A gamma camera count rate saturation correction method for whole-body planar imaging.

Whole-body (WB) planar imaging has long been one of the staple methods of dosimetry, and its quantification has been formalized by the MIRD Committee in pamphlet no 16. One of the issues not specifically addressed in the formalism occurs when the count rates reaching the detector are sufficiently high to result in camera count saturation. Camera dead-time effects have been extensively studied, but all of the developed correction methods assume static acquisitions. However, during WB planar (sweep) imaging, a variable amount of imaged activity exists in the detector's field of view as a function of time and therefore the camera saturation is time dependent. A new time-dependent algorithm was developed to correct for dead-time effects during WB planar acquisitions that accounts for relative motion between detector heads and imaged object. Static camera dead-time parameters were acquired by imaging decaying activity in a phantom and obtaining a saturation curve. Using these parameters, an iterative algorithm akin to Newton's method was developed, which takes into account the variable count rate seen by the detector as a function of time. The algorithm was tested on simulated data as well as on a whole-body scan of high activity Samarium-153 in an ellipsoid phantom. A complete set of parameters from unsaturated phantom data necessary for count rate to activity conversion was also obtained, including build-up and attenuation coefficients, in order to convert corrected count rate values to activity. The algorithm proved successful in accounting for motion- and time-dependent saturation effects in both the simulated and measured data and converged to any desired degree of precision. The clearance half-life calculated from the ellipsoid phantom data was calculated to be 45.1 h after dead-time correction and 51.4 h with no correction; the physical decay half-life of Samarium-153 is 46.3 h. Accurate WB planar dosimetry of high activities relies on successfully compensating for camera saturation which takes into account the variable activity in the field of view, i.e. time-dependent dead-time effects. The algorithm presented here accomplishes this task.

Isochorismate synthase (PchA), the first and rate-limiting enzyme in salicylate biosynthesis of Pseudomonas aeruginosa.

In Pseudomonas aeruginosa the extracellular metabolite and siderophore pyochelin is synthesized from two major precursors, chorismate and l-cysteine via salicylate as an intermediate. The regulatory role of isochorismate synthase, the first enzyme in the pyochelin biosynthetic pathway, was studied. This enzyme is encoded by pchA, the last gene in the pchDCBA operon. The PchA protein was purified to apparent electrophoretic homogeneity from a PchA-overexpressing P. aeruginosa strain. The native enzyme was a 52-kDa monomer in solution, and its activity strictly depended on Mg(2+). At pH 7.0, the optimum, a K(m) = 4.5 microm and a k(cat) = 43.1 min(-1) were determined for chorismate. No feedback inhibitors or other allosteric effectors were found. The intracellular PchA concentration critically determined the rate of salicylate formation both in vitro and in vivo. In cultures grown in iron-limiting media to high cell densities, overexpression of the pchA gene resulted in overproduction of salicylate as well as in enhanced pyochelin formation. From this work and earlier studies, it is proposed that one important factor influencing the flux through the pyochelin biosynthetic pathway is the PchA concentration, which is determined at a transcriptional level, with pyochelin acting as a positive signal and iron as a negative signal.

Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women.

The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber. On one occasion the subjects consumed caffeinated coffee and on the other occasion, decaffeinated coffee. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%). The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. During the next day, in postabsorptive basal conditions, the thermogenic effect of coffee had vanished, but a significant increase in lipid oxidation was observed in both groups. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively). Caffeine increased urinary epinephrine excretion. Whereas urinary caffeine excretion was similar in both groups, obese women excreted more theobromine, theophylline, and paraxanthine than lean women. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects.

Appropriateness and long-term discontinuation rate of biological therapies in ulcerative colitis.

BACKGROUND: Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome. METHODS: We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents. Appropriateness of the first-line anti-TNFα treatment was assessed using detailed criteria developed during the European Panel on the Appropriateness of Therapy for UC. Treatment discontinuation as an outcome was assessed for categories of appropriateness. RESULTS: Appropriateness of the first-line biological treatment was determined in 186 UC patients. For 64% of them, this treatment was considered appropriate. During follow-up, 37% of all patients discontinued biological treatment, 17% specifically because of failure. Time-to-failure of treatment was significantly different among patients on an appropriate biological treatment compared to those for whom the treatment was considered not appropriate (p=0.0007). Discontinuation rate after 2years was 26% compared to 54% between those two groups. Patients on inappropriate biological treatment were more likely to have severe disease, concomitant steroids and/or immunomodulators. They were also consistently more likely to suffer a failure of efficacy and to stop therapy during follow-up. CONCLUSION: Appropriateness of first-line anti-TNFα therapy results in a greater likelihood of continuing with the therapy. In situations where biological treatment is uncertain or inappropriate, physicians should consider other options instead of prescribing anti-TNFα agents.

Performance of an ICU ventilator and two turbin-based ventilators dedicated to non invasive ventilation (NIV) in simulated high inspiratory effort and rate: a NIV-bench-study.

INTRODUCTION. The role of turbine-based NIV ventilators (TBV) versus ICU ventilators with NIV mode activated (ICUV) to deliver NIV in case of severe respiratory failure remains debated. OBJECTIVES. To compare the response time and pressurization capacity of TBV and ICUV during simulated NIV with normal and increased respiratory demand, in condition of normal and obstructive respiratory mechanics. METHODS. In a two-chamber lung model, a ventilator simulated normal (P0.1 = 2 mbar, respiratory rate RR = 15/min) or increased (P0.1 = 6 mbar, RR = 25/min) respiratory demand. NIV was simulated by connecting the lung model (compliance 100 ml/mbar; resistance 5 or 20 l/mbar) to a dummy head equipped with a naso-buccal mask. Connections allowed intentional leaks (29 ± 5 % of insufflated volume). Ventilators to test: Servo-i (Maquet), V60 and Vision (Philips Respironics) were connected via a standard circuit to the mask. Applied pressure support levels (PSL) were 7 mbar for normal and 14 mbar for increased demand. Airway pressure and flow were measured in the ventilator circuit and in the simulated airway. Ventilator performance was assessed by determining trigger delay (Td, ms), pressure time product at 300 ms (PTP300, mbar s) and inspiratory tidal volume (VT, ml) and compared by three-way ANOVA for the effect of inspiratory effort, resistance and the ventilator. Differences between ventilators for each condition were tested by oneway ANOVA and contrast (JMP 8.0.1, p\0.05). RESULTS. Inspiratory demand and resistance had a significant effect throughout all comparisons. Ventilator data figure in Table 1 (normal demand) and 2 (increased demand): (a) different from Servo-i, (b) different from V60.CONCLUSION. In this NIV bench study, with leaks, trigger delay was shorter for TBV with normal respiratory demand. By contrast, it was shorter for ICUV when respiratory demand was high. ICUV afforded better pressurization (PTP 300) with increased demand and PSL, particularly with increased resistance. TBV provided a higher inspiratory VT (i.e., downstream from the leaks) with normal demand, and a significantly (although minimally) lower VT with increased demand and PSL.

20 years of eosinophilic esophagitis in Olten county: population-based, prospective documentation of an increasing incidence

Background and Aims: Eosinophilic Esophagitis (EoE) is reported with increasing frequency over the last two decades. However, it is still unknown whether this reflects a true increase in incidence or just an increased awareness by gastroenterologists. Therefore, we evaluated the incidence and cumulative prevalence of EoE in Olten county over the last 20 years. Methods: Olten county is an area of approximately 91,000 inhabitants without pronounced demographic changes in the last two decades. EoE evaluation is based upon two gastroenterology centers and one pathology center. No public programs for increased EoE awareness were implemented in this region. All EoE patients diagnosed from 1989 to 2009 were entered prospectively into the Olten county database. Results: Fourty-six patients (76% males, mean age 41±16 yrs) were diagnosed with EoE from 1989 to 2009. Ninety-four percent presented with dysphagia. In 70% of the patients concomitant allergies were found. The number of upper endoscopies per year was stable during the entire observation period. An average annual incidence rate of 2/100,000 was found (range 0-8) with a marked increase in the period from 2001 to 2009. A current cumulative EoE prevalence of 43/100,000 inhabitants was calculated. The mean diagnostic delay (time from first symptoms to diagnosis) was 4.3 years from 1989 to 1998 and 4.8 years from 1999 to 2009. Conclusions: Over the last 20 years, a significant increase in EoE incidence was found in a stable indicator region of Switzerland. The constant rate of upper endoscopies, the constant diagnostic delay, as well as the lack of EoE awareness programs in Olten county indicate a true increase in EoE incidence.

Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.

BACKGROUND: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. RESULTS: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. CONCLUSIONS: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.

Quantifying network properties in multi-electrode recordings: spatiotemporal characterization and inter-trial variation of evoked gamma oscillations in mouse somatosensory cortex in vitro.

Linking the structural connectivity of brain circuits to their cooperative dynamics and emergent functions is a central aim of neuroscience research. Graph theory has recently been applied to study the structure-function relationship of networks, where dynamical similarity of different nodes has been turned into a "static" functional connection. However, the capability of the brain to adapt, learn and process external stimuli requires a constant dynamical functional rewiring between circuitries and cell assemblies. Hence, we must capture the changes of network functional connectivity over time. Multi-electrode array data present a unique challenge within this framework. We study the dynamics of gamma oscillations in acute slices of the somatosensory cortex from juvenile mice recorded by planar multi-electrode arrays. Bursts of gamma oscillatory activity lasting a few hundred milliseconds could be initiated only by brief trains of electrical stimulations applied at the deepest cortical layers and simultaneously delivered at multiple locations. Local field potentials were used to study the spatio-temporal properties and the instantaneous synchronization profile of the gamma oscillatory activity, combined with current source density (CSD) analysis. Pair-wise differences in the oscillation phase were used to determine the presence of instantaneous synchronization between the different sites of the circuitry during the oscillatory period. Despite variation in the duration of the oscillatory response over successive trials, they showed a constant average power, suggesting that the rate of expenditure of energy during the gamma bursts is consistent across repeated stimulations. Within each gamma burst, the functional connectivity map reflected the columnar organization of the neocortex. Over successive trials, an apparently random rearrangement of the functional connectivity was observed, with a more stable columnar than horizontal organization. This work reveals new features of evoked gamma oscillations in developing cortex.

Escalating epidemiology of eosinophilic esophagitis: 21 years of prospective population-based documentation in Olten county

Background and Aims: Eosinophilic Esophagitis (EoE) is detected with a dramatically increasingfrequency during the last decades. However, it is still unknown whether this reflects atrue increase in incidence or just an increased awareness by gastroenterologists. We therefore,prospectively assessed incidence and prevalence of EoE in an epidemiologically well definedindicator area over the last 21 years. Methods: Olten County is an area of approximately90,000 inhabitants without pronounced demographic changes during the last two decades.Two EoE-experienced gastroenterologists and one pathology centre are responsible forcovering the gastroenterological service of the area. No public programs for increasingawareness of EoE were implemented in this region. Since 1989 all individuals with confirmeddiagnosis of EoE living in Olten County were entered prospectively into the database. Results:Forty-six patients (76% males, mean age 41±16 yrs) were diagnosed with EoE between1989 and 2009. Ninety-four percent of patients presented with dysphagia. An average annualincidence rate of 1.88/100,000 was found (range 0-8) with a marked increase in the periodfrom 2004 to 2009. The cumulative EoE prevalence rose up to 35.1/100,000 inhabitantsin 2009. No significant change was observed for the median diagnostic delay, as it was 3years from 1989 to 1998 and 2 years from 1999 to 2009 with age < 40 years representinga risk factor for retarded diagnosis. The number of upper endoscopies per year increasedby 63% in the period from 1999 to 2009 compared to the years 1989 to 1998 which ismarkedly less then the increase in the incidence rate of 150% for the same periods. Conclusions:Over the last 21 years, a significant increase in EoE incidence and prevalence wasfound in an epidemiologically stable indicator region of Switzerland. The constant diagnosticdelay, the number of newly diagnosed EoE cases that was much more pronounced thanthe modest increase of performed upper endoscopies, as well as the lack of EoE awarenessprograms in Olten County indicates a true increase in EoE incidence.

Division of labour influences the rate of ageing in weaver ant workers.

The evolutionary theory of ageing predicts that the timing of senescence has been primarily shaped by the extrinsic mortality rate, which causes selection intensity to decline over time. One difficulty in testing the evolutionary theory of ageing is that extrinsic mortality risk is often confounded with body size and fecundity, which may also directly affect lifespan. Social insects with a pronounced division of labour between worker castes provide a unique opportunity to study the direct effect of extrinsic mortality on the evolution of ageing rates independently of body size, reproductive effort and genetic configuration. In the weaver ant, Oecophylla smaragdina, the major (large) workers perform the risky tasks outside the nest, while the minor (small) workers stay within the highly protected arboreal nest. Hence, this pronounced division of labour is associated with high differences in extrinsic mortality risks. The evolutionary theory of ageing predicts that the minor workers should have a longer intrinsic lifespan than the major workers. In line with this prediction, we found that in a protected environment the minor workers lived significantly longer than the major workers did. Hence, the ageing rate appears to have been moulded by variation in the extrinsic mortality rate independently of size, reproductive effort and genetic configuration.

High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.