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.

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.

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.

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.

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.

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."

Changes in exercise capacity, quality of life and fatigue in cancer patients during an intervention.

The study explored the interdependence of changes in oxygen uptake, quality of life and cancer-related side-effect fatigue during a 4-month exercise intervention. Participants were during adjuvant (curative) or palliative therapy and post-adjuvant therapy (finished within the previous 12 months). Aerobic exercise capacity (VO2 peak), quality of life and fatigue symptom (EORTC QLQ-C30) were obtained in 101 cancer patients (30-77 years). After initial examination, patients participated in supervised and/or home-based training interventions. Patients were re-examined after 16-20 weeks and stratified into 3 subgroups (terciles) with respect to the absolute change in VO2 peak. The ANCOVA, with significant covariate effect for pretest fatigue score (F(5,101) = 8.150, P < 0.001), indicated significant differences between groups in outcome measures (P < 0.001). Based on the absolute change of VO2 peak (1.9 ± 1.7; 1.8 ± 0.8; 5.7 ± 2.8 ml/kg/min) there were significant differences in the quality of life improvement (17.2 ± 15.1 vs. 4.8 ± 22.0 points, P < 0.05) and cancer-related fatigue reduction (-6.1 ± 30.7; -11.5 ± 20.9; -21.2 ± 21.4 points) between upper and lower tercile. The findings point towards a relationship of exercise capacity enhancement, quality of life improvement and fatigue symptom reduction during and shortly after cancer treatment.

[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.

Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer.

BACKGROUND: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. METHODS: Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks. RESULTS: Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%). CONCLUSION: Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.

A randomised multicentre phase II study with cisplatin/docetaxel vs oxaliplatin/docetaxel as first-line therapy in patients with advanced or metastatic non-small cell lung cancer.

BACKGROUND: This study was designed to compare cisplatin/docetaxel with oxaliplatin/docetaxel in patients with advanced and metastatic non-small lung cancer as a first-line treatment. METHODS: Patients were randomly assigned to receive either cisplatin 75 mg m(-2) and docetaxel 75 mg m(-2) every 3 weeks or oxaliplatin 85 mg m(-2) and docetaxel 50 mg m(-2) every 2 weeks. The primary end point was response rate, and secondary end points were toxicity, time to progression and overall survival. RESULTS: A total of 88 patients (median age: 65 (39-86) years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95% CI: 33-61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17-43%) in the oxaliplatin/docetaxel arm (P=0.118). There was no significant difference in time to progression (6.3 vs 4.9 months, P=0.111) and median overall survival (11.6 vs 7.0 months, P=0.102) with cisplatin/docetaxel vs oxaliplatin/docetaxel, although slight trends favouring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs 11%), any grade fatigue (81% vs 59%), complete alopecia (76% vs 27%), any grade leukopenia (84% vs 61%) and grade 3/4 leukopenia (44% vs 14%) and neutropenia (56% vs 27%). CONCLUSION: Oxaliplatin/docetaxel has activity in metastatic non-small cell lung cancer, but it seems to be inferior to cisplatin/docetaxel.

Spectroscopy of element 115 decay chains.

A high-resolution α, x-ray, and γ-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated α-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z=115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z>112. Comprehensive Monte Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.

Validity of the six-minute walk test in cancer patients.

The present study evaluated the validity of the six-minute walk test (6MWT) in cancer patients. 50 subjects (36 f, 14 m; 57.4±10.2 years; during (56%) or off (44%) cancer treatment) performed a 6MWT and a spiroergometry on a cycle ergo-meter (0+25 W, 3 min) to evaluate maximum exercise capacity (VO2peak). A subsample (n=30) completed a retest of the 6MWT within 2-7 days. Patients covered a distance of 594±81 m during 6MWT at an average intensity of 86.3±9.6% of HRmax and achieved a VO2peak of 21.2±4.86 ml · kg - 1 · min - 1 during cycle ergometry. The distance walked correlated significantly (p<0.001) with VO2peak (r=0.67) and perceived physical function (EORTC QLQ-C30 physical function subscale) (r=0.55). Concerning reliability the intraclass correlation coefficient was r=0.93 (95%CI: +0.86;+0.97; p<0.001) and the coefficient of variation 3%. During retest participants walked 3.1% (95%CI: +1.1; +5.2) farther and achieved a higher RPE (+1.0; 95%CI: +0.3;+1.8). Limits of agreement were between - 43.1 and 76.4 m. In cancer patients the 6MWT seems to be as valid and reliable as in healthy elderly, cardiac and pulmonary patients. Thus, it can be recommended for use in cancer patients.

Exercise effects on HRV in cancer patients.

The present study evaluated the effects of physical exercise on heart rate variability (HRV) in cancer patients. 3 matched groups of each 15 tumour patients (60.4±8.9 years, 27 male, 18 female) were recruited: Physical exercise group 1 (acute treatment), Physical exercise group 2 (post treatment) and non-intervention group (acute treatment, no exercise). Exercise group patients received counselling for exercise and participated in a Nordic-Walking program. Short-term HRV-recordings, assessments of fatigue and quality of life (QoL) were performed prior to and 16 weeks after the exercise program initiation. MANCOVA revealed group × time differences in total power frequency domain of HRV and QoL (p<0.05). TP follow-up scores [logms(2)] differed significantly between non-intervention and intervention post treatment (2.0±0.5 vs. 2.6±0.5), but not between non-intervention and intervention during acute treatment. QoL follow-up scores differed significantly between non-intervention and intervention during acute treatment (47±15 vs. 64±18) and post treatment (47±15 vs. 69±19). Exercise enhances cardiac autonomic regulation of tumour patients during and after acute treatment. Because of the association of higher HRV-parameters and prolonged survival in cancer patients, improvement in autonomic control may be an important goal of exercise.

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.

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.

BACKGROUND: To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. RESULTS: Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). CONCLUSIONS: Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.