Eosinophilia in Dermatologic Disorders

Eosinophil infiltration can be observed in skin disorders, such as allergic/immunologic, autoimmune, infectious, and neoplastic diseases. Clinical presentations are variable and include eczematous, papular, urticarial, bullous, nodular, and fibrotic lesions; pruritus is a common symptom in all. In this review, we present representative eosinophilic skin diseases according to their clinical pattern, together with histologic findings and diagnostic procedures. We also discuss the potential roles of eosinophils in the pathogenesis of dermatologic disorder. Current pathogenesis-based diagnostic and therapeutic approaches are outlined.

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.

Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction

BACKGROUND The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. OBJECTIVES This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. METHODS The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. RESULTS Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21). CONCLUSIONS Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938).

Virtual Patients in continuing medical education and residency training: a pilot project for acceptance analysis in the framework of a residency revision course in pediatrics.

AIM Virtual patients (VPs) are a one-of-a-kind e-learning resource, fostering clinical reasoning skills through clinical case examples. The combination with face-to-face teaching is important for their successful integration, which is referred to as "blended learning". So far little is known about the use of VPs in the field of continuing medical education and residency training. The pilot study presented here inquired the application of VPs in the framework of a pediatric residency revision course. METHODS Around 200 participants of a pediatric nephology lecture ('nephrotic and nephritic syndrome in children') were offered two VPs as a wrap-up session at the revision course of the German Society for Pediatrics and Adolescent Medicine (DGKJ) 2009 in Heidelberg, Germany. Using a web-based survey form, different aspects were evaluated concerning the learning experiences with VPs, the combination with the lecture, and the use of VPs for residency training in general. RESULTS N=40 evaluable survey forms were returned (approximately 21%). The return rate was impaired by a technical problem with the local Wi-Fi firewall. The participants perceived the work-up of the VPs as a worthwhile learning experience, with proper preparation for diagnosing and treating real patients with similar complaints. Case presentations, interactivity, and locally and timely independent repetitive practices were, in particular, pointed out. On being asked about the use of VPs in general for residency training, there was a distinct demand for more such offers. CONCLUSION VPs may reasonably complement existing learning activities in residency training.

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly

We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. What is Known: • Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

Adult Asylum Seekers from the Middle East Including Syria in Central Europe: What Are Their Health Care Problems?

Background Forced displacement related to persecution and violent conflict has reached a new peak in recent years. The primary aim of this study is to provide an initial overview of the acute and chronic health care problems of asylum seekers from the Middle East, with special emphasis on asylum seekers from Syria. Methods Our retrospective data analysis comprised adult patients presenting to our emergency department between 01.11.2011 and 30.06.2014 with the official resident status of an “asylum seeker” or “refugee” from the Middle East. Results In total, 880 patients were included in the study. Of these, 625 (71.0%) were male and 255 (29.0%) female. The median age was 34 (range 16–84). 222 (25.2%) of our patients were from Syria. The most common reason for presentation was surgical (381, 43.3%), followed by medical (321, 36.5%) and psychiatric (137, 15.6%). In patients with surgical presentations, trauma-related problems were most common (n = 196, 50.6%). Within the group of patients with medical presentation, acute infectious diseases were most common (n = 141, 43.9%), followed by neurological problems (n = 70, 21.8%) and gastrointestinal problems (n = 47, 14.6%). There were no differences between Syrian and non-Syrian refugees concerning surgical or medical admissions. The most common chronic disorder of unclear significance was chronic gastrointestinal problems (n = 132, 15%), followed by chronic musculoskeletal problems (n = 108, 12.3%) and chronic headaches (n = 78, 8.9%). Patients from Syria were significantly younger and more often suffered from a post-traumatic stress disorder than patients of other nationalities (p<0.0001, and p = 0.05, respectively). Conclusion Overall a remarkable number of our very young group of patients suffered from psychiatric disorders and unspecified somatic symptoms. Asylum seekers should be carefully evaluated when presenting to a medical facility and physicians should be aware of the high incidence of unspecified somatic symptoms in this patient population.In general, there is no major difference between asylum seekers from Syria when compared to other nationalities of asylum seekers from the Middle East.

Large-scale dust jets in the coma of 67P/Churyumov-Gerasimenko as seen by the OSIRIS instrument onboard Rosetta

Context. During the most recent perihelion passage in 2009 of comet 67P/Churyumov-Gerasimenko (67P), ground-based observations showed an anisotropic dust coma where jet-like features were detected at similar to 1.3 AU from the Sun. The current perihelion passage is exceptional as the Rosetta spacecraft is monitoring the nucleus activity since March 2014, when a clear dust coma was already surrounding the nucleus at 4.3 AU from the Sun. Subsequently, the OSIRIS camera also witnessed an outburst in activity between April 27 and 30, and since mid-July, the dust coma at rh similar to 3.7-3.6 AU preperihelion is clearly non-isotropic, pointing to the existence of dust jet-like features. Aims. We aim to ascertain on the nucleus surface the origin of the dust jet-like features detected as early as in mid-July 2014. This will help to establish how the localized comet nucleus activity compares with that seen in previous apparitions and will also help following its evolution as the comet approaches its perihelion, at which phase most of the jets were detected from ground-based observations. Determining these areas also allows locating them in regions on the nucleus with spectroscopic or geomorphological distinct characteristics. Methods. Three series of dust images of comet 67P obtained with the Wide Angle Camera (WAC) of the OSIRIS instrument onboard the Rosetta spacecraft were processed with different enhancement techniques. This was made to clearly show the existence of jet-like features in the dust coma, whose appearance toward the observer changed as a result of the rotation of the comet nucleus and of the changing observing geometry from the spacecraft. The position angles of these features in the coma together with information on the observing geometry, nucleus shape, and rotation, allowed us to determine the most likely locations on the nucleus surface where the jets originate from. Results. Geometrical tracing of jet sources indicates that the activity of the nucleus of 67P gave rise during July and August 2014 to large-scale jet-like features from the Hapi, Hathor, Anuket, and Aten regions, confirming that active regions may be present on the nucleus localized at 60. northern latitude as deduced from previous comet apparitions. There are also hints that large-scale jets observed from the ground are possibly composed, at their place of origin on the nucleus surface, of numerous small-scale features.

Revisiting the ISN Flow Parameters, using a variable IBEX pointing strategy

The Interstellar Boundary Explorer (IBEX) has observed the interstellar neutral (ISN) gas flow over the past 6 yr during winter/spring when the Earth's motion opposes the ISN flow. Since IBEX observes the interstellar atom trajectories near their perihelion, we can use an analytical model based upon orbital mechanics to determine the interstellar parameters. Interstellar flow latitude, velocity, and temperature are coupled to the flow longitude and are restricted by the IBEX observations to a narrow tube in this parameter space. In our original analysis we found that pointing the spacecraft spin axis slightly out of the ecliptic plane significantly influences the ISN flow vector determination. Introducing the spacecraft spin axis tilt into the analytical model has shown that IBEX observations with various spin axis tilt orientations can substantially reduce the range of acceptable solutions to the ISN flow parameters as a function of flow longitude. The IBEX operations team pointed the IBEX spin axis almost exactly within the ecliptic plane during the 2012-2014 seasons, and about 5° below the ecliptic for half of the 2014 season. In its current implementation the analytical model describes the ISN flow most precisely for the spin axis orientation exactly in the ecliptic. This analysis refines the derived ISN flow parameters with a possible reconciliation between velocity vectors found with IBEX and Ulysses, resulting in a flow longitude lambda∞ = 74.°5 ± 1.°7 and latitude beta∞ = -5.°2 ± 0.°3, but at a substantially higher ISN temperature than previously reported.

Lichtheimia Infection in a Lymphoma Patient: Case Report and a Brief Review of the Available Diagnostic Tools

We describe the case of a patient with a T-lymphoblastic lymphoma whose disseminated mucormycosis was diagnosed with delay, and we address the diagnostic and therapeutic decision-making process and review the diagnostic workup of patients with potential IFD. The diagnosis was delayed despite a suggestive radiological presentation of the patient's pulmonary lesion. The uncommon risk profile (T-lymphoblastic lymphoma, short neutropenic phases) wrongly led to a low level of suspicion. The diagnosis was also hampered by the lack of indirect markers for infections caused by Mucorales, the low sensitivity of both fungal culture and panfungal PCR, and the limited availability of species-specific PCR. A high level of suspicion of IFD is needed, and aggressive diagnostic procedures should be promptly initiated even in apparently low-risk patients with uncommon presentations. The extent of the analytical workup should be decided on a case-by-case base. Diagnostic tests such as the galactomannan and β-D-glucan test and/or PCR on biological material followed by sequencing should be chosen according to their availability and after evaluation of their specificity and sensitivity. In high-risk patients, preemptive therapy with a broad-spectrum mould-active antifungal agent should be started before definitive diagnostic findings become available.

Unfair Advantage: An Intriguing Example of Legal Transformation in the Swiss Private Law

This paper demonstrates a mixed approach to the theme of the instrumentality of law by both analysing the goal of a legal transformation and the techniques adapted to achieve it. The correct recognition of a certain practical necessity has lead the Swiss Federal Tribunal to an intriguing judgement “Fussballclub Lohn-Fall” of 1997. The legal remedies provided for cases of unfair advantage have been then creatively modified praeter legem. The adaptation was strongly influenced by foreign legal patterns. The Swiss Code of Obligations of 1911 provides a norm in art. 21 on unfair advantage (unconscionable contract), prescribing that if one party takes unjustified advantage over the weaknesses of another in order to receive an excessive benefit, such a contract is avoidable. Its wording has been shaped over a hundred years ago and still remains intact. However, over the course of the 20th century the necessity for a more efficient protection has arisen. The legal doctrine and jurisprudence were constantly pointing out the incompleteness of the remedies provided by art. 21 of the Code of Obligations. In the “Fussballclub Lohn-Fall” (BGE 123 III 292) the Swiss Federal Tribunal finally introduced the possibility to modify the contract. Its decision has been described as “a sign of the zeitgeist, spirit of the time”. It was the Swiss legal doctrine that has imposed the new measure under the influence of the German “quantitative Teilnichtigkeit” (quantitative partial nullity). The historical heritage of the Roman laesio enormis has also played its role.

The Emergence of Open Hardware Phenomena in Different Technological Environments

Dannie Jost gave an introductory presentation on the emergence on open hardware phenomena, including synthetic biology and other technological environments at the HEPTech Workshop on Open Hardware on June 13 held at the GSI, Darmstadt (Germany). The workshop was organized by CERN and GSI. This event addressed the OSHW phenomenon and its implications for academia and industry with special attention to knowledge and technology transfer issues. Consideration was given to the various aspects of open source hardware development, and how these are dealt with in academia and industry. Presentations from legal experts, academics, practitioners and business provided input for the discussions and exchange of ideas.

Reflections on the Nature of Preferentialism in Services Trade

The Graduate Institute organized an academic workshop and roundtable on the occasion of EFTA's 50th Anniversary in Geneva under the chairmanship of H.E. Doris Leuthard, President of the Swiss Confederation. Pierre Sauve, Deputy Managing Director and Director of Studies, WTI and Co-leader, NCCR-Trade work programme on preferentialism and Anirudh Shingal, Senior Research Fellow, WTI and Co-leader, NCCR-Trade work programme on impact assessment of trade, co-authored a paper on the nature of preferentialism in services trade, which Anirudh presented at the workshop. The event was extremely well-attended by high profile dignitaries and academics including President Leuthard; Director General of the WTO, Pascal Lamy; trade ministers of Brazil and Finland; Jan Kubis, Executive Secretary of the UNECE and several current and former ambassadors. The academic workshop, moderated by Theresa Carpenter (Graduate Institute, Geneva), began in the morning with Prof. Victor Norman's (Norwegian School of Economics & Business Administration) presentation on the future of EFTA. Other presentations included those by Prof. Peter Egger (ETH Zurich) on the structural estimation of gravity models with market entry dynamics and by Prof. Richard Baldwin (Graduate Institute, Geneva) on 21st century regionalism. The high-profile Panel in the afternoon, moderated by Prof. Richard Baldwin, was led by President Leuthard who spoke on free trade agreements and the multilateral trading system in 2020. The keynote address at the Panel was delivered by Prof. Jagdish Bhagwati (Coulmbia University), who spoke on strengthening defences against protectionism and liberalizing trade.

The role of the G20 in WTO governance

Report by Professor Sungjoon Cho, Associate Professor of Law, Chicago-Kent College of Law (Chair), and Charlotte Sieber-Gasser, Doctoral Research Fellow, World Trade Institute, University of Bern, Session 27, WTO Public Forum 2010: The Forces Shapping World Trade, pp.29-33. In the course of the financial crisis, the global geography of power has shifted from G8 to G20. The latter, although representing roughly two thirds of global trade, consists of relatively a small number of global players and is consequently excluding many others from decision-making at the international stage. Nevertheless, the G20 has been successful in its reaction to the financial crisis and became therewith an important new player within the international community. When highlighting how the G20 might interfere with the WTO, the panel voiced concerns over the political legitimacy of the G20, given the limited number of members and the global impact of its decisions. It agreed on the impression that although the G20 intends to extend its debates from the financial sector to world economy in general, it has so far little achieved in this direction, particularly when it comes to moving the Doha agenda forward. It remains, thus, open how the G20 will evolve in the coming few years, and what mandates it will shed or adopt. So far, the G20 has complemented the WTO and international financial institutions in handling the financial crisis. Yet, even if there is little evidence pointing towards a less cooperative role in the future, the desirability of a G20 commitment in WTO trade negotiations has yet to be debated. The panel concluded by providing ideas on how the potential of the G20 might be used to serve global interests even better in the future. In their concluding remarks, the panellists agreed that it remains to be seen whether or not the G20 will further broaden its agenda. Given the ebbing away of the financial crisis there is even the question whether the G20 will remain an important international forum for financial collaboration, or whether it has already served its cause and will eventually disappear from the international stage. The Chair concluded the well attended and lively panel with voicing the hope that the two international bodies – the G20 and the WTO – will work in a positive way together in the future and face the challenges and opportunities in their collaboration to the benefit of everyone.