Solvation of Na+, K+ and their dimers in helium

Helium atoms bind strongly to alkali cations which, when embedded in liquid helium, form so‐called snowballs. Calculations suggest that helium atoms in the first solvation layer of these snowballs form rigid structures and that their number (n) is well defined, especially for the lighter alkalis. However, experiments have so far failed to accurately determine values of n. We present high‐resolution mass spectra of Na+Hen, K+Hen, Na2+Hen and K2+Hen, formed by electron ionization of doped helium droplets; the data allow for a critical comparison with several theoretical studies. For sodium and potassium monomers the spectra indicate that the value of n is slightly smaller than calculated. Na2+Hen displays two distinct anomalies at n=2 and n=6, in agreement with theory; dissociation energies derived from experiment closely track theoretical values. K2+Hen distributions are fairly featureless, which also agrees with predictions

The submersion of sodium clusters in helium nanodroplets: Identification of the surface → interior transition

The submersion of sodium clusters beyond a critical size in helium nanodroplets, which has recently been predicted on theoretical grounds, is demonstrated for the first time. Confirmation of a clear transition from a surface location, which occurs for alkali atoms and small clusters, to full immersion for larger clusters, is provided by identifying the threshold electron energy required to initiate Na n cluster ionization. On the basis of these measurements, a lower limit for the cluster size required for submersion, n ≥ 21, has been determined. This finding is consistent with the recent theoretical prediction

The submersion of sodium clusters in helium nanodroplets: Identification of the surface → interior transition

The submersion of sodium clusters beyond a critical size in helium nanodroplets, which has recently been predicted on theoretical grounds, is demonstrated for the first time. Confirmation of a clear transition from a surface location, which occurs for alkali atoms and small clusters, to full immersion for larger clusters, is provided by identifying the threshold electron energy required to initiate Nan cluster ionization. On the basis of these measurements, a lower limit for the cluster size required for submersion, n ≥ 21, has been determined. This finding is consistent with the recent theoretical prediction

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, that is, age 6 years. However, impact of dietary relaxation on long-term outcomes is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations (Boy et al., J Inherit Metab Dis, 2017;40(1):75-101; Kolker et al., J Inherit Metab Dis 2011;34(3):677-694; Kolker et al., J Inherit Metab Dis, 2007;30(1):5-22) and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes

Alternativen zu Säuglingsnahrungen auf Kuhmilchproteinbasis

Die natürliche Ernährung eines gesunden Säuglings ist das Stillen. Ist Stillen oder die Fütterung von Muttermilch nicht möglich, kann Frauenmilch für die Ernährung des Säuglings erwogen werden, sofern diese aus einer qualifizierten Humanmilchbank stammt. Vom Kauf von Frauenmilch aus dem Internet wird wegen Risiken einer Infektionsübertragung und einer unzureichenden Milchqualität strikt abgeraten. Aufgrund der geringen Verfügbarkeit, der hohen Kosten sowie möglicher Nachteile der Ernährung mit Spendermilch im Vergleich zum Stillen sind industriell gefertigte Säuglingsnahrungen das Mittel der Wahl zur Ernährung des gesunden, reifgeborenen Säuglings, wenn Stillen nicht oder nur partiell möglich ist. Kuhmilchprotein ist die am häufigsten verwendete Eiweißkomponente. Die Nachfrage nach anderen auf Tiermilchen basierten sowie vegetarischen bzw. veganen Alternativen steigt. Im Folgenden werden verschiedene Alternativen bezüglich ihrer Eignung betrachtet. Säuglingsnahrungen auf Basis von Ziegenmilchprotein stellen für gesunde, reifgeborene Säuglinge eine zugelassene und geeignete Alternative zu kuhmilchproteinbasierten Säuglingsnahrungen dar. Für Säuglingsnahrungen aus anderen Tiermilchen (z. B. Kamel‑, Schaf‑, Pferde- oder Büffelmilch) sind keine belastbaren Daten zu Eignung und Sicherheit bekannt, und sie sind in der Europäischen Union nicht zugelassen. Säuglingsnahrungen auf der Grundlage von Sojaproteinisolaten sind in der Europäischen Union zugelassen. Sie werden für die allgemeine Verwendung im 1. Lebenshalbjahr durch die Ernährungskommission nicht empfohlen, insbesondere weil potenziell nachteilige Effekte von enthaltenen Isoflavonen nicht ausgeschlossen werden können. Ab der Geburt und in den ersten Lebensmonaten sollte die Gabe von Sojanahrungen auf Indikationen wie eine bestehende Galaktosämie, die sehr seltene kongenitale Laktoseintoleranz sowie bei familiärem Wunsch nach veganer Ernährungsweise und aus anderen weltanschaulichen Gründen begrenzt werden. Im 2. Lebenshalbjahr ist die Zufuhrmenge pro Kilogramm Körpergewicht deutlich niedriger, sodass das Risiko unerwünschter Wirkungen als wesentlich geringer eingeschätzt wird. Zu neuerdings angebotenen Nahrungen auf der Grundlage einer Mischung aus Soja- und Kuhmilchprotein sind keine Daten zur Prüfung von Sicherheit und Eignung bekannt, sodass hierzu keine Empfehlung ausgesprochen werden kann. Von der Verwendung von Säuglingsnahrung auf der Grundlage von hydrolysiertem Reisprotein wird auch aufgrund hoher berichteter Arsengehalte abgeraten. Auch von einer häuslichen Selbstherstellung von Säuglingsnahrungen wird aufgrund eines erhöhten Risikos für eine nichtbedarfsgerechte Nährstoffzufuhr und für Infektionen abgeraten. // The natural nutrition of a healthy infant is breastfeeding. If breastfeeding or feeding of breast milk is not possible, feeding of donor human milk may be considered. The safety of donor milk can only be ensured if it is provided by a qualified human milk bank. The use of informally shared donor milk or the use of human milk purchased through the internet is strongly discouraged because of the risk of transmitting infections and of insufficient milk quality. Due to low availability, high costs and concerns about poorer nutritional quality of donor milk compared to breastfeeding, industrially manufactured infant formula is the preferred alternative for feeding healthy full-term infants that cannot or cannot be fully breastfed. Milk-based infant formula is most frequently made from cow’s milk protein; however, there is an increasing popularity of vegetarian or vegan formulas and of formulas based on different animal milks other than cow’s milk. Goat’s milk-based infant formulas represent an approved and suitable alternative to cow’s milk for healthy, full-term infants. Reliable data on the suitability and safety are unavailable for formulas based on other animal milks (e.g., camel, horse, sheep or buffalo milk), and these are not approved for infant feeding in the European Union. Infant formulas based on soybean protein isolates are approved in the European Union. They are not generally recommended by the Nutrition Committee for infant feeding in the first half year of life because potentially harmful effects of isoflavones derived from soybeans cannot be excluded; however, soybean protein isolate-based formulas may be reservedly used after birth and in the first months of life for infants affected by galactosemia, the very rare hereditary lactose intolerance manifest at birth, a vegan family lifestyle or other familial convictions. In the second half year of life the intake amount per kilogram body weight is much less so that the risk of undesired effects is estimated to be much lower. For the recently provided nutrition based on a mixture of soybean and cow’s milk proteins, no data on testing of the safety and suitability are known, so that no recommendations can be made on this. The use of infant formula based on hydrolyzed rice protein is not recommended because of concerns about possible high arsenic contamination. The use of homemade infant formulas is discouraged due to the high risk of introducing infections and of possible nutritional imbalances of macronutrients and micronutrients

Integration und Desintegration der Kulturen im europäischen Mittelalter

Das mittelalterliche Europa war keine christliche Einheitskultur, sondern geprägt von vielfältigen Prozessen des Kontakts und der Abgrenzung zwischen Kulturen, bei denen die drei monotheistischen Religionen Christentum, Judentum und Islam eine herausragende Rolle spielten. Seit 2005 erforscht das DFG-Schwerpunktprogramm "Integration und Desintegration der Kulturen im europäischen Mittelalter" die Geschichte Europas als Geschichte kultureller Differenzen. Der Band dokumentiert die Dynamiken und Erträge eines wissenschaftsorganisatorischen Experiments: Gegliedert in fächerübergreifende Arbeitsgruppen, erforschten 24 Einzelprojekte aus 14 Disziplinen Integrations- und Desintegrationsprozesse von Skandinavien bis Ägypten, von der Iberischen Halbinsel bis zu den Steppen Zentralasiens in komparativem Zugriff; sie präsentieren ihre Ergebnisse nun in Beiträgen, die von mehreren Autorinnen und Autoren gemeinsam verfasst worden sind. Dabei werden Begriffe wie "Kultur" problematisiert und schon eingeführte Konzepte wie "Integration/Desintegration", "Inklusion/Exklusion", "Hybridisierung" und "Transfer" als Instrumente transkultureller Mediävistik auf den Prüfstand gestellt. Das Ende der Laufzeit des Schwerpunktprogramms gibt zugleich Anlass, methodisch-theoretische Einsichten der gemeinsamen Forschung wie auch praktische Erfahrungen bei der transdisziplinären Zusammenarbeit zu bilanzieren

The submersion of sodium clusters in helium nanodroplets: Identification of the surface -> interior transition

The submersion of sodium clusters beyond a critical size in helium nanodroplets, which has recently been predicted on theoretical grounds, is demonstrated for the first time. Confirmation of a clear transition from a surface location, which occurs for alkali atoms and small clusters, to full immersion for larger clusters, is provided by identifying the threshold electron energy required to initiate Nan cluster ionization. On the basis of these measurements, a lower limit for the cluster size required for submersion, n ≥ 21, has been determined. This finding is consistent with the recent theoretical prediction

NGS-based BRCA1/2 mutation testing of high-grade serous ovarian cancer tissue: results and conclusions of the first international round robin trial

With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advances in routine tumor test methodologies due to the large size of both genes and the lack of mutational hot spots. Classical focused screening approaches, like Sanger sequencing, do not allow for a sensitive, rapid, and economic analysis of tumor tissue. Next-generation sequencing (NGS) approaches employing targeted panels for BRCA1/2 to interrogate formalin-fixed and paraffin-embedded tumor samples from either surgical resection or biopsy specimens can overcome these limitations. Although focused NGS methods have been implemented by few centers in routine molecular diagnostics for the analysis of some druggable oncogenic mutations, the reliable diagnostic testing of the entire coding regions of BRCA1 and BRCA2 was a new challenge requiring extensive technological improvement and quality management. Here, we describe the implementation and results of the first round robin trial for BRCA1/2 mutation testing in tumor tissue that was conducted in central Europe on May 2015, shortly after the approval and prior to the official release of olaparib. The high success rate of 81 % (21/26 test centers) demonstrates that BRCA1/2 multicenter mutation testing is well feasible in FFPE tumor tissue, extending to other tumor entities beyond ovarian cancer. The high number of test centers passing the trial demonstrates the success of the concerted efforts by German, Swiss, and Austrian pathology centers to ensure quality-controlled NGS-based testing and proves the potential of this technology in routine molecular pathology. On the basis of our results, we provide recommendations for predictive testing of tumor tissue for BRCA1/2 to clinical decision making in ovarian cancer patients

PD-L1 testing of non-small cell lung cancer using different antibodies and platforms: a Swiss cross-validation study.

With the approval of pembrolizumab for first- and second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC), PD-L1 testing by immunohistochemistry (IHC) has become a necessity. However, the DAKO autostainer ASL48 for the FDA approved DAKO 22C3 pharmDx assay is not broadly available in Switzerland and other parts of Europe. The primary goal of this study was to cross-validate the 22C3 anti-PD-L1 antibody on Benchmark Ultra (VBMU) and Leica Bond (LBO) immunostainers. IHC protocols were developed for 22C3 on both platforms with the 22C3phDx using ASL48 as reference. A tissue microarray (TMA) was constructed from 23 NSCLC specimens with a range of PD-L1 staining results. Empty TMA sections and the 22C3 antibody were distributed to 16 participants for staining on VBMU (8 centers) and/or LBO (12 centers) using the centrally developed protocols. Additionally the performance of the Ventana SP263 assay was tested in five centers. IHC scoring was performed centrally. Categorical PD-L1 staining (0-49% vs. 50-100%) did not significantly differ between centers using VBMU, whereas data from LBO were highly variable (p < 0.001). The SP263 assay was well concordant with 22C3 on VBMU and with 22C3 pharmDx. PD-L1 IHC using a standardized 22C3 protocol on VBMU provides satisfactory results in most centers. The SP263 assay is confirmed as a valid alternative to 22C3 pharmDx. 22C3 PD-L1 IHC on LBO shows major staining variability between centers, highlighting the need for local validation and adjustment of protocols

Status quo of ALK testing in lung cancer: results of an EQA scheme based on in-situ hybridization, immunohistochemistry, and RNA/DNA sequencing

With this external quality assessment (EQA) scheme, we aim to investigate the diagnostic performance of the currently available methods for the detection of ALK alterations in non-small cell lung cancer on a national scale, namely, in situ hybridization (ISH), immunohistochemistry (IHC), and RNA/DNA sequencing (NGS). The EQA scheme cohort consisted of ten specimens, including four ALK positive and six ALK negative samples, which were thoroughly pretested using IHC, ISH, and RNA/DNA NGS. Unstained tumor sections were provided to the 57 participants, and the results were retrieved via an online questionnaire. ISH was used by 29, IHC by 38, and RNA/DNA sequencing by 19 participants. Twenty-eight institutions (97%) passed the ring trial using ISH, 33 (87%) by using IHC, and 18 (95%) by using NGS. The highest sensitivity and interrater agreement (Fleiss ' kappa) was observed for RNA/DNA sequencing (99%, 0.975), followed by ISH (94%, 0.898) and IHC (92%, 0.888). However, the proportion of samples that were not evaluable due to bad tissue quality was also higher for RNA/DNA sequencing (4%) compared with ISH (0.7%) and IHC (0.5%). While all three methods produced reliable results between the different institutions, the highest sensitivity and concordance were observed for RNA/DNA sequencing. These findings encourage the broad implementation of this method in routine diagnostic, although the application might be limited by technical capacity, economical restrictions, and tissue quality of formalin-fixed samples