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Caroline Beutner,1 Susann Forkel,1 Sidhi Gupta,1 Thomas Fuchs,1 Michael P Schön,1,2 Johannes Geier,2,3 Timo Buhl1,2 1Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany; 2Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen, Göttingen, Germany; 3Information Network of Departments of Dermatology (IVDK), University of Göttingen, Göttingen, GermanyCorrespondence: Caroline BeutnerDepartment of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Georg August University, Robert Koch-Str. 40, Göttingen D-37075, GermanyTel +495513966402Email caroline.beutner@med.uni-goettingen.deIntroduction: The prevalence of airway allergies in Europe has increased from 23% to 31% in recent years. Polysensitization is associated with the development and severity of relevant allergies, particularly allergic asthma.Objective: We investigated age- and sex-dependent monosensitization and polysensitization profiles as well as patterns of sensitization using skin prick test (SPT) reactivity to the most common aeroallergens.Patients and Methods: From 1998 to 2017, SPTs were retrospectively analyzed in 2886 symptomatic patients, referred to the University Medical Center Göttingen, located in central Germany. The major aeroallergen groups early flowering tree pollen, grass pollen, and house dust mites were evaluated in this study. Wheal diameters ≥ 2 mm were considered positive during the entire study period.Results: Polysensitization to the most common aeroallergen groups increased significantly over 20 years. Boys and young men displayed the most remarkable rise in total sensitization rates in our study group over time.Discussion: Our patient-based study demonstrates a continuing increase in polysensitization rates over the last 20 years, with boys and young men being most frequently affected. Our data—without being a population-based study—suggest a scenario with climbing rates of allergic rhinitis and asthma.Keywords: aeroallergens, polysensitization, sensitization pattern, skin prick test

There is widespread concern regarding the safety of silver-mercury amalgam dental restorations, yet little evidence to support their harm or safety. We examined whether mercury dental amalgams are adversely associated with cognitive functioning in a cross-sectional sample of healthy working adults. We studied 550 adults, 30-49 years of age, who were not occupationally exposed to mercury. Participants were representative of employees at a major urban medical center. Each participant underwent a neuropsychologic test battery, a structured questionnaire, a modified dental examination, and collection of blood and urine samples. Mercury exposure was assessed using a) urinary mercury concentration (UHg); b) the total number of amalgam surfaces; and c) the number of occlusal amalgam surfaces. Linear regression analysis was used to estimate associations between each marker of mercury exposure and each neuropsychologic test, adjusting for potential confounding variables. Exposure levels were relatively low. The mean UHg was 1.7 microg/g creatinine (range, 0.09-17.8); the mean total number of amalgam surfaces was 10.6 (range, 0-46) and the mean number of occlusal amalgam surfaces was 6.1 (range, 0-19). No measure of exposure was significantly associated with the scores on any neuropsychologic test in analyses that adjusted for the sampling design and other covariates. In a sample of healthy working adults, mercury exposure derived from dental amalgam restorations was not associated with any detectable deficits in cognitive or fine motor functioning. [ABSTRACT FROM AUTHOR]

Healthcare workers often suffer from occupational skin disease frequently caused by allergic sensitization. Therefore the patch-test results and important patient history items of 31,849 patients recorded between 1992 and 1995 in the 24 allergy departments participating in the Information Network of Departments of Dermatology (IVDK) were evaluated. Significantly increased sensitization rates common to the healthcare sector as a whole were found for the vaccine preservative thiomersal (12.6% vs. 4.9%), the surface and instrument disinfectants glutardialdehyde (9.9% vs. 2.6%), formaldehyde (3.6% vs. 2.1%) and glyoxal (4.2% vs. 1.4%), and for the compounds of the thiuram mix (6.7% vs. 2.6%) present in protective gloves. Formaldehyde seems to lose its importance, but glyoxal must be added to the list of occupational allergens in the healthcare sector. In addition, occupation-specific sensitization was observed, with fragrances in massage therapists (16.1% vs. 10.6%) and nurses (13.8% vs. 11.4%), as well as with methacrylates in dental technicians. The often assumed importance of drugs as type-IV allergens was not confirmed, at least in terms of quantity. The identification of subgroups of increased risk and of occupation- specific allergens could be the basis of targeted preventive action in the healthcare sector. [ABSTRACT FROM AUTHOR]

Background: Sublingual varices (SV) and their predictive potential for other clinical parameters is a much studied topic in oral medicine. SVs have been well studied as predictive markers for many common diseases such as arterial hypertension, cardiovascular disease, smoking, type 2 diabetes mellitus and age. Despite many prevalence studies, it is still unclear how the reliability of SV inspection affects its predictive power. The aim of this study was to quantify the inspection reliability of SV., Methods: In a diagnostic study, the clinical inspection of 78 patients by 23 clinicians was examined for the diagnosis of SV. Digital images of the underside of the tongue were taken from each patient. The physicians were then asked to rate them for the presence of sublingual varices (0/1) in an online inspection experiment. Statistical analysis for inter-item and inter-rater reliability was performed in a τ-equivalent measurement model with Cronbach's [Formula: see text] and Fleiss κ., Results: The interrater reliability for sublingual varices was relatively low with κ = 0.397. The internal consistency of image findings for SV was relatively high with α≈ 0.937. This shows that although SV inspection is possible in principle, it has a low reliability R. This means that the inspection finding (0/1) of individual images often cannot be reproduced stably. Therefore, SV inspection is a difficult task of clinical investigation. The reliability R of SV inspection also limits the maximum linear correlation [Formula: see text] of SV with an arbitrary other parameter Y. The reliability of SV inspection R = 0.847 limits the maximum correlation to [Formula: see text] (SV, Y) = 0,920-a 100% correlation was a priori not achievable in our sample. To overcome the problem of low reliability in SV inspection, we propose the RA (relative area) score as a continuous classification system for SV, which normalises the area of visible sublingual veins to the square of the length of the tongue, providing a dimensionless measure of SV., Conclusions: The reliability of the SV inspection is relatively low. This limits the maximum possible correlation of SV with other (clinical) parameters. SV inspection reliability is an important indicator for the quality of SV as a predictive marker. This should be taken into account when interpreting previous studies on SV and has implications for future studies. The RA score could help to objectify the SV examination and thus increase its reliability., (© 2023. The Author(s).)

Objectives: Patients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years)., Design: Retrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status., Setting: Data were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe)., Participants: KPNC health plan members with moderate or severe AD (2007-2018)., Primary and Secondary Outcome Measures: Malignancy IRs and 95% CIs per 1000 person-years were calculated., Results: 7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma., Conclusions: This study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations., Competing Interests: Competing interests: MMH, FX, CPQ and SBS are full-time employees of KPNC and received payment from Pfizer Inc. for the study used in this publication. JG is a former employee and a shareholder of Pfizer Inc. ARL is an employee and shareholder of Pfizer Inc. MMA received royalty payments from UptoDate for publications related to skin cancer and also received grant funding to her institution from Pfizer Inc. for the study described in this publication., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1-3.2), 2.0 (1.5-2.5), 1.6 (1.2-2.1), and 0.7 (0.5-1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians., Competing Interests: Monique M. Hedderson, Fei Xu, Charles P. Quesenberry, and Sneha Sridhar are full-time employees of Kaiser Permanente Northern California and received grant funding from Pfizer Inc. for the study discussed in this publication. Jamie Geier is a former employee of and shareholder of Pfizer Inc. Adina R. Lemeshow is an employee and shareholder of Pfizer Inc. Maryam M. Asgari received royalty payments from UptoDate for publications related to skin cancer and received grant funding to her institution from Pfizer Inc. for the study described in this publication., (Copyright: © 2022 Hedderson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Iron plays an important role in mammalian physiological processes. It is a critical component for the function of many proteins, including enzymes that require heme and iron-sulfur clusters. However, excess iron is also detrimental because of its ability to catalyze the formation of reactive oxygen species. As a result, cellular and systemic iron levels are tightly regulated to prevent oxidative damage. Iron deficiency can lead to a number of pathological conditions, the most prominent being anemia. Iron deficiency should be corrected to improve adult patients' symptoms and to facilitate normal growth during fetal development and childhood. However, inappropriate use of intravenous iron in chronic conditions, such as cancer and heart failure, in the absence of clear iron deficiency can lead to unwanted side effects. Thus, this form of therapy should be reserved for certain patients who cannot tolerate oral iron and need rapid iron replenishment. Here, we will review cellular and systemic iron homeostasis and will discuss complications of iron deficiency.

Chronic loss of Augmenter of Liver Regeneration (ALR) results in mitochondrial myopathy with cataracts; however, the mechanism for this disorder remains unclear. Here, we demonstrate that loss of ALR, a principal component of the MIA40/ALR protein import pathway, results in impaired cytosolic Fe/S cluster biogenesis in mammalian cells. Mechanistically, MIA40/ALR facilitates the mitochondrial import of ATP-binding cassette (ABC)-B8, an inner mitochondrial membrane protein required for cytoplasmic Fe/S cluster maturation, through physical interaction with ABCB8. Downregulation of ALR impairs mitochondrial ABCB8 import, reduces cytoplasmic Fe/S cluster maturation, and increases cellular iron through the iron regulatory protein-iron response element system. Our finding thus provides a mechanistic link between MIA40/ALR import machinery and cytosolic Fe/S cluster maturation through the mitochondrial import of ABCB8, and offers a potential explanation for the pathology seen in patients with ALR mutations., Competing Interests: HC, JS, XJ, GS, TS, JG, KS No competing interests declared, HA Reviewing editor, eLife, (© 2021, Chang et al.)

Objective: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry., Methods: IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively., Results: For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively., Conclusion: In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Fish, crustaceans, and mollusks are among the most potent allergenic foods of animal origin and are thus important triggers of work-related immediate-food allergies. In Germany, work-related seafood allergies are of great importance in the fishing and processing industries as well as in the areas of food preparation, food control, and food sales. There is no causal therapy of seafood allergy, only the strict and lifelong avoidance of allergens remains. The following recommendations serve to assess the impact of a seafood allergy with regard to the work opportunities ended by it for the assessment of the reduction of earning capacity (MdE (German for Minderung der Erwerbsfähigkeit)) in the context of the occupational disease number 5101 of the Annex to the German regulation for occupational diseases. As a special feature of work-related seafood allergy with regard to insurance law aspects, it must be taken into account that there is a potential risk of systemic reaction with subsequent multi-organ involvement. For the estimation of MdE in the general labor market, the impact of a seafood allergy can therefore be assessed, depending on its clinical severity, as generally "mild" to "severe" in justified individual cases., (© Dustri-Verlag Dr. K. Feistle.)

Apple proliferation is an economically important disease and a threat for commercial apple cultivation. The causative pathogen, the bacterium ' Candidatus Phytoplasma mali', is mainly transmitted by Cacopsylla picta , a phloem-feeding insect that develops on the apple tree ( Malus spp.). To investigate the feeding behavior of adults of the phytoplasma vector Cacopsylla picta in more detail, we used deep sequencing technology to identify plant-specific DNA ingested by the insect. Adult psyllids were collected in different apple orchards in the Trentino-South Tyrol region of northern Italy. DNA from the whole body of the insect was extracted and analyzed for the presence of plant DNA by performing PCR with two plant-specific primers that target the chloroplast regions trnH-psbA and rbcLa . DNA from 23 plant genera ( trnH ) and four plant families ( rbcLa ) of woody and herbaceous plant taxa was detected. Up to six and three plant genera and families, respectively, could be determined in single specimens. The results of this study contribute to a better understanding of the feeding behavior of adult Cacopsylla picta .

Background: The implementation of treat-to-target principles in rheumatoid arthritis (RA) has not been fully investigated in patients with inadequate response to tumor necrosis factor (TNF) inhibitor treatment., Objectives: To evaluate the prevalence of an inadequate response to initial TNF inhibitor treatment at 6 and 12 months among patients with RA in a real-world patient registry, as well as the delay in therapy adjustment and its impact on disease activity and patient-reported outcome (PRO) measures., Methods: This analysis is based on data of patients with moderate or severe disease activity (Clinical Disease Activity Index [CDAI] score >10) who were included in the Consortium of Rheumatology Researchers of North America (Corrona) RA registry, a prospective, observational database. The patients had never received treatment with a biologic disease-modifying antirheumatic drug (DMARD) and had initiated treatment with a TNF inhibitor (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between October 2001 and December 2014. We evaluated treatment response (CDAI score ≤10), select PRO measures, and treatment changes at 6 months. Patients who had an inadequate response to TNF inhibitor therapy at 6 months and continued to use their initial TNF inhibitor were evaluated again at 12 months., Results: This retrospective analysis included 2282 patients. At 6 months, 1732 (75.9%) of the patients continued to use their initial TNF inhibitor; of these, 803 (46.4%) patients had an inadequate response to treatment. Of the 803 patients who had an inadequate response at 6 months, 488 (60.8%) continued their initial treatment at 12 months. Of these 488 patients, 315 (64.5%) had an inadequate response at 12 months, and 173 (35.5%) had a response. Numerically greater improvements in all PRO measures were observed for patients who responded to therapy compared with patients with an inadequate response., Conclusions: In this real-world analysis of data from the Corrona RA registry, a considerable proportion of patients with RA had an inadequate response to the initial TNF inhibitor therapy at 6 and 12 months. Many patients continued to have moderate or high disease activity, without accelerating treatment (eg, addition or increase in the dose of concurrent conventional synthetic DMARDs or a TNF inhibitor), contrary to treat-to-target principles, thus remaining at risk for accumulating joint damage and disability.

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the incidence of non-melanoma skin cancer (NMSC) across the tofacitinib RA development programme., Methods: NMSC events (through August 2013) were identified in patients receiving tofacitinib in two Phase (P)1, eight P2, six P3 and two long-term extension (LTE) studies. In P123 studies, tofacitinib was administered at various doses (1-30 mg twice daily [BID], 20 mg once daily), as monotherapy or with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate. In LTE studies, patients from qualifying P123 studies received tofacitinib 5 or 10 mg BID. Crude incidence rates (IRs; patients with events/100 patient-years) for first NMSC event were evaluated across doses and over time., Results: In the overall population, comprising data from 18 studies (15,103 patient-years), 83 of 6092 tofacitinib-treated patients had NMSC events. The IR for NMSC (0.55 [95% confidence interval, 0.45-0.69] overall population) was stable up to 84 months of observation. IRs for tofacitinib 5 and 10 mg BID in combined P123 trials were 0.61 (0.34-1.10) and 0.47 (0.24-0.90), respectively. Corresponding IRs for LTE studies were 0.41 (0.26-0.66) and 0.79 (0.60-1.05)., Conclusions: The IR for NMSC across the tofacitinib RA clinical development programme was low and remained stable over time. The IR for NMSC in LTE studies was numerically but not significantly higher with tofacitinib 10 versus 5 mg BID; an inverse dose relationship was observed in P123 trials. Longer follow-up is required to confirm these results.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib)., Methods: A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods., Results: The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively., Conclusions: In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.

Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene group, are important allergens in Asteraceae (Compositae) plants. As a screening tool, the Compositae mix, consisting of five Asteraceae plant extracts with allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is part of several national patch test baseline series. However, the SL content of the Compositae mix may vary due to the source material. Therefore, a simple spectrophotometric method for the quantitative measurement of SLs with the α-methylene-γ-butyrolactone moiety was developed, giving the percentage of allergenic compounds in plant extracts. The method has been validated and five Asteraceae extracts, namely feverfew (Tanacetum parthenium L.), tansy (Tanacetum vulgare L.), arnica (Arnica montana L.), yarrow (Achillea millefolium L.), and German chamomile (Chamomilla recutita L. Rauschert) that have been used in routine patch test screening were evaluated. A good correlation could be found between the results obtained using the proposed spectrophotometric method and the corresponding clinical results. Thus, the introduced method is a valuable tool for evaluating the allergenic potential and for the simple and efficient quality control of plant extracts with allergenic potential.

Observers adapted to a field of randomly coloured twinkling tiles, in which was embedded a faint, subthreshold green letter. Observers failed to discern this letter, but they readily reported its pink afterimage afterwards. This demonstrates a storage of changing colours over time; adaptation occurs for the average of each retinal point.

The Chevreul illusion is a well-known 19(th) century brightness illusion, comprising adjacent homogeneous grey bands of different luminance, which are perceived as inhomogeneous. It is generally explained by lateral inhibition, according to which brighter areas projected to the retina inhibit the sensitivity of neighbouring retinal areas. Lateral inhibition has been considered the foundation-stone of early vision for a century, upon which several computational models of brightness perception are built. One of the last strongholds of lateral inhibition is the Chevreul illusion, which is often illustrated even in current textbooks. Here we prove that lateral inhibition is insufficient to explain the Chevreul illusion. For this aim, we placed the Chevreul staircase in a luminance ramp background, which noticeably changed the illusion. In our psychophysical experiments, all 23 observers reported a strong illusion, when the direction of the ramp was identical to that of the staircase, and all reported homogeneous steps (no illusion) when its direction was the opposite. When the background of the staircase was uniform, 14 saw the illusion, and 9 saw no illusion. To see whether the change of the entire background area or that of the staircase boundary edges were more important, we placed another ramp around the staircase, whose direction was opposite to that of the original, larger ramp. The result is that though the inner ramp is rather narrow (mean = 0.51 deg, SD = 0.48 deg, N = 23), it still dominates perception. Since all conditions of the lateral inhibition account were untouched within the staircase, lateral inhibition fails to model these perceptual changes. Area ratios seem insignificant; the role of boundary edges seems crucial. We suggest that long range interactions between boundary edges and areas enclosed by them, such that diffusion-based models describe, provide a much more plausible account for these brightness phenomena, and local models are insufficient.

The six-dimensional exchange density Gamma(X)(r1,r2) is a measure of electron delocalization at the Hartree-Fock level. Fixation of r1 to a constant point results in a three-dimensional function, which displays electron delocalization that originates from r1 in position space. In this work, the dimensionality of Gamma(X)(r1,r2) is lowered from six to four by integration with regard to r2 over sphere surfaces of radius d, centered at r1 = r. The resulting radial exchange density Gamma(X)(d,r) is visualized for constant d values as a function of r. This approach indicates regions of position space which are origins of delocalization over a certain distance d. The shape of these regions very strongly depends on d. Structures similar to pi orbital densities are observed at large d values (4.5 au) in unsaturated carbon compounds, while smaller values (1.5 au) can result in structures, which resemble the Laplacian of the electron density. The abundance of different spatial structures inherent in the radial exchange density implies interesting capabilities for the orbital-independent interpretation of electronic structures in position space.

The Laplacian of the negative exchange-correlation density (with respect to coordinate r(2)), nabla<(r)2>(2)[-Gamma(sigma1)(sigma2)(XC) (r(1),r(2))] = nabla(r)2(2)X(sigma1)(sigma2)(r(1),r(2)), is proposed as an instrument for the analysis of electron delocalization in real space. It determines local concentrations in the amount of electrons that are delocalized from a reference point r(1) over space. Integration of the reference coordinate r(1) over an atomic basin Omega(n) gives the function nabla(2)X(sigma1)(sigma2)(Omega(n);r), which contains detailed information about the spatial shape of the delocalization that originates from an atom in a molecule. Its isosurface representations are richly structured and resemble molecular orbitals in their complexity and partly also in their shape. The sum over all nabla(2)X(sigma1)(sigma2)(Omega(n);r) functions of a molecule equals the Laplacian of the electron density nabla(2)rho(r), for which it provides a meaningful partitioning into atomic contributions.

Metal-stabilized phenoxyl radicals appear to be important intermediates in a variety of enzymatic oxidations. We report that transition metal coordination also supports an aminyl radical, resulting in a stable crystalline complex: [Rh(I)(trop2N.)(bipy)]+OTf- (where trop is 5-H-dibenzo[a,d]cycloheptene-5-yl, bipy is 2,2'-bipyridyl, OTf- is trifluorosulfonate). It is accessible under mild conditions by one-electron oxidation of the amide complex [Rh(I)(trop2N)(bipy)], at a potential of -0.55 volt versus ferrocene/ferrocenium. Both electron paramagnetic resonance spectroscopy and density functional theory support 57% localization of the unpaired spin at N. In reactions with H-atom donors, the Rh-coordinated aminyl behaves as a nucleophilic radical.

Objectives: To quantify the risk of contact allergy (CA) to important ubiquitous allergens associated with certain occupations, in particular the construction industry, and to identify possible time trends, controlling for potential confounding variables., Methods: Bivariate as well as Poisson regression analysis of standardized anamnestic and patch test data comprising 82,561 patients assessed in the 33 German and Austrian contact dermatitis units of the Information Network of Departments of Dermatology (IVDK) between 1992 and 2000., Results: CA to five of the 18 (groups of) allergens considered here were observed significantly more often in construction workers: dichromate, epoxy resin (BADGE), cobalt, thiurams and N-isopropyl-p-phenylenediamine (IPPD). Multifactorial analysis confirmed an increased risk of CA to these allergens in construction workers, compared with other occupations. A very strong association between cobalt and chromate allergy was found in construction workers (OR 39.1, 95% CI 21.1-79.6)., Conclusions: Dichromate is still an prominent allergen in construction workers; as yet, there is only weak evidence of a decrease in Germany. Therefore, the addition of ferrous sulphate to cement, which has been a successful intervention in other countries, should be promoted further. Although CA to other important occupational allergens like thiurams, IPPD and epoxy resin or cobalt (very often associated with dichromate CA) is less frequent, prevention should address these allergens, too. The use of protective gloves with minimal intrinsic CA risk, e.g. due to thiurams in (synthetic) rubber or chromate in leather gloves, should be promoted.