Precise Measurement of the D

We report a measurement of the D^{0} and D^{+} lifetimes using D^{0}→K^{-}π^{+} and D^{+}→K^{-}π^{+}π^{+} decays reconstructed in e^{+}e^{-}→cc[over ¯] data recorded by the Belle II experiment at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The data, collected at center-of-mass energies at or near the ϒ(4S) resonance, correspond to an integrated luminosity of 72 fb^{-1}. The results, τ(D^{0})=410.5±1.1(stat)±0.8(syst) fs and τ(D^{+})=1030.4±4.7(stat)±3.1(syst) fs, are the most precise to date and are consistent with previous determinations.

Search for B

A search for the flavor-changing neutral-current decay B^{+}→K^{+}νν[over ¯] is performed at the Belle II experiment at the SuperKEKB asymmetric energy electron-positron collider. The data sample corresponds to an integrated luminosity of 63 fb^{-1} collected at the ϒ(4S) resonance and a sample of 9 fb^{-1} collected at an energy 60 MeV below the resonance. Because the measurable decay signature involves only a single charged kaon, a novel measurement approach is used that exploits not only the properties of the B^{+}→K^{+}νν[over ¯] decay, but also the inclusive properties of the other B meson in the ϒ(4S)→BB[over ¯] event, to suppress the background from other B meson decays and light-quark pair production. This inclusive tagging approach offers a higher signal efficiency compared to previous searches. No significant signal is observed. An upper limit on the branching fraction of B^{+}→K^{+}νν[over ¯] of 4.1×10^{-5} is set at the 90% confidence level.

Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Search for Axionlike Particles Produced in e

We present a search for the direct production of a light pseudoscalar a decaying into two photons with the Belle II detector at the SuperKEKB collider. We search for the process e^{+}e^{-}→γa, a→γγ in the mass range 0.2

The current chemical biology tool box for studying ion channels.

Ion channels play important roles in human physiology and their dysfunction is linked to a variety of diseases. This has sparked considerable interest in their molecular function and pharmacology and generated a need to manipulate them with great precision. The use of high-sensitivity electrophysiological methods allows for the implementation of chemical biology manipulations, as even minute protein amounts can be studied. For example, modification of solvent-accessible cysteines is a powerful tool to site-selectively modify proteins through the introduction of charged moieties or those with fluorescent properties. This has been harnessed to study ion conduction pathways and monitor conformational dynamics. In ligand-directed chemistry, a high-affinity ligand is used to modify an ion channel with a chemical probe via a reactive linker. While these approaches are typically limited to extracellular positions, genetic code expansion provides a means to introduce non-canonical amino acids in any position of the protein. This enables the insertion of subtle analogues of naturally occurring side chains or the protein backbone, as well as amino acids with fluorescent, cross-linking or photo-switchable properties. Finally, protein semi-synthesis enables the simultaneous insertion of multiple modifications, including those that would not be tolerated by the ribosomal translation machinery. Collectively, these chemical biology tools have overcome various shortcomings of conventional mutagenesis and vastly expanded the scope of possible modifications and the type of ion channels they can be applied to. Their application in both heterologous and native cell systems will no doubt play an increasingly important role in ion channel research.

Adapting epicutaneous patch testing protocols to assess immediate-type skin reactions.

OBJECTIVE: During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product, use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate with use tests with respect to irritation elicited by skincare (leave-on) products. METHODS/RESULTS: A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that consumer acceptance would probably be low and the studies were discontinued. Immediate-type reactions are rare but have been described for some substances used in cosmetics. These unexpected results were nevertheless intriguing and prompted the start of a journey to see if patch test protocols could be modified to assess these reactions. An occlusive short-term patch test protocol with an application period of 20 min was developed. Successful identification of the spontaneous reactions became possible. Furthermore, there was a correlation between the intensity of reactions observed in the short-term patch test and those observed in the controlled in-use studies. Short-term patch testing using the developed protocol can therefore reliably be used as a screening method, for example in the development and optimization of cosmetic formulations containing ingredients that could cause spontaneous reactions, for instance of non-immunological contact urticaria type. CONCLUSION: The lessons learned from this studies indicate that simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter.

OBJECTIF: Lors du développement de formulations cosmétiques, les méthodes in vitro et in vivo sont des outils essentiels utilisés pour évaluer de manière fiable le potentiel d'irritation cutanée d'un produit ou d'un ingrédient. Le test épicutané (protocoles d'application uniques et / ou multiples) est utilisé depuis longtemps comme méthode initiale in vivo pour dépister les éventuelles propriétés d'irritation cutanée d'une substance ou d'une formulation. Afin de confirmer la douceur et l'acceptation dermatologique et / ou consommateur d'un produit, des tests d'usage sont souvent effectués ultérieurement. Une étude a donc été initiée pour voir dans quelle mesure les résultats des tests épicutanés correspondent aux tests d'usage en ce qui concerne l'irritation provoquée par les produits de soin (sans rinçage). MÉTHODES/RÉSULTATS: Un certain nombre de formulations cosmétiques différentes ont été évaluées dans les deux tests. Bien que les résultats du test épicutané n'indiquent pas de potentiels d'irritation substantiels, des réactions de type immédiat (picotements et rougeurs) ont été observées chez certains volontaires. Celles-ci ont disparu en à peu près 1 heure. Bien que transitoires, ces réactions de type 5 suggéraient que l'acceptation du consommateur serait probablement faible et les études ont été interrompues. Les réactions de type immédiat 6 sont rares mais ont été évoquées en relation avec certaines substances utilisées en cosmétique. Ces résultats inattendus étaient néanmoins intrigants et ont incité le lancement d'un processus pour voir si les protocoles de test épicutané pouvaient être modifiés pour évaluer ces réactions. Un protocole de test épicutané à court terme occlusif avec une période d'application de 20 min a été développé, permettant l'identification réussie des réactions spontanées. Il a été de plus constate une corrélation entre l'intensité des réactions observées dans le test épicutané à court terme et celles observées dans les test d'usage contrôlés. Le test épicutané à court terme utilisant le protocole développé peut donc être utilisé de manière fiable comme méthode de dépistage, par exemple dans le développement et l'optimisation de formulations cosmétiques contenant des ingrédients qui pourraient provoquer des réactions spontanées, par exemple de type urticaire de contact non immunologique. CONCLUSION: Les leçons tirées de ces études indiquent que de simples modifications des protocoles de test existants peuvent révéler des informations importantes sur les réactions cutanées. Ces modifications peuvent ensuite être utilisées pour créer d'autres blocs de construction dans le développement et l'optimisation de stratégies de test pour des formulations cosmétiques qui offrent des conceptions d'études fiables pour les réactions possibles que les développeurs de produits peuvent rencontrer.

[Neurofeedback-based motor imagery training for rehabilitation after stroke]. / Neurofeedback-gestütztes Bewegungsvorstellungstraining zur Rehabilitation nach einem Schlaganfall.

Mental training, including motor observation and motor imagery, has awakened much academic interest. The presumed functional equivalence of motor imagery and motor execution has given hope that mental training could be used for motor rehabilitation after a stroke. Results obtained from randomized controlled trials have shown mixed results. Approximately half of the studies demonstrate positive effects of motor imagery training but the rest do not show an additional benefit. Possible reasons why motor imagery training has so far not become established as a robust therapeutic approach are discussed in detail. Moreover, more recent approaches, such as neurofeedback-based motor imagery or closed-loop systems are presented and the potential importance for motor learning and rehabilitation after a stroke is discussed.

Improving vacuum-UV (VUV) photolysis of organic compounds in water with a phosphor converted xenon excimer lamp emitting at 193 nm.

A novel vacuum ultraviolet excimer lamp emitting light at 193 nm was used to investigate the degradation of organic micropollutants in ultrapure water and wastewater treatment plant (WWTP) effluent. Overall, light at 193 nm proved to be efficient to degrade the investigated micropollutants (diclofenac, diatrizoic acid, sulfamethoxazole). Experiments with WWTP effluent proved the ability of radiation at 193 nm to degrade micropollutants which are hardly removed with commonly used oxidation technologies like ozonation (diatrizoic acid, ethylenediaminetetraacetic acid, perfluorooctanoic acid, and perfluorooctanesulfonic acid).

F-EVAR does not Impair Renal Function more than Open Surgery for Juxtarenal Aortic Aneurysms: Single Centre Results.

OBJECTIVE: To compare the results of elective open surgical repair (OSR) and total endovascular repair of juxtarenal aortic aneurysms (JAA), with either the Cook Zenith or the Vascutek Anaconda fenestrated stent grafts (F-EVAR) in a university hospital setting. PATIENTS AND METHODS: Between April 1999 and July 2014, of 926 patients with an abdominal aortic aneurysm, 69 were juxtarenal, where 34 had an elective OSR and 35 had F-EVAR. A post-operative rise of baseline creatinine by >50% and/or deterioration of estimated glomerular filtration rate by 25% were defined as renal failure. RESULTS: The demographics of the patients were similar except for heart insufficiency, peripheral arterial disease, and pre-existing renal artery stenosis (p < .05). Median aneurysm diameters were 57 mm (range 50-80 mm) and 56 mm (range 36-64 mm) (p = .194), respectively, and the median pre-operative serum creatinine levels were 94 µmol/L (range 65-286 µmol/L) and 96 µmol/L (range 57-333 µmol/L) (p = .871) with median estimated glomerular filtration rate of 68 mL/min (range 21-117 mL/min) and 70 mL/min (range 18-114 mL/min) (p = .308) in the open and endovascular groups, respectively. The technical success (OSR versus F-EVAR) was 100% versus 94.3% with complete exclusion of the aneurysms in all cases. Median procedure time was 171 versus 188 min. During median in hospital stay of 11 versus 7 days (p = .05), mortality was 0 versus 2.9% and new onset of post-operative renal insufficiency was detected in 26.5% versus 8.5% patients (p = .05), although with 11.8% versus 5.7% being persistent (p = .428). During follow up, statistically similar new (late or persistent post-operative) renal insufficiency was detected in 14.7% versus 8.8% with dialysis in 3% of patients in each group with similar mortality within the 24 months. CONCLUSIONS: This retrospective analysis demonstrates that OSR might be combined with more acute post-operative renal impairment than F-EVAR for JAA, but with similar intermediate term procedure related mortality and renal outcomes.

Severe thrombocytopenia in hantavirus-induced nephropathia epidemica.

Nephropathia epidemica is a milder form of hemorrhagic fever with renal syndrome, caused by Puumala virus. The clinical picture is characterized by a rapid loss of renal function (acute kidney injury) and thrombocytopenia. The purpose of the current analysis was to compare the clinical course of patients presenting with or without severe thrombocytopenia. In 47 out of 456 patients with acute nephropathia epidemica, the nadir count of thrombocytes was available for the acute course of the disease. The clinical course of these patients was further analyzed. No major bleeding (e.g., intracranial bleeding or gastrointestinal bleeding) occurred in either group. Creatinine peak levels were higher and proteinuria was more frequently present in the severely thrombocytopenic group. In conclusion, severe thrombocytopenia is common in nephropathia epidemica and is associated with a more severe course of the disease; however, bleeding complications are rare.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis.

OBJECTIVE: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). METHODS: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. RESULTS: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). CONCLUSIONS: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

Coulomb excitation of 104Sn and the strength of the 100Sn shell closure.

A measurement of the reduced transition probability for the excitation of the ground state to the first 2+ state in 104Sn has been performed using relativistic Coulomb excitation at GSI. 104Sn is the lightest isotope in the Sn chain for which this quantity has been measured. The result is a key point in the discussion of the evolution of nuclear structure in the proximity of the doubly magic nucleus 100Sn. The value B(E2; 0+ → 2+) = 0.10(4) e2b2 is significantly lower than earlier results for 106Sn and heavier isotopes. The result is well reproduced by shell model predictions and therefore indicates a robust N = Z = 50 shell closure.

Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn.

The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During ß(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of (100)Sn, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the ß-decay of (100)Sn, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear ß-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, (100)In, are well reproduced by modern, large-scale shell model calculations.

A typical Wegeners granulomatosis -- but not pauci-immune!

We present a the case of 58-year old man who was admitted to hospital with typical clinical features (bloody nasal discharge, arthralgia, acute kidney injury with a nephritic syndrome) consisting with Wegeners granulomatosis (WG). CT-scan showed pulmonary nodules and antineutrophil cytoplasmatic antibodies (ANCA) were elevated. A kidney biopsy showed a crescentic glomerulonephritis, but not pauci-immune-immune with a histopathological staining of a mesangioproliferative IgA-glomerulonephritis. The patient was put on prednisolone and i.v. cyclophosphamid (CYCLOPS-protocol (1). The anti-proteinase-3 antibody titer decreased and the CT-scan showed decreased activity of Wegener's granulomatosis (BVAS 26 dropped to 2) and the patient`s serum creatinine level was stable. The exact nosological relation of mesangial IgA-nephropathy to WG is still unclear. This case underlines that knowledge of renal histology is essential in the management of patients with renal disease, especially in patients with hematuria and/or proeinuria with positive ANCA.

16+ spin-gap isomer in 96Cd.

A ß-decaying high-spin isomer in (96)Cd, with a half-life T(1/2)=0.29(-0.10)(+0.11) s, has been established in a stopped beam rare isotope spectroscopic investigations at GSI (RISING) experiment. The nuclei were produced using the fragmentation of a primary beam of (124)Xe on a (9)Be target. From the half-life and the observed γ decays in the daughter nucleus, (96)Ag, we conclude that the ß-decaying state is the long predicted 16(+) "spin-gap" isomer. Shell-model calculations, using the Gross-Frenkel interaction and the πν(p(1/2),g(9/2)) model space, show that the isoscalar component of the neutron-proton interaction is essential to explain the origin of the isomer. Core excitations across the N=Z=50 gaps and the Gamow-Teller strength, B(GT) distributions have been studied via large-scale shell-model calculations using the πν(g,d,s) model space to compare with the experimental B(GT) value obtained from the half-life of the isomer.

[Hypertension due to aortic coarctation--a missed clinical diagnosis]. / Hypertonie bei Aortenisthmusstenose--eine übersehene klinische Diagnose.

HISTORY AND FINDINGS: A 30-year-old woman presented to our emergency department with severe headaches, dizziness and uncontrolled hypertension. She had arterial hypertension and a known heart murmur since adolescence. Previous medical work up did not reveal any cause for secondary hypertension. Recently her blood pressure had been difficult to control. A systolic murmur as well as absent inguinal and feet pulses were notable at the physical examination. INVESTIGATIONS: When performing doppler ultrasound the closing pressures of the dorsalis pedis arteries were only 70 mm Hg compared to a blood pressure reading of 160 mm Hg on the upper arms. Thoracic magnetic resonance imaging showed subtotal aortic coarctation causing the differences in blood pressures. Echocardiography and cardiac catheterization additionally revealed a moderately stenosed bicuspid aortic valve, the pressure gradient across the coarctation was 30 mm Hg. THERAPY AND COURSE: Despite the severity of the coarctation an interventional approach was favoured instead of a classical operative therapy. Balloon dilatation with stent implantation was performed without complications. Since the intervention blood pressure have remained normotensive, the coarctation gradient being markedly reduced. CONCLUSIONS: In young patients with arterial hypertension, as well as in cases of severe and refractory hypertension, causes of secondary hypertension must be looked for and excluded. Especially when hypertension occurs in adolescence, aortic coarctation should be taken into account, in addition to renal or endocrine causes. A thorough physical examination with cardiac auscultation and checking of all peripheral pulses is the crucial step to the diagnosis.

[Salt appetite, cramps and palpitations in a 21-year old medical secretary]. / Salzhunger, Krämpfe und Palpitationen bei einer 21-jährigen Arzthelferin.

Hypokalemia is a common finding. The clinical presentation can be paralyses and cardiac arrhythmias. We present a normotensive young woman with salt appetite, cramps and palpitations. In our case report the patient shows a positive family history for hypopotassemia, a metabolic alkalosis with hypotension, and hypocalciuria with an increased urinary potassium loss. The levels of renin and aldosterone were elevated. After a negative testing for metabolites of diuretics, we obtained a positive result of the suspected SLC12A3 genetic test. This mutation leads to a failure of the thiazide-sensitive sodium-2-chloride-cotransporter, the so called Gitelman syndrome, which presents similar to a chronic thiazide therapy. The Gitelman syndrome is a rare disease with renal potassium loss and hypotension. Especially in young patients around the age of twenty or in patients with chronic intractable hypopotassemia a Gitelman syndrome should be considered.

[A 65-year-old man with history of claudication, palpable purpura and livedo reticularis]. / Claudicatio intermittens, palpable Purpura und Livedo reticularis bei einem 65-jährigen Patienten.

HISTORY AND ADMISSION FINDINGS: A 65-year-old man was admitted with history of claudication symptoms and painful skin lesions of the lower legs. Physical examination showed palpable purpura of the lower legs and livedo reticularis, most marked at the forefoot and toes. INVESTIGATIONS: Computed tomography (CT) showed an aortic mass 2 cm above the bifurcation. This was treated after angiography with a covered stent. Biopsy of the skin lesions showed no sign of vasculitis and no cholesterol crystals. TREATMENT AND COURSE: The patient was discharged and remained symptom-free for 9 months. He was readmitted at that time with recurrent complaints. CT revealed a subtotal stenosis of the aortic stent. A skin biopsy showed CD31-positive tumor cells in small arteries. Biopsy of a new osteolytic lesion in the ileum confirmed the diagnosis of angiosarcoma of the aorta. The patient decided in favor of palliative care and was discharged from the hospital. CONCLUSION: Primary tumors of the aorta, although they are rare, should be considered in the presence of an intravascular mass with stenosis to blood flow. A skin biopsy is easy to conduct and often leads to the final diagnosis.