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Basal cell carcinoma (BCC) portends a notoriously favorable prognosis in most patients with morbidity limited to localized destruction and recurrence. Metastatic BCC (mBCC) is an unexpected outcome affecting less than 1% of patients with a known primary lesion and predominantly involves regional lymph nodes. Reports of isolated bone involvement and spinal cord compression are rare. In the cases we identified in the literature, patients presented with massive primary lesions on the trunk that had been present for years and that were often still present at the time of diagnosis. Additionally, histology of distant metastatic lesions typically reveals aggressive subtypes. Herein, we report a case of mBCC in a patient with a history of BCC involving the cheek; the lesion was excised more than 10 years ago. He was referred to our institution for acutely worsening back pain and multifocal neurologic deficits. Clinical symptoms and radiographic findings demonstrated isolated bone involvement, with multiple lytic bone lesions and spinal cord compression noted on imaging studies. Biopsy revealed nests of small basaloid cells with peripheral palisading and immunohistochemical staining consistent with the unexpected diagnosis of mBCC, nodular subtype. Our case illustrates that a historically resected primary lesion may cause distant metastasis after a decade and that nonaggressive subtypes can also be implicated. We also provide insight into the potential pathogenesis of this manifestation.

Photosynthetic light harvesting requires efficient energy transfer within dynamic networks of light harvesting complexes embedded within phospholipid membranes. Artificial light harvesting models are valuable tools for understanding the structural features underpinning energy absorption and transfer within chromophore arrays. Most artificial light harvesting complexes are static or in the solution phase, rather than in a two-dimensional fluid environment as in natural photosynthesis. We have developed a method for attaching a protein-based light harvesting model to a supported lipid bilayer (SLB), which provides an extended fluid membrane surface stably associated with a solid substrate. The protein model consisted of the tobacco mosaic viral capsid proteins (TMV) that were gene-doubled to create a tandem dimer (dTMV). Assemblies of dTMV were shown to break the facial symmetry of the double disk to allow for differentiation between the disk faces. Single reactive lysine and cysteine residues were incorporated into opposing surfaces of each monomer of the dTMV assemblies. This allowed for the site-selective attachment of both chromophores for light absorption and a peptide for attachment to the SLB. A cysteine modification strategy using the enzyme tyrosinase was employed for the bioconjugation of a peptide containing a polyhistidine tag for association with SLBs. The dual-modified dTMV complexes showed significant association with SLBs and exhibited mobility on the bilayer. The techniques used herein offer a new method for protein-surface attachment and provide a platform for evaluating excited state energy transfer events in a dynamic, fully synthetic artificial light harvesting system.Significance StatementHere we have constructed a model photosynthetic membrane containing proteins, chromophores, lipids, and aqueous components, all of which can be modified in their composition. This model is based on an asymmetric disk assembly consisting of engineered tandem dimers of the tobacco mosaic viral capsid protein (dTMV). We have developed methods to achieve dye conjugation and attachment of a supported lipid bilayers (SLB) site selectively on distinct protein surfaces. These dye-labeled protein complexes exhibit mobility on the SLB, resulting in a dynamic model of light harvesting membranes using entirely synthetic components. Additionally, this unique asymmetric assembly of TMV and the facile methods for protein functionalization are expected to expand the tunability of model light harvesting systems.

The T cell receptor (TCR) is a complex molecular machine that directs the activation of T cells, allowing the immune system to fight pathogens and cancer cells. Despite decades of investigation, the molecular mechanism of TCR activation is still controversial. One of the leading activation hypotheses is the allosteric model. This model posits that binding of pMHC at the extracellular domain triggers a dynamic change in the transmembrane (TM) domain of the TCR subunits, which leads to signaling at the cytoplasmic side. We sought to test this hypothesis by creating a TM ligand for TCR. Previously we described a method to create a soluble peptide capable of inserting into membranes and bind to the TM domain of the receptor tyrosine kinase EphA2 (Alves et al., eLife 2018). Here we show that the approach is generalizable to complex membrane receptors, by designing a membrane ligand for TCR. We observed that the designed peptide caused a reduction of Lck phosphorylation of TCR at the CD3ζ subunit. As a result, in the presence of this Peptide Inhibitor of TCR (PITCR), the proximal signaling cascade downstream of TCR activation was significantly dampened in T cells. Co-localization and co-immunoprecipitation results in DIBMA native nanodiscs confirmed that PITCR was able to bind to the TCR. We propose that PITCR binds into a crevice present between the TM helices of the CD3ζ and CD3ε(δ) subunits. Our results additionally indicate that PITCR disrupts the allosteric changes in the compactness of the TM bundle that occur upon TCR activation, lending support to the allosteric TCR activation model. The TCR inhibition achieved by PITCR might be useful to treat inflammatory and autoimmune diseases and to prevent organ transplant rejection, as in these conditions aberrant activation of TCR contributes to disease.

Background Ewing’s sarcoma (ES) within the genitourinary tract are relatively unheard of and those within the external male genitalia are even rarer. To our knowledge, this is the first known case of primary ES within the paratesticular region in an adult. Case presentation We present a case of a 24-year-old man with a right sided testicular mass on examination that was initially characterized as an adenomatoid tumor on ultrasound. After the patient was lost to follow up over the course of 9 months, the testicular mass grew significantly and was excised with pathology revealing primary paratesticular Ewing’s sarcoma. This rare case emphasizes the importance of elucidating between the broad differentials of paratesticular masses, including the rare presentation of primary ES and adds a review of the literature of ES in the external male genitalia. Conclusions Rare differentials such as this case should be considered in patients with paratesticular masses. Further diagnostic and management algorithms for extraosseous Ewing Sarcoma, particularly in the adult population, are warranted.

Objective To determine if patients with reported BL allergies have increased odds of developing SSI compared to reported NBL allergic patients. Summary of background data SSI represent a significant risk of morbidity and mortality for patients. Cefazolin-based perioperative antibiotic prophylaxis is the guideline-recommended drug-of-choice for most procedures. Due to over-reporting of BL allergies, many patients may not receive guideline-directed cephalosporin-based prophylaxis, which may result in an increased SSI rate. Methods A single-center retrospective cohort design study was performed. Data was collected on all targeted surgical procedures: cesarean section, vaginal, and abdominal hysterectomy, colon, laminectomy, and spinal fusion surgeries. Results During the study period, 2676 procedures were analyzed with 454 (17%) and 2222 (83%) in reported BL and NBL allergic cohorts, respectively. Significantly more SSI developed in the BL cohort versus NBL cohort (3.1% vs 1.5%, odds ratio 2.015; 95% confidence interval, 1.090-3.724; P = 0.023). Through a multivariate logistic regression, receipt of a NBL antibiotic regimen was the only variable to have a significant effect on SSI rate (adjusted odds ratio, 3.815; 95% confidence interval, 1.142-12.749; P = 0.030). Conclusion Reported BL allergic patients have an increased odds of developing SSI in comparison to NBL allergic patients. The increased risk is likely related to administration of NBL antibiotic regimens in comparison to BL-based regimens. Thorough antibiotic allergy history collection can be a valuable SSI prevention tool to safely increase the proportion of patients receiving BL regimen.

The natural peptide-major histocompatibility complex (pMHC) ligand for T cell receptors (TCRs) is inactive from solution yet capable of activating T cells at single-molecule levels when membrane-associated. This distinctive feature stems from the mechanism of TCR activation, which is thought to involve steric phosphatase exclusion as well as direct mechanical forces. It is possible to defeat this mechanism and activate T cells with solution ligands by cross-linking pMHC or using multivalent antibodies to TCR. However, these widely used strategies activate TCRs through a nonphysiological mechanism and can produce different activation profiles than natural, monovalent, membrane-associated pMHC. Here, we introduce a strictly monovalent anti-TCRβ H57 Fab’ ligand that, when coupled to a supported lipid bilayer via DNA complementation, triggers TCRs and activates nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT) with a similar potency to pMHC in primary murine T cells. Importantly, like monovalent pMHC and unlike bivalent antibodies, monovalent Fab’-DNA triggers TCRs only when physically coupled to the membrane, and only around 100 individual Fab’:TCR interactions are necessary to stimulate early T cell activation.

DWI-Jahrbuch ��� Diakoniewissenschaft in Forschung und Lehre, Bd. 47: (2020/2021): Diakoniewissenschaft in Forschung und Lehre

LAT assembly into a two-dimensional protein condensate is a prominent feature of antigen discrimination by T cells. Here, we use single-molecule imaging techniques to resolve the spatial position and temporal duration of each pMHC:TCR molecular binding event while simultaneously monitoring LAT condensation at the membrane. An individual binding event is sufficient to trigger a LAT condensate, which is self-limiting, and neither its size nor lifetime is correlated with the duration of the originating pMHC:TCR binding event. Only the probability of the LAT condensate forming is related to the pMHC:TCR binding dwell time. LAT condenses abruptly, but after an extended delay from the originating binding event. A LAT mutation that facilitates phosphorylation at the PLC-γ1 recruitment site shortens the delay time to LAT condensation and alters T cell antigen specificity. These results identify a function for the LAT protein condensation phase transition in setting antigen discrimination thresholds in T cells.

About one in three patients with heart failure (HF) have depression. Comorbid HF and depression are associated with poor outcomes and increased health care burden. Clinical guidelines recommend routine depression screening in patients with HF.Depression screening was not being systematically implemented in an outpatient cardiology clinic.To create a sustainable process for a cardiology clinic to screen adults with chronic HF for depression, identify patients who have an elevated depression screening score and initiate an evidence-based treatment algorithm for patients with depressive symptoms.A nurse practitioner (NP)-led process improvement project administered the Patient Health Questionnaire (PHQ-9) tool to patients with HF. The score was reviewed by the NP and, if elevated, addressed with assessment and plan. Compliance was measured by the percentage of patients screened. Clinical impact was measured by percentage of patients with an elevated score with a documented treatment plan.Postimplementation results for four Plan-Do-Study-Act cycles were 38%, 68%, 72%, and 66%, respectively, with a total 63% of patients screened during the entire project. Twenty unique patients (13.2%) had elevated PHQ-9 scores; all had a documented treatment plan.We demonstrated how a screening protocol and an accompanying treatment algorithm can be successfully implemented in an outpatient cardiology clinic. Elements of success included a standardized screening protocol, a clinical support algorithm for treatment/referral, an optimized electronic medical record, and a follow-up system for patients with significant depressive symptoms. Stakeholder engagement throughout the project informed iterative changes and provided direction for sustainability.

Under physiological conditions, peptide-MHC (pMHC) molecules can trigger T-cell receptors (TCRs) as monovalent ligands that are sparsely distributed on the plasma membrane of an antigen-presenting cell. TCR can also be activated by artificial clustering, such as with pMHC tetramers or antibodies; however, these strategies circumvent many of the natural ligand discrimination mechanisms of the T cell and can elicit non-physiological signaling activity. We have recently introduced a synthetic TCR agonist composed of an anti-TCRβ Fab’ antibody fragment covalently bound to a DNA oligonucleotide, which serves as a membrane anchor. This Fab’-DNA ligand efficiently activates TCR as a monomer when membrane-associated and exhibits a potency and activation profile resembling agonist pMHC. In this report, we explore the geometric requirements for effective TCR triggering and cellular activation by Fab’-DNA ligands. We find that T cells are insensitive to the ligand binding epitope on the TCR complex, but that length of the DNA tether is important. Increasing the intermembrane distance spanned by Fab’-DNA:TCR complexes decreases TCR triggering efficiency and T cell activation potency, consistent with the kinetic-segregation model of TCR triggering. These results establish design parameters for construction of synthetic TCR agonists that are able to activate polyclonal T cell populations, such as T cells from a human patient, in a similar manner as the native pMHC ligand.STATEMENT OF SIGNIFICANCEWe report geometric requirements for potent T cell activation by synthetic TCR ligands that mimic biophysical properties of the native pMHC ligand, but have the additional ability to activate polyclonal T cell populations. We find that increasing the space between apposed membranes at TCR binding events decreases ligand potency, but that changing the ligand’s binding epitope on the TCR has essentially no effect. The observed decrease in potency with increased ligand height is attributed to the longer ligands’ attenuated ability to trigger TCR at binding events.

Die Kombination aus Basalinsulin und GLP-1-Rezeptoragonist (RA) wurde 2015 als Option fur die letzte Eskalationsstufe in die Leitlinienempfehlungen zum Typ-2-Diabetes aufgenommen. Die beiden subkutan zu applizierenden Antidiabetika erganzen sich hinsichtlich ihrer jeweils fuhrenden Wirkungen und der Limitationen. Basalinsulin wirkt uberwiegend zwischen den Mahlzeiten bzw. im Nuchternzustand, wahrend GLP-1-RA vor allem den ubermasigen postprandialen Blutzuckeranstieg verhindern. GLP-1-RA haben zudem ein geringes intrinsisches Hypoglykamierisiko, reduzieren das Korpergewicht und beeinflussen kardiovaskulare Risikofaktoren positiv. Fur Basalinsulin sind im Gegensatz zu GLP-1-RA keine Dosisobergrenzen vorgegeben. Allerdings gehen mit dem Start einer Insulintherapie Nachteile hinsichtlich Hypoglykamien und Gewichtszunahme einher. Daher sind Patienten, die mit GLP-1-RA allein ihre Therapieziele erreichen, ohne Insulin besser versorgt. In einer Ubersichtsarbeit werden Studienergebnisse zu Kombinationen aus Basalinsulin und GLP-1-RA versus Vergleichstherapien dargestellt. Die meisten Studien wurden bei mit Basalinsulin vorbehandelten Patienten durchgefuhrt. Die Zugabe von GLP-1-RA war dabei fur gewohnlich mit einer signifikanten Gewichtsabnahme verbunden und fuhrte zudem zu einer im Vergleich zur Basalinsulin-Dosissteigerung zusatzlichen Reduktion des HbA1c-Wertes. Die Zugabe eines kurzwirksamen Insulins zu einer bestehenden Basalinsulintherapie ermoglichte gegenuber der Zugabe eines GLP-1-RA zwar vergleichbare HbA1c-Reduktionen, erhohte jedoch zugleich die Anzahl der Hypoglykamieepisoden und fuhrte zu ungunstigeren Korpergewichtsverlaufen. Die Fixkombination von Insulin degludec und Liraglutid (IDegLira) zeigte eine effektive und relativ gleichmasige Blutzuckerreduktion im 24-Stunden-Zeitraum gegenuber Basalinsulin bzw. GLP-1-RA alleine. Kombinationen aus Basalinsulin und einem GLP-1-RA verbessern insbesondere gegenuber einer Dosiserhohung des Basalinsulins oder der Zugabe eines kurzwirksamen Insulins bei vielen Patienten mit Typ-2-Diabetes die glykamische Einstellung ohne nennenswerte Erhohung des Hypoglykamierisikos und ohne Gewichtszunahme.

The neutron flux and fission power profiles through a fuel bundle and across a fuel element are important aspects of nuclear fuel analysis in multi-scale/multi-physics modelling of Pressurized Heavy Water Reactors (PHWRs) with advanced fuel bundles. Fuel channels in many existing PHWRs are horizontal. With ageing, pressure tubes creep and fuel bundles in these pressure tubes are eccentrically located, which results in an asymmetric coolant flow distribution between the top and bottom of the fuel bundles. The diametral change of the pressure tube due to creep is not constant along the fuel channel; it reaches a maximum in the vicinity of the maximum neutron flux location. The cross-sectional asymmetric positioning of fuel bundles in a crept pressure tube contributes to an asymmetric power distribution within a ring of fuel elements. Modern reactor physics lattice codes (such as WIMS-AECL 1 ) are capable of predicting the details of power distribution from basic principles. Thermalhydraulics subchannel codes (such as ASSERT-PV) use models to describe inhomogeneous power distribution within and across fuel elements (e.g., flux tilt model, different powers in different ring elements, or radial power profiles). In this work, physics and thermalhydraulics codes are applied to quantify the effect of eccentricity of a fuel bundle on power variations across it and within a fuel element, and ultimately on the fuel temperature distribution and fuel centerline temperature, which is one of the indicators of fuel performance under normal operating conditions (NOC). Due to fissioning, Xe and Kr gases are produced, which contribute to the internal gas pressure within an element. The increase in gas pressure may jeopardize the fuel element integrity (sheath rupture). On the other hand, fission gas is produced as a function of neutron flux/power and diffuses to the grain boundaries and fuel-pellet interface as a function of fuel temperature. Therefore, it is important to know the fuel temperatures and distributions within the fuel.

Work in clinical studies is generally more elaborate and therefore more time-consuming in comparison to the clinical routine. The purpose of this study was to systematically investigate the time consumption in the German ophthalmological clinical trial centers.The members of the working group of the German Ophthalmology Society clinical study centers (Arbeitsgemeinschaft DOG Klinische Studienzentren) were asked to fill in three questionnaires about best estimations for the time spent on study-related procedures and administration. Additionally, work sampling was performed for each employee at each study center over a period of 3 weeks.The questionnaires were completed by 9 of the 11 centers. Overall, 5504 working hours were recorded. On an average working day, the time spent for both documentation and administration averaged 4 h each. Operative interventions consumed a significant amount of time (2.8 h), as did ophthalmological examinations (2.5 h) and obtaining informed consent (1.5 h). The recorded time consumption for visual acuity testing, informed consent and documentation was well aligned with the best estimates of the three questionnaires. By contrast, interventions, ophthalmological examinations and biomaterial sample handling were underrated in the best estimations.A considerable amount of time in clinical studies is spent on documentation and administration. From work sampling, ophthalmological examinations and biomaterial sampling turned out to be surprisingly time consuming. This is probably due to preparation and postprocessing tasks. It is important to consider this when calculating the overall costs of a clinical study. In addition, many administrative activities cannot be attributed to specific patients and can therefore not be compensated on the basis of case payments alone. Additional remuneration is required to fully cover the costs in an ophthalmological study center.

Insulin degludec (IDeg) ist ein Basalinsulin mit einem stabilen, flachen Wirkprofil und einer gleichmasigen Verteilung des blutzuckersenkenden Effekts uber 24 Stunden. Mit der arzneimittelrechtlichen Zulassung stellen sich Fragen zur klinisch-praktischen Anwendung bei speziellen Patientengruppen. Pharmakokinetische Daten weisen darauf hin, dass eine generelle Dosisanpassung von IDeg aufgrund einer Nieren- oder Leberfunktionseinschrankung nicht notwendig ist. Jedoch sind als Vorsichtsmasnahme intensivierte Uberwachungen des Blutzuckers und individuelle Anpassungen der Insulindosis erforderlich. Zu alteren Patienten ab 65 Jahren liegen Daten aus dem Phase-3-Studienprogramm zu IDeg vor, da die Studien volljahrige Patienten ohne Alterslimit einschlossen. Eine Metaanalyse der Daten zu Patienten ab 65 Jahren aus sieben Studien ergab die Nicht-Unterlegenheit fur IDeg im Vergleich zu Insulin glargin (IGlar) hinsichtlich der HbA1c-Reduktion. In den funf Studien zum Typ-2-Diabetes waren zudem signifikant weniger bestatigte Hypoglykamien in der IDeg-Gruppe (n = 589) mit 6,19 Ereignissen pro Patientenjahr versus 6,89 Ereignisse pro Patientenjahr in der IGlar-Gruppe (n = 265) zu verzeichnen (geschatzte Ereignisrate 0,76, 95 % CI: 0,61; 0,95, p

Tennis injuries are not uncommon, and efforts have been made to reduce the risk of these injuries. There are a number of different factors that have been shown to influence injury rates of tennis players, in particular patient-related risks. Therefore, the purpose of this study was to investigate the epidemiology of tennis-related injuries. Specifically, we evaluated: 1) demographics; 2) incidence and trends of injuries; and 3) incidence and trends of body parts that were injured.This study utilized the National Electronic Injury Surveillance System (NEISS) database to collect all tennis-related sprains/strains that occurred between January 1, 2010 and December 31, 2016. Patients were stratified into four groups based on their age: 13 years and younger, 14 to 29 years, 30 to 54 years, and 55 years and older. Race was reported as white, black, Hispanic, Asian, Native Hawaiian, American Indian, Multiracial, and not stated. The various types of tennis-related injuries that occurred, and the different body parts that were affected were identified.There were a total of 150,747 tennis-related injuries that occurred during the study period. Thirty-nine percent of all injuries occurred in patients aged 55 years and older, 25% in patients between the ages of 14 and 29 years, 24% occurred between the ages of 30 and 54 years, and 12% occurred in patients aged 13 years and younger. In terms of gender, 56% were men and 44% were women. In terms of race, injuries most commonly occurred in patients who were white (48%). The most common overall injury pattern was sprains/strains, which represented 32% of all reported injuries, followed by fractures (15%) and contusions (11%). The most commonly injured body parts were the ankle (13%), wrist (9.4%), upper-trunk (8.5%), knee (7.8%), and lower-trunk (6.7%). Over the study period, there was a significant decrease in ankle injuries (R2=0.691, p=0.021) and a significant increase in upper-trunk injuries (R2=0.695, p=0.020).The present study provided important insight regarding tennis-related injuries in terms of demographics, injury types, and injury patterns. This information is paramount for the future treatment of all tennis-related injuries and for the implementation of prevention strategies for those injuries which are most prevalent.

Therefore, the purpose of this study was to evaluate the short-term perioperative outcomes of PD patients who underwent total knee arthroplasty (TKA). We specifically evaluated: (1) perioperative surgical and medical complications; (2) lengths of stay (LOS); and (3) total hospital charges. The Nationwide Inpatient Sample was used to identify PD patients who underwent TKA between 2002 and 2013. To control for potential confounders, PD TKA and non-PD TKA patients were propensity score matched (1:3) based on age, sex, ethnicity, Charlson Comorbidity Index, and insurance type. A total of 31,979 PD and 95,596 non-PD TKA patients were included. PD patients had a 44% higher risk of suffering from any complication (OR 1.44; 95% CI 1.35–1.54), a 45% increased risk for any medical complication (OR 1.45; 95% CI 1.36–1.55), and a 9% higher risk for any surgical complication (OR 1.09; 95% CI 0.84–1.41). Compared to the matched cohort, PD patients had a mean LOS that was 6.5% longer (95% CI 5.46–7.54) and mean total hospital charges that were 3.05% higher (95% CI 1.99–4.11). PD patients are more likely to have postoperative complications, longer LOS, and higher costs after TKA than non-PD TKA patients. Since many of these complications can be prevented, a team-based multi-specialty patient optimization is needed. Level III, therapeutic study.

To determine the effort required to provide a service, the United States Medicare uses Relative Value Units (RVUs). Consequently, higher RVUs are assigned to the procedures or services that require more effort, which ultimately means the physician will be properly compensated for the additional effort required. In total ankle arthroplasty (TAA), revision cases usually are more technically challenging and require more effort than primary TAA. Therefore, the purpose of this study was to compare the: 1) RVUs; 2) length-of-surgery; 3) RVU per unit of time between primary and revision total ankle arthroplasty; and 4) the individualized idealized surgeon annual cost difference analysis.We utilized the American College of Surgeons, National Surgical Quality Improvement Program database from 2008 to 2015 to identify patients who underwent either a primary Current Procedural Terminology [CPT]: 27702) or revision (CPT: 27703) TAA. There were a total of 653 patients, 586 of which underwent a primary, and 67 who underwent a revision, TAA. The mean RVUs, length of surgery (in minutes), and RVU per minute, were calculated. Dollar amount per minute, per case, per day, and per year, to find an individualized idealized surgeon annual cost difference, were also calculated. An analysis of variance was used to compare variables between primary and revision TAA. A p-value of less than 0.05 was used to determine statistical significance.The mean RVU was significantly higher in revision versus primary TAA (16.93 vs. 14.41, p=0.001). However, there was no significant difference in the mean lengths of surgery between primary and revision TAA (160 vs. 157 minutes, p=0.613). Additionally, the mean RVU per minute was significantly higher in revision versus primary TAA (0.13 vs. 0.10, p=0.001).Based on the results of this study, it appears that revision TAA cases are appropriately assigned a higher RVU per minute for performing them as they require more effort and are more challenging compared to the primary TAA. Furthermore, not only did the revision cases have lower mean lengths of surgery, but they also maintained a higher RVU per minute. Therefore, orthopaedists can use this information to further help them yield the best potential practice design.

In this study, we expand upon the biogeography of biological soil crusts (BSCs) and provide molecular insights into the microbial community and biochemical dynamics along the vertical BSC column structure, and across a transect of increasing BSC surface coverage in the central Mojave Desert, CA, United States. Next generation sequencing reveals a bacterial community profile that is distinct among BSCs in the southwestern United States. Distribution of major phyla in the BSC topsoils included Cyanobacteria (33 ± 8%), Proteobacteria (26 ± 6%), and Chloroflexi (12 ± 4%), with Phormidium being the numerically dominant genus. Furthermore, BSC subsurfaces contained Proteobacteria (23 ± 5%), Actinobacteria (20 ± 5%), and Chloroflexi (18 ± 3%), with an unidentified genus from Chloroflexi (AKIW781, order) being numerically dominant. Across the transect, changes in distribution at the phylum (p < 0.0439) and genus (p < 0.006) levels, including multiple biochemical and geochemical trends (p < 0.05), positively correlated with increasing BSC surface coverage. This included increases in (a) Chloroflexi abundance, (b) abundance and diversity of Cyanobacteria, (b) OTU-level diversity in the topsoil, (c) OTU-level differentiation between the topsoil and subsurface, (d) intracellular ATP abundances and catalase activities, and (e) enrichments in clay, silt, and varying elements, including S, Mn, Co, As, and Pb, in the BSC topsoils. In sum, these studies suggest that BSCs from regions of differing surface coverage represent early successional stages, which exhibit increasing bacterial diversity, metabolic activities, and capacity to restructure the soil. Further, these trends suggest that BSC successional maturation and colonization across the transect are inhibited by metals/metalloids such as B, Ca, Ti, Mn, Co, Ni, Mo, and Pb.

Hintergrund: Insulin degludec (IDeg) ist ein Basalinsulin mit stabilem, flachem Wirkprofil und gleichmasiger Verteilung des blutzuckersenkenden Effekts uber 24 Stunden. Die terminale Halbwertszeit von IDeg ist mit ca. 25 Stunden im Mittel um den Faktor 2 langer als bei Insulin glargin (IGlar). Dies konnte eine tageszeitlich flexiblere Gabe als bei den bisher verfugbaren Basalinsulinen ermoglichen.

Hintergrund: Die Studie zur Qualitatssicherung in der operativen Therapie der Adipositas (GBSR) untersucht seit 2005 die aktuelle Situation der Adipositas- und metabolischen Chirurgie in Deutschland. Mithilfe einer Onlinedatenbank werden die Daten prospektiv erfasst und retrospektiv analysiert. Die Datenerfassung erfolgt in Zusammenarbeit mit dem Institut fur Qualitatssicherung in der operativen Medizin der Otto-von-Guericke-Universitat Magdeburg. Methode: Im Rahmen der prospektiven freiwilligen Datenerfassung werden die Primaroperationen sowie die Re- und Redo-Eingriffe erfasst. Hierbei werden unter anderem Daten zur Antibiotikaprophylaxe dokumentiert und ausgewertet. Ergebnisse: Seit dem Jahr 2005 ist ein stetiger Anstieg der dokumentierten Primaroperationen zu verzeichnen. Die vorliegende Auswertung zur Antibiotikaprophylaxe bezieht sich auf 12 296 Primareingriffe mit 684 Magenballonimplantationen (BIB), 2950 Magenbandoperationen (Gastric Banding, GB), 5115 Magenbypassoperationen (RYGBP), 120 biliopankreatische Diversionen nach Scopinaro (BPD), 164 Duodenal-Switch-Eingriffe (DS), 3125 Sleeve-Gastrektomien (SG) und 138 weitere Operationen. Insgesamt erfolgte bei 77,3 % der Patienten bei der Primaroperation eine Antibiotikaprophylaxe. Patienten mit Komorbiditaten erhalten signifikant haufiger eine Antibiotikaprophylaxe als Patienten ohne Begleiterkrankungen. Beim Vergleich der Wundinfektionsrate fur das GB und die SG findet sich kein signifikanter Unterschied. Fazit: Die Anzahl Adipositas- und metabolisch-chirurgischer Eingriffe hat in Deutschland zugenommen. Zur Notwendigkeit und Dosierung der Antibiotikaprophylaxe existieren in der Literatur nur Empfehlungen geringer Evidenz. Aufgrund der Daten der Qualitatssicherungsstudie fur operative Therapie in Deutschland ergibt sich die Empfehlung perioperativer Antibiotikagaben in Abhangigkeit der Komorbiditaten, des BMI und der Operationsdauer.

Hintergrund: Empfehlungen und Grenzwerte fur die Prufung des Kontrastsehens existieren bisher nur fur mesopische, nicht aber fur photopische Tests. Wahrend mesopische Tests in der Augenheilkunde sehr verbreitet sind, stehen in der Arbeits- und Betriebsmedizin auch photopische Kontrasttests zur Verfugung. Im Hinblick auf die im Juli 2011 in Kraft getretene Anlage 6 der Fahrerlaubnisverordnung (FeV) wurden die Spezifitat, Sensitivitat und Test-Retest-Reliabilitat vorhandener Testverfahren gepruft sowie praktikable Grenzwerte ermittelt. Methoden: Wir untersuchten multizentrisch Patienten mit Medientrubungen, gesunde Probanden und ein arbeitsmedizinisches Kollektiv. Die verwendeten Tests waren Optovist EU und Binoptometer 4P, sowie die Pelli-Robson-Tafel unter standardisierter Beleuchtung (LUVIS). Alle Tests werden mit dem Mesotest II verglichen. Beim Studiendesign wurden die Empfehlungen der Qualitatssicherungs-Kommission der Deutschen Ophthalmologischen Gesellschaft (DOG) zur Prufung des Kontrastsehens und Grenzwertermittlung beachtet. Ergebnisse: Es konnten 64 Kataraktpatienten (Alter 42–70 Jahre, Median 62 J.), 50 Piloten (Alter 40–69 Jahre, Median 53,5 J.) und 109 Beschaftigte der BVG (Alter 40–59 Jahre, Median 50 J.) rekrutiert werden. Alle Verfahren zeigten eine gute Trennscharfe zwischen der Patientengruppe und den beiden gesunden Kollektiven (AUC 0,86–0,99). Fur beide Einblickgerate ergab sich ein Grenzwert von 15 % Weber-Kontrast, der hiermit fur Untersuchungen nach FeV empfohlen wird. Die Test-Retest-Reliabilitat erwies sich fur alle Tests hoch mit signifikanten Pearson-Korrelationskoeffizienten von 0,77 bis 0,94 und Wiederholbarkeitskoeffizienten zwischen 0,08 und 0,4. Die Standardentfernung der Pelli-Robson-Tafel von 1 m kann fur FeV-Untersuchungen nicht empfohlen werden, vielmehr sind die Ergebnisse bei 3 m Prufdistanz den anderen Verfahren ebenburtig. Fur die Pelli-Robson-Tafel auf 3 m ergibt sich ein vorlaufiger Grenzwert von 1,65. Schlussfolgerungen: Praktikable Grenzwerte im Sinne der gerechten und gleichen Behandlung von Bewerbern liegen hiermit vor. Die Einblickgerate (Binoptometer 4P und Optovist EU) erwiesen sich als geeignet und erreichten erwartungsgemas entsprechend ihrer ahnlichen lichttechnischen Daten den gleichen Grenzwert. In 1 m Distanz ist der Pelli-Robson-Test nicht sensitiv genug. Da die Entfernung von 3 m bei der Pelli-Robson-Tafel nur bei 55 Kataraktpatienten und 10 Piloten gepruft werden konnte, ist die Untersuchung der neuen Distanz bei groseren Kollektiven notwendig.

It is necessary to use the same CAD platform for standardization and efficient design collaboration between project partners. ITER has selected CATIA with ENOVIA as the primary CAD and integration tool. During the preparation of the CAD infrastructure, there were several difficulties with respect to information technology (IT). ITER design is classified as mechanical and plant. The procurement arrangement is divided into three types; functional specification, detailed design, and build to print. Therefore, it is important to prepare the suitable prerequisites according to the design type, and to comply with CAD methodologies to avoid trial and error. This paper presents how to overcome the difficulties and how to perform the CAD activities for ITER Korea procurement packages including important matters on a CAD infrastructure in a big project.

Insulin degludec (IDeg) ist ein neues lang wirksames Basalinsulin. Aufgrund des stabilen, flachen Wirkprofils von IDeg kommt es zu einer gleichmasigen Verteilung des blutzuckersenkenden Effekts uber 24 h, wobei die Wirkung uber 24 h hinausgeht. Fur IDeg wurde ein umfassendes Phase-3-Studienprogramm, in dem mehr als 4200 Patienten mit Typ-1-Diabetes und Typ-2-Diabetes in unterschiedlichen Erkrankungsstadien mit IDeg behandelt wurden, durchgefuhrt. Zur Basis-Bolus-Therapie mit IDeg liegen 2 Phase-3-Studien vor, die im Vergleich zu Insulin glargin ein signifikant geringeres Risiko fur nachtliche Hypoglykamien bei Patienten mit Typ-1- bzw. Typ-2-Diabetes zeigen. Auserdem wurde die Rate der Gesamthypoglykamien bei der Therapie des Typ-2-Diabetes mit IDeg signifikant reduziert. IDeg stellt einen Fortschritt im Bereich der Diabetes-Therapie dar, da im Vergleich zu Insulin glargin bei mindestens gleich guter Effektivitat (HbA 1c -Reduktion) weniger Hypoglykamien (insbesondere nachtliche) auftraten.