New Constraint on the Local Relic Neutrino Background Overdensity with the First KATRIN Data Runs.

We report on the direct search for cosmic relic neutrinos using data acquired during the first two science campaigns of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity molecular tritium gas source are analyzed by a high-resolution MAC-E filter around the end point at 18.57 keV. The analysis is sensitive to a local relic neutrino overdensity ratio of η<9.7×10^{10}/α (1.1×10^{11}/α) at a 90% (95%) confidence level with α=1 (0.5) for Majorana (Dirac) neutrinos. A fit of the integrated electron spectrum over a narrow interval around the end point accounting for relic neutrino captures in the tritium source reveals no significant overdensity. This work improves the results obtained by the previous neutrino mass experiments at Los Alamos and Troitsk. We furthermore update the projected final sensitivity of the KATRIN experiment to η<1×10^{10}/α at 90% confidence level, by relying on updated operational conditions.

Incidence of Drug-Induced Delirium During Treatment With Antidepressants or Antipsychotics: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2016.

OBJECTIVES: Successful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium. METHODS: This observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics. RESULTS: A total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID. CONCLUSIONS: With an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.

Galactorrhea during antipsychotic treatment: results from AMSP, a drug surveillance program, between 1993 and 2015.

Galactorrhea is a well-known adverse drug reaction (ADR) of numerous antipsychotic drugs (APD) and is often distressing for those affected. Methodological problems in the existing literature make it difficult to determine the prevalence of symptomatic hyperprolactinemia in persons treated with APDs. Consequently, a large sample of patients exposed to APDs is needed for more extensive evaluation. Data on APD utilization and reports of galactorrhea caused by APDs were analyzed using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2015. 320,383 patients (175,884 female inpatients) under surveillance were treated with APDs for schizophrenia and other indications. A total of 170 events of galactorrhea caused by APDs were identified (0.97 cases in 1000 female inpatient admissions). Most cases occurred during the reproductive age with the highest incidence among patients between 16 and 30 years (3.81 cases in 1000 inpatients). The APDs that were most frequently imputed alone for inducing galactorrhea were risperidone (52 cases and 0.19% of all exposed inpatients), amisulpride (30 resp. 0.48%), and olanzapine (13 resp. 0.05%). In three cases, quetiapine had a prominent role as a probable cause for galactorrhea. High dosages of the imputed APDs correlated with higher rates of galactorrhea. Galactorrhea is a severe and underestimated condition in psychopharmacology. While some APDs are more likely to cause galactorrhea, we identified a few unusual cases. This highlights the importance of alertness in clinical practice and of taking a patient's individual situation into consideration.

Bound on 3+1 Active-Sterile Neutrino Mixing from the First Four-Week Science Run of KATRIN.

We report on the light sterile neutrino search from the first four-week science run of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are analyzed by a high-resolution MAC-E filter down to 40 eV below the endpoint at 18.57 keV. We consider the framework with three active neutrinos and one sterile neutrino. The analysis is sensitive to the mass, m_{4}, of the fourth mass state for m_{4}^{2}≲1000 eV^{2} and to active-to-sterile neutrino mixing down to |U_{e4}|^{2}≳2×10^{-2}. No significant spectral distortion is observed and exclusion bounds on the sterile mass and mixing are reported. These new limits supersede the Mainz results for m_{4}^{2}≲1000 eV^{2} and improve the Troitsk bound for m_{4}^{2}<30 eV^{2}. The reactor and gallium anomalies are constrained for 100<Δm_{41}^{2}<1000 eV^{2}.

Digital health technologies for osteopaths and allied healthcare service providers: A scoping review.

Background: Digital health technologies are poised to revolutionise the healthcare industry by improving accessibility to services and patient outcomes. The novel coronavirus disease-19 (COVID-19) pandemic has presented unprecedented challenges for the delivery of allied healthcare and has catalysed rapid adoption of telehealth. As such, allied healthcare consumers and providers stand to benefit from the capabilities of the digital health movement, ultimately justifying a scoping review of current and emerging technologies. Objective: To provide decision makers with up-to-date information on the allied health applications of new and emerging digital health technologies; their evidence of efficacy, scope of use, and limitations. Methods: A scoping review of the literature was conducted, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. To synthesise original research, MEDLINE, CINAHL, and EMBASE databases were searched from 2010 to June 2020 and reference lists were examined for randomised control trials analysing the efficacy of these technologies in allied health applications. Results: A total of 14 articles were included with a focus on common musculoskeletal conditions managed by allied health service providers. Studies were selected for data extraction after abstract and full-text screening by three independent reviewers. The results of this review indicate that telehealth technology effectively monitors and progresses patient care, while mobile health applications provide remote support and enable data collection. Conclusion: Emerging trends suggest that digital technologies serve as promising adjuncts to allied healthcare. Further research is warranted regarding the safety and efficacy of digital health technologies in this context.

The TRIXS end-station for femtosecond time-resolved resonant inelastic x-ray scattering experiments at the soft x-ray free-electron laser FLASH.

We present the experimental end-station TRIXS dedicated to time-resolved soft x-ray resonant inelastic x-ray scattering (RIXS) experiments on solid samples at the free-electron laser FLASH. Using monochromatized ultrashort femtosecond XUV/soft x-ray photon pulses in combination with a synchronized optical laser in a pump-probe scheme, the TRIXS setup allows measuring sub-picosecond time-resolved high-resolution RIXS spectra in the energy range from 35 eV to 210 eV, thus spanning the M-edge (M1 and M2,3) absorption resonances of 3d transition metals and N4,5-edges of rare earth elements. A Kirkpatrick-Baez refocusing mirror system at the first branch of the plane grating monochromator beamline (PG1) provides a focus of (6 × 6) µm2 (FWHM) at the sample. The RIXS spectrometer reaches an energy resolution of 35-160 meV over the entire spectral range. The optical laser system based on a chirped pulse optical parametric amplifier provides approximately 100 fs (FWHM) long photon pulses at the fundamental wavelength of 800 nm and a fluence of 120 mJ/cm2 at a sample for optical pump-XUV probe measurements. Furthermore, optical frequency conversion enables experiments at 400 nm or 267 nm with a fluence of 80 and 30 mJ/cm2, respectively. Some of the first (pump-probe) RIXS spectra measured with this setup are shown. The measured time resolution for time-resolved RIXS measurements has been characterized as 287 fs (FWHM) for the used energy resolution.

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9}) eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation.

Non-linear soft x-ray methods on solids with MUSIX-the multi-dimensional spectroscopy and inelastic x-ray scattering endstation.

With the intense and coherent x-ray pulses available from free-electron lasers, the possibility to transfer non-linear spectroscopic methods from the laser lab to the x-ray world arises. Advantages especially regarding selectivity and thus information content as well as an improvement of signal levels are expected. The use of coherences is especially fruitful and the example of coherent x-ray/optical sum-frequency generation is discussed. However, many non-linear x-ray methods still await discovery, partially due to the necessity for extremely adaptable and versatile instrumentation that can be brought to free-electron lasers for the analysis of the spectral content emitted from the sample into a continuous range of emission angles. Such an instrument (called MUSIX) is being developed and employed at FLASH, the free-electron laser in Hamburg and is described in this contribution together with first results.

Qualitative analysis of the contributions of nutritionists to the development of an online instrument for monitoring the food intake of schoolchildren.

BACKGROUND: The Consumo Alimentar e Atividade Fisica de Escolares (CAAFE) questionnaire is an online research tool that has been developed to enable the self-report of physical activity and diet by Brazilian schoolchildren aged 7-10 years. Formative research was conducted with nutritionists during the development of the web-based questionnaire. The suggestions and insights obtained were used to design a tool to monitor schoolchildren's food consumption based on the concept of healthy and unhealthy food indicators. The present study aimed to report the focus group discussions conducted with nutritionists concerning the CAAFE questionnaire. METHODS: Focus group discussions were conducted using a semi-structured questionnaire, and these were then analysed thematically. RESULTS: Twenty-four nutritionists participated (four focus groups; average per group: six people); the majority (n = 22) had experience with 7-10-year-old children. Four themes emerged: (i) healthy and unhealthy food indicators; (ii) suggestions for the online instrument; (iii) potential applications; and (iv) challenges for its construction. CONCLUSIONS: Comments made by nutritionists enabled the construction of an instrument that is able to answer questions related to food consumption in schools and at home.

First Experimental Characterization of Microwave Emission from Cosmic Ray Air Showers.

We report the first direct measurement of the overall characteristics of microwave radio emission from extensive air showers. Using a trigger provided by the KASCADE-Grande air shower array, the signals of the microwave antennas of the Cosmic-Ray Observation via Microwave Emission experiment have been read out and searched for signatures of radio emission by high-energy air showers in the GHz frequency range. Microwave signals have been detected for more than 30 showers with energies above 3×10^{16} eV. The observations presented in this Letter are consistent with a mainly forward-directed and polarized emission process in the GHz frequency range. The measurements show that microwave radiation offers a new means of studying air showers at E≥10^{17} eV.

Single-chain factor XII exhibits activity when complexed to polyphosphate.

BACKGROUND: The mechanism underpinning factor XII autoactivation was originally characterized with non-physiological surfaces, such as dextran sulfate (DS), ellagic acid, and kaolin. Several 'natural' anionic activating surfaces, such as platelet polyphosphate (polyP), have now been identified. OBJECTIVE: To analyze the autoactivation of FXII by polyP of a similar length to that found in platelets (polyP70 ). METHODS AND RESULTS: PolyP70 showed similar efficacy to DS in stimulating autoactivation of FXII, as detected with amidolytic substrate. Western blotting revealed different forms of FXII with the two activating surfaces: two-chain αFXIIa was formed with DS, whereas single-chain FXII (scFXII; 80 kDa) was formed with polyP70 . Dissociation of scFXII from polyP70 abrogated amidolytic activity, suggesting reversible exposure of the active site. Activity of scFXII-polyP70 was enhanced by Zn(2+) and was sensitive to NaCl concentration. A bell-shaped concentration response to polyP70 was evident, as is typical of surface-mediated reactions. Reaction of scFXII-polyP70 with various concentrations of S2302 generated a sigmoidal curve, in contrast to a hyperbolic curve for αFXIIa, from which a Hill coefficient of 3.67 was derived, indicative of positive cooperative binding. scFXII-polyP70 was more sensitive to inhibition by H-d-Pro-Phe-Arg-chloromethylketone and corn trypsin inhibitor than αFXIIa, but inhibition profiles for C1-inhibitor were similar. Active scFXII-polyP70 was also able to cleave its physiological targets FXI and prekallikrein to their active forms. CONCLUSIONS: Autoactivation of FXII by polyP, of the size found in platelets, proceeds via an active single-chain intermediate. scFXII-polyP70 shows activity towards physiological substrates, and may represent the primary event in initiating contact activation in vivo.

Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study.

This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.

Do patients with paranoid and disorganized schizophrenia respond differently to antipsychotic drugs?

OBJECTIVE: The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. METHOD: We reanalyzed the original data from five different randomized drug trials comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing 427 paranoid and 296 disorganized patients with schizophrenia. RESULTS: Both the disorganized and the paranoid group showed a substantial improvement of the BPRS total score within the first 4 weeks. In the paranoid group, mean (±SD) BPRS reduction was 16.9 (±14.6) (t = 24.06, df = 426, P < 0.001) and in the disorganized group 17.0 (±15.9) (t = 18.49, df = 295, P < 0.001). An analysis of covariance (ancova) controlling for BPRS at baseline and the influence of different trial protocols showed significant differences between diagnostic groups (F = 13.47, df = 1, P < 0.001), Cohen's D 0.31 (CI = 0.16-0.46). Paranoid patients improved by 4.8 BPRS points more than disorganized patients (adjusted means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for the disorganized group. CONCLUSION: We conclude that amisulpride is effective in disorganized as well as in paranoid schizophrenia, but that symptom reduction in the disorganized subtype is less pronounced.

Seizures during antidepressant treatment in psychiatric inpatients--results from the transnational pharmacovigilance project "Arzneimittelsicherheit in der Psychiatrie" (AMSP) 1993-2008.

RATIONALE: There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. OBJECTIVE: This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. RESULTS: Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed--the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. CONCLUSIONS: The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk.

Equipercentile linking of the BPRS and the PANSS.

The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) are the most frequently used scales to rate the symptoms of schizophrenia. There are many situations in which it is important to know what a given total score or a percent reduction from baseline score of one scale means in terms of the other scale. We used the equipercentile linking method to identify corresponding scores of simultaneous BPRS and PANSS ratings in 3767 patients from antipsychotic drug trials. Data were collected at baseline and at weeks 1, 2, 4 and 6. BPRS total scores of 18, 30, 40 and 50 roughly corresponded to PANSS total scores of 31, 55, 73 and 90, respectively. An absolute BPRS improvement of 10, 20, 30, 40 points corresponded to a PANSS improvement of 15, 32, 50, and 67. A percentage improvement of the BPRS total score from baseline of 19%, 30%, 40% and 50% roughly corresponded to percentage PANSS improvement of 16%, 25%, 35%, and 44%. Thus a given PANSS percent improvement was always lower than the corresponding BPRS percent improvement, on the average by 4-5%. A reason may be the higher number of items used in the PANSS. These results are important for the comparison of trials that used these rating scales. We present a detailed conversion table in an online supplement.

[The early development of brachytherapy of the prostate: a study on technique application in the development of urology]. / Zur frühen Entwicklung der Brachytherapie der Prostata : Eine Studie zur Technikanwendung in der Urologieentwicklung.

Within recent years brachytherapy of the prostate has become a treatment of choice. The treatment can be dated back up to the beginning of the twentieth century. It is interesting that the urological routes have never been explored directly by authors of articles and textbooks in the field of radiology and radiooncology.

Increase of antipsychotic medication in depressive inpatients from 2000 to 2007: results from the AMSP International Pharmacovigilance Program.

While international guidelines recommend monotherapy with antidepressants for depressed patients, recent investigation has demonstrated augmenting effects of antipsychotics (APs) in patients with major depression. We set out to investigate the use of APs in a European sample of depressed inpatients and the possible changes in their prescription over the period from 2000 to 2007. On two reference days in the years 2000 (32 psychiatric institutions, N=1078) and 2007 (54 psychiatric institutions, N=1826), the following data were recorded for all depressed inpatients (ICD-10: F32.00, F32.01, F32.1, F32.10, F32.11, F32.2, F33.0, F33.00, F33.01, F33.1, F33.10, F33.11, F33.2), monitored as part of the AMSP (Arzneimittelsicherheit in der Psychiatrie) surveillance programme: age, sex, ICD-10 diagnosis and all medication applied on that day. Depressed inpatients with psychotic symptoms were excluded. We found a significant increase in the number of AP-treated inpatients from 37.9% in 2000 to 45.8% in 2007 (χ²=17.257, p<0.001). The number of inpatients who received an atypical AP rose significantly between 2000 and 2007, from 12.8% to 28.3% (χ²=93.37, p<0.001). On the contrary, the percentage of inpatients receiving typical APs showed a significant decrease from 30.2% to 24.1% over the same period (χ²=13.179, p<0.001). Examining only the subgroup of severely depressed inpatients we found an increase in the number of AP-treated inpatients, but this was not statistically significant (χ²=2.047, p=0.15). Our study revealed a significant increase in the usage of atypical APs. However, this effect was not only due to augmentation strategies for severely depressed inpatients. Further studies are needed to examine possible putative effects of AP augmentation treatment in mild to moderate depression.

Kneelike structure in the spectrum of the heavy component of cosmic rays observed with KASCADE-Grande.

We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.

[The William P. Didusch Center for Urologic History of the American Urological Association: new exciting approaches in presenting urologic history, not only in the USA - a personal guided tour]. / Das "William P. Didusch Center for Urologic History der American Urological Association" : Neue, spannende Ansätze zur Urologiegeschichte in den USA -- ein persönlicher Rundgang.

The Didusch Center for Urologic History encompasses a rich and varied collection of drawings, photographs, and instruments of historical importance to urology, many displayed in the urological exhibits during the American Urological Association (AUA) conventions. The Center also houses a library devoted to urological and early medical texts and the AUA archives and is the institution of research in all fields of urologic history in the USA. The museum collection features most of Didusch's original drawings, as well as an impressive instrument collection acquired primarily through donations by urologists. The original William P. Didusch Museum (now known as the William P. Didusch Center for Urologic History) was originally housed in the AUA's Baltimore City headquarters building. Upon the association's move to Linthicum, MD in 2003, the museum has evolved into the William P. Didusch Center for Urologic History and taken on new tasks and responsibilities that include the topic of research in urologic history.

[New forms of scientific communication of medical societies: thoughts on scientific collections and museums for urology]. / Neue Formen der Wissenskommunikation medizinischer Fachgesellschaften : Gedanken zu wissenschaftlichen Sammlungen und Museen für Urologie.

Collections from medical societies which are not connected with a university or another public institution cannot be legitimized on the basis of the argument of conserving historical heritage. Even the museum itself with its many tasks and classical site of scientific communication comes into public view and becomes a topic of scientific interest.