Scoping Out the Limits of "Arms" Under the Second Amendment

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Cross-calibration of the Transition Radiation Detector of AMS-02 for an Energy Measurement of Cosmic-Ray Ions

Since May 2011 the AMS-02 experiment is installed on the International Space Station and is observing cosmic radiation. It consists of several state-of-the-art sub-detectors, which redundantly measure charge and energy of traversing particles. Due to the long exposure time of AMS-02 of many years the measurement of momentum for protons and ions is limited systematically by the spatial resolution and magnetic field strength of the silicon tracker. The maximum detectable rigidity for protons is about 1.8~TV, for helium about 3.6~TV. We investigate the possibility to extend the range of the energy measurement for heavy nuclei ($Z\geq2$) with the transition radiation detector (TRD). The response function of the TRD shows a steep increase in signal from the level of ionization at a Lorentz factor $\gamma$ of about 500 to $\gamma\approx20000$, where the transition radiation signal saturates. For heavy ions the signal fluctuations in the TRD are sufficiently small to allow an energy measurement with the TRD beyond the limitations of the tracker. The energy resolution of the TRD is determined and reaches a level of about 20\% for boron ($Z=5$). After adjusting the operational parameters of the TRD a measurement of boron and carbon could be possible up to 5~TeV/nucleon.Comment: Accepted for publication in Advances in Space Researc

The positive and negative syndrome scale for schizophrenia

The modern debate about schizophrenia began over 100 years ago, with Kraepelin’s description of “dementia praecox”. Despite this, central aspects of the disease remain mysterious and the disease itself is still associated with a high probability of an enduring limitation of the patient’s quality of life. While several conceptions of schizophrenia exist and are still under discussion, at least a provisional consensus regarding a valid measure of schizophrenia seems to have been reached: The Positive and Negative Syndrome Scale (PANSS) quantifies the current state of a person with schizophrenia by combining 30 different schizophrenia-associated symptoms into a single scale value. Even though the scale is widely used and is the measure of choice in many clinical trials, its psychometric properties are still the reason for serious confusion. In many research papers, one important fact about the PANSS is overlooked: it is an interval scale and, therefore, straightforward calculations of proportions are not appropriate. In other words, calculating simple percentage changes is incorrect and a prior scale correction is required. These kinds of calculations often appear in conjunction with responder analyses, as the definition of response is usually based on a predefined cut-off in terms of percent scale change. Two of the presented papers of this thesis are dealing with this urgent problem: using real data as well as simulated data sets, it is shown that ignoring the scale level of the PANSS can, in many cases, even lead to false test decisions concerning an examined treatment effect. Furthermore, an analysis of the problem’s urgency with regard to academic discussions, performed by way of a systematic study of literature in the highest-ranked journals dealing with schizophrenia, showed that incorrect calculations are widespread in the literature and that there is a strong need for a general clarification. As incorrectly calculated percent changes might be a reason for the published low cut-offs of response, as e.g. 20% or 30% cut-offs, the third included article in this thesis analyzes the association of correctly calculated percent changes in the PANSS with a generally measured therapy response. An equipercentile linking of percent PANSS changes and the improvement item of the Clinical Global Impression Scale (CGI) confirmed the choice of a considerably higher response cut-off of 50%. The combined conclusion of the three included articles is the emphasis on the need for a general methodological consensus in schizophrenia research. Valid and replicable research is only possible on the basis of generally accepted methods that rely on the correct application of scale theory in these studies

Exploring the Full Potential of Photocatalytic Carbon Dioxide Reduction Using a Dinuclear Re2Cl2 Complex Assisted by Various Photosensitizers

Photosensitizing units have already been applied to enable light-driven catalytic reduction of CO2 with mononuclear rhenium complexes. However, dinuclear catalytic systems that are able to activate CO2 in a cooperative bimetallic fashion have only rarely been combined with photosensitizers. We here present detailed studies on the influence of additional photosensitizers on the catalytic performance of a dirhenium complex (Re2Cl2) and present correlations with spectroscopic measurements, which shed light on the reaction mechanism. The use of [Ir(dFppy)3] (Ir, dFppy=2-(4,6-difluorophenyl)pyridine)) resulted in considerably faster CO2 to CO transformation than [Cu(xant)(bcp)]PF6 (Cu, xant=xantphos, bcp=bathocuproine). Emission quenching studies, transient absorption as well as IR spectroscopy provide information about the electron transfer paths of the intermolecular systems. It turned out that formation of double reduced species [Re2Cl2]2− along with an intermediate with a Re−Re bond ([ReRe]) can be taken as an indication of multi-electron storage capacity. Furthermore, under catalytic conditions a CO2-bridged intermediate was identified.German Research FoundationDFG http://dx.doi.org/10.13039/501100001659Peer Reviewe

Stability of remission rates in a 3-year follow-up of naturalistic treated depressed inpatients

Background Remission is a common outcome of short-term trials and the main goal of acute and longterm treatment. The longitudinal stability of remission has rarely been investigated under naturalistic treatment conditions. Methods Naturalistic multisite follow-up study. Three-year symptomatic long-term outcome of initially hospitalized tertiary care patients (N = 784) with major depressive episodes. Remission rates as well as the switch rates between remission and non-remission were reported. Results After one, two and three years 62 %, 59 % and 69 % of the observed patients met criteria for remission. During the follow-up 88 % of all patients achieved remission. 36 % of maintained remission from discharge to 3-years, 12 % of all patients never reached remission and 52 % percent showed a fluctuating course switching from remission to non-remission and vice versa. There was considerable transition between remission and non-remission. For example, from discharge to 1 year, from 1 to 2, and from 2 to 3 years 25 %, 21 % and 11 % lost remission. Conclusion Cumulative outcome rates are encouraging. Absolute rates at predefined endpoints as well as the fluctuations between these outcomes reflect the variable and chronic nature of major depression

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6~weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6~weeks. The baseline hsCRP levels and the ACE subgroups did not~show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself