Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

Dual-comb optical parametric oscillator in the mid-infrared based on a single free-running cavity.

We demonstrate a free-running single-cavity dual-comb optical parametric oscillator (OPO) pumped by a single-cavity dual-comb solid-state laser. The OPO ring cavity contains a single periodically-poled MgO-doped LiNbO3 (PPLN) crystal. Each idler beam has more than 245-mW average power at 3550 nm and 3579 nm center wavelengths (bandwidth 130 nm). The signal beams are simultaneously outcoupled with more than 220 mW per beam at 1499 nm and 1496 nm center wavelength. The nominal repetition rate is 80 MHz, while the repetition rate difference is tunable and set to 34 Hz. To evaluate the feasibility of using this type of source for dual-comb applications, we characterize the noise and coherence properties of the OPO signal beams. We find ultra-low relative intensity noise (RIN) below -158 dBc/Hz at offset frequencies above 1 MHz. A heterodyne beat note measurement with a continuous wave (cw) laser is performed to determine the linewidth of a radio-frequency (RF) comb line. We find a full-width half-maximum (FWHM) linewidth of around 400 Hz. Moreover, the interferometric measurement between the two signal beams reveals a surprising property: the center of the corresponding RF spectrum is always near zero frequency, even when tuning the pump repetition rate difference or the OPO cavity length. We explain this effect theoretically and discuss its implications for generating stable low-noise idler combs suitable for high-sensitivity mid-infrared dual-comb spectroscopy (DCS).

Erratum: First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

This corrects the article DOI: 10.1103/PhysRevLett.125.011801.

51-W average power, 169-fs pulses from an ultrafast non-collinear optical parametric oscillator.

We present a high power optical parametric oscillator (OPO) synchronously pumped by the second-harmonic of a modelocked 1030-nm thin-disk laser (TDL) oscillator. The OPO delivers an average power of 51.1 W around degeneracy (1030 nm) with a 10.2-MHz repetition-rate. After extra-cavity dispersion compensation using dispersive mirrors, we obtain a pulse duration of 169 fs, which is 4.6× shorter than the TDL pulse duration of 770 fs. The TDL has 250 W average power, which is converted to 215 W at the second-harmonic. Hence, the OPO exhibits a high photon conversion efficiency of 47% (ratio of signal photons to 515-nm pump photons). Moreover, the OPO generates a peak power of 26.2 MW, which is very similar to the 28.0-MW peak power of the TDL. To facilitate continuous tuning around degeneracy and convenient extraction of the pump and idler beams, the OPO is operated in a noncollinear configuration. A linear cavity configuration was chosen since it offers easy alignment and straightforward cavity length tuning. To the best of our knowledge, this source has the highest average power generated by any ultrafast OPO, and the shortest pulse duration for any >5-W OPO. This result is an important step to adding wavelength tunability to high power Yb-based laser sources without the complexity of either laser or parametric amplifier systems.

The Soret coefficients of the ternary system water/ethanol/triethylene glycol and its corresponding binary mixtures.

Thermodiffusion in ternary mixtures is considered prototypic for the Soret effect of truly multicomponent systems. We discuss ground-based measurements of the Soret coefficient along the binary borders of the Gibbs triangle of the highly polar and hydrogen bonding ternary DCMIX3-system water/ethanol/triethylene glycol. All three Soret coefficients decay with increasing concentration, irrespective of the choice of the independent component, and show a characteristic sign change as a function of temperature and/or composition. With the exception of triethylene glycol/ethanol at high temperatures, the minority component always migrates toward the cold side. All three binaries exhibit temperature-independent fixed points of the Soret coefficient. The decay of the Soret coefficient with concentration can be related to negative excess volumes of mixing. The sign changes of the Soret coefficients of the binaries allow to draw far-reaching conclusions about the signs of the Soret coefficients of the corresponding ternary mixtures. In particular, we show that at least one ternary composition must exist, where all three Soret coefficients vanish simultaneously and no steady-state separation is observable.

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model.

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment.

Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-ß decay experiment which operates high-purity germanium detectors enriched in ^{76}Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c^{2} to 1 MeV/c^{2}. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c^{2} have been set. As an example, at a mass of 150 keV/c^{2} the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of g_{ae}<3×10^{-12} and α^{'}/α<6.5×10^{-24} at 90% credible interval, respectively, were obtained.

Final Results of GERDA on the Search for Neutrinoless Double-ß Decay.

The GERmanium Detector Array (GERDA) experiment searched for the lepton-number-violating neutrinoless double-ß (0νßß) decay of ^{76}Ge, whose discovery would have far-reaching implications in cosmology and particle physics. By operating bare germanium diodes, enriched in ^{76}Ge, in an active liquid argon shield, GERDA achieved an unprecedently low background index of 5.2×10^{-4} counts/(keV kg yr) in the signal region and met the design goal to collect an exposure of 100 kg yr in a background-free regime. When combined with the result of Phase I, no signal is observed after 127.2 kg yr of total exposure. A limit on the half-life of 0νßß decay in ^{76}Ge is set at T_{1/2}>1.8×10^{26} yr at 90% C.L., which coincides with the sensitivity assuming no signal.

Development of selected bacterial groups of the rectal microbiota of healthy calves during the first week postpartum.

AIMS: The intestinal microbiota of newborn calves is largely unexplored even if it is of great significance for their future health. Therefore, the aim of the study was to gain a better insight into the development dynamics of certain bacterial groups during the first week of life. METHODS AND RESULTS: Faecal samples of healthy Simmental calves (dual-purpose breed; n = 80), bottle fed and raised in a dairy farm were taken immediately after birth and at 6/12/24/48/72/168 h (h) after birth. Samples were analysed using cultural, biochemical and molecular-biological methods. The aerobe, anaerobe, Enterobacteriaceae and Enterococcus counts of healthy calves increased significantly between 6 and 24 h postpartum (P <0·05). Apart from the anaerobes, bacterial counts decreased after reaching a plateau at 24-48 h. Enterococcus faecalis was detected in significantly higher counts compared to E. faecium (P <0·05). Lactobacilli developed more slowly and increased until day 7 after birth to a mean value of 6·8 × 107  CFU per g. MALDI-TOF analysis of 2338 lactobacilli isolates resulted in 36 different species. CONCLUSIONS: Lactobacillus reuteri became the most common Lactobacillus sp. during the first week of life. SIGNIFICANCE AND IMPACT OF THE STUDY: This fact seems to be very important for the calf's intestinal health because L. reuteri is known to show in vitro bactericidal effects against bacterial pathogens and anti-infective activities against rotaviruses and Cryptosporidium parvum.

Vesicle shrinkage in hydrous phonolitic melt during cooling.

The ascent of hydrous magma prior to volcanic eruptions is largely driven by the formation of H2O vesicles and their subsequent growth upon further decompression. Porosity controls buoyancy as well as vesicle coalescence and percolation, and is important when identifying the differences between equilibrium or disequilibrium degassing from textural analysis of eruptive products. Decompression experiments are routinely used to simulate magma ascent. Samples exposed to high temperature (T) and pressure (P) are decompressed and rapidly cooled to ambient T for analysis. During cooling, fluid vesicles may shrink due to decrease of the molar volume of H2O and by resorption of H2O back into the melt driven by solubility increase with decreasing T at P < 300 MPa. Here, we quantify the extent to which vesicles shrink during cooling, using a series of decompression experiments with hydrous phonolitic melt (5.3-3.3 wt% H2O, T between 1323 and 1373 K, decompressed from 200 to 110-20 MPa). Most samples degassed at near-equilibrium conditions during decompression. However, the porosities of quenched samples are significantly lower than expected equilibrium porosities prior to cooling. At a cooling rate of 44 K·s-1, the fictive temperature T f, where vesicle shrinkage stops, is up to 200 K above the glass transition temperature (T g), Furthermore, decreasing cooling rate enhances vesicles shrinkage. We assess the implications of these findings on previous experimental degassing studies using phonolitic melt, and highlight the importance of correctly interpreting experimental porosity data, before any comparison to natural volcanic ejecta can be attempted.

Porphyromonas gingivalis lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain.

AIM: To determine whether Porphyromonas gingivalis lipopolysaccharide (LPS) can directly activate trigeminal neurons, to identify which receptors are involved and to establish whether activation leads to secretion of the neuropeptide calcitonin gene-related peptide (CGRP) and/or the translocation of NF-κB. METHODOLOGY: Mouse trigeminal ganglion (TG) cells were cultured in vitro for 2 days. The effect of P. gingivalis LPS (20 µg mL-1 ) on calcium signalling was assessed (by calcium imaging using Cal-520 AM) in comparison with the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100 µmol L-1 ), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1 µmol L-1 ) and high potassium (60 mmol L-1 KCl). TG cultures were pre-treated with either 1 µmol L-1 CLI-095 to block Toll-like receptor 4 (TLR4) signalling or with 3 µmol L-1 HC-030031 to block TRPA1 signalling. CGRP release was determined using ELISA, and nuclear translocation of NF-κB was investigated using immunocytochemistry. Data were analysed by one-way analysis of variance, followed by Bonferroni's post hoc test as appropriate. RESULTS: Porphyromonas gingivalis LPS directly exerted a rapid excitatory response on sensory neurons and non-neuronal cells (P < 0.001 to P < 0.05). The effects on neurons appear to be mediated via TLR4- and TRPA1-dependent pathways. The responses were accompanied by an increased release of CGRP (P < 0.001) and by NF-κB nuclear translocation (P < 0.01). CONCLUSIONS: Porphyromonas gingivalis LPS directly activated trigeminal sensory neurons (via TLR4 and TRPA1 receptors) and non-neuronal cells, resulting in CGRP release and NF-κB nuclear translocation. This indicates that P. gingivalis can directly influence activity in trigeminal sensory neurons and this may contribute to acute and chronic inflammatory pain.

[Conservative treatment of periprosthetic humeral fractures years after cemented fracture prostheses : A case series]. / Konservative Therapie periprothetischer Humerusfrakturen Jahre nach zementierter Frakturprothese : Eine Fallserie.

BACKGROUND: The exact incidence of postoperative periprosthetic humeral fractures (PPHF) months or years after fracture-related implantation of a hemiprosthesis is unknown. The currently available literature is predominantly concerned with operative treatment approaches. As a rule, these involved older patients and severe fracture conditions so that severe complications and unsatisfactory healing results were described. This article presents an alternative conservative treatment approach which is discussed based on the results of treatment. PATIENTS AND METHODS: Between 2011 and 2016 a conservative treatment of 5 female patients with PPHF could be carried out. Of the patients 4 were clinically and radiologically controlled at a mean follow-up time of 23 months. The fifth patient died 2 months after the trauma and only partial information of the treatment was available. RESULT: There were no intrahospital complications and just one posthospital complication. In the case of the patient who later died, repeated and unauthorized removal of the upper arm brace occurred in the nursing institution resulting in a lesion of the radial nerve. Of the four patients who completed treatment, three were very satisfied with the outcome of treatment. The mean DASH (Disabilities of Arm, Shoulder and Hand) and Oxford shoulder scores were on average 74 and 25 points, respectively. At the time of the follow-up examination all patients were free of pain, without the use of analgesics; however, there were still some limitations in the activities of daily life, which in three of the four patients was similar to the results following implantation of the fracture prosthesis. CONCLUSION: The conservative treatment of PPHF can be a safe treatment option in multimorbid and chronically ill patients. A close outpatient control and good patient compliance are important. In incompliant and dementia patients, the risk of failure of conservative treatment is increased.

Complications and results of the arthrodesis after total ankle arthroplasty failure: a retrospective monocentric study of 12 cases.

INTRODUCTION: Total ankle arthroplasty (TAA) has the objective to maintain the range of motion of the tibiotarsal joint and to preserve the nearby joints. However, the complication rate and failures remain quite high after TAA. The main objective of the study was to evaluate the improvement in the functional scores of the tibiotarsal arthrodesis after TAA failure. The secondary objective was to assess the specific complications. MATERIALS AND METHODS: This monocentric retrospective series includes 12 patients (nine men, three women, average age 52.5 years) operated between 2003 and 2018. An iliac graft was used in all cases. The arthrodesis was stabilized either by screws or by retrograde nailing. RESULTS: The reoperation was due to painful malleolar conflicts or loosening. The AOFAS score increased from 38/100 to 67/100 (51-86) post-operatively. The fusion was acquired at 3.7 months (3-6) except in two cases. DISCUSSION AND CONCLUSION: The 83% primary fusion rate is in the low average of the literature and 92% fusion rate in the high average after reoperation. All patients were improved even in two non-unions. The results of this study confirm that the arthrodesis after TAA failure is a reliable alternative to the TAA replacement. However, they are lower than those after a first-line arthrodesis.

Studies of pear-shaped nuclei using accelerated radioactive beams.

There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.

Team planning discussion and clinical performance: a prospective, randomised, controlled simulation trial.

Planning held before emergency management of a critical situation might be an invaluable asset for optimising team preparation. The purpose of this study was to investigate whether a brief planning discussion improved team performance in a simulated critical care situation. Forty-four pairs of trainees in anaesthesia and intensive care were randomly allocated to either an intervention or control group before participating in a standardised simulated scenario. Twelve different scenarios were utilised. Groups were stratified by postgraduate year and simulated scenario, and a facilitator was embedded in the scenario. In the intervention group, the pairs had an oral briefing followed by a 4-min planning discussion before starting the simulation. The primary end-point was clinical performance, as rated by two independent blinded assessors on a score of 0-100 using video records and pre-established scenario-specific checklists. Crisis resource management and stress response (cognitive appraisal ratio) were also assessed. Two pairs were excluded for technical reasons. Clinical performance scores were higher in the intervention group; mean (SD) 51 (9) points vs. 46 (9) in the control group, p = 0.039. The planning discussion was also associated with higher crisis resource management scores and lower cognitive appraisal ratios, reflecting a positive response. A 4-min planning discussion before a simulated critical care situation improved clinical team performance and cognitive appraisal ratios. Team planning should be integrated into medical education and clinical practice.

Improved Limit on Neutrinoless Double-ß Decay of

The GERDA experiment searches for the lepton-number-violating neutrinoless double-ß decay of ^{76}Ge (^{76}Ge→^{76}Se+2e^{-}) operating bare Ge diodes with an enriched ^{76}Ge fraction in liquid argon. The exposure for broad-energy germanium type (BEGe) detectors is increased threefold with respect to our previous data release. The BEGe detectors feature an excellent background suppression from the analysis of the time profile of the detector signals. In the analysis window a background level of 1.0_{-0.4}^{+0.6}×10^{-3} counts/(keV kg yr) has been achieved; if normalized to the energy resolution this is the lowest ever achieved in any 0νßß experiment. No signal is observed and a new 90% C.L. lower limit for the half-life of 8.0×10^{25} yr is placed when combining with our previous data. The expected median sensitivity assuming no signal is 5.8×10^{25} yr.

Evolution of the IgE and IgG repertoire to a comprehensive array of allergen molecules in the first decade of life.

BACKGROUND: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. OBJECTIVE: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years. METHODS: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™). RESULTS: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule. CONCLUSIONS: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects.

The transcription factor XBP1s restores hippocampal synaptic plasticity and memory by control of the Kalirin-7 pathway in Alzheimer model.

Neuronal network dysfunction and cognitive decline constitute the most prominent features of Alzheimer's disease (AD), although mechanisms causing such impairments are yet to be determined. Here we report that virus-mediated delivery of the active spliced transcription factor X-Box binding protein 1s (XBP1s) in the hippocampus rescued spine density, synaptic plasticity and memory function in a mouse model of AD. XBP1s transcriptionally activated Kalirin-7 (Kal7), a protein that controls synaptic plasticity. In addition, we found reduced levels of Kal7 in primary neurons exposed to Aß oligomers, transgenic mouse models and human AD brains. Short hairpin RNA-mediated knockdown of Kal7 altered synaptic plasticity and memory formation in naive mice. Further, reduction of endogenous Kal7 compromised the beneficial effects of XBP1s in Alzheimer's model. Hence, our findings reveal that XBP1s is neuroprotective through a mechanism that engages Kal7 pathway with therapeutic implications in AD pathology.

[Atypical distal tibial shaft fractures in a patient with bilateral TKA and antiresorptive treatment]. / Atypische distale Tibiaschaftfrakturen bei liegenden KTEP beidseits unter antiresorptiver Therapie.

There are many cases in the literature that describe atypical femur fractures under antiresorptive therapy. Other localizations of fractures of this genesis, especially if occurring bilaterally, are rare. This case reports about the diagnosis, treatment and process of a 76-year old patient, who within a 4­month period suffered from bilateral distal tibial shaft fractures, after years of treatment with bisphosphonates, strontium ranelate and denosumab.