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).

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.

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.

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of 76 Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

Pulse shape analysis in Gerda Phase II.

The GERmanium Detector Array (Gerda) collaboration searched for neutrinoless double- ß decay in 76 Ge using isotopically enriched high purity germanium detectors at the Laboratori Nazionali del Gran Sasso of INFN. After Phase I (2011-2013), the experiment benefited from several upgrades, including an additional active veto based on LAr instrumentation and a significant increase of mass by point-contact germanium detectors that improved the half-life sensitivity of Phase II (2015-2019) by an order of magnitude. At the core of the background mitigation strategy, the analysis of the time profile of individual pulses provides a powerful topological discrimination of signal-like and background-like events. Data from regular 228 Th calibrations and physics data were both considered in the evaluation of the pulse shape discrimination performance. In this work, we describe the various methods applied to the data collected in Gerda Phase II corresponding to an exposure of 103.7 kg year. These methods suppress the background by a factor of about 5 in the region of interest around Q ß ß = 2039  keV, while preserving ( 81 ± 3 ) % of the signal. In addition, an exhaustive list of parameters is provided which were used in the final data analysis.

Characterization of inverted coaxial 76 Ge detectors in GERDA for future double- ß decay experiments.

Neutrinoless double- ß decay of 76 Ge is searched for with germanium detectors where source and detector of the decay are identical. For the success of future experiments it is important to increase the mass of the detectors. We report here on the characterization and testing of five prototype detectors manufactured in inverted coaxial (IC) geometry from material enriched to 88% in 76 Ge. IC detectors combine the large mass of the traditional semi-coaxial Ge detectors with the superior resolution and pulse shape discrimination power of point contact detectors which exhibited so far much lower mass. Their performance has been found to be satisfactory both when operated in vacuum cryostat and bare in liquid argon within the Gerda setup. The measured resolutions at the Q-value for double- ß decay of 76 Ge ( Q ß ß  = 2039 keV) are about 2.1 keV full width at half maximum in vacuum cryostat. After 18 months of operation within the ultra-low background environment of the GERmanium Detector Array (Gerda) experiment and an accumulated exposure of 8.5 kg · year, the background index after analysis cuts is measured to be 4 . 9 - 3.4 + 7.3 × 10 - 4 counts / ( keV · kg · year ) around Q ß ß . This work confirms the feasibility of IC detectors for the next-generation experiment Legend.

Calibration of the Gerda experiment.

The GERmanium Detector Array (Gerda) collaboration searched for neutrinoless double- ß decay in 76 Ge with an array of about 40 high-purity isotopically-enriched germanium detectors. The experimental signature of the decay is a monoenergetic signal at Q ß ß = 2039.061 ( 7 )  keV in the measured summed energy spectrum of the two emitted electrons. Both the energy reconstruction and resolution of the germanium detectors are crucial to separate a potential signal from various backgrounds, such as neutrino-accompanied double- ß decays allowed by the Standard Model. The energy resolution and stability were determined and monitored as a function of time using data from regular 228 Th calibrations. In this work, we describe the calibration process and associated data analysis of the full Gerda dataset, tailored to preserve the excellent resolution of the individual germanium detectors when combining data over several years.

Characterization of 30 76 Ge enriched Broad Energy Ge detectors for GERDA Phase II.

The GERmanium Detector Array (Gerda) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double-beta decay of 76 Ge into 76 Se+2e - . Gerda has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new 76Ge enriched detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the Hades underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for Gerda Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the accuracy of pulse shape simulation codes.

Discriminant ability of the Eating Assessment Tool-10 to detect aspiration in individuals with amyotrophic lateral sclerosis.

BACKGROUND: Oropharyngeal dysphagia is prevalent in individuals with amyotrophic lateral sclerosis (ALS) leading to malnutrition, aspiration pneumonia, and death. These factors necessitate early detection of at-risk patients to prolong maintenance of safe oral intake and pulmonary function. This study aimed to evaluate the discriminant ability of the Eating Assessment Tool (EAT-10) to identify ALS patients with unsafe airway protection during swallowing. METHODS: Seventy ALS patients completed the EAT-10 survey and underwent a standardized videofluoroscopic evaluation of swallowing. Two blinded raters determined airway safety using the Penetration Aspiration Scale (PAS). A between groups anova (safe vs penetrators vs aspirators) was conducted and sensitivity, specificity, area under the curve (AUC), and likelihood ratios calculated. KEY RESULTS: Mean EAT-10 scores for safe swallowers, penetrators, and aspirators (SEM) were: 4.28 (0.79) vs 7.10 (1.79) vs 20.50 (3.19), respectively, with significant differences noted for aspirators vs safe swallowers and aspirators vs penetrators (p < 0.001). The EAT-10 demonstrated good discriminant ability to accurately identify ALS penetrator/aspirators (PAS ≥3) with a cut off score of 3 (AUC: 0.77, sensitivity: 88%, specificity: 57%). The EAT-10 demonstrated excellent accuracy at identifying aspirators (PAS ≥6) utilizing a cut off score of 8 (AUC: 0.88, sensitivity: 86%, specificity: 72%, likelihood ratio: 3.1, negative predictive value: 95.5%). CONCLUSIONS & INFERENCES: The EAT-10 differentiated safe vs unsafe swallowing in ALS patients. This patient self-report scale could represent a quick and meaningful aide to dysphagia screening in busy ALS clinics for the identification and referral of dysphagic patients for further instrumental evaluation.

Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral neuropathy: a clinical and electrophysiologic study.

AIMS: The appearance of peripheral neuropathy is the dose-limiting toxicity in many chemotherapy protocols, and glutamine has been proposed as a potentially neuroprotective agent in patients receiving paclitaxel. MATERIALS AND METHODS: In this non-randomised study, we assessed neurologic signs and symptoms, and changes in nerve-conduction studies in 46 consecutive patients given high-dose paclitaxel either with (n=17) or without (n=29) glutamine. Neurological assessments and electrodiagnostic studies were carried out at baseline and at least 2 weeks (median 32 days) after treatment. RESULTS: Patients who received glutamine developed significantly less weakness (P = 0.02), less loss of vibratory sensation (P = 0.04) and less toe numbness (P = 0.004) than controls. The per cent change in the compound motor action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes after paclitaxel treatment was lower in the glutamine group, but this finding was not statistically significant in these small groups. CONCLUSIONS: In this study, serial neurologic assessment of patient symptoms and signs seemed to be a better indicator of a possible glutamine effect than sensory- or motor-nerve-conduction studies. Prospective randomised trials are needed to clarify the effect of glutamine on paclitaxel and other types of chemotherapy-induced neuropathy.

Team for the Assessment of Psychiatric Services (TAPS) Project 33: prospective follow-up study of long-stay patients discharged from two psychiatric hospitals.

OBJECTIVE: The purpose of this study was to evaluate the policy of closing psychiatric hospitals and replacing their functions with community-based services. METHOD: All long-stay nondemented patients in two U.K. hospitals scheduled for closure were assessed with a series of schedules. All patients in one hospital and a proportion of those in the other hospital were reassessed 1 year after discharge to community facilities. RESULTS: Of the 737 patients discharged from the two hospitals, 24 died before follow-up, two by suicide. Follow-up was successful for 94.6% of the survivors. Only seven patients were lost to follow-up and are presumed to have become homeless. Only two patients went to prison, one briefly. There was very little change in patients' psychiatric symptoms or social behavior problems. The community homes provided a much less restrictive environment than the hospital wards. Discharged patients were very appreciative of their increased freedom, and over 80% wished to stay in their community homes. There was an increase in the proportion of patients with incontinence and immobility. The patients' social lives were enriched by an increase in friends, and some made contact with neighbors and others in the community. However, there was a decrease in contact with relatives following discharge. CONCLUSIONS: When the capital and revenue resources of a psychiatric hospital are reinvested in community services, based on staffed houses, there are few problems with crime or homelessness. With such well-resourced services, the benefits greatly outweigh the disadvantages for both old and new long-stay patients.

A "dystrophic" variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene.

OBJECTIVES: To identify the disease-causing mutation and its molecular consequence for a clinically distinct type of myotonic myopathy. BACKGROUND: The authors encountered a unique myotonic disorder of early onset in a 37-year-old man and his 47-year-old sister. METHODS: After examining known loci of inherited myotonic disorders, the authors looked for mutations within the CLCN1 gene using single strand conformation polymorphism and direct sequencing. To investigate the disease mechanism, reverse transcriptase PCR analyses of total RNA were performed. RESULTS: In the proband and his affected sister, two novel mutations comprising a compound heterozygous state in the CLCN1 gene were identified: 1) a base (G) insertion in exon 7 generating a premature termination codon (fs289X) in the D5 domain, and 2) a C-to-T substitution in exon 23 resulting in a missense mutation (P932L). These mutations accompanied a clinical phenotype that is distinguishable from recessive myotonia congenita by progressive generalized muscle weakness, severe distal muscle atrophy, joint contractures, high serum creatine kinase levels, and conspicuous myopathic changes on muscle histopathology. Reverse transcriptase PCR analyses detected only the P932L mutant mRNA in skeletal muscle, suggesting that the fs289X mRNA is degraded rapidly. CONCLUSIONS: These data suggest that fs289X is a null mutation, rendering the patients with the compound heterozygous genotype of fs289X/P932L to exclusively express P932L homomeric channels that may have caused the "dystrophic" phenotype.

Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain. METHODS: This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics. RESULTS: Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.

Excess deaths attributable to influenza in England and Wales: age at death and certified cause.

The multiple regression statistical method has already been used to estimate excess deaths attributable to influenza in England and Wales by winter period. Now we report further studies of deaths by age group and certified cause of death. During the ten winters since the influenza A/Hong Kong (H3N2) virus first arrived (1968/69 to 1977/78) there have been about 120,000 excess deaths. Of these about 82% were estimated to be in those aged 65+ years, 17% in the 40-64 year age group and 1% in younger adults. Sixty-seven per cent were certified as due to respiratory disease and 31% due to circulatory system disease. Respiratory deaths increased in all age groups during an epidemic, but of the deaths certified as due to circulatory disease, cerebrovascular deaths were mostly in the 65+ age group and ischaemic heart disease deaths in the 40-64 year age group. In this 40-64 year age group there was evidence that the effects of cold weather and epidemic influenza were multiplicative rather than additive. During the worst influenza winter of 1969/70 respiratory deaths increased by approximately 55% and circulatory system deaths by 4%. Deaths in the elderly increased by 10%, in those aged 40-60 years by 8% and in younger adults by 4%. There was no evidence that excess deaths are followed by a deficit during the following year.

Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial. RESEARCH DESIGN AND METHODS: Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days. RESULTS: A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache. CONCLUSIONS: Tramadol provides long-term relief of the pain of diabetic neuropathy.

A thermodynamic analysis of the Collander equation and establishment of a reference solvent for use in drug partitioning studies.

A thermodynamic analysis of the Collander equation, ln PI = a + b ln PII (I and II refer to two different partitioning systems with partition coefficients PI and PII, respectively), is given and applied to three forms of correlation. The intercept, a, is shown to have no general fundamental significance whereas the slope, b is shown to reflect differences in non-aqueous solvent properties; b is also shown to be of use in scaling solvent behaviour to select solvents which closely represent biological membrane properties for use in partitioning studies. Laboratory and literature data are subjected to the analysis.

Quality of life of long-stay patients discharged from two psychiatric institutions.

OBJECTIVE: The study compared the quality of life of long-stay psychiatric patients after they had been discharged to community residences for one year with that of long-stay patients who remained hospitalized. METHODS: Long-stay patients (that is, those with stays of at least one year) who were discharged from two psychiatric hospitals in London were closely matched with patients likely to stay in the hospital for another year. Baseline (in-hospital) and one-year follow-up assessments were conducted using six instruments to measure factors related to quality of life such as problems in social functioning and size of the social network. RESULTS: A total of 494 discharged patients were compared with 279 patients who remained in the hospital. The death rate did not differ between the two groups. Only six discharged patients became vagrants, and only two were imprisoned, one briefly. Discharged patients were living under much less restrictive conditions, they preferred their life in the community, and the number of their friends increased, as did the number of acquaintances in the community such as neighbors. No adverse effects of discharge on mental state or social behavior were noted. CONCLUSIONS: The results indicate that community care is a beneficial alternative to long-term care in psychiatric hospitals for the majority of patients, provided it is well planned and adequate resources are available.

Emotional distress in doctors: sources, effects and help sought.

All doctors in a London Teaching Hospital were sent a self-administered, anonymous questionnaire, to study past episodes of emotional distress. We inquired about frequency of past and current emotional distress, sources of distress, effects on work and home life, type of help sought and perceived outcome of that help. Of 320 doctors, 210 (66%) responded. One hundred and forty-one (68%) reported previous episodes of moderate or severe emotional distress. Logistic regression revealed that distress was significantly more common in younger doctors and in women. Many respondents reported work problems as causing their distress and work was frequently adversely affected by episodes of distress. Professional help was rarely sought; non-professional help was from family and friends. Current emotional distress was related to a history of past distress, especially among the most junior doctors. We conclude that past emotional distress is reported by most doctors, with work pressures an important contributing factor. Doctors do not appear to use available sources of professional help. Our findings confirm that doctors have difficulty disclosing psychological problems. Specific programmes aimed at prevention and management of distress in doctors need to be initiated and evaluated.