simultaneously, at the location of the laser spot. Repeating the process for different positions of the laser spot along the crack length, we obtain the distribution of the crack width and depth. We show that the crack has an almost constant depth (0.7 mm) and width (1.5 µm) along 0.7 mm and features a fast reduction in both quantities until the crack vanishes. The results prove the ability of laser-spot lock-in thermography to fully characterize quantitatively narrow cracks, even below 1 µm.     

SNaPshot and StripAssay as valuable alternatives to direct sequencing for KRAS mutation detection in colon cancer routine diagnostics

Although direct sequencing is the gold standard for KRAS mutation detection in routine diagnostics, it remains laborious, time consuming, and not very sensitive. Our objective was to evaluate SNaPshot and the KRAS StripAssay as alternatives to sequencing for KRAS mutation detection in daily practice. KRAS exon 2-specific PCR followed by sequencing or by a SNaPshot reaction was performed. For the StripAssay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. To test sensitivities, dilution series of mutated DNA in wild-type DNA were made. Additionally, direct sequencing and SNaPshot were evaluated in 296 colon cancer samples. Detection limits of direct sequencing, SNaPshot, and StripAssay were 20%, 10%, and 1% tumor cells, respectively. Direct sequencing and SNaPshot can detect all 12 mutations in KRAS codons 12 and 13, whereas the StripAssay detects 10 of the most frequent ones. Workload and time to results are comparable for SNaPshot and direct sequencing. SNaPshot is flexible and easy to multiplex. The StripAssay is less time consuming for daily laboratory practice. SNaPshot is more flexible and slightly more sensitive than direct sequencing. The clinical evaluation showed comparable performances between direct sequencing and SNaPshot. The StripAssay is rapid and an extremely sensitive assay that could be considered when few tumor cells are available. However, found mutants should be confirmed to avoid risk of false positives.     

Deciphering CD137 (4‐1BB) signaling in T‐cell costimulation for translation into successful cancer immunotherapy

CD137 (4‐1BB, TNF‐receptor superfamily 9) is a surface glycoprotein of the TNFR family which can be induced on a variety of leukocyte subsets. On T and NK cells, CD137 is expressed following activation and, if ligated by its natural ligand (CD137L), conveys polyubiquitination‐mediated signals via TNF receptor associated factor 2 that inhibit apoptosis, while enhancing proliferation and effector functions. CD137 thus behaves as a bona fide inducible costimulatory molecule. These functional properties of CD137 can be exploited in cancer immunotherapy by systemic administration of agonist monoclonal antibodies, which increase anticancer CTLs and enhance NK‐cell‐mediated antibody‐dependent cell‐mediated cytotoxicity. Reportedly, anti‐CD137 mAb and adoptive T‐cell therapy strongly synergize, since (i) CD137 expression can be used to select the T cells endowed with the best activities against the tumor, (ii) costimulation of the lymphocyte cultures to be used in adoptive T‐cell therapy can be done with CD137 agonist antibodies or CD137L, and (iii) synergistic effects upon coadministration of T cells and antibodies are readily observed in mouse models. Furthermore, the signaling cytoplasmic tail of CD137 is a key component of anti‐CD19 chimeric antigen receptors that are used to redirect T cells against leukemia and lymphoma in the clinic. Ongoing phase II clinical trials with agonist antibodies and the presence of CD137 sequence in these successful chimeric antigen receptors highlight the importance of CD137 in oncoimmunology.     

Hospital quality choice and market structure in a regulated duopoly

This paper analyzes the optimal structure of a regulated health care industry in a model in which the regulator cannot enforce what hospitals do (unverifiable quality of health) or does not know what hospitals know (incomplete information about production costs) or both. We show that if quality is unverifiable the choice between monopoly and duopoly does not change with respect to the verifiable case but, if there are fixed costs (assumed to be quality dependent) and the monopoly is the optimal market structure, the quality level of the operative hospital decreases. Asymmetry of information introduces informational rents that can be reduced by increasing the most efficient hospital's market share. A monopoly is chosen more often.     

Markers of Inflammation and Mortality in a Cohort of Patients With Alcohol Dependence

Inflammation and intestinal permeability are believed to be paramount features in the development of alcohol-related liver damage. We aimed to assess the impact of 3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on mid-term mortality of patients with alcohol dependence.This longitudinal study included patients with alcohol dependence admitted for hospital detoxification between 2000 and 2010. Mortality was ascertained from clinical charts and the mortality register. Associations between markers of inflammation and all-cause mortality were analyzed with mortality rates and Cox proportional hazards regression models.We also performed a subgroup analysis of mortality rates in patients with anemia, based on their mean corpuscular volume (MCV).We included 909 consecutive patients with alcohol dependence. Patients were mostly male (80.3%), had a median age of 44 years (interquartile range [IQR]: 38–50), and upon admission, their median alcohol consumption was 192 g/day (IQR: 120–265). At admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels >4.5 mg/dL; and 365 (49.5%) had ferritin levels >200 ng/mL. At the end of follow-up (median 3.8 years [IQR: 1.8–6.5], and a total of 3861.07 person-years), 118 patients had died (12.9% of the study population). Cox regression models showed that the presence of anemia at baseline was associated with mortality (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11–2.52, P < 0.01); no associations were found between mortality and high fibrinogen or high ferritin levels.A subgroup of patients with anemia was analyzed and compared to a control group of patients without anemia and a normal MCV. The mortality ratios of patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41–7.26; P < 0.01) and 3.39 (95% CI: 1.86–6.43; P < 0.01), respectively.Patients with alcohol dependence admitted for detoxification had an increased risk of death when anemia was present at admission. More accurate markers of systemic inflammation are needed to serve as prognostic factors for poor outcomes in this subset of patients.     

Histoplasmosis: a study of 158 cases in Venezuela, 2000-2005

Histoplasmosis, a granulomatous disease caused by Histoplasma capsulatum, is endemic in Venezuela. We conducted the current study to appraise retrospectively the demographic data, clinical features, diagnostic methods, and treatment of patients with histoplasmosis from January 2000 to December 2005.We reviewed the medical records of outpatient cases with a diagnosis of histoplasmosis and considered clinical samples processed at our laboratory. We collected demographic, epidemiologic, and clinical data from each case as available, including results of any mycologic examinations performed. Treatment and outcome data were available for some patients.We assessed 158 cases of histoplasmosis: 103 (65.2%) patients came from the Caracas metropolitan area; 53 were associated with acquired immunodeficiency syndrome (AIDS), 14 with tuberculosis, and 8 with paracoccidioidomycosis. Six pediatric patients were malnourished. Epidemiologic data suggested histoplasmosis in most cases. Patients received treatment with itraconazole and/or amphotericin B.Our results may reflect changes in the epidemiology occurring in Venezuela, perhaps due to environmental changes and the presence of AIDS. Several mycologic exams are necessary to ensure a proper diagnosis. More reliable data and statistics on this infection are necessary to monitor outbreaks closely and to establish if there is an epidemic pattern.     

Rehabilitation Program in Adult Congenital Heart Disease Patients with Pulmonary Hypertension

Introduction. It is commonly believed that physical activity may have a negative impact on pulmonary hypertension patients. The object of this study is to determine the tolerability of a directed exercise program in congenital heart disease patients with pulmonary hypertension. Methods. Eight congenital heart disease patients with pulmonary hypertension were studied and followed up during a 1-year period. Four of them were enrolled in a 3-month rehabilitation program. Results. No significant changes in analytical data, hand and leg strength, or quality of life were seen at the end of the training program in rehabilitation and nonrehabilitation patients. However, patients in the rehabilitation group improved 6 minutes' walk test minimum hemoglobin oxygen saturation and functional class after ending the training program without having adverse events such as progression of symptoms or heart failure. Conclusions. Cardiopulmonary rehabilitation appears to be a safe intervention in patients with congenital heart disease and pulmonary hypertension.     

Lipomatous hypertrophy of the interatrial septum associated with fatty replacement of the ventricular myocardium: a case report

Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare benign entity characterized by the excessive fat deposition in the interatrial septum with typical sparing of the fossa ovalis. We report a case of a 61-year-old woman with an incidentally found LHIS associated with fatty replacement of the ventricular myocardium and epicardial mediastinal lipomatosis diagnosed by computed tomography (CT) and MRI.