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This paper introduces the concept of a 2D range-modulator as a static device for generating spread-out Bragg peaks at very small distances to the target. The 2D range-modulator has some distinct advantages that can be highly useful for different research projects in particle therapy facilities. Most importantly, it creates an instantaneous, quasi-static irradiation field with only one energy, thus decreasing irradiation time tremendously. In addition, it can be manufactured fast and cost efficiently and its SOBP width and shape can be adjusted easily for the specific purpose/experiment. As the modulator is a static element, there is no need for rotation (e.g. like in a modulation wheel) or lateral oscillation and due to the small base structure period it can be positioned close to the target. Two different rapid prototyping manufacturing techniques were utilized. The modulation properties of one polymer and one steel modulator were investigated with both simulations and measurements. For this purpose, a sophisticated water phantom system (WERNER), that can perform fast, completely automated and high resolution dose measurements, was developed. Using WERNER, the dose distribution of a modulator can be verified quickly and reliably, both during experiments, as well as in a time constrained clinical environment. The maximum deviation between the Monte Carlo simulations and dose measurements in the spread-out Bragg peak region was 1.4% and 4% for the polymer and steel modulator respectively. They were able to create spread-out Bragg peaks with a high degree of dose homogeneity , thus validating the whole process chain, from the mathematical optimization and modulator development, to manufacturing, MC simulations and dose measurements. Combining the convenience, flexibility and cost-effectiveness of rapid prototyping with the advantages of highly customizable modulators, that can be adapted for different experiments, the 2D range-modulator is considered a very useful tool for a variety of research objectives. Moreover, we have successfully shown that the manufacturing of 2D modulators with high quality and high degree of homogeneity is possible, paving the way for the further development of the more complex 3D range-modulators, which are considered a viable option for the very fast treatment of moving targets and/or FLASH irradiation.

Diabetes mellitus geht bei rund 80% der Patienten mit Hautveranderungen einher. Diese treten insbesondere bei schlecht eingestellten Blutglukosewerten auf und sind teilweise signifikant mit extrakutanen Diabeteskomplikationen assoziiert.

Psoriasis is a chronic skin disease with a high mental burden. Well-known comorbidities include depression, anxiety, as well as alcohol and tobacco addiction, however, there is barely any evidence on other addictions. The aim of this study was to estimate the prevalence of the six most common addictions among psoriasis patients in Germany and to determine associated clinical factors. Dermatologists working in four dermatological clinics and 32 practices across Germany recruited patients between September 2018 and November 2019. This cross-sectional study contained questionnaires on six addictions, depression, anxiety, and the Dermatology Life Quality Index (DLQI). In addition, scores for the Psoriasis Area and Severity Index (PASI) were obtained by physicians. Overall, 502 patients (43.4% women; mean age: 49.7 ± 14.6 years) were included. Positive addictions were found in 30.3% for daily smoking, 8.6% for alcohol, 1.2% for gambling, 3.8% for internet use, 3.6% for food, and 6.0% for drugs. Younger age was associated with a higher probability of addiction except for alcohol dependency. The PASI was only significantly associated with smoking. Addictions seem to be common among psoriasis patients. Further research should include comprehensive data and control groups, furthermore, standardised screenings and early referrals could represent first steps to improve people-centred healthcare for patients with psoriasis.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. Objectives In this study AD characteristics and its atopic comorbidities are compared in smoking and nonsmoking AD patients. Methods TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included into TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analyzed comparing AD disease characteristics and comorbidities in smokers versus non-smokers. Results Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n=352; 38.8%) and nonsmokers, however lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to nonsmoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than nonsmokers. Total IgE levels were more elevated in smokers and they displayed a younger age at initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to nonsmokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. Conclusions German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Background Limited timely, cost-effective, and regional availability of healthcare data is considered one of the limiting factors for timely analyses in the field of health services research and thus for healthcare delivery to the general population. Thus, Internet search engine analyses are coming into focus in this context. Objectives What contribution can data on the volume of Internet searches for various diseases make to the health care of the German population? Where is the potential and where are the limitations? Methods A review of the current literature and a selective overview of Internet search engine analyses of dermatological, allergological, and infectious diseases published in the last 4 years in Germany were performed. Results By analyzing web search data, temporal developments such as seasonality, months with the highest interest, and geographical differences can be mapped at the national, state (Bundeslander), and city level and major points of interest (e.g., skin cancer of the eye or anal itching) regarding a certain health topic can be identified. In addition, some studies were able to show correlations between search volume and external factors (e.g., temperature, care structure) and to registered cases (e.g., skin cancer, Lyme disease). Conclusion Web search data, given the limitations noted, are able to directly provide spatiotemporal mapping regarding the needs of the Internet-using population. They are particularly useful in situations where traditional health data are limited or unavailable.

Computational science depends on complex, data intensive applications operating on datasets from a variety of scientific instruments. A major challenge is the integration of data into the scientist’s workflow. Recent advances in dynamic, networked cloud resources provide the building blocks to construct reconfiguration, end-to-end infrastructure that can increase scientific productivity, but applications are not taking advantage of them. In our previous work, we introduced DyNamo, that enabled CASA scientists to improve the efficiency of their operations and effortlessly leverage capabilities of the cloud resources available to them that previously remained underutilized. However, the provided workflow automation did not satisfy all the operational requirements of CASA. Custom scripts were still in production to manage workflow triggering, while multiple layer 2 connections would have to be allocated to maintain network QoS requirements. To address these issues, we enhance the DyNamo system with advanced network manipulation mechanisms, end-to-end infrastructure monitoring and ensemble workflow management capabilities. DyNamo’s Virtual Software Defined Exchange (vSDX) capabilities have been extended, enabling link adaptation, flow prioritization and traffic control between endpoints. These new features allow us to enforce network QoS requirements for each workflow ensemble and can lead to more fair network sharing. Additionally, to accommodate CASA’s operational needs we have extended the newly integrated Pegasus Ensemble Manager with event based triggering functionality, that improves managing CASA’s workflow ensembles. The Pegasus Ensemble Manager, apart from managing the workflow ensembles can also create conditions for a more fair resource usage, by employing throttling techniques to reduce compute and network resource contention. We evaluate the effects of the DyNamo’s vSDX policies by using two CASA workflow ensembles competing for network resources, and we show that traffic shaping of the ensembles can lead to a fairer sharing of the network links. Finally, we study how changing the Pegasus Ensemble Manager’s throttling for each of the two workflow ensembles affects their performance while they compete for the same network resources, and we assess if this approach is a viable alternative compared to the vSDX policies.

Background Health care professionals have to judge the appropriateness of treatment in critical care on a daily basis. There is general consensus that critical care interventions should not be performed when they are inappropriate. It is not yet clear which chances of survival are considered necessary or which risk for serious disabilities is acceptable in quantitative terms for different stakeholders to start intensive care treatment. Methods We performed an anonymous online survey in a random sample of 1,052 participants recruited via email invitation and social media. Age, sex, nationality, education, professional involvement in health care, critical care medicine and treatment decisions in critical care medicine as well as personal experience with critical illness were assessed as potential influencing variables. Participants provided their opinion on the necessary chances of survival and the acceptable risk for serious disabilities to start a high-risk or uncomfortable therapy for themselves, relatives or for their patients on a scale of 0–100%. Results Answers ranged from 0 to 100% for all questions. A three-peak pattern with different distributions of the peaks was observed. Sex, education, being a health care professional, being involved in treatment decisions and religiosity influence these opinions. Male respondents and those with a university education would agree that a risky and uncomfortable treatment should be started even with a low chance of survival for themselves, relatives and patients. More respondents would choose a lower necessary chance of survival (0–33% survival) when deciding for patients compared to themselves or relatives to start a risky and uncomfortable treatment. On the other hand, the majority of respondents would accept only a low risk of severe disability for both themselves and their patients. Conclusion No cut-off can be identified for the necessary chances of survival or the acceptable risk of disability to help quantify the “inappropriateness” of critical care treatment. Sex and education are the strongest influencing factors on this opinion. The large variation in personal opinions, depending on demographic and personality variables and education needs to be considered in the communication between health care professionals and patients or surrogates.

Modifications of risk-adjustment systems used to pay health plans in individual health insurance markets typically seek to reduce selection incentives at the individual and group levels by adding variables to the payment formula. Adding variables can be costly and lead to unintended incentives for upcoding or service utilization. While these drawbacks are recognized, they are hard to quantify and difficult to balance against the concrete, measurable improvements in fit that may be achieved by adding variables to the formula. This paper takes a different approach to improving the performance of health plan payment systems. Using the HHS-HHC V0519 model from the Marketplaces as a starting point, we constrain fit at the individual and group level to be as good or better than the current payment model while reducing the number of variables in the model. We introduce three elements in the design of plan payment: reinsurance, constrained regressions, and machine learning methods for variable selection. The fit performance of our alternative formulas with many fewer variables is as good or better than the current HHS-HHC V0519 formula.

Astronomical intensity interferometry enables quantitative measurements of the source geometry by measuring the photon fluxes in individual telescopes and correlating them, rather than correlating the electromagnetic waves’ amplitudes. This simplifies the realization of large telescope baselines and high angular resolutions. Imaging Atmospheric Cherenkov Telescopes (IACTs), intended to detect the optical emission of γ-ray-induced air showers, are excellent candidates to perform intensity correlations in the optical at reasonable signal-to-noise ratios. The detected coherence time is on the scale of (10−12)–(10−15) s – depending on the optical bandwidth of the measurement – which challenges the detection system to work in a stable and accurate way. We developed an intensity interferometry set-up applicable to IACTs, which measures the photocurrents from photomultipliers and correlates them offline, and as such is designed to handle the very large photon rates provided by the telescopes. We present measurements in the lab simulating starlight using a xenon lamp and measured at different degrees of temporal and spatial coherence. Necessary calibration procedures are described with the goal of understanding the measurements quantitatively. Measured coherence times between $5\,$femtoseconds (corresponding signal-to-background ratio 5 × 10−7) and $110\,$femtoseconds (signal-to-background ratio 10−5) are in good agreement with expectations, and so are the noise levels in the correlations, reaching down to 6 × 10−8, after measurements between $30\,$min and $1\,$h.

Post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) are complex and chronic conditions that result in impairment across a number of clinically significant domains. Although the two diagnoses reflect distinct clinical syndromes, they often present comorbidly. Furthermore, the comorbidity of the two diagnoses predicts increased symptomatology and may also result in treatment difficulties that would not arise when treating PTSD without a concurrent BPD diagnosis. The challenging nature of comorbid PTSD and BPD diagnoses has led to an increased interest in integrative approaches to treating both diagnoses together. Recent research has suggested that the integration of prolonged exposure (PE; an evidence-based therapy for PTSD) and dialectical behavior therapy (DBT; an evidence-based therapy for BPD) into one treatment approach (CBT–PE) can offer superior outcomes when compared to treating each diagnosis separately. However, at this time, the literature does not document any such examinations with regards to cognitive processing therapy (CPT), another evidence-based therapy for PTSD. This paper reflects a first step towards exploring the integration of CPT and DBT. In this case, a female-identified military Veteran seeking care at a Veterans Affairs healthcare system was treated utilizing integrated, though sequential, CPT and DBT. The clinical results of this case are discussed, as are the implications for other clinicians considering integrating CPT and DBT.

Die autosomal-dominanten Genodermatosen Morbus Darier und Morbus Hailey-Hailey stellen Dermatologen vor besondere Herausforderungen. Trotz ahnlicher Pathogenese, die in einer verminderten Adhasion suprabasaler Keratinozyten aufgrund defekter ATPasen in epidermalen Calciumkanalen besteht, unterscheiden sich die beiden Erkrankungen in klinischem Bild und Therapiemoglichkeiten erheblich. Der Morbus Darier ist gekennzeichnet durch braunlich-erythematose, keratotische Papeln in seborrhoischen und intertriginosen Arealen, welche zu grosflachigen Lasionen konfluieren konnen. Betroffene mit Morbus Hailey-Hailey entwickeln vornehmlich intertriginos Papulovesikel und Blaschen, aus denen oft erythematose Plaques mit Erosionen und schmerzhaften Fissuren entstehen. Die Lebensqualitat ist aufgrund von Beschwerden (Juckreiz, Brennen, Schmerzen), Korpergeruch und des chronischen Verlaufs deutlich eingeschrankt. Die Therapieoptionen sind immer noch limitiert. Antiseptika und topische Glukokortikoide bilden eine wichtige Saule der Therapie, bei Superinfektionen ist oft eine systemische antiinfektiose Therapie erforderlich. Ablative Masnahmen wie Dermabrasion und CO2 -Laser-Therapie konnen bei intertriginosem Morbus Hailey-Hailey zu langfristiger Erscheinungsfreiheit fuhren, temporare Besserungen wurden auch durch intralasionale Botulinumtoxin-Injektionen erzielt. Unter den Systemtherapeutika liegt beim Morbus Darier die beste Evidenz fur das hierfur zugelassene Acitretin vor. Die Wirksamkeit von Immunsuppressiva und -modulatoren ist uneinheitlich. Niedrig dosiertes Naltrexon zeigt bei Morbus Hailey-Hailey zufriedenstellendere Ergebnisse als bei Morbus Darier. Der vorliegende CME-Artikel fasst das aktuelle Wissen uber die beiden Dermatosen unter Berucksichtigung neuer Entwicklungen zusammen.

Duplications on Chromosome 22q11.2 (22q11.2 dup) are associated with a wide spectrum of physical and neurodevelopmental features. In this chart review, physical, developmental, and behavioral features of 28 patients with 22q11.2 dup (median age = 17.11 years) are reported, and phenotypes of de novo and inherited duplications are compared. Common medical anomalies include nutritional problems (57%), failure to thrive (33%), transient hearing impairment (52%), and congenital heart defects (33%). Developmental, speech-language, and motor delay are common in infancy, while attention (64%), learning (60%), and motor problems (52%) are typically reported at primary school age. Attention-deficit/hyperactivity disorders are diagnosed in 44%. Median full-scale intelligence quotient is in the borderline range (IQ 76), with one-fifth of patients having mild intellectual disability. Longitudinal data in 11 patients, with the first assessment at a median age of 5.2 years and the second assessment at a median age of 8.8 years, indicate that almost two-third of patients have a relative stable cognitive trajectory, whereas one-third show a growing into deficit profile. In patients with de novo duplications, there is a trend of more failure to thrive, while more patients with inherited duplications follow special education.

ObjectiveTo compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs).MethodsPatients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication.ResultsData of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs.ConclusionOur results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.

Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-021-01260-x.

Background The rotator cable (RCa) is an important articular-sided structure of the cuff capsular complex that helps prevent suture pull out during rotator cuff repairs (RCRs) and plays a role in force transmission. Yet, the RCa cannot be located during bursal-sided RCRs. The purpose of this study is to develop a method to locate the RCa in the subacromial space and compare its bursal- and articular-sided dimensions. Methods In 20 fresh-frozen cadaveric specimens, the RCa was found from the articular side, outlined with stitches, and then evaluated from the bursal side using an easily identifiable reference point, the intersection of a line bisecting the supraspinatus (SS) tendon and posterior SS myotendinous junction (MTJ). Four bursal-sided lengths were measured on the SS-bisecting line as well as the RCa’s outside anteroposterior base. For the articular-sided measurements, the rotator cuff capsular complex was detached from bone and optically scanned creating 3D solid models. Using the 3D models, 4 articular-sided lengths were made, including the RCa’s inside and outside anteroposterior base. Results The RCa’s medial arch was located 9.9 ± 5.6 mm from the reference point in 10 intact specimens and 4.1 ± 2.4 mm in 10 torn specimens (P = .007). The RCa’s width was 10.9 ± 2.1 mm, and the distance from the lateral edge of the RCa to the lateral SS insertion was 13.9 ± 4.8 mm. The bursal- and articular-sided outside anteroposterior base measured 48.1 ± 6.4 mm and 49.6 ± 6.5 mm, respectively (P = .268). The average inside anteroposterior base measurement was 37.3 ± 5.9 mm. Discussion The medial arch of the RCa can be reliably located during subacromial arthroscopy using the reference point, analogous to the posterior SS MTJ. The RCa is located 10 mm in intact and 4 mm in torn tendons (P = .007) from the posterior SS MTJ. If the above 6-mm shift in location of the RCa is not taken into consideration during rotator cuff suture placement, it could negatively affect time zero repair strength. The inside anteroposterior base of the RCa measures on average 37 mm; therefore, rotator cuff tears measuring >37 mm are at risk of rupturing part or all of the RCa’s 2 humeral attachments, which if not recognized and addressed could impact postoperative function.

Figurierte Erytheme (FE) sind eine ätiopathophysiologisch heterogene Gruppe von Erkrankungen mit typischen anulären erythematösen Hautveränderungen. Die Diagnose wird in erster Linie aufgrund des klinischen Bildes in Verbindung mit histologischen Befunden gestellt; oft handelt es sich um Ausschlussdiagnosen. Während einige Autoren FE eher als Reaktionsmuster denn als eigenständige klinische Entitäten betrachten, identifizierten andere vier klassische FE: Erythema anulare centrifugum, Erythema gyratum repens, Erythema migrans und Erythema marginatum. Die Differenzialdiagnosen der FE sind vielfältig und oft schwierig. Wir schlagen daher einen diagnostischen Algorithmus für FE vor, der die Diagnosen nach zeitlicher Entwicklung und klinisch-histologischem Phänotyp der verschiedenen Subtypen unterscheidet. Da einige FE in Verbindung mit Malignomen auftreten können, sind umsichtige Ärzte beim Umgang mit diesen Entitäten gefragt.

Ziel der Studie Untersuchung der Rate falsch-positiver SIMS-Resultate bei gesunden Kontrollprobanden und Patienten auserhalb eines forensischen oder rehabilitativen Kontexts. Methodik Neben dem SIMS wurden Variablen uber Fremdratings (PANSS, Hamilton-Skala, MMSE) erfasst. Zielpunkte waren die SIMS- Scores bei Gesunden und einzelnen Patientengruppen und die Zusammenhange zwischen dem SIMS-Score und weiteren Variablen. Ergebnisse Patienten mit einer Schizophrenie (n=30) oder einer Depression (n=32) erzielten im Vergleich mit gesunden Probanden (n=36) haufiger SIMS-Scores >16. Patienten mit einer amnestischen Storung (n=15) schnitten im Vergleich hierzu unauffallig ab. Bei depressiven Patienten mit einem auffalligen SIMS-Resultat zeigte sich sowohl ein signifikanter Zusammenhang mit dem Vorliegen einer weiteren psychiatrischen Diagnose als auch eine Korrelation zwischen den Summenwerten auf der Hamilton-Skala und den Werten auf 2 Subskalen des SIMS (NI, AF). Schlussfolgerung Weitere Validierungsstudien des SIMS sind erforderlich, sollte dieses Instrument auch kunftig in der klinischen Praxis angewendet werden. Die Spezifitat des SIMS weist wahrscheinlich eine Abhangigkeit vom Untersuchungskontext auf. Objective Assessment of the rate of false-positive results of the Structured Inventory of Malingered Symptomatology (SIMS) in healthy controls and authentic patients outside the forensic or rehabilitative context. Methods Beyond the SIMS scores, further variables (PANSS, Hamilton scale, MMSE) were obtained. SIMS scores of healthy individuals were compared with the SIMS scores of the different groups of patients. Additionally, correlations between the SIMS scores and other variables were investigated. Results Patients with psychotic disorders (n=30) or depressive episodes (n=32) more frequently achieved SIMS scores >16 as compared to healthy controls. In comparison, patients with amnestic disorders (n=15) had inconspicuous SIMS scores. Depressed patients with positive SIMS results were significantly more likely to be diagnosed with another psychiatric disorder and the scores of these patients on the Hamilton scale were correlated with positive results on 2 subscales of the SIMS (NI, AF). Conclusion If this instrument is to applied in clinical practice in the future, further validation of the SIMS is necessary. The specificity of the SIMS seems to be context-related.

The discussion about globalization has included the topic of working conditions in international supply chains for many years. In this context, the International Labour Organization (ILO) has focused on Special Economic Zones (SEZ), especially, the so-called Export Processing Zones (EPZ). It is common for developing countries to attract investors by offering special framework conditions, for example, the granting of tax holidays and the repeal of national labour protection laws (in cases where such laws exist). In recognition of this practice, many years ago the ILO developed compliance guidelines on "decent work." In this paper, Juan Carlos Hiba addresses this issue from the ILO's perspective. Marina Jentsch discusses why the topic is still relevant by comparing developments (or lack thereof) in recent years and uses data from the textile industry to illustrate certain points. The World Trade Organization (WTO) and some regional trade agreements increasingly show a trend to restrict the use of subsidies and countervailing measures and provide rules addressing the special treatment of free trade zones and their incentive systems. In the final section, Klaus J. Zink discusses the future of these zones in light of the increasing criticism levelled at the ecological impacts of production and the working and living conditions of workers.Globalisierung und Arbeitsbedingungen in globalen Wertschöpfungsketten sind schon seit vielen Jahren ein Thema – insbesondere auch der International Labour Organization (ILO). Von besonderem Interesse sind in diesem Kontext die sogen. Export Processing Zones (EPZ). In diesen Sonderwirtschaftszonen vor allem in Entwicklungsländern gelten besondere Rahmenbedingungen, die Investoren anziehen sollen. Dazu zählen z. B. Steuerbefreiungen, aber manchmal auch die Negierung von Arbeitsschutzgesetzen. Daher hat die ILO schon vor vielen Jahren die Einhaltung der Bedingungen für „decent work“ gefordert. Juan Carlos Hiba behandelt diese Problematik aus der Perspektive der ILO und deren Initiativen. Marina Jentsch stellt die nach wie vor existierende Relevanz der Thematik durch den Vergleich der (teilweise nicht vorhandenen) Entwicklung in den letzten Jahren dar. Beispielhaft sollen dazu die Daten der Textilindustrie herangezogen werden. Die Regeln der Welthandelsorganisation (WTO) im Hinblick auf das Verbot von Subventionen und Kompensationsmaßnahmen, aber auch regionale Handelsabkommen schränken die Sonderstellung der Freihandelszonen bezüglich ihrer Anreizsysteme ab einer bestimmten Größe immer mehr ein. Darüber hinaus verstärkt sich die Kritik an den Arbeits- und Lebensbedingungen der Mitarbeiter sowie ggf. an den ökologischen Auswirkungen der Produktion. Daher diskutiert Klaus J. Zink die Zukunft dieser Zonen.

Nucleos(t)ide analogues, with a proven record of safety and efficacy, have been the therapy of choice for over a decade for the treatment of chronic hepatitis B. The approval of tenofovir alafenamide (TAF) in 2016 provided an additional treatment option. The aim of this study was to evaluate the characteristics and clinical outcomes of patients treated with TAF in usual clinical practice. Retrospective data from electronic health records was obtained from those enrolled in TARGET-HBV, a longitudinal observational cohort study of patients with chronic hepatitis B managed according to local practice standards at community and academic medical centers throughout the U.S. Of 500 patients enrolled, most were male (66%) and of Asian race (66%) with median age of 55 years. Cirrhosis was evident in 15%. Most patients (82%) had switched to TAF after treatment with other antivirals. The perceived safety profile of TAF was cited as the primary reason for changing therapy (32%). TAF was well tolerated and only 4 patients discontinued therapy due to adverse event during a median duration of TAF dosing of 74 weeks. Among those with paired laboratory data 12–18 months after switching to TAF, biochemical response and HBV DNA suppression was maintained. Most patients had normal renal function which was essentially unchanged throughout follow-up. TAF is frequently utilized in routine clinical practice due to the perception of its improved safety profile. The current study supports the growing body of evidence regarding the safety and effectiveness of TAF. Trial Registration ClinicalTrials.gov identifier: NCT03692897, https://clinicaltrials.gov/ct2/show/NCT03692897 .

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line–derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.

Summary Background and objectives Due to the development of new anti‐psoriatic drugs in combination with improved structures for implementation throughout Germany, the medical care of psoriasis patients has markedly improved. In this study we investigated the real‐life utilization of the health care system and identified reasons for dissatisfaction in affected individuals. Patients and methods This non‐interventional cross‐sectional study was conducted as an anonymous online survey from 12/2018 to 01/2019 in Germany. Participants with a self‐reported physician‐confirmed diagnosis of psoriasis and symptoms answered questions about their disease, its influence on daily life and their medical care. Results 649 participants with a mean age of 42.5 ± 13.7 years and equal gender distribution (male: 50.2 %) were evaluated. 54.1 % received medical treatment at the time of the study, 45.9 % did not. Among the participants with medical care, 59.3 % were only moderately or less satisfied with their treatment. Reasons for dissatisfaction with the medication included lack of efficacy and side effects. Participants without medical treatment specified a physician’s lack of time as a main reason for not seeking medical help. Conclusions Despite the availability of efficient therapeutic options in Germany, many individuals with psoriasis are not satisfied. This under‐treated group was identified as a new target population.

Introduction Chronic urticaria (CU) is an unpredictable disease, with high disease burden and a significant negative impact on quality of life, especially in patients of working age. Many patients are undertreated, and there is poor awareness of strategies to manage patients with CU in the real-world setting. The current study aimed to gain a better understanding of CU from the patients’ perspective, including the body areas most affected by wheals and angioedema, the disease burden and current use of the healthcare system. Methods A nationwide online survey was performed in Germany involving individuals who reported a diagnosis of CU and experienced symptoms within 3 months prior to inclusion. Results This self-report survey included 1037 participants (89.2% female), with a mean ± standard deviation (SD) age of 33.4 ± 11.0 years and a mean ± SD disease duration of 10.0 ± 9.4 years. On average, participants suffered from urticaria symptoms for 3.0 ± 4.3 years before diagnosis. In 73% of participants, symptoms worsened due to external factors, with the majority specifying stress in their personal life or work-related stress as eliciting factors. Within the previous 3 months, 87.4 and 44.1% of participants experienced wheals and angioedema, respectively, at multiple body areas, and most (79.6%) participants had uncontrolled symptoms as measured with the Urticaria Control Test. Despite the high burden of disease, 60.3% of participants stated that they were not currently receiving treatment. The most commonly used therapies to treat CU were oral (72.8%) and non-prescription (43.3%) and prescription (47.3%) topical drugs, with 18.0% of the participants receiving injectable/infused drugs. Conclusion The majority of the participants responding to the survey reported that CU is not sufficiently controlled, thereby severely influencing a highly productive time in their life. The body areas most affected by wheals and angioedema are specified, based on data provided by a large group of affected participants. A greater awareness of disease burden and available treatment options is needed. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00537-5.

Travel can facilitate SARS-CoV-2 introduction. To reduce introduction of SARS-CoV-2 infections, the state of Alaska implemented a program on June 6, 2020, for arriving air, sea, and road travelers that required either molecular testing for SARS-CoV-2, the virus that causes COVID-19, or a 14-day self-quarantine after arrival. The Alaska Department of Health and Social Services (DHSS) used weekly standardized reports submitted by 10 participating Alaska airports to evaluate air traveler choices to undergo testing or self-quarantine, traveler test results, and airport personnel experiences while implementing the program. Among 386,435 air travelers who arrived in Alaska during June 6-November 14, 2020, a total of 184,438 (48%) chose to be tested within 72 hours before arrival, 111,370 (29%) chose to be tested on arrival, and 39,685 (10%) chose to self-quarantine without testing after arrival. An additional 15,112 persons received testing at airport testing sites; these were primarily travelers obtaining a second test 7-14 days after arrival, per state guidance. Of the 126,482 airport tests performed in Alaska, 951 (0.8%) results were positive, or one per 406 arriving travelers. Airport testing program administrators reported that clear communication, preparation, and organization were vital for operational success; challenges included managing travelers' expectations and ensuring that sufficient personnel and physical space were available to conduct testing. Expected mitigation measures such as vaccination, physical distancing, mask wearing, and avoidance of gatherings after arrival might also help limit postarrival transmission. Posttravel self-quarantine and testing programs might reduce travel-associated SARS-CoV-2 transmission and importation, even without enforcement. Traveler education and community and industry partnerships might help ensure success.

Objective To measure COVID‐19 vaccine acceptance and related factors to undercover nurses' concerns and fears. Design A cross‐sectional study. Sample The study included 639 nurses; 83% were women and 80% under 50 years. Measurement A self‐administered questionnaire was used. It included demographic characteristics, COVID‐19‐related fears and concerns, COVID‐19 vaccine perceived benefits, and intention toward getting the vaccine. Results Forty percent of the nurses planned to get the vaccine when available, 41% would take it later when adequate protection and safety were presented, and 18% would never take it. Significant factors associated with vaccination intention were as follows: age (adjusted OR 1.42, 95% CI: 1.02–1.99); lack of knowledge about the vaccine (adjusted OR 2.6, 95% CI 1.81–3.8); concern about long‐term side effects (adjusted OR 2.0, 95% CI 1.4–2.9); fear of injection (adjusted OR 1.5, 95% CI 1.04–2.13); natural immunity preference (adjusted OR 5.8, 95% CI 4.5–8.3); media misrepresentation (adjusted OR 1.7, 95% CI 1.2–2.4); and getting COVID‐19 from the vaccine (adjusted OR 1.5, 95% CI 1.1–2.1). Conclusion COVID‐19 vaccine safety and side‐effects concerns impact nurses' intentions to accept the vaccine and may result in low acceptance rates. Urgent action is needed to address these fears and raise confidence, as nurses' vaccine‐related decisions can affect the public's vaccine acceptance.

The perpetual burden of tuberculosis (TB) keeps drawing the focus of research on this disease. Among other risk factors (e.g., poor living conditions, malnutrition, smoking, HIV infection, etc.), being in close contact with a TB infected person requires special attention. For a better understanding of the disease, paleopathological investigations concerning TB have been carried out with various techniques for a long a time; nevertheless, analysis of incidence among family members is hardly possible in past populations. An exceptional group of naturally mummified individuals, the collection of the Vác mummies (Hungary, 18th century CE), is known about the large TB incidence rate, which has been revealed by aDNA analysis. Besides the high rate of TB infection, another interesting aspect of the collection is that in some cases, the family connections could be reconstructed. In this paper, we present the mycocerosic acid profiles gained by HPLC-HESI-MS measurements of two Vác mummies, who were mother and daughter according to the personal records. Earlier metagenomic analysis already revealed mixed M. tuberculosis infection with the same bacterial strains in both individuals; moreover, the same bacterial strains were recorded in both cases.

BACKGROUND The annual conference of the European Academy of Dermatology and Venereology is one the largest dermatology conferences worldwide. OBJECTIVES Network analysis can be used for in-depth insight into trending topics and underlying trends at the congress. MATERIALS & METHODS Network analysis was employed to assess the entirety of the submitted abstracts to the congress in 2019. The data were processed, analysed, and visualised using easy-to-understand network graphs. Topics were then compared to their respective global burden (Disease Adjusted Life Years [DALYs]) and the number of respective publications on PubMed in the year 2018. RESULTS Overall, 1,280 lecture titles and 1,941 poster titles were included in the final analysis. The most frequently used terms were "patients" (n = 473), "treatment" (n = 301), and "psoriasis" (n = 335). Relative to DALYs, "psoriasis" (+21.9%) among others, was rather over-represented, while "fungal skin diseases" (-7.6%) and "urticaria" (-6.4%) were under-represented. Compared to the relative number of PubMed publications in 2018, "psoriasis" (+20.3%), "acne" (+7.9%), and "alopecia" (+3.1%) were over-represented, while "melanoma" (-22.5%), "dermatitis" (-4.2%) and "pruritus" (-3.4%) were rather under-represented. CONCLUSION The network analysis showed that the congress was a patient and therapy-centred event. An explanation for the particular focus on chronic inflammatory skin diseases and melanoma would be the introduction of new therapies at the congress. To delineate trends over time, a longitudinal network analysis including several congresses should be conducted and could be used to determine additional topics to be included in future events.

Maintaining pace with ongoing changes due to digitalization is challenging for manufacturing companies. For successful implementation of digitalization, manufacturing companies must consider their existing technical systems, organizational structures, and processes, as well as social aspects. With the support of a maturity model, a company-specific digitalization level can be evaluated to provide manufacturing companies with an initial insight into their particular status quo; this can serve as a starting point for future optimization and digitalization projects. Furthermore, the results of such an analysis allow objective comparison of different areas within the company and with competitors. In this paper, the “Integrierte Arbeitssystemgestaltung in digitalisierten Produktionsunternehmen” (InAsPro) maturity model is presented, which considers the Development, Production, and Assembly product lifecycle phases, as well as Aftersales, and assesses their digitalization level focusing on the four dimensions of Technology, Organization, Social Issues, and Corporate Strategy. The maturity model’s rating scale distinguishes between four maturity levels. The results given by the InAsPro maturity model for an entire company are presented, along with those for each product lifecycle phase. Extensive descriptions for each specific maturity level are also provided.

Real-world evidence (RWE), derived from data from “real-world” clinical practice and medical product utilization, is an increasingly important source of evidence that holds great potential to incre...

A manufacturing system collects big and heterogeneous data for tasks such as product quality modeling and data-driven decision-making. However, as the size of data grows, timely and effective data utilization becomes challenging. We propose an unsupervised data filtering method to reduce manufacturing big data sets with multi-variate continuous variables into informative small data sets. Furthermore, to determine the appropriate proportion of data to be filtered, we propose a filtering information criterion (FIC) to balance the tradeoff between the filtered data size and the information preserved. The case study of a babycare manufacturing and a simulation study have shown the effectiveness of the proposed method.

The coronavirus disease 2019 pandemic may require rationing of various medical resources if demand exceeds supply. Theoretical frameworks for resource allocation have provided much needed ethical guidance, but hospitals still need to address objective practicalities and legal vetting to operationalize scarce resource allocation schemata. To develop operational scarce resource allocation processes for public health catastrophes, including the coronavirus disease 2019 pandemic, five health systems in Maryland formed a consortium-with diverse expertise and representation-representing more than half of all hospitals in the state. Our efforts built on a prior statewide community engagement process that determined the values and moral reference points of citizens and health-care professionals regarding the allocation of ventilators during a public health catastrophe. Through a partnership of health systems, we developed a scarce resource allocation framework informed by citizens' values and by general expert consensus. Allocation schema for mechanical ventilators, ICU resources, blood components, novel therapeutics, extracorporeal membrane oxygenation, and renal replacement therapies were developed. Creating operational algorithms for each resource posed unique challenges; each resource's varying nature and underlying data on benefit prevented any single algorithm from being universally applicable. The development of scarce resource allocation processes must be iterative, legally vetted, and tested. We offer our processes to assist other regions that may be faced with the challenge of rationing health-care resources during public health catastrophes.

Altres ajuts: European Academy of Dermatology and Venereology (EADV, No. 2016-012 to MP). Background: Itch is a common symptom in the general population. Affected individuals often do not seek medical consultation and rely on Internet searches to obtain information regarding their itch. Objectives: The aim of this study was to attain insights into common concerns of the general population regarding itch can by analysing itch-related Internet search behaviour. Methods: Google AdWords Keyword Planner was used to assess search volumes for itch-related terms in 15 European countries between September 2014 and August 2018. All identified keywords were qualitatively categorized. Itch-related terms were descriptively analysed and are shown as number of searches/100 000 inhabitants. Results: The search volume for the keyword 'itch' per 100 000 inhabitants was highest in Northern Europe, followed by Eastern, Central and Southern Europe. In 4/15 countries, itch was searched for more often in the autumn/winter months compared to in the spring/summer months. Most itch-related terms were related to dermatological conditions such as inflammatory skin diseases (e.g. psoriasis, atopic dermatitis), allergic or immunologic conditions (e.g. urticaria), and infectious diseases or infestations (e.g. scabies). In terms of body location, genitoanal itch dominated the searches. Symptoms and signs related to itch, possible non-dermatological aetiologies, and treatment options were also among the most searched terms. Conclusions: These analyses provided for the first time insights into the search behaviour patterns related to itch across Europe. People from Northern and Eastern Europe are more likely to seek online information regarding itch. Causes for the itch, especially dermatological conditions, and genitoanal itch are the most important concerns for Internet users. This unconventional and inexpensive method identifies medical needs of people beyond the medical setting, including people who do not seek medical consultation. Accordingly, the data could be used to guide public health interventions and manage respective inhabitants' medical needs.

Recently, magnetic tunnel junctions (MTJs) with superparamagnetic free layers (sMTJs) have been proposed as key components in probabilistic bits (p-bits). However, the average fluctuation rates of sMTJs are very sensitive to slight variations in the device dimensions, which creates a major obstacle to their realization in large-scale networks. One possible solution is to implement dual-biasing on p-bits to offset the effects of variations through onboard corrections. In our previous work, we demonstrated that dual-biasing has the unique capability of separate control over the high- and low-state dwell times, which adds an extra degree of tunability in the signals generated. However, these studies investigated dual-biasing on thermally stable MTJs; therefore, the maximum switching rates were lower than the gigahertz rates desired for sMTJ-based p-bit circuits. While dual-biasing on sMTJs rather than thermally stable MTJs would improve the switching rates, some of the flexibility and robustness of dual-biasing may be sacrificed due to the sensitivity of sMTJs. In this letter, we applied the dual-biasing method on 10 MTJs with varying thermal stability factors to test if sMTJs can achieve the same degree of separation between high- and low-state dwell-time tunability as thermally stable MTJs. Our results show that two degrees of tunability was achieved on all MTJs tested, thus demonstrating that dual-biased p-bits can achieve switching rates equal to or greater than single-biased sMTJs.