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The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (Pfemale≤ 5 × 10−8; Pmale> 5 × 10−8) and 142 were male-specific (Pmale≤ 5 × 10−8; Pfemale> 5 × 10−8); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1. Analyses of gene-by-sex interactions and sexually dimorphic effects identified four genomic regions, showing female-specific associations with diastolic BP or pulse pressure, including the chromosome 13q34-COL4A1/COL4A2locus. Notably, female-specific pulse pressure-associated loci exhibited enriched acetylated histone H3 Lys27 modifications in arterial tissues and a female-specific association with fibromuscular dysplasia, a female-biased vascular disease; colocalization signals included Chr13q34: COL4A1/COL4A2, Chr9p21: CDKN2B-AS1and Chr4q32.1: MAP9regions. Sex-specific and sex-biased polygenic associations of BP traits were associated with multiple cardiovascular traits. These findings suggest potentially clinically significant and BP sex-specific pleiotropic effects on cardiovascular diseases.

Automated process control has been used for a long time. Innovation and information technology achievements have made it possible to use automation in the State governance. Algorithm-based automated decisions are integral part of the concept of e-Government. Automated decisions are becoming more and more prevalent in modern society of the EU. Using automated decisions in public administration is a challenge for Administrative Law, because it has to evolve and keep up with the usage of new technologies, keep the legal balance between the cost-efficiency and operational flexibility of the State in general and at the same time ensure the protection of rights of individuals in each Member State and in the EU as a whole. Estonia is EU Member State and its public sector uses automated decisions but there are no direct legal provisions regarding what automated decision is, what are the conditions for issuing them, what are the safeguards to avoid the violation of rights of individuals etc. The right to issue automated decision is based only on the authorisation norm stipulated in a specific act regulating the field of activity of administrative authority. The Estonian Unemployment Insurance Fund is one of the administrative authorities which issues automated decisions in its field of activity. The aim of this paper is to examine and find out whether the automated decisions used by Estonian Unemployment Insurance Fund comply with the general principles of administrative procedure and the EU rules on data protection but also to identify aspects where legal adjustment is needed and propose legislative amendments. The paper is based on the analysis of relevant scientific books, articles, legal acts, supported by relevant case law and other sources.

Die Kombination aus Positronenemissionstomographie (PET) und Computertomographie (CT) ist bei Kopf-Hals-Tumorpatienten in einigen Indikationen bereits ein etabliertes Verfahren, z. B. zur Primariusdetektion bei Cancer-of-Unknown-Primary(CUP)-Syndrom oder auch nach primärer Radio(chemo)therapie zur Evaluation des Therapieansprechens, insbesondere auch hinsichtlich des Nodalstatus. In manchen Fällen kann bei PET-negativem Befund so eine Salvage-Neck-Dissection vermieden werden. Im Rahmen der Primärdiagnostik bei bekanntem Primarius kann die PET-CT-Bildgebung v. a. zur Evaluation einer Fernmetastasierung eingesetzt werden. In der lokalen Ausdehnungsbestimmung bei Erstdiagnose hat die PET-basierte Bildgebung gemäß aktuellen Leitlinien (noch) keinen Stellenwert. Eine Herausforderung ist aktuell die noch eingeschränkte Kostenerstattung durch die Krankenkassen, welche sich auf bestimmte Indikationen beschränkt, und die noch fehlende flächendeckende Versorgung.

Immuntherapeutische Agenzien haben mittlerweile einen festen Stellenwert in der Therapie verschiedenster Tumorentitäten inklusive der plattenepithelialen Kopf-Hals-Karzinome. Initial wurden sie im palliativen Setting eingesetzt, zunehmend aber auch in kurativer Intention, z. B. als Neoadjuvanz. In der heutigen Forschung geht es u. a. darum zu klären, welche Patienten von der Therapie profitieren und welche Kombinationstherapien erfolgreich sind. Im vorliegenden Artikel werden die relevanten Erkenntnisse der beiden internationalen Krebskongresse 2022 zusammengefasst.

Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P< 5 × 10−8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P= 6.2 × 10−14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P= 1.1 × 10−12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P= 7.2 × 10−4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.

Glycosylation of small molecules can significantly improve their physicochemical and biological properties. Only recently, decisive improvements in the biotechnological production of small-molecule glucosides (SMGs) have resulted in a large number of these compounds now being commercially available. In this study, we have analyzed a number of physical, chemical, and biological parameters of 31 SMGs, including solubility, stability, melting and pyrolysis points, partition coefficient log P, minimum inhibitory concentration against Escherichia coli(MIC), and enzymatic degradability. The properties such as water solubility, pH stability, and MICs of the glycosides were strongly dependent on the structures of the respective aglycones, which is why the SMG clustered according to their aglycones in most cases. Phenolic and furanone glucosides were readily hydrolyzed by saliva and skin microflora, whereas monoterpenol glycosides were poorer substrates for the enzymes involved. The results of this comparative analysis of SMGs provide valuable information for elucidating the biological functions of SMGs and the future technological applications of these useful natural products.

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Recent work in Diachronic Construction Grammar (DCxG) has foregrounded the importance of multiple sources of a particular construction, as well as promoting the idea that constructions are organised as a network of knowledge. The research presented in this article explores the ways in which multiple sources play a role at various stages in constructional change, and the effects of this on the structure of the language network. We aim to show how an account of language structure that focuses on links between constructions may be useful in tracking the various stages in the development of a new construction.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.annemergmed.2010.03.032 Byline: Murat Bas (a), Jens Greve (b), Klaus Stelter (c), Henning Bier (a), Thomas Stark (a), Thomas K. Hoffmann (b), Georg Kojda (d) Abstract: The pathophysiology of angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema most likely resembles that of hereditary angioedema, ie, it is mainly mediated by bradykinin-induced activation of vascular bradykinin B2 receptors. We hypothesize that the bradykinin B2 receptor antagonist icatibant might be an effective therapy for ACEi-induced angioedema. Author Affiliation: (a) Hals-, Nasen- und Ohrenklinik, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany (b) Department of Otorhinolaryngology, University of Essen, Essen, Germany (c) Department of Otorhinolaryngology, University of Munich, Munich, Germany (d) Institute of Pharmacology and Clinical Pharmacology, University of Duesseldorf, Dusseldorf, Germany Article History: Received 27 September 2009; Revised 9 November 2009; Revised 11 December 2009; Revised 15 January 2010; Revised 8 February 2010; Accepted 22 March 2010 Article Note: (footnote) Please see page 279 for the Editor's Capsule Summary of this article., Supervising editor: Richard C. Dart, MD, PhD, Author contributions: MB, JG, and KS defined the research theme. MB, HB, TKH, and GK designed the methods and study design, analyzed the data, interpreted the results, and wrote the article. TS assisted with associated data collection and their interpretation. All authors have contributed to, seen, and approved the article. MB takes responsibility for the paper as a whole., Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement., Publication date: Available online May 5, 2010., Reprints not available from the authors.

Objective: The efficiency of laryngovideostroboscopy (LVS)in detecting premalignancies of the vocal fold and early glottic cancer was determined in a prospective monocentric study. In addition, the recovery rate of the mucosal membrane on the vocal fold after surgical intervention was determined by LVS.Methods: We included 159 patients with a leukoplakia of the vocal folds and 50 healthy controls. Clinicopathological data and LVScharacteristics (amplitude, mucosal wave, nonvibratory segment, glottic closure, phase symmetry, periodicity) at the lesion site were obtained and compared with the histopathological results. LVSparameters were recorded before cordectomy and in a 12-month follow-up interval. Patients who had prior laryngosurgery, radiotherapy, or laryngeal scarring were excluded.Results: Absent or greatly reduced mucosal waves were found in all patients with an invasive carcinoma, in 94% with a severe intraepithelial neoplasia (SIN III), in 38% with a moderate squamous intraepithelial neoplasia (SIN II), in 32% with a mild squamous intraepithelial neoplasia (SIN I), and in 23% with a hyperkeratosis without dysplasia. The sensitivity and specificity of LVSin predicting an invasive carcinoma based on the absence or reduction of mucosal waves was 0.96 and 0.90, respectively. Following surgical intervention, the recovery rate of the mucosal wave and amplitude was 12% in the invasive carcinoma group, 36% in the SIN III group and up to 80% for both these parameters in the SIN I, SIN II, and hyperkeratosis groups.Conclusion: LVSis a valid tool to identify early glottic carcinoma and its high risk premalignancy carcinoma in situ (CIS). Even when there is no definitive differentiation between SIN I and II, the invasive character of a CIS and an invasive glottic carcinoma can be identified. Especially strobosopic signs of abnormal amplitude and/or mucosal waves, particularly phoniatric halt, are an early indication for a CIS or an invasive carcinoma.

Hydrothermal humification of the digestate feedstock created about 37.5 wt% artificial humic acids in both solid and liquid phases.Increasing the alkaline content of the reaction media significantly decreased the aromatic content in the process liquid while increasing the concentration of organic acids and sugars.There was little to no gas production observed in the HTH process at higher alkaline contents, indicating carbon preservation in the liquid and solid phases.Anaerobic processing of the hydrothermal humification (HTH) process liquid resulted in a 158.6% increase in methane production compared to the primary biomass.The organic acid concentrations decreased after the anaerobic fermentation, while the main HTH product, artificial humic acids, remained nearly unchanged.

In der Didaktik wird Kooperation in der Regel eher aus der Perspektive der Lernmotive und des sozialen Lernens als aus der des fachlichen Lernens betrachtet. Anhand videographierter Unterrichtssituationen im Naturwissenschaftsunterricht wird im vorliegenden Beitrag rekonstruiert, welche Vorstellungen und Überzeugungen von Schüler*innen (S*S) sich in Interaktionen gemeinsamer Experimentierphasen und in den beobachteten fachbezogenen, gegenständlichen Tätigkeiten niederschlagen. Eine Interaktionsanalyse auf der Grundlage der Dokumentarischen Methode (DM) erfasst die Schülervorstellungen und den durch die Lehrkraft geschaffenen Orientierungsrahmen sowohl auf der Ebene des konjunktiven wie des kommunikativen Wissens. Am Videomaterial werden insgesamt acht z. T. für den Naturwissenschaftsunterricht spezifische Orientierungen der S*S zur Kooperation und zum gemeinsamen Lernen beim Experimentieren rekonstruiert, die sich im Handeln der S*S dokumentieren. Die Ergebnisse werden vor dem Hintergrund der aus fachdidaktisch-normativer Sicht intendierten Lernziele, Kooperationsanlässe und Handlungsabläufe diskutiert. In der Diskussion wird auf methodologischer Ebene der Erkenntnisgewinn durch die Analyse von Schülervorstellungen mittels der DM herausgestellt.

IMPORTANCE: The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated. OBJECTIVE: To assess the association between consumption of common caffeinated products and the risk of arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses. EXPOSURES: Daily coffee intake and genetic polymorphisms that affect caffeine metabolism. MAIN OUTCOMES AND MEASURES: Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes. RESULTS: A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P &lt; .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P &lt; .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism–related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia. CONCLUSIONS AND RELEVANCE: In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.

Background Numerous techniques for correction of deviated noses have been described. Nevertheless, surgical management is challenging even for experienced rhinosurgeons. Often, a “residual deformity” after functional septorhinoplasty (SRP) due to a deviated pyramid syndrome may remain.Objective Therefore, the purpose of this study was to determine how frequent functional SRP in patients with a deviated nose results in “successful” straightening of the external nose based on standardized angle measurements. Possible influences having a positive or negative effect on the surgical success were identified.Methods Photo documentation of 607 patients with deviated noses (304 women, 303 men, median age 30 years) before and after nasal surgery were retrospectively analyzed using standardized angle measurements. The pre- and postoperative photos of the faces were anthropometrically measured. The median follow-up was 6 months.Results A “straight” deviated nose (I-type) was present in 225 patients (37%), a C-shaped nose (C-type) in 382 patients (63%). More than 75% of the patients presented a facial asymmetry. Based on angle measurements alone, a total of 452 (75%) noses were straightened or postoperatively improved. 155 noses (25%) still showed a biometric deviation. The I- or C-type had no relevant influence on outcome.Conclusion A purely biometric analysis of crooked noses is difficult and its importance is limited due to commonly pre-existing facial asymmetries. The risk of a “residual deviation” after rhinoplasty in patients with deviated noses must not be underestimated. This fact should be addressed as part of the informed consent. In particular, it should be mentioned that the surgical outcome can remain well below the patient’s aesthetic expectations. Not rarely, a revision surgery may be necessary.

Plasma lipids are known heritable risk factors for cardiovascular disease, but increasing evidence also supports shared genetics with diseases of other organ systems. We devised a comprehensive three-phase framework to identify new lipid-associated genes and study the relationships among lipids, genotypes, gene expression and hundreds of complex human diseases from the Electronic Medical Records and Genomics (347 traits) and the UK Biobank (549 traits). Aside from 67 new lipid-associated genes with strong replication, we found evidence for pleiotropic SNPs/genes between lipids and diseases across the phenome. These include discordant pleiotropy in the HLAregion between lipids and multiple sclerosis and putative causal paths between triglycerides and gout, among several others. Our findings give insights into the genetic basis of the relationship between plasma lipids and diseases on a phenome-wide scale and can provide context for future prevention and treatment strategies.

The majority of sediment transported from rivers to the global oceans is moved in suspension as fine particles. Thereby, the transported sediment shapes the physical environment regarding erosive and accumulative processes. Temporal variations in sediment supply and transport lead to unquantified uncertainties in annual load estimates, requiring high‐resolution data sets and a sound understanding of site‐specific catchment characteristics. We investigate the temporal variability of suspended sediment transport in four catchments in Germany with highly different discharge regimes and catchment sizes (<1,000 km2to >100,000 km2). The data set consists of high‐resolution 15‐min turbidity measurements with daily discharge and frequent manual sampling. Utilizing a bootstrap approach based on the 15‐min time series, we assessed the impact of the sampling interval on annual load estimates for less frequent data sets. We use the sediment load exceedance time (Ts80%) as a measure of variability and relate it to uncertainties in annual load estimates. Since low‐frequency data sets rely on sediment rating curves, we performed a sensitivity analysis of the rating parameters a, b, and ε. Our results indicate a negative exponential relationship between Ts80% and uncertainties in annual load estimates. Based on the Ts80%, we can derive the shortest sampling frequency necessary to obtain annual load estimates with an error of <20% over varying discharge regimes. Additionally, Ts80% is linked to rating exponent b, with low b‐values indicating high Ts80%‐values and lower variability, and high b‐values indicating higher variability. On their way to the global oceans, rivers transport sediment. The transported sediment can be divided into two main fractions: fine particles and coarse sediment. Fine particles are distributed over the entire water column and represent most of the mass (sediment load) that is transported by rivers. The sediment load for rivers is not constant and varies significantly over time. Thereby, it is challenging to determine (annual) sediment loads with high accuracy. Through the combination of specialized sensors, which measure continuously, and manual water samples it is possible to reduce uncertainties in the calculation of sediment loads. First, we investigate how much data is necessary to calculate annual sediment loads with as little uncertainty as possible. Second, we investigate how much time is necessary to transport the majority (80%) of the annual sediment load. Third, we investigate how interpolation and extrapolation of small/infrequent data sets affects uncertainties in the calculation of annual sediment loads. Our results help planners and users of sediment transport data to refine (existing) sampling schemes and interpret low‐resolution data sets. Negative exponential relationship between sediment load exceedance time and uncertainties in annual load estimatesOptimal sampling frequency can be derived from uncertainty‐sediment load exceedance time functionSediment rating exponent bis directly linked to sediment load exceedance time Negative exponential relationship between sediment load exceedance time and uncertainties in annual load estimates Optimal sampling frequency can be derived from uncertainty‐sediment load exceedance time function Sediment rating exponent bis directly linked to sediment load exceedance time

Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs.

Friction, pressure, shearing forces and abrasion can produce a variety of skin changes, particularly on the hands, feet, knees, and elbows. These conditions include corns and calluses. Estimates of the incidence of corns and calluses are placed at nearly 160 for each 1,000 people, of which only about 3 require medical attention. Corns are well defined, conical in shape and are produced by a thickening of the outer layer of the skin (stratum corneum); they normally contain a hard inner core. Calluses are more diffuse than corns but also involve thickening of the stratum corneum. Unlike the corn, the callus lacks a hard central core. Both of these conditions may be confused with a plantar wart, which appears on the sole or plantar surface of the foot. While the cause of warts is viral, corns and calluses are often produced by tight shoes and abnormal gaits. Corns and calluses are frequently the result of friction against clothing and protective equipment, particularly poorly fitting shoes. In some cases calluses may be protective. For example, the feet of runners or the hands of ball players may respond to repetitive abrasion by forming calluses. The fundamental treatment is to eliminate the causative pressure or friction. Corrective footwear or changes made to the shoes are the first step in relieving the problem. Soaking the corn or callus, cutting away the upper layers, and applying pharmaceuticals such as silver nitrate or salicylic acid are frequently treatments. In some cases injecting a silicone fluid into the area to act as a cushion is used. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Introduction Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) is defined by intolerance to cyclooxygenase 1 inhibitors, chronic rhinosinusitis with recurrent nasal polyps, and/or intrinsic bronchial asthma. Long-term administration of acetylsalicylic acid (ASA) after desensitization has been used to mitigate these sequelae, but the optimal dose and balancing symptom relief and side effects remain unsettled.Methods Retrospective data analysis of 85 patients with NERD receiving maintenance therapy of 300 mg ASA was followed by questionnaires (our own, not validated and the Sino-Nasal Outcome Test-20). We received responses from 55 patients and examined 30 of them clinically.Results Patients with no ASA-associated side effects were 56.4% (56 of 85 patients) of the cohort. In this study, 60% (33 of 55 patients) continued prophylaxis of 300 mg ASA daily for an average of 34.7 months. Elective surgery was the most frequent cause of discontinuation of ASA (21.8%; 12 of 55 patients). Rhinomanometry values were significantly improved with ASA (P< .05; Wilcoxon), but there was no significant reduction in nasal polyposis or improvement in olfaction at the time of follow-up examination.Conclusions Minor clinical improvements were identified. Side effects were well tolerated by most patients, and no serious sequelae occurred. The indications for long-term ASA therapy in NERD patients remain unsettled.

Flavonoids are products from specialized metabolism that contribute to fruit sensorial (color) and nutritional (antioxidant properties) quality. Here, using a pseudo full-sibling F1progeny previously studied for fruit sensorial quality of cultivated strawberry (Fragaria × ananassa), we explored over two successive years the genetic architecture of flavonoid-related traits using liquid chromatography electrospray ionization tandem mass spectrometry (13 compounds including anthocyanins, flavonols, and flavan-3-ols) and colorimetric assays (anthocyanins, flavonoids, phenolics, and total antioxidant capacity (ferric reducing antioxidant power and Trolox equivalent antioxidant capacity)). Network correlation analysis highlighted the high connectivity of flavonoid compounds within each chemical class and low correlation with colorimetric traits except for anthocyanins. Mapping onto the female and male linkage maps of 152 flavonoid metabolic quantitative trait loci (mQTLs) and of 26 colorimetric QTLs indicated colocalization on few linkage groups of major flavonoid- and taste-related QTLs previously uncovered. These results pave the way for the discovery of genetic variations underlying flavonoid mQTLs and for marker-assisted selection of strawberry varieties with improved sensorial and nutritional quality.

Purpose: Currently no detailed in vivo imaging of the intracranial vessel wall exists. Ex vivo histologic images can provide information about the intracranial aneurysm (IA) wall composition that is useful for the understanding of IA development and rupture risk. For a 3D analysis, the 2D histologic slices must be incorporated in a 3D model which can be used for a spatial evaluation of the IA’s morphology, including analysis of the IA neck. Methods: In 2D images of histologic slices, different wall layers were manually segmented and a 3D model was generated. The nuclei were automatically detected and classified as round or elongated, and a neural network-based wall type classification was performed. The information was combined in a software prototype visualization providing a unique view of the wall characteristics of an IA and allowing interactive exploration. Furthermore, the heterogeneity (as variance of the wall thickness) of the wall was evaluated. Result: A 3D model correctly representing the histologic data was reconstructed. The visualization integrating wall information was perceived as useful by a medical expert. The classification produces a plausible result. Conclusion: The usage of histologic images allows to create a 3D model with new information about the aneurysm wall. The model provides information about the wall thickness, its heterogeneity and, when performed on cadaveric samples, includes information about the transition between IA neck and sac.

Extradiol dioxygenase chemistry is essential for catechol breakdown. The largest natural reservoir of catechols, or 1,2-dihydroxybenzenes, is the plant woody-tissue polymer lignin. Vicinal–oxygen–chelate (VOC) dioxygenases make up the largest group of characterized extradiol dioxygenases, and while most are found as part of catabolic pathways degrading a variety of natural and human-made aromatic rings, L-DOPA (l-3,4-dihydroxyphenylalanine) dioxygenase is a VOC enzyme that participates in the biosynthesis of a natural product. All VOC superfamily members shared conserved elements of catalysis, yet despite decades of investigation of VOC enzymes, the relationships between VOC domain architecture and enzymatic function remain complex and poorly understood. Herein, we present evidence that L-DOPA dioxygenase is the representative member of a new topological class of VOC extradiol dioxygenases. Guided by its evolutionary similarity to glyoxylase enzymes, we performed a careful investigation of the Streptomyces lincolnensisL-DOPA dioxygenase (LmbB1) active site through mutagenesis, kinetic, and pH studies. Our results demonstrate that the L-DOPA dioxygenase reaction depends upon an active-site tyrosine and histidine and is remarkably resilient to mutation, even at the iron-ligating residues. Evaluation of the cleavage reaction as a function of pH supports the role of a histidine in acid–base catalysis. The active-site architecture is functionally consistent with the existing knowledge of VOC extradiol dioxygenase catalysis.

Objectives: This study is set to analyze clinicopathological factors predicting the recovery of unilateral vocal fold paralysis (UVP) in patients after thyroid gland surgery. The quality of voice was additionally assessed in these patients.Methods: The charts and videolaryngostroboscopy (VLS) examinations of 84 consecutive patients with a complete UVP after surgery of the thyroid gland were retrospectively reviewed. Patients were divided into 2 groups: patients who fully recovered from vocal fold paralysis and those who failed to recover after a follow-up of 12 months. The quality of voice was analyzed among other things by determining the Voice Handicap Index (VHI).Results: The UVP fully recovered in 52 of 84 (61.9%) patients. Positive mucosal waves (pMWs) on the paralyzed side, a minimal glottic gap <3 mm seen at the first postoperative VLS, age ≤50 years, and surgery duration ≤120 minutes were associated factors for a complete recovery of nerve function. The voice parameters improved independently from recovery of the paralysis in 90% of the patients.Conclusions: For patients with a poor prognosis of a UVP, early intervention may be beneficial. Thus, predicting factors for a full recovery of vocal fold motion would be a valuable tool. In our cohort, about 60% of recoveries could have been predicted using the above-mentioned parameters. Good quality of voice was independently reached in 90% of the cases.

German electric utilities are taking steps to reduce their carbon dioxide (CO2) emissions. At present, they are spending $500 million annually to lower CO2 emissions through demand- and supply-side management measures. These include a shift to cogeneration plants, the replacement of coal with natural gas, improving the efficiency of fossil fuel-fed turbines and the development of alternative energy resources. The sector, which contributed 270 million t. in 1993, accounts for 30% of the country's CO2 emissions., The Greenhouse effect - the warming of the earth's atmosphere as a result of a man made change in its composition - has become an issue of worldwide debate. Attention [...]

Background: A 34 year old Hispanic male patient presented himself in the emergency room with recurring severe asthma that was unresponsive to b-adrenergic and steroid therapy. Spirometry demonstrated significant airflow obstruction. Objective: We sought to test the ability of low voltage vagus nerve stimulation to induce bronchodilation and improve airflow.Method: A percutaneous electrode was inserted into the patient's neck and positioned to lie in the vicinity of the carotid sheath. Following placement, stimulation was administered and the signal amplitude slowly increased until muscle twitching or discomfort was reported by the patient then reduced to a comfortable level. Results: Within minutes of stimulation, the patient reported reduced dyspnea that was confirmed by spirometry fifteen minutes later ([FEV.sub.1] increased from 2.70 L to 3.18 L). The [FEV.sub.1] remained elevated during the 180min treatment (3.29 [+ or -] 0.04 L) and at 30min post stimulation (3.36 L). The [FEV.sub.1] then decreased to 2.84 L 60min after stimulation ended. Conclusion: This finding indicates that low voltage vagus nerve stimulation could be a useful critical care treatment to alleviate smooth muscle bronchoconstriction and offer a new therapeutic approach to the treatment of acute asthma. Keywords: Asthma | vagus nerve stimulation | bronchoconstriction | bronchodilation | dyspnea | FEV1 | spirometry, Introduction Asthma is a common chronic lung disease characterized by pulmonary inflammation and bronchoconstriction resulting in dyspnea. When severe, asthma can be life threatening and require emergency medical treatment and [...]

Kenosha on the Go By John Doyle and the Kenosha Streetcar Society. Arcadia Publishing, 420 Wando Park Blvd., Mount Pleasant, SC 29464; (888) 313-2665; www.arcadiapublishing. com; 6 1/2 x 9 […]

Large and deep defects resulting from lateral skull base surgery represent a challenge to the head and neck surgeon. Different microvascular free flaps have specific advantages and disadvantages. While the pedicled pectoralis major flap is considered a “work horse,” it comes with a rather short pedicle. The aim of this study was to analyze the vascular anatomy of the pectoralis major flap and assess its suitability for microvascular transfer. Anatomical studies have been performed on 6 Thiel-fixed cadavers allowing a harvest of 12 flaps by the same surgeon. Measurements of the pedicle’s length and vessel diameters have been taken with a ruler and caliper. The mean pedicle length and mean diameters (Ø) of the thoracoacromial artery and concomitant vein were found to be 9.8 cm, Ø 4.2 mm, and Ø 4.9 mm, respectively. These results suggest the potential utility of a free pectoralis major flap with microvascular anastomosis.

Upper airway stenosis (UAS) is a common problem for anesthesiologists in laryngology as well as head and neck surgery, but it may lead to life-threatening situations if it is undetected. This retrospective case series was performed on patients who had UAS and presented with severe dyspnea or encountered difficulties in airway management. To assess the severity of UAS, the degree of stenosis was calculated using computed tomography scans and direct endoscopy. Lung function test was collected, and measured values were extracted as percentage of predicted reference values. Lower and higher grade stenoses were defined by Cotton-Myer classification and median degree of stenosis. Median of detected stenoses was 73% (64%-85%), with 7 of 10 patients classified as Cotton-Myer grade 3. Lung function tests showed typical parameter shifts as known from obstructive pulmonary diseases (OPDs). Furthermore, statistical analyses showed a significant higher value of residual volume (RV)/total lung capacity (TLC) in patients with higher grade stenosis (P< .05), whereas forced expiratory volume in 1 second /vital capacity (FEV1/VC) did not show a significant difference in same subgroups. In conclusion, the elevation of RV/TLC with concomitant normal FEV1/VC in symptomatic patients could be used to demarcate rare UAS from common OPD. Moreover, RV–TLC ratio might be used to distinguish between low- and high-grade UAS. But further epidemiological studies will be necessary to validate these findings.Level of evidence: 4.