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Legacy data in the form of historical aerial imagery can be used to investigate geomorphological change over time. This data can be used to improve research about the preservation and visibility of the archaeological record, and it can also aid heritage management. This paper presents a composite Image-Based Modelling workflow to generate 3D models, historical orthophotos, and historical digital elevation models from images from the 1970s. This was done to improve the interpretation of survey data from the early Roman colony of Aesernia. The main challenge was the lack of high-resolution recent digital elevation models and ground control points, and a general lack of metadata. Therefore, spatial data from various sources had to be combined. To assess the accuracy of the final 3D model, the RMSE was calculated. While the workflow appears effective, the low accuracy of the initial data limits the usefulness of the model for the study of geomorphological change. However, it can be implemented to aid sample area selection when preparing archaeological fieldwork. Additionally, when working with existing survey datasets, areas with a high bias risk resulting from post-depositional processes can be indicated.

Inspired by the observation of a distributed time delay in the nonlinear response of an optical resonator, we investigate the effects of a similar delay on a noise-driven mechanical oscillator. For a delay time that is commensurate with the inverse dissipation rate, we find stable limit cycles. For longer delays, we discover a regime of chaotic dynamics associated with a double scroll attractor. We also analyze the effects of time delay on the spectrum and oscillation amplitude of the oscillator. Our results point to new opportunities for nonlinear energy harvesting, provided that a nonlinearity with distributed time delay can be implemented in mechanical systems., Comment: 4 figures, 7 pages

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PurposeTo determine the role of18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) in children with fever of unknown origin (FUO).MethodsThis retrospective single-center study included 110 children (0–18 years) with FUO who underwent FDG-PET/CT between 2010 and 2019. The diagnostic value of FDG-PET/CT for identifying cause of fever was calculated, treatment modifications after FDG-PET/CT were assessed, and logistic regression analyses were performed to identify clinical and biochemical factors associated with FDG-PET/CT outcome.ResultsIn 53 out of 110 patients (48%), FDG-PET/CT identified a (true positive) cause of fever. Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) were the most common causes of FUO. In 42 patients (38%), no cause of fever was found on FDG-PET/CT. In 58 out of 110 patients (53%), treatment modifications were made after FDG-PET/CT. FDG-PET/CT achieved a sensitivity of 85.5%, specificity of 79.2%, positive predictive value of 84.1%, and negative predictive value of 80.9%. On multivariate logistic regression, C-reactive protein was positively associated with finding a true positive focus of fever on FDG-PET/CT (OR = 1.01 (95% CI 1.00–1.02) per mg/L increase in CRP), while leukocyte count was negatively associated with finding a true positive focus of fever (OR = 0.91 (95% CI 0.85–0.97) per 109leukocytes/L increase).ConclusionFDG-PET/CT is a valuable diagnostic tool in the evaluation of children with FUO, since it may detect a true underlying cause in almost half (48%) of all cases where none was found otherwise. It allows full-body evaluation in patients without disease-specific symptoms on one examination. CRP and leukocyte count were significantly associated with FDG-PET/CT results, which may contribute to a priori assessment on the outcome of FDG-PET/CT. Future research could be aimed at evaluating more patient-specific factors to prospectively estimate the added value of FDG-PET/CT in children with FUO.

Exceptional points (EPs) -- spectral singularities of non-Hermitian linear systems -- have recently attracted great interest for sensing. While initial proposals and experiments focused on enhanced sensitivities neglecting noise, subsequent studies revealed issues with EP sensors in noisy environments. Here we propose a single-mode Kerr-nonlinear resonator for exceptional sensing in noisy environments. Based on the resonator's dynamic hysteresis, we define a signal that displays a square-root singularity akin to an EP. In contrast to EP sensors, our sensor has a signal-to-noise ratio that increases with the measurement speed, and a precision enhanced at the square-root singularity. Remarkably, averaging the signal can quickly enhance and then degrade the precision. These unconventional features open up new opportunities for fast and precise sensing beyond the constraints of linear systems. While we focus on optical sensing, our approach can be extended to other hysteretic systems., Comment: 8 pages, including 1 page of supplemental material

High Voltage-High Humidity High Temperature Reverse Bias (HV-H3TRB) is the standard to test power modules for humidity driven degradation. This test has contributed significantly to detect and fix weak points in device designs, especially of the junction termination. Thus, the latest junction termination designs offer unprecedented humidity robustness. This work reports on a comparative HV-H3TRB test on 1.7 kV IGBT modules with chips sets of two consecutive generations tested at two different test voltages each. The progress in the chip design and material composition provides more than an order of magnitude better performance in HV-H3TRB. Failure analyses have indicated vastly reduced degrees of aluminium corrosion in the junction termination area, leading to a slowed down failure mechanism.

Objective Clinical T2N0 esophageal carcinoma is a heterogenous disease frequently complicated by inaccurate staging. Incorrect staging may lead to suboptimal treatment for patients with unidentified local-regionally advanced disease. Therapeutic options for these patients remain controversial. We sought to evaluate the outcomes of patients with cT2N0 who underwent esophagectomy as either primary therapy or after neoadjuvant treatment. Methods This was a multi-institutional collaboration of 26 high-volume esophageal centers. Patients with complete staging who underwent elective resection from 2002 to 2012 were included. Three treatment groups were identified; primary esophagectomy, preoperative chemotherapy, and preoperative chemoradiation (CXRT). Pretreatment variables were explored for independent predictors of long-term outcomes. The primary esophagectomy subgroup was evaluated for stage migration. Results In total, 767 patients were evaluated; 35% (268) had preoperative therapy (195 CXRT, 73 chemotherapy). Staging accuracy was 14% (70/499), with pT 0 in 39% (195). Preoperative treatment modality (none, CXRT, chemotherapy) was not identified as a predictor of outcome (median survival 63, 70, 71 months, respectively, P = .956). Longitudinal tumor length >3.25 cm was predictive of pN+ for the primary esophagectomy cohort as well as adenocarcinoma histology only (odds ratio 2.2 and 2.4, respectively, P Conclusions Current treatment options for patients with cT2N0M0 do not reveal a comparative survival advantage to preoperative therapy. Pretreatment tumor length can identify a subgroup of patients at risk for understaging (pN+). The incidence of overstaging suggests that organ-sparing approaches (endoscopic resection) may play a future role in appropriately selected patients.

Objective: To determine the minimum incidence and minimum prevalence rates of small-fiber neuropathy (SFN) in a well-defined region in the southern part of the Netherlands. Methods: In this cross-sectional study with retrospective data collection, we used data of patients diagnosed with pure SFN at our Small Fiber Neuropathy Center between January 2006 and December 2011 to calculate minimum incidence and prevalence rates. Results: A total of 88 patients were diagnosed with SFN (mean age 56.9 years, SD 11.8, range 34–81; 44.3% women, 55.7% men). The overall minimum incidence over 2010 and 2011 was 11.73 (95% confidence interval 7.12–18.22) cases/100,000 inhabitants/year. The overall minimum prevalence was 52.95 (95% confidence interval 42.47–65.23) cases/100,000. Incidence and prevalence rates were higher in men than in women, as were the rates in elderly patients compared with younger patients. Conclusions: The minimum incidence and prevalence rates of SFN are presented. We found that SFN is more frequently seen in men and more often diagnosed in elderly patients. These rates probably are an underestimation and are expected to increase in the coming years, since the awareness of SFN is increasing worldwide.

The diagnosis of small fiber neuropathy (SFN) has been recently defined as typical symptoms due to small nerve fiber dysfunction accompanied by reduced intra-epidermal nerve fiber density (IENFD) or abnormal temperature threshold testing (TTT). Guidelines have been published for the assessment of IENFD. However, international guidelines for TTT are lacking. This paper presents a systematic literature review on reported TTT methods and provides recommendations for its future use in studies evaluating patients. A total of 164 papers fulfilled pre-defined requirements and were selected for review. Over 15 types of instruments are currently being used with a variety of methodological approaches for location, stimulus application, and sensation qualities examined. Consensus is needed to standardize the use of TTT as a diagnostic and follow-up tool in patients.

Background The assessment of the esophagogastricjunction (EGJ) is the most challenging aspect of clin-ical esophageal manometry. Although conventionalmanometric systems can be optimized toward inter-rogating specific aspects of the EGJ, they are too lim-ited in recording channels and/or fidelity for acomprehensive assessment. The technological ad-vantages inherent in high resolution manometry(HRM) with esophageal pressure topography (EPT)analysis substantially change this equation providinga technology sufficiently robust to dynamically recordthe contractile activity within the EGJ with both goodfidelity and good spatial resolution.Purpose This review is an update on our under-standing of the application of HRM and EPT to theanalysis of EGJ function. With respect to sphincterrelaxation, the integrated relaxation pressure (IRP) hasproven to be a robust metric in differentiating intactfrom impaired EGJ relaxation. In the process, it re-vealed that impaired EGJ relaxation could occur notonly in the setting of achalasia but also with othercauses of EGJ outflow obstruction including hiatushernia. The morphological description of the EGJ byEPT has also revealed not only a spectrum of ab-normality ranging from an intact sphincter to overtherniation, but also the surprise finding of sponta-neous conversion among sphincter configurations,emphasizing its dynamic nature. With respect tobarrier function, preliminary data have refocused onthe crural diaphragm as a key-differentiating featurebetween preserved and compromised function. Fi-nally, although the accomplishments summarizedabove are substantial, much work remains to fullyexploit the potential of EPT in the clinical character-ization of the EGJ.Keywords esophagogastricjunction,gastro-esophagealrefluxdisease,loweresophagealsphincter,manometry.Abbreviations: CD, crural diaphragm; EGJ, esophagoga-stric junction; GERD, gastro-esophageal reflux disease;HRM, high resolution manometry; LES, lower esophagealsphincter.

Our understanding of esophageal disease and the foregut has evolved over the past 100 years, especially in recent times. Modern diagnostic technologies and new management paradigms have provided progressive insights into the anatomy, physiology, and normal and abnormal function of the esophagus, as well as improving patient care. Yet, the relationship between the esophagus and its close neighbor, the spine, is rarely discussed and likely underappreciated. Anatomic proximity and intertwined pathophysiology led early investigators to postulate relationships between esophageal disease and spinal abnormalities. More recent studies have illustrated a link between spinal disease and hiatal hernias. Objective radiographic measurements of kyphoscoliosis have correlated with increased hiatal hernia formation. Spinal abnormalities and disease of the esophageal hiatus are becoming more common in our aging population, with each carrying significant risk of morbidity and decreased quality of life. Operative planning and subsequent hiatal hernia repair must be undertaken in the context of these spinal abnormalities. A historical review of past publications related to the subject forms the basis for this publication, thus revealing insight and improving our understanding of the association between spinal abnormalities and hiatal hernias.

Microparticles from poly(D,L-lactic-co-glycolic acid) [PLGA] are of steadily rising interest for the delivery of antigens to immune cells and the induction of a long-lasting immune response for vaccination or immunological tumor therapy. However, if the desired vaccine contains only weak antigens and fails to activate the antigen presenting cells (APC), the opposite effect, i.e., the induction of immunotolerance may be observed. Therefore, it was the aim of this study to show the ability of protein loaded PLGA microparticles to additionally carry a specific, surface-coated maturation signal to human dendritic cells (DC), i.e., the most potent APC. Polyinosine-polycytidylic acid [poly(I:C)], a ligand of Toll-like receptor (TLR) 3, was efficiently bound either in a single layer or a multilayer attempt to the surface of diethylaminoethyl dextran modified PLGA microparticles. These particles were effectively phagocytized by DC ex vivo and induced a maturation similar to that achieved with a cytokine cocktail or higher concentrations of soluble poly(I:C). In conclusion, the concept of surface coating of biodegradable microparticles with selected TLR ligands might successfully be used in DC-based cell therapies for cancer or in vaccination trials to induce DC maturation and specifically amplify the immunological response to encapsulated antigens.

Item does not contain fulltext BACKGROUND AND AIMS: Currently, eradication of Barrett's epithelium is preferably achieved using radiofrequency ablation (RFA) or spray cryoablation (SCA). However, both modalities suffer from drawbacks such as the need for sizing, multiple deployment steps, large controller units (RFA), imprecise dosing and need for gas-venting (SCA). The new Cryoballoon Focal Ablation System (CbFAS) may address these limitations. This study assessed the safety, feasibility, and dose response of the CbFAS in patients with flat Barrett's epithelium with or without dysplasia. PATIENTS AND METHODS: In this multicenter, prospective non-randomized trial, 39 patients were each treated with one or two ablations of 6, 8, or 10 seconds. Symptoms were assessed immediately and 2 days post-cryoablation. Follow-up endoscopy was performed 6 - 8 weeks post-procedure to assess response. Outcome parameters were incidence of adverse events, pain, esophageal stricture formation, and ablation response by cryogen dose. RESULTS: Of 62 ablations, 56 (10 with 6 seconds, 28 with 8 seconds, 18 with 10 seconds) were successfully performed. Six ablations failed because of device malfunction (n = 3) and procedural or anatomic issues (n = 3). Median procedure time was 7 minutes (interquartile range [IQR] 4 - 10). No major adverse events occurred; six patients experienced a minor mucosal laceration requiring no intervention. Mild pain was reported by 27 % of patients immediately after cryoablation and by 14 % after 2 days. No strictures were evident at follow-up. Full squamous regeneration was seen in 47 treated areas (6 [60 %] of the 6-second areas; 23 [82 %] of the 8-second areas; 18 [100 %] of 10-second areas). CONCLUSIONS: Focal cryoablation of Barrett's epithelium with the CbFAS is feasible and safe, resulting in squamous regeneration in the majority of patients.

The molecular pathogenesis of Barrett's esophagus is poorly understood. Evidence suggests that at a phenotypic level, the metaplastic process begins with the transformation of squamous epithelium in the distal esophagus to cardiac mucosa, which subsequently becomes intestinalized. The homeobox gene Cdx-2 has been shown to be an important transcriptional regulator of embryonic differentiation and maintenance of adult intestinal type epithelium. We hypothesized that Cdx-2 gene expression levels increase with the phenotypic transformation of normal squamous mucosa to the intestinalized columnar mucosa of Barrett's esophagus. Endoscopic biopsies were obtained at the gastroesophageal junction in patients with symptoms of gastroesophageal reflux disease and classified according to histology: normal squamous mucosa (n = 62), cardiac mucosa (n = 19), oxynto-cardiac mucosa (n = 14), and intestinal metaplasia (n = 15). Duodenal biopsies (n = 26) served as the columnar control. After laser capture microdissection and RNA isolation, gene expression levels of Cdx-2 were measured in each tissue type by quantitative reverse transcription polymerase chain reaction. Consistent with its known function, Cdx-2 gene expression levels were highest in duodenal mucosa and nearly absent in squamous epithelium. There was a stepwise increase in Cdx-2 gene expression from cardiac to Barrett's epithelium (P < 0.001). Expression levels of Cdx-2 in cardiac and oxynto-cardiac mucosa were 40-70 times higher and Barrett's mucosa 400 times higher than that found in squamous epithelium. Relative expression of the homeobox gene Cdx-2, known to induce differentiation of intestinal type epithelium, increases in a stepwise fashion during the phenotypic transformation of distal esophageal squamous mucosa to cardiac columnar mucosa and to the intestinalized columnar mucosa of Barrett's esophagus. Therefore, Cdx-2 may be a potential biomarker to detect the early transition to Barrett's esophagus.

Myocardial oxygen consumption can be determined by using carbon 11-acetate (11C-acetate) and positron emission tomography (PET). The aim of this study was to validate planar 11C-acetate scintigraphy in healthy individuals by relating the myocardial clearance rate of dynamic 11C-acetate scintigraphy with the rate-pressure product, which is used as a measure of cardiac work. Also, the optimal curve-fitting procedure of the time-activity curve and the intraobserver and interobserver variation of determining the clearance rates were assessed.Six subjects were studied at rest, and seven subjects were studied during dobutamine stimulation. Imaging was performed with a planar camera equipped with high-energy collimators for 45 minutes after the injection of 185 MBq of 11C-acetate. Myocardial time-activity curves were corrected for decay. During the study, heart rates and blood pressures were measured to calculate the rate-pressure product. Myocardial time-activity curves showed a clear biphasic pattern. Clearance rates were expressed in k values. The best fitting procedure, as assessed by means of the lowest error of k and the best correlation with the rate-pressure product, proved to be a monoexponential fit on the first part of the time-activity curve (kmono). Subjects studied during dobutamine infusion had significantly higher rate-pressure product (15.0 +/- 2.1*10(3) vs 8.6 +/- 1.2*10(3), P.001) and 11C-acetate clearance rates (kmono = 0.0657 +/- 0.0110 vs 0.0313 +/- 0.0056, P.0001) than subjects studied at rest. There was low intraobserver and interobserver variation in determining kmono values. A significant correlation between the rate-pressure product and the monoexponential clearance rate was found (kmono = 5.11*10(-6)*RPP-0.012; r = 0.94, P.001).The estimation of myocardial oxygen consumption is feasible with planar 11C-acetate scintigraphy. Clearance rates and the relation with the rate-pressure product are similar to those reported in PET studies. This technique may be used for the assessment and follow-up of global myocardial metabolic abnormalities, eg, in patients with hypertensive heart disease, cardiomyopathy, myocarditis, and valvular disease.

The aim of this study was to investigate the swelling properties and the biocompatibility of a novel tissue expander material. The self-inflating material is a hydrogel consisting of a modified copolymer of methylmethacrylate and N-vinyl-2-pyrrolidone, which takes up water by osmosis. To increase the swelling volume, the primarily neutral gel material was modified by converting it into an ionized gel. To study the swelling and pressure behavior of the material, the anhydrous gel cylinders were equilibrated in distilled water, saline, and sugar solutions. The biocompatibility was investigated in cell culture. We tested the hydrogel eluate after swelling for cytotoxicity and mutagenicity using the cell lines MRC-5 and P3X63 Ag8 653 (Ag8). Furthermore, particles of the material were added to cell cultures to induce foreign body reactions and to verify its influence on monocyte differentiation. The material has a swelling capacity (Q = maximum swelling volume/anhydrous volume) of 5 to 50 depending on the degree of ionization of the polymer network. In this study, two polymer modifications with a swelling equilibrium of Q = 11.1 and 30 in water were tested. The swelling ratio also depends on concentration and ion content of the equilibration medium. The highest swelling capacity was found in water, the lowest in Ringer's solution. The swelling of the anhydrous material with the swelling capacity of Q = 11.1 fits best the average purpose of material properties for tissue expansion and generates a maximal hydrostatic pressure of approximately 235 mmHg. Effects on cell proliferation were detected only at the highest eluate concentration tested (i.e., eluate: culture medium = 1:1), which was far beyond physiological values, whereas mutagenicity was absent. Monocytes neither migrated nor tightly attached to the hydrogel. They neither phagocytose the material nor did they show any sign of a foreign body reaction, e.g., formation of multinucleated giant cells or monocyte proliferation. In the presence of hydrogel material, the differentiation processes of monocytes to macrophages or dendritic cells, respectively, were found to be undisturbed. From these results, we conclude that there is a high biocompatibility of the expander material, which may be a favorable and interesting candidate for further clinical applications.

Storungen der pharyngooesophagealen Phase des Schluckens, inkl. Zenker-Divertikel, resultieren aus Anderungen der neuromuskularen Vorgange, die beim Kauen, zu Beginn des Schluckens und bei der Beforderung der Speise vom Oropharynx in den cervicalen Oesophagus beteiligt sind. Obwohl eine Reihe von Mechanismen zur Erklarung der Entstehung des Zenker-Divertikels vorgeschlagen wurde – inkl. Storung der Sphincterkoordination, Schlucken gegen einen geschlossenen oberen Oesophagussphincter (OOS), versagende OOS-Relaxation, hypertensiver „spastischer“ OOS –, weisen neuere Untersuchungen darauf hin, das eine veranderte Compliance des cricopharyngealen Segments an der Pathophysiologie des Zenker-Divertikels beteiligt ist. Manometrisch kann eine Relaxation auch dann vorkommen, wenn anatomisch keine Offnung erfolgt ist. Eine fehlende Koordination ist ungewohnlich. Complianceanderungen sind mit einer speziellen cricopharyngealen Manometrie nachweisbar als Verminderung der Sphincteroffnung oder als Erhohung des Boluspassagedrucks. Diese Storungen normalisieren sich nach Diverticulektomie und cricopharyngealer Mytomie.

A structurally intact and competent lower esophageal sphincter in the experimental model shortens and becomes incompetent during gastric distention. The aim of this study was to evaluate postprandial reflux as an indirect measure of this volume-induced sphincter shortening and incompetency. Reflux (pH4) in the 2-hour period following a meal was retrospectively analyzed from the 24-hour esophageal pH recordings of 94 healthy volunteers and 609 symptomatic patients. Forty-six percent of patients had pathologic postprandial reflux (95th percentile of normal). The prevalence was lower in patients with a structurally intact compared to a defective lower esophageal sphincter (32% vs. 58%; P0.001). Pathologic postprandial reflux was greater in patients with abnormal compared to normal findings on 24-hour pH study (76% vs. 21%; P0.001). Patients with a normal 24-hour pH study and postprandial reflux had shorter sphincter lengths (2.33 vs. 2.82 cm; P0.001) and lower pressures (10.78 vs. 14.24 mm Hg; P0.005). A hiatal hernia increased the prevalence of postprandial reflux (P0.001) in all patients (67% vs. 38%) and in the subgroup with a structurally intact sphincter (75% vs. 27%, P0.001). Postprandial reflux is a dynamic indicator of sphincter competency, and increases as the structural sphincter characteristics deteriorate and is augmented by a hiatal hernia.

A new model for studying the initial events of granuloma formation in vitro is presented using heat killed Candida albicans immobilized on the surface of plastic culture wells. Human monocytes were induced to accumulate and to proliferate, forming multinucleated giant cells (MGC) and epitheloid cells within 4 days of culture. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6 were detected in culture supernatants. These monokines, and additionally macrophage colony stimulating factor (M-CSF), were also detected immunocytochemically. The granuloma formation was inhibited by Dexamethasone (Dex), Pentoxifylline (POF), or interferon-gamma (IFN-gamma) in a dose-dependent manner. Antibodies to M-CSF reduced the granuloma formation to a great extent with a striking reduction of monocyte proliferation. Using antibodies to TNF-alpha the authors found a complete inhibition of the granuloma including MGC formation and monocyte proliferation.

SummaryP-selectin is a 140 kD protein found in the α-granules of platelets and the Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on the cell surface and also secreted into plasma. Whether the circulating soluble P-selectin (sP-selectin) originates from platelets, endothelial cells, or both, is not known. We studied the level of sP-selectin in diseases with different platelet counts, with or without evidence of endothelial cell activation. Endothelial cell activation was confirmed by the detection of sE-selectin and EDl-fibronectin. A significant positive correlation between platelet count and sP-selectin concentration was observed in healthy controls, and in patients with thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n = 47; p This study suggests that platelets are the major source of circulating sP-selectin in healthy individuals. Endothelial cell activation is associated with an increased sP-selectin concentration per platelet.

The diagnosis of small fiber neuropathy (SFN) has been recently defined as typical symptoms due to small nerve fiber dysfunction accompanied by reduced intra-epidermal nerve fiber density (IENFD) or abnormal temperature threshold testing (TTT). Guidelines have been published for the assessment of IENFD. However, international guidelines for TTT are lacking. This paper presents a systematic literature review on reported TTT methods and provides recommendations for its future use in studies evaluating patients. A total of 164 papers fulfilled pre-defined requirements and were selected for review. Over 15 types of instruments are currently being used with a variety of methodological approaches for location, stimulus application, and sensation qualities examined. Consensus is needed to standardize the use of TTT as a diagnostic and follow-up tool in patients.

The introduction of high-resolution manometry (HRM) has been a significant advance in esophageal diagnostics. Normative values however are currently based upon a single set of published reference values, and multiple new metrics have been added over the past several years. Our goal was to provide a second set of 'normal-values' and to include all current metrics suggested by the 2012 Chicago classification. Sixty-eight subjects without foregut symptoms or previous surgery (median age 25.5 years, ranging from 20-58 years, 53% female) underwent esophageal motility assessment via an established standardized protocol. Normative thresholds were calculated for esophago-gastric junction (EGJ) characteristics (resting, relaxation, intrabolus pressure, and lengths) as well as for esophageal body strength (contraction amplitudes at multiple levels, distal contractile integral, integrity of peristalsis) and wave propagation (contractile front velocity, distal latency). Overall, our findings where strikingly similar to the previously described metrics derived from 75 control subjects of the Northwestern group. This suggests a high degree of reproducibility of HRM.

Summary The introduction of high-resolution manometry (HRM) has been a significant advance in esophageal diagnostics. Normative values however are currently based upon a single set of published reference values, and multiple new metrics have been added over the past several years. Our goal was to provide a second set of ‘normal-values’ and to include all current metrics suggested by the 2012 Chicago classification. Sixty-eight subjects without foregut symptoms or previous surgery (median age 25.5 years, ranging from 20–58 years, 53% female) underwent esophageal motility assessment via an established standardized protocol. Normative thresholds were calculated for esophago-gastric junction (EGJ) characteristics (resting, relaxation, intrabolus pressure, and lengths) as well as for esophageal body strength (contraction amplitudes at multiple levels, distal contractile integral, integrity of peristalsis) and wave propagation (contractile front velocity, distal latency). Overall, our findings where strikingly similar to the previously described metrics derived from 75 control subjects of the Northwestern group. This suggests a high degree of reproducibility of HRM.

Purpose To address the factors that surgeons use to decide between 2 options for treatment when the evidence is inconclusive. Methods We tested the null hypothesis that the factors surgeons use do not vary by training, demographics, and practice. A total of 337 surgeons rated the importance of 7 factors when deciding between treatment and following the natural history of the disease and 12 factors when deciding between 2 operative treatments using a 5-point Likert scale between "very important" and "very unimportant." Results According to the percentages of statements rated very important or somewhat important, the most popular factors influencing recommendations when evidence is inconclusive between treatment and following the natural course of the illness were "works in my hands," "familiarity with the treatment," and "what my mentor taught me." The most important factors when evidence shows no difference between 2 surgeries were "fewer complications," "quicker recovery," "burns fewer bridges," "works in my hands" and "familiarity with the procedure." Europeans rated "works in my hands" and "cheapest/most resourceful" of significantly greater importance and "what others are doing," "highest reimbursement," and "shorter procedure" of significantly lower importance than surgeons in the United States. Observers with fewer than 10 years in independent practice rated "what my mentor taught me," "what others are doing" and "highest reimbursement" of significantly lower importance compared to observers with 10 or more years in independent practice. Conclusions Surgeons deciding between 2 treatment options, when the evidence is inconclusive, fall back to factors that relate to their perspective and reflect their culture and circumstances, more so than factors related to the patient's perspective, although this may be different for younger surgeons. Clinical relevance Hand surgeons might benefit from consensus fallback preferences when evidence is inconclusive. It is possible that falling back to personal comfort makes us vulnerable to unhelpful commercial and societal influences.

This study reports the CT appearance of changes in the liver due to retractor injury during surgery for upper gastrointestinal malignancy.Ten patients underwent CT examination of the abdomen before (n = 6) and after (n = 10) IV contrast enhancement 2-6 months after surgical resection of malignancy involving the gastric cardia. At each operation, a modified Weinberg's retractor was placed under the lateral segment of the left lobe of the liver to retract it and expose the esophagogastric junction.A sharply marginated, focal, hypodense lesion with no mass effect was shown in the lateral segment of the left lobe of the liver on unenhanced scans in six patients. Irregular enhancement was present after contrast injection in all 10 patients. All patients had a normal preoperative CT of the liver. No patient revealed clinical or laboratory evidence of liver metastasis or abscess.Focal hepatic injury due to intraoperative retraction has a typical location and CT appearance that can aid in recognition of the injury.

The assessment of the esophagogastric junction (EGJ) is the most challenging aspect of clinical esophageal manometry. Although conventional manometric systems can be optimized toward interrogating specific aspects of the EGJ, they are too limited in recording channels and/or fidelity for a comprehensive assessment. The technological advantages inherent in high resolution manometry (HRM) with esophageal pressure topography (EPT) analysis substantially change this equation providing a technology sufficiently robust to dynamically record the contractile activity within the EGJ with both good fidelity and good spatial resolution.This review is an update on our understanding of the application of HRM and EPT to the analysis of EGJ function. With respect to sphincter relaxation, the integrated relaxation pressure (IRP) has proven to be a robust metric in differentiating intact from impaired EGJ relaxation. In the process, it revealed that impaired EGJ relaxation could occur not only in the setting of achalasia but also with other causes of EGJ outflow obstruction including hiatus hernia. The morphological description of the EGJ by EPT has also revealed not only a spectrum of abnormality ranging from an intact sphincter to overt herniation, but also the surprise finding of spontaneous conversion among sphincter configurations, emphasizing its dynamic nature. With respect to barrier function, preliminary data have refocused on the crural diaphragm as a key-differentiating feature between preserved and compromised function. Finally, although the accomplishments summarized above are substantial, much work remains to fully exploit the potential of EPT in the clinical characterization of the EGJ.

The Jamar dynamometer has been widely used in various chronic illnesses and has demonstrated its strength as a potential prognostic indicator. Various stratified normative values have been published using different methodologies, leading to conflicting results. No study used statistical techniques considering the non-Gaussian distribution of the obtained grip strength (GS) values. Jamar GS was assessed in 720 healthy participants, subdivided into seven age decade groups consisting of at least 50 men and 50 women each. Normative values (median and fifth values) were calculated using quantile regressions with restricted cubic spline functions on age. Possible confounding personal factors (hand dominance, length, weight, hobby, and job categorization) were examined. Clinically applicable revised normative values for the Jamar dynamometer, stratified for age and gender, are presented. Hand dominance had no influence. Other personal factors only minimally influenced final values. This study provides revised normative GS values for the Jamar dynamometer.

Studies of the natural history of gastroesophageal reflux disease (GERD) indicate that most patients have limited disease responsive to simple lifestyle, dietary and medical therapy and do not go on to develop complications. Thus the majority of patients manifest a relatively benign form of the disease and do not need antireflux surgery. Indeed, expanding the indications for surgery to include patients with lesser forms of the disease will only serve to lessen the overall rate of successful surgery. However, approximately 25% of the patients with GERD will develop recurrent or progressive disease. It is this population of patients that is best suited to surgical therapy. Although at present there is no reliable method to identify which patients will develop progressive disease, there are several factors that predispose patients to complications and failure of medical therapy. These factors should be identified early in the course of therapy and taken into account when considering therapeutic alternatives.

To investigate the differentiation and activation of monocytes, the combined effects of 1,25-dihydroxyvitamin D3 (D3) and IL-4 on human blood monocytes were examined with respect to expression of MHC class-II antigens, accessory activity, and phagocytic capacity. IL-4 was reported to upregulate the expression of MHC class-II antigens and accessory activity of monocytes. The experiments described here demonstrate that D3 inhibits the expression of all three subtypes of MHC class-II antigens (HLA-DR, -DP and -DQ) as well as the accessory activity of monocytes, both in a dose- and time-dependent manner. However, D3 enhances the immunoglobulin- and complement-dependent phagocytosis by monocytes in a dose- and time-dependent manner. When monocytes are treated with both IL-4 and D3, the effects of D3 are reverted by IL-4, suggesting that IL-4 induces the development of monocytes into accessory cells, whereas D3 stimulates differentiation of monocytes into classical macrophages. These findings provide further evidence for the contention that, depending on defined stimuli, monocytes may develop either into accessory cells or into classical macrophages.

The scope and limitations of the enzymatic resolution of α,α-disubstituted α-amino acid amides by an amino acid amidase from Mycobacterium neoaurum and of the corresponding ethyl esteis with Pig liver estetase (PLE) have been studied. Moderate enantiomeric excesses were obtained with PLE, with only a narrow substrate specificity. Mycobacterium neoaurum on the contrary yields a broad range of S-α,α-disubstituted α-amino acids 1 and the corresponding R-amides 2.

The vagal neural crest adjacent to the first seven somites gives rise to both ganglionic and ectomesenchymal derivatives. Ganglionic derivatives are the neurons and supportive cells of the enteric nervous system (ENS), cardiac, and dorsal root ganglia. Ectomesenchymal derivatives are cells in the cardiac outflow tract and the mesenchymal components of thymus and parathyroids. Ectomesenchymal derivatives are formed by a segment of the vagal neural crest, from the level of the otic vesicle down to the caudal boundary of the third somite, called the cardiac neural crest. We performed neural crest ablations to study regional differences within the avian vagal neural crest with regard to the formation of the ENS. Ablation of the entire vagal neural crest from the mid-otic vesicle down to the seventh somite plus the nodose placode resulted in the absence of ganglia in the midgut (jejunum and ileum) and hindgut (colon). The foregut (esophagus, proventriculus, gizzard, and duodenum) was normally innervated. After ablation of the vagal neural crest adjacent to somites 3-5, ganglia were absent in the hindgut. Ablations of vagal neural crest not including this segment had no effect on the formation of the ENS. We surmise that the innervation of the hindgut in vivo depends specifically on the neural crest adjacent to somites 3-5, whereas innervation of the midgut can be accomplished by all segments within the vagal neural crest. The foregut can also be innervated by a source outside the vagal neural crest. To study intrinsic differences between various vagal neural crest segments regarding ENS formation, we performed chorioallantoic membrane cocultures of segments of quail vagal neural anlage and E4 chicken hindgut. We found that all vagal neural crest segments were able to give rise to enteric ganglia in the hindgut. When the neural crest of somites 6 and 7 was included in the segment, we also found melanocytes in the hindgut, suggesting that this segment is more related to trunk neural crest. Furthermore, we found that the vagal neural anlage from older embryos (> 18 somites) showed an increased potential to form enteric ganglia. This suggests that vagal neural crest cells that have been in prolonged contact with the neural tube in vivo, because of either late emigration or delayed migration, have an increased probability to form enteric ganglia.

Objective: To evaluate 5-year survival of patients with locally advanced esophageal cancer (LAEC) who have undergone multimodality treatment with complete histopathologic response. Background: Patients with LAEC may obtain excellent local-regional response to multimodality therapy. The overall benefit of a complete histopathologic response, when no viable tumor is present in the surgical specimen, is incompletely understood and existing data are limited to single-center studies with relatively few patients. The aim of this multicenter study was to define the outcome of patients with complete histopathologic response after multimodality therapy for LAEC. Methods: The study population included 299 patients (229 male, 70 female; median age: 60 years) with LAEC (cT2N1M0, T3-4N0-1M0; 181 adenocarcinomas, 118 squamous carcinomas) who underwent either neoadjuvant radiochemotherapy (n = 284) or chemotherapy (n = 15) followed by esophagectomy at 6 specialized centers: Europe (3) and United States (3). All patients in the study had stage ypT0N0M0R0 after resection. Results: Esophagectomy with thoracotomy (n = 255) was more frequent than with a transhiatal approach (n = 44). The median number of analyzed lymph nodes in the surgical specimens was 20 (minimum–maximum: 1–77). Thirty-day mortality rate was 2.4% and 90-day mortality rate was 5.7%. Overall 5-year survival rate was 55%. The disease-specific 5-year survival rate was 68%, with a recurrence rate of 23.4% (n = 70; local vs distant recurrence: 3.3% vs 20.1%). Cox regression analysis identified age as the only independent predictor of survival, whereas gender, histology, type of esophagectomy, type of neoadjuvant therapy, and the number of resected lymph nodes had no prognostic impact. Conclusion: Patients with histopathologic complete response at the time of resection of LAEC achieve excellent survival.

The scope and limitations of the enzymatic resolution of α,α-disubstituted α-amino acid amides by an amino acid amidase from Mycobacterium neoaurum and of the corresponding ethyl esteis with Pig liver estetase (PLE) have been studied. Moderate enantiomeric excesses were obtained with PLE, with only a narrow substrate specificity. Mycobacterium neoaurum on the contrary yields a broad range of S-α,α-disubstituted α-amino acids 1 and the corresponding R-amides 2.

In this study, the mechanisms underlying stimulation of T-cell proliferation by human blood dendritic cells (BDC) and their differentiation have been defined with a panel of monoclonal antibodies (MoAbs). It was found that the MoAbs against LFA-1 (CD11a), CD11c, LFA-3 (CD58), ICAM-1 (CD54) or HLA-DR could significantly suppress T-cell proliferation in an allogeneic mixed lymphocyte reaction (P < 0.05), while being unable to inhibit clustering of BDC with T cells. Addition of anti-CD18 or CD45 MoAbs increased the size of clusters after 18 h of culture, but had no effect on the proliferation of T cells (P < 0.05). The suppressive effect of the MoAbs may be viewed not as an inhibition of contact between BDC and T cells, but rather as a blocking of co-stimulatory signals for T-cell activation, which are mediated by interaction of the adhesion molecules. After depleting the BDC preparations of monocytes, we used a double staining in FACS analysis to demonstrate that BDC do not express specific T (CD3), B (CD20 and CD21) and myeloid cell markers (CD11b, CD13 and CD14), but abundant class II antigens. This pattern remained unaltered after 8 days of culture in the presence of 100 U/ml GM-CSF, although a threefold increase of HLA-DQ and ICAM-1 molecules on the cultured cells was observed.

Using the CELLO detector, we have measured cross sections for the processγγ→π + π − in the mass range 0.75–1.9 GeV/c2. A partial wave fit to the data indicates the presence of a sizeableS-wave amplitude with signs of resonant behaviour. Values for the γγ width of thef 2(1270) are given, showing the model-dependence of this quantity. At higher dipion masses, the model of Brodsky and Lepage is found to give an order of magnitude description of the data.

We present measurement of the π0γ*γ, ηγ*γ and η′γ*γ form factors. The π0-form factor is for the first time observed in the space-like region. The transition form factor of the η-meson is determined from its decay modes π+π-π0, π+π-γ and the neutral decay mode γγ. The decay of the η′ is observed in the decay channels ργ, ηπ+π- with η→γγ and in the four charged prong final state stemming from ηπ+π- with the η decaying into π+π-(π0/γ). All form factors agree well with a simple ρ-pole predicted by the vector meson dominance model and also with the QCD inspired Brodsky-Lepage model. © 1991 Springer-Verlag.

We have measured the cross section andQ2-dependence of the reaction γγ→ multihadrons, using the CELLO detector at DESY, for visible final-state masses between 4 and 9 GeV. The data are well fitted by an incoherent sum of Generalised Vector Meson Dominance and Quark Parton Model terms, but at lowQ2 require the addition of a third component which resembles the QPM but is less two-jet-like. With and without this term, the GVDM cross section atQ2=0 is found to be 200±20 and 250±25 nb, respectively.

Differential cross section data of the CELLO experiment on pair production of muons, taus, and heavy quarks ine+e−-annihilation are presented and analysed, together with our data on Bhabha scattering, in terms of compositeness effects characterized by the mass scale Λ. We discuss difficulties in the combination of limits Λ from different experiments. The appropriate parameter to combine different results turns out to be ɛ=±1/Λ2, which is in contrast to Λ Gaussian distributed.

We have studied the ρ0 production rate in the reaction ξξ→3π+3π− in the energy range 1.6≦W γγ≦7.5 GeV with the CELLO detector at PETRA. Our analysis points to a substantial yield of ρ0ρ0π+π− events in particular atW γγ>4.0 GeV. We give cross sections for the ρ02π+2π− and ρ0ρ0π+π− final states and calculate upper limits for the reaction γγ→ρ0ρ0 (1700) →ρ0ρ0π+π−.

We present results of an analysis of the reaction γγ → ωϱ in the two-photon process e + e − → ϵ + e − 2 π + 2 π − π 0 in the untagged mode. The cross section is largely compatible with previous determinations; however, we do not confirm the enhancement claimed at 1.9 GeV. All observed ω's are accompanied by ϱ's in the recoiling ππ spectrum. An angular correlation analysis shows that the data is not dominated by a single spin-parity state, thus establishing severe constraints on qq q q models which predict J P = 2 + .

The intermittency structure of multihadronic e + e − annihilation is analyzed by evaluating the factorial moments F 2 − F 5 in three-dimensional Lorentz invariant phase space as a function of the resolution scale. We interpret our data in the language of fractal objects. It turns out that the fractal dimension depends on the resolution scale in a way that can be attributed to geometrical resolution effects and dynamical effects, such as the π 0 Dalitz decay. The LUND 7.2 hadronization model provides an excellent description of the data. There is no indication of unexplained multiplicity fluctuations in small phase space regions.