A mixed splicing procedure for economic time series

This note develops a flexible methodology for splicing economic time series that avoids the extreme assumptions implicit in the procedures most commonly used in the literature. It allows the user to split the required correction to the older of the series being linked between its levels and growth rates on the basis what he knows or conjectures about the persistence of the factors that account for the discrepancy between the two series that emerges at their linking point. The time profile of the correction is derived from the assumption that the error in the older series reflects the inadequate coverage of emerging sectors or activities that grow faster than the aggregate.

A homing procedure for studying spatial memory in immature and adult rodents

In this procedure, subjects learn the spatial position of one hole out of many, that allows them to escape from a large open-field into their home cage. The arena is circular and can be rotated between trials so that no proximal landmark is permanently associated with the target hole. This task is thus similar to the Morris water maze procedure, since subjects must remember the position of the escape hole relative to extra-arena cues only. In addition it allows studying the importance of olfactory cues such as scent marks in or around a hole. Since the motivation is to reach home and the motor requirement is low, this task provides a useful alternative to the Morris place navigation task for studying spatial orientation in weanling or senescent rats. Examples are given showing that various behavioural parameters provide a good estimation as how subjects learn this task.

Adaptable pulmonary artery band for late arterial switch procedure in transposition of the great arteries.

BACKGROUND: In late-diagnosed transposition of the great arteries (TGA), the left ventricle (LV) involutes as it pumps against low resistance and needs retraining by applying a pulmonary artery band (PAB) in preparation for an arterial switch operation. We report our experience with a telemetrically adaptable band compared with classic banding. METHODS: Ten patients underwent retraining of the LV, 4 patients with an adaptable band and progressive weekly tightening of the band (group 1) and 6 patients with a traditional band (group 2). RESULTS: Mean weight and age at pulmonary band placement was 5.8 ± 2.36 kg and 11.7 ± 11.1 months for group 1 and 5.0 ± 2.3 kg and 6.4 ± 7.6 months for group 2. Time between palliation and switch procedure was 4.2 months in both groups. Group 1 showed an initial mean pulmonary gradient of 25.5 ± 4.43 mm Hg with a 5% closure of the device. The mean gradient increased with progressive closure to 63.5 ± 9.8 mm Hg at the time of the arterial switch operation. There were no reinterventions or deaths in this group. In group 2, the mean pulmonary gradient increased with growth from 49 ± 21.4 mm Hg to 68.4 ± 7.86 mm Hg at the time of the switch procedure. However, 4 of these patients required reoperations during retraining: 2 needed 1 reoperation and 2 needed 2 reoperations. Two patients died-1 after banding and 1 after the switch operation. CONCLUSIONS: Retraining of the LV by the adaptable device allows precise control of the tightening, avoids repetitive operations, and diminishes morbidity.

111In-pentetreotide scintigraphy: procedure guidelines for tumour imaging.

This document provides general information about somatostatin receptor scintigraphy with (111)In-pentetreotide. This guideline should not be regarded as the only approach to visualise tumours expressing somatostatin receptors or as exclusive of other nuclear medicine procedures useful to obtain comparable results. The aim of this guideline is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of (111)In-pentetreotide scintigraphy.

TT virus infection in children and adults who visited a general hospital in the south of Brazil for routine procedure

TT virus (TTV) is a newly described nonenveloped human virus, with a circular, negative-stranded DNA genome, that was first identified in the blood of a patient with posttransfusion hepatitis of unknown etiology. PCR primers and conditions used for TTV DNA amplification may greatly influence the level of TTV detection in serum. Three PCR assays, with different regions of the genome as targets, were used to test TTV DNA in 130 sera from children and adults visiting a hospital in the south of Brazil, most of them for routine procedure. Forty-four percent of adult sera and 73% of sera from children aged 0-10 years were TTV positive with at least one PCR assay. However, the three assays were able to detect only 33%, 35%, and 70% of the total positive samples. Our results showed a high prevalence of TTV infection in the south of Brazil, particularly among young children, and confirmed the necessity of performing several PCR assays to assess the true TTV prevalence in a determined population.

Inhibition of the polymerase chain reaction by sputum samples from tuberculosis patients after processing using a silica-guanidiniumthiocyanate DNA isolation procedure

With the objective to evaluate PCR-mediated detection of Mycobacterium tuberculosis DNA as a diagnostic procedure for diagnosis of tuberculosis in individuals attending ambulatory services in Primary Health Units of the City Tuberculosis Program in Rio de Janeiro, Brazil, their sputum samples were collected and treated with a DNA extraction procedure using silica-guanidiniumthiocyanate. This procedure has been described to be highly efficient for extraction of different kind of nucleic acids from bacteria and clinical samples. Upon comparing PCR results with the number of acid-fast bacilli, no direct relation was observed between the number of bacilli present in the sample and PCR positivity. Part of the processed samples was therefore spiked with pure DNA of M. tuberculosis and inhibition of the PCR reaction was verified in 22 out of 36 (61%) of the samples, demonstrating that the extraction procedure as originally described should not be used for PCR analysis of sputum samples.

Multiple nodules of the scrotum: histopathological findings and surgical procedure. A study of five cases.

BACKGROUND: Multiple nodules of the scrotum are uncommonly reported. Their origin is controversial. Treatment is always surgical but the best procedure is still to be determined. MATERIALS AND METHODS: Five new cases are reported with description of the histopathological findings and surgical procedure. RESULTS: Nodules of the scrotum were more frequent in patients with dark skin suggesting an ethnic susceptibility. No other predisposing factors were noted. Screening for disturbances of phosphate or calcium balance was negative. The following histopathological findings were observed: non-calcified epidermoid cysts (3 patients), calcified epidermoid cysts (1 patient) and nodular calcifications without epithelial or glandular structures (1 patient). Subtotal excisions of the scrotum wall using tumescent anaesthesia were performed in all patients without any significant complications. Cosmetic results were excellent. No new lesions were observed during the 1-year follow-up period. CONCLUSIONS: Most cases of multiple nodules of the scrotum are due to non-calcified epidermoid cysts. The term scrotal calcinosis is therefore probably abusively used by many authors. Some cases of nodular calcifications may be due to dystrophic calcification of epidermoid cysts, but calcifications may also occur without any visible epithelial or glandular structure. Subtotal excision of the scrotum wall is a safe and effective surgical procedure to treat multiple nodules of the scrotum. Cosmetic results are excellent and recurrences are rare.

Assessment of left coronary artery beat-to-beat repositioning in order to propose an optimal acquisition window for coronary MRA

Introduction: Coronary magnetic resonance angiography (MRA) is a medical imaging technique that involves collecting data from consecutive heartbeats, always at the same time in the cardiac cycle, in order to minimize heart motion artifacts. This technique relies on the assumption that coronary arteries always follow the same trajectory from heartbeat to heartbeat. Until now, choosing the acquisition window in the cardiac cycle was based exclusively on the position of minimal coronary motion. The goal of this study was to test the hypothesis that there are time intervals during the cardiac cycle when coronary beat-to-beat repositioning is optimal. The repositioning uncertainty values in these time intervals were then compared with the intervals of low coronary motion in order to propose an optimal acquisition window for coronary MRA. Methods: Cine breath-hold x-ray angiograms with synchronous ECG were collected from 11 patients who underwent elective routine diagnostic coronarography. Twenty-three bifurcations of the left coronary artery were selected as markers to evaluate repositioning uncertainty and velocity during cardiac cycle. Each bifurcation was tracked by two observers, with the help of a user-assisted algorithm implemented in Matlab (The Mathworks, Natick, MA, USA) that compared the trajectories of the markers coming from consecutive heartbeats and computed the coronary repositioning uncertainty with steps of 50ms until 650ms after the R-wave. Repositioning uncertainty was defined as the diameter of the smallest circle encompassing the points to be compared at the same time after the R-wave. Student's t-tests with a false discovery rate (FDR, q=0.1) correction for multiple comparison were applied to see whether coronary repositioning and velocity vary statistically during cardiac cycle. Bland-Altman plots and linear regression were used to assess intra- and inter-observer agreement. Results: The analysis of left coronary artery beat-to-beat repositioning uncertainty shows a tendency to have better repositioning in mid systole (less than 0.84±0.58mm) and mid diastole (less than 0.89±0.6mm) than in the rest of the cardiac cycle (highest value at 50ms=1.35±0.64mm). According to Student's t-tests with FDR correction for multiple comparison (q=0.1), two intervals, in mid systole (150-200ms) and mid diastole (550-600ms), provide statistically better repositioning in comparison with the early systole and the early diastole. Coronary velocity analysis reveals that left coronary artery moves more slowly in end systole (14.35±11.35mm/s at 225ms) and mid diastole (11.78±11.62mm/s at 625ms) than in the rest of the cardiac cycle (highest value at 25ms: 55.96±22.34mm/s). This was confirmed by Student's t-tests with FDR correction for multiple comparison (q=0.1, FDR-corrected p-value=0.054): coronary velocity values at 225, 575 and 625ms are not much different between them but they are statistically inferior to all others. Bland-Altman plots and linear regression show that intra-observer agreement (y=0.97x+0.02 with R²=0.93 at 150ms) is better than inter-observer (y=0.8x+0.11 with R²=0.67 at 150ms). Discussion: The present study has demonstrated that there are two time intervals in the cardiac cycle, one in mid systole and one in mid diastole, where left coronary artery repositioning uncertainty reaches points of local minima. It has also been calculated that the velocity is the lowest in end systole and mid diastole. Since systole is less influenced by heart rate variability than diastole, it was finally proposed to test an acquisition window between 150 and 200ms after the R-wave.

Quantification of nicotine, cotinine, trans-3'-hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC-tandem mass-spectrometry procedure for a clinical study on smoking cessation.

A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5mL of plasma, using a mixed-mode cation exchange support. Chromatographic separations were performed on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1×100mm, 1.7μm). A gradient program was used, with a 10mM ammonium formate buffer pH 3/acetonitrile mobile phase at a flow of 0.4mL/min. The compounds were detected on a triple quadrupole mass spectrometer, operated with an electrospray interface in positive ionization mode and quantification was performed using multiple reaction monitoring. Matrix effects were quantitatively evaluated with success, with coefficients of variation inferior to 8%. The procedure was fully validated according to Food and Drug Administration guidelines and to Société Française des Sciences et Techniques Pharmaceutiques. The concentration range was 2-500ng/mL for nicotine, 1-1000ng/mL for cotinine, 2-1000ng/mL for trans-3'-hydroxycotinine and 1-500ng/mL for varenicline, according to levels usually measured in plasma. Trueness (86.2-113.6%), repeatability (1.9-12.3%) and intermediate precision (4.4-15.9%) were found to be satisfactory, as well as stability in plasma. The procedure was successfully used to quantify nicotine, its metabolites and varenicline in more than 400 plasma samples from participants in a clinical study on smoking cessation.

Novel MLPA procedure using self-designed probes allows comprehensive analysis for CNVs of the genes involved in Hirschsprung disease.

Background: Hirschsprung disease is characterized by the absence of intramural ganglion cells in the enteric plexuses, due to a fail during enteric nervous system formation. Hirschsprung has a complex genetic aetiology and mutations in several genes have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis. In this study, we have looked for CNVs in some of the genes related to Hirschsprung (EDNRB, GFRA1, NRTN and PHOX2B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach. Methods: CNVs screening was performed in 208 HSCR patients using a self-designed set of MLPA probes, covering the coding region of those genes. Results: A deletion comprising the first 4 exons in GFRA1 gene was detected in 2 sporadic HSCR patients and in silico approaches have shown that the critical translation initiation signal in the mutant gene was abolished. In this study, we have been able to validate the reliability of this technique for CNVs screening in HSCR. Conclusions: The implemented MLPA based technique presented here allows CNV analysis of genes involved in HSCR that have not been not previously evaluated. Our results indicate that CNVs could be implicated in the pathogenesis of HSCR, although they seem to be an uncommon molecular cause of HSCR.

Surgical procedure in immunoglobulin G4-related ascending aortitis?

Immunoglobulin G4 (IgG4)-related fibroinflammatory systemic disease accounts for 7% of all noninfectious aneurysms of the thoracic aorta. A patient was admitted with a symptomatic ascending aortic aneurysm and thickened aortic wall (outer/inner diameter 55/45 mm), which was replaced. Probes revealed IgG4-related aortitis associated with a primary tuberculosis infection. Corticosteroid and antituberculosis therapies were used, and the patient's clinical evolution was favorable. The optimal treatment strategy of IgG4-related aortitis, a new entity, remains vague. Inner aortic diameter alone does not justify aortic replacement, but wall thickening may mimic intramural hematoma. In this particular case of IgG4-related aortitis, immunosuppressive treatment alone, as an alternative to a surgical procedure, may be debatable.