Rapid disintegration and weakening of ice shelves in North Greenland.

The glaciers of North Greenland are hosting enough ice to raise sea level by 2.1 m, and have long considered to be stable. This part of Greenland is buttressed by the last remaining ice shelves of the ice sheet. Here, we show that since 1978, ice shelves in North Greenland have lost more than 35% of their total volume, three of them collapsing completely. For the floating ice shelves that remain we observe a widespread increase in ice shelf mass losses, that are dominated by enhanced basal melting rates. Between 2000 and 2020, there was a widespread increase in basal melt rates that closely follows a rise in the ocean temperature. These glaciers are showing a direct dynamical response to ice shelf changes with retreating grounding lines and increased ice discharge. These results suggest that, under future projections of ocean thermal forcing, basal melting rates will continue to rise or remain at high level, which may have dramatic consequences for the stability of Greenlandic glaciers.

On the adsorption and reactivity of element 114, flerovium.

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

First Study on Nihonium (Nh, Element 113) Chemistry at TASCA.

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p 1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p 1/2 and 7p 3/2 orbitals. One unpaired electron in the outermost 7p 1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

Spectroscopy along Flerovium Decay Chains: Discovery of

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 µs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

[Calcium, phosphate and the calcium-sensing receptor : A proinflammatory combination in rheumatoid arthritis]. / Calcium, Phosphat und der Calcium-Sensing-Rezeptor : Ein proinflammatorischer Mix bei rheumatoider Arthritis.

Calcium and phosphate are necessary for the functionality of the organism and the cellular metabolism. In the form of hydroxyapatite, calcium and phosphate stabilize bone and teeth, but deposition of calcium phosphate in soft tissue or the vasculature can have devastating consequences. To prevent ectopic calcification, calcium and phosphate are stabilized by fetuin-A/alpha-2-HS-glycoprotein as non-crystalline, 60-100 nm-sized calciprotein particles (CPP) in extracellular fluids. An increase of the CPP concentration in the extracellular fluid beyond a certain threshold results in pro-inflammatory responses in monocytes and macrophages, which includes the activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome resulting in the release of interleukin-1ß and interleukin-18. The release of pro-inflammatory cytokines as a result of increased CPPs is enhanced in rheumatoid arthritis (RA). The calcium-sensing receptor plays a major role in this mechanism by modulating the uptake (macropinocytosis) of CPPs and thereby increasing the pro-inflammatory potential. Bone erosion and subsequent release of calcium and phosphate during the etiopathology of RA can therefore aggravate the joint inflammation in this disease.

Severe mesenteric ischemia with multiple organ failure in a patient previously treated with a humanized monoclonal antibody against programmed death receptor-1 (pembrolizumab), a case of pembrolizumab associated catastrophic antiphospholipid syndrome?

Immune checkpoint inhibitors are used in the treatment of different types of tumors including melanoma and non-small cell lung carcinoma. The use of these inhibitors is associated with a broad spectrum of immune-related adverse effects. Here we report a case of a patient admitted to the intensive care unit with multiple organ failure due to catastrophic antiphospholipid syndrome following treatment with pembrolizumab, an immune checkpoint inhibitor, because of metastatic melanoma. The presented patient had multiple organ failure of lung, gastro-intestinal, renal, and the liver. Vascular thrombosis was confirmed by both imaging (pulmonary embolism on computed tomography-thorax) and histopathological examination of the intestines. In combination with the presence of IgA anti-cardiolipin antibodies and initially IgM anti-cardiolipin antibodies, catastrophic antiphospholipid syndrome was suspected. Despite treatment with plasmapheresis and corticosteroids, the patient died due to multiple organ failure. Catastrophic antiphospholipid syndrome is difficult to recognize and has high mortality rates despite supportive treatment. In this case report, discussion is provided regarding the possible immunological mechanism behind catastrophic antiphospholipid syndrome during or after treatment with immune checkpoint inhibitors. It is important to realize that in modern intensive care unit, more patients with immune-related adverse effects of the treatment with immune checkpoint inhibitors will be admitted, because of an increase in the number of patients treated with these checkpoint inhibitors. When these patients are admitted on the intensive care unit, multi-disciplinary consultation is important because of the difficulty of early recognition and optimal treatment of these possible lethal side effects.

Search for Electron-Capture Delayed Fission in the New Isotope

The electron-capture decay followed by a prompt fission process was searched for in the hitherto unknown most neutron-deficient Md isotope with mass number 244. Alpha decay with α-particle energies of 8.73-8.86 MeV and with a half-life of 0.30_{-0.09}^{+0.19} s was assigned to ^{244}Md. No fission event with a similar half-life potentially originating from spontaneous fissioning of the short-lived electron-capture decay daughter ^{244}Fm was observed, which results in an upper limit of 0.14 for the electron-capture branching of ^{244}Md. Two groups of fission events with half-lives of 0.9_{-0.3}^{+0.6} ms and 5_{-2}^{+3} ms were observed. The 0.9_{-0.3}^{+0.6} ms activity was assigned to originate from the decay of ^{245}Md. The origin of eight fission events resulting in a half-life of 5_{-2}^{+3} ms could not be unambiguously identified within the present data while the possible explanation has to invoke previously unseen physics cases.

Prognostic factors and follow-up parameters in patients with paroxysmal nocturnal hemoglobinuria (PNH): experience of the Austrian PNH network.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by a deregulated complement system, chronic Coombs-negative, intravascular hemolysis, and a variable clinical course with substantial risk to develop thromboembolic events. We analyzed diagnostic and prognostic parameters as well as clinical endpoints in 59 adult patients suffering from PNH in 5 hematology centers in Austria (observation period: 1978-2015). Median follow-up time was 5.6 years. The median clone size at diagnosis amounted to 55% and was higher in patients with classical PNH (81%) compared to patients with PNH associated with aplastic anemia (AA) or myelodysplastic syndromes (MDS) (50%). The clone size also correlated with lactate dehydrogenase (LDH) levels. In one patient, anemia improved spontaneously and disappeared with complete normalization of LDH after 16 years. Seventeen patients received therapy with eculizumab. The rate of thromboembolic events was higher in the pre-eculizumab era compared with eculizumab-treated patients but did not correlate with the presence of age-related clonal hematopoiesis or any other clinical or laboratory parameters. Peripheral blood colony-forming progenitor cell counts were lower in PNH patients compared with healthy controls. Only two patients with classical PNH developed MDS. Overall, 7/59 patients died after 0.5-32 years. Causes of death were acute pulmonary hypertension, Budd-Chiari syndrome, and septicemia. Overall survival (OS) was mainly influenced by age and was similar to OS measured in an age-matched healthy Austrian control cohort. Together, compared with previous times, the clinical course and OS in PNH are favorable, which may be due to better diagnosis, early recognition, and eculizumab therapy.

Publisher's Note: Hydrogen Bonds in Excited State Proton Transfer [Phys. Rev. Lett. 117, 163002 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.163002.

Hydrogen Bonds in Excited State Proton Transfer.

Hydrogen bonding interactions between biological chromophores and their surrounding protein and solvent environment significantly affect the photochemical pathways of the chromophore and its biological function. A common first step in the dynamics of these systems is excited state proton transfer between the noncovalently bound molecules, which stabilizes the system against dissociation and principally alters relaxation pathways. Despite such fundamental importance, studying excited state proton transfer across a hydrogen bond has proven difficult, leaving uncertainties about the mechanism. Through time-resolved photoelectron imaging measurements, we demonstrate how the addition of a single hydrogen bond and the opening of an excited state proton transfer channel dramatically changes the outcome of a photochemical reaction, from rapid dissociation in the isolated chromophore to efficient stabilization and ground state recovery in the hydrogen bonded case, and uncover the mechanism of excited state proton transfer at a hydrogen bond, which follows sequential hydrogen and charge transfer processes.

Label-free impedimetric biosensor for Salmonella Typhimurium detection based on poly [pyrrole-co-3-carboxyl-pyrrole] copolymer supported aptamer.

The Gram-negative bacterium, Salmonella Typhimurium (S. Typhimurium) is a food borne pathogen responsible for numerous hospitalisations and deaths all over the world. Conventional detection methods for pathogens are time consuming and labour-intensive. Hence, there is considerable interest in faster and simpler detection methods. Polypyrrole-based polymers, due to their intrinsic chemical and electrical properties, have been demonstrated to be valuable candidates for the fabrication of chemo/biosensors and functional surfaces. Similarly aptamers have been shown to be good alternatives to antibodies in the development of affinity biosensors. In this study, we report on the combination of poly [pyrrole-co-3-carboxyl-pyrrole] copolymer and aptamer for the development of a label-less electrochemical biosensor suitable for the detection of S. Typhimurium. Impedimetric measurements were facilitated by the effect of the aptamer/target interaction on the intrinsic conjugation of the poly [pyrrole-co-3-carboxyl-pyrrole] copolymer and subsequently on its electrical properties. The aptasensor detected S. Typhimurium in the concentration range 10(2)-10(8) CFU mL(-1) with high selectivity over other model pathogens and with a limit of quantification (LOQ) of 100 CFU mL(-1) and a limit of detection (LOD) of 3 CFU mL(-1). The suitability of the aptasensor for real sample detection was demonstrated via recovery studies performed in spiked apple juice samples. We envisage this to be a viable approach for the inexpensive and rapid detection of pathogens in food, and possibly in other environmental samples.

Electrochemo-dynamical characterization of polypyrrole actuators coated on gold electrodes.

Polypyrrole coated gold wires were subjected to consecutive square current waves in LiClO4 aqueous solutions using the same constant anodic and cathodic charge. Parallel in situ diameter variations were followed using a laser scan micrometer. The procedure was repeated by changing one experimental variable every time: applied current, electrolyte concentration or working temperature to perform electrochemodynamical characterization of the system. On average, the diameter follows a linear variation of the consumed charge, as expected for any faradaic system, although a high dispersion was attained in the data. Such deviations were attributed to the presence of irreversible hydrogen evolution at the gold/polypyrrole interface at cathodic potentials more than 0.0 V vs. Ag/AgCl, detected and quantified from separated coulovoltammetric responses. Despite this parallel hydrogen evolution the consumed energy during reactions is a robust sensor of the working conditions. In conclusion a gold support, the metal most used for technological applications of conducting polymers, should be avoided when a device is driven by current flow in the presence of aqueous solutions, water contamination or moisture: a fraction of the charge will be consumed by hydrogen generation with possible degradation of the device.

New Short-Lived Isotope

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

[Hygiene in otorhinolaryngology: Requirements and reality]. / Hygiene in der Hals-Nasen-Ohren-Heilkunde: Anforderungen und Beobachtungen.

Considering the physiological contamination of skin and mucous membranes in the ear, nose, and throat region by facultative pathogen microorganisms, as well as the increase in multidrug resistant organisms (MDRO), it is mandatory that hygienic procedures be observed in ENT institutions, in order to prevent transmission of bacteria and infections in patients. General guidelines for hygiene in otorhinolaryngology are presented based on the recommendations published by the German Commission on Hospital Hygiene and Infection Prevention (KRINKO). These encompass hand hygiene, surface disinfection, and reprocessing of medical devices. The correct reprocessing of the various components of ENT treatment units (including endoscopes, water bearing systems) is reported. Although law requires and KRINKO recommends that manufacturers of medical devices publish instructions for reprocessing their products, these reprocessing recommendations are often insufficient. Manufacturers should thus be called upon to improve their recommendations. In this paper, the requirements for handling of ENT treatment units are compared with the observations made by the Public Health Department in 7 ENT clinics and 32 ENT practices in Frankfurt/Main, Germany, in 2014.

Rapid detection of cefotaxime-resistant Escherichia coli by LC-MS.

Antibiotic resistance is an unsolved healthcare problem with increasing impact on patient management in the last years. In particular, multidrug resistance among Gram-negative bacterial strains has become the most pressing challenge. In order to deliver the most efficacious antimicrobial therapy with minimum delay, rapid diagnostic tests are required in order to detect multidrug resistant pathogens early during infection. In line with these efforts, we have developed a mass spectrometry-based assay for the rapid determination of ampicillin and cefotaxime resistance. The assay quantifies beta-lactamase activities towards ampicillin and cefotaxime within a turnaround time of 150 min, which is substantially faster than classical susceptibility testing.

Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8+ T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer.

Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study.

[Hygiene in endoscopy in clinic and practice 2013 in comparison with 2003--structure and process quality]. / Struktur- und Prozessqualität bei der Aufbereitung flexibler Endoskope in Klinik und Praxis in Frankfurt am Main--2013 im Vergleich zu 2003.

BACKGROUND: Endoscopy is an important part of modern medical diagnostics and therapy. The invasive procedures are however associated with a risk to transmit infections. Against this background the KRINKO has published the "Hygienic requirements for the reprocessing of flexible endoscopes and endoscopic accessories" in 2002 and has updated these recommendations in 2012. In 2003 and 2013 all gastroenterological facilities in Frankfurt am Main using flexible endoscopes were monitored for compliance with the recommendations. METHODS: The inspections were performed after prior notice by a staff member of the health authority using a checklist which had been developed on the basis of the current KRINKO recommendations. RESULTS: In both years all institutions performing endoscopic procedures were visited: 2003 15 hospitals and 23 practices; 2013 14 clinics and 10 practices. In 2013 (data for 2003 in brackets) 100 % (93 %) of the hospitals and 60 % (22 %) of practices reprocessed their endoscopes by automated methods. The appropriate reprocessing and filling of water bottles for rinsing the scope channels with sterile water and the sterilisation of accessories were satisfactorily performed in 2003 and 2013 by all hospitals. However in 2013 only 90 % (2003: 74 %) of the practices correctly reprocessed water bottles and 80 % (52 %) used sterile water for filling the bottle. In 2013 100 % (2003: 57 %) of the practices correctly sterilised accessory instruments, while 2 practices used disposable, i. e., single-use materials. In 2013 all institutions performed microbiological tests according to KRINKO recommendations, while in 2003 all hospitals but only 43 % of the practices could present such tests. DISCUSSION: While the gastroenterological departments of Frankfurt hospitals already complied with the KRINKO recommendations in 2003, the inspection of several practices in 2003 had revealed considerable shortcomings in the implementation of these recommendations. Subsequently the practices have improved their hygiene management.

Nuclear chemistry. Synthesis and detection of a seaborgium carbonyl complex.

Experimental investigations of transactinoide elements provide benchmark results for chemical theory and probe the predictive power of trends in the periodic table. So far, in gas-phase chemical reactions, simple inorganic compounds with the transactinoide in its highest oxidation state have been synthesized. Single-atom production rates, short half-lives, and harsh experimental conditions limited the number of experimentally accessible compounds. We applied a gas-phase carbonylation technique previously tested on short-lived molybdenum (Mo) and tungsten (W) isotopes to the preparation of a carbonyl complex of seaborgium, the 106th element. The volatile seaborgium complex showed the same volatility and reactivity with a silicon dioxide surface as those of the hexacarbonyl complexes of the lighter homologs Mo and W. Comparison of the product's adsorption enthalpy with theoretical predictions and data for the lighter congeners supported a Sg(CO)6 formulation.

48Ca+249Bk fusion reaction leading to element Z = 117: long-lived α-decaying 270Db and discovery of 266Lr.

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."