The spectrum of massless Dirac fermions on the surface of a topological insulator in a perpendicular magnetic field contains a -independent “zeroth Landau level”, protected by chiral symmetry. If the Dirac equation is discretized on a lattice by the method of “Wilson fermions”, the chiral symmetry is broken and the zeroth Landau level is broadened when has spatial fluctuations. We show how this lattice artefact can be avoided starting from an alternative nonlocal discretization scheme introduced by Stacey. A key step is to spatially separate the states of opposite chirality in the zeroth Landau level, by adjoining and regions.
View lessA supercurrent on the proximitized surface of a topological insulator can cause a delocalization transition of a Majorana fermion bound to a vortex core as a zero mode. Here we study the dynamics of the deconfinement, as a manifestation of the Magnus effect (the coupling of the superflow to the velocity field in the vortex). The initial acceleration of the Majorana fermion is ±2v2FK/ℏ, perpendicular to the Cooper pair momentum K, for a ±2π winding of the superconducting phase around the vortex. The quasiparticle escapes with a constant velocity from the vortex core, which we calculate in a semiclassical approximation and compare with computer simulations.
View lessBackground: Therapeutic options for migraine prevention in non-responders to monoclonal antibodies (mAbs) targeting Calcitonin Gene-Related Peptide (CGRP) and its receptor are often limited. Real-world data have shown that non-responders to the CGRP-receptor mAb erenumab may benefit from switching to a CGRP ligand mAb. However, it remains unclear whether, vice versa, erenumab is effective in non-responders to CGRP ligand mAbs. In this study, we aim to assess the efficacy of erenumab in patients who have previously failed a CGRP ligand mAb.
Methods: This monocentric retrospective cohort study included patients with episodic or chronic migraine in whom a non-response (< 30% reduction of monthly headache days during month 3 of treatment compared to baseline) to the CGRP ligand mAbs galcanezumab or fremanezumab led to a switch to erenumab, and who had received at least 3 administrations of erenumab. Monthly headache days were retrieved from headache diaries to assess the >= 30% responder rates and the absolute reduction of monthly headache days at 3 and 6 months of treatment with erenumab in this cohort.
Results: From May 2019 to July 2022, we identified 20 patients who completed 3 months of treatment with erenumab after non-response to a CGRP ligand mAb. Fourteen patients continued treatment for >= 6 months. The >= 30% responder rate was 35% at 3 months, and 45% at 6 months of treatment with erenumab, respectively. Monthly headache days were reduced from 18.6 +/- 5.9 during baseline by 4.1 +/- 3.1 days during month 3, and by 7.0 +/- 4.8 days during month 6 compared to the month before treatment with erenumab (p < 0.001, respectively). Responders and non-responders to erenumab did not differ with respect to demographic or headache characteristics.
Conclusion: Switching to erenumab in non-responders to a CGRP ligand mAb might be beneficial in a subgroup of resistant patients, with increasing responder rates after 6 months of treatment. Larger prospective studies should aim to predict which subgroup of patients benefit from a switch.
View lessMethods to discretize the Hamiltonian of a topological insulator or topological superconductor, without giving up on the topological protection of the massless excitations (respectively, Dirac fermions or Majorana fermions) are reviewed. The method of tangent fermions, pioneered by Richard Stacey, is singled out as being uniquely suited for this purpose. Tangent fermions propagate on a 2+1-dimensional space-time lattice with a tangent dispersion: in dimensionless units. They avoid the fermion doubling lattice artefact that will spoil the topological protection, while preserving the fundamental symmetries of the Dirac Hamiltonian. Although the discretized Hamiltonian is nonlocal, as required by the fermion-doubling no-go theorem, it is possible to transform the wave equation into a generalized eigenproblem that is local in space and time. Applications that are discussed include Klein tunneling of Dirac fermions through a potential barrier, the absence of localization by disorder, the anomalous quantum Hall effect in a magnetic field, and the thermal metal of Majorana fermions.
View lessThis study evaluated the reliability and comprehensiveness of the Unified classification system (UCPF), Wright & Cofield, Worland and Kirchhoff classifications and related treatment recommendations for periprosthetic shoulder fractures (PPSFx). Two shoulder arthroplasty specialists (experts) and two orthopaedic residents (non-experts) assessed 20 humeral-sided and five scapula-sided cases of PPSFx. We used the unweighted Cohen's Kappa (?) for measuring the intra-observer reliability and Krippendorff's alpha (a) for measuring the inter-observer reliability. The inter-rater reliabilities for the Wright & Cofield and Worland classifications were substantial for all groups. The expert and non-expert groups for UCPF also showed substantial inter-rater agreement. The all-rater group for the UCPF and the expert and non-expert group for the Kirchhoff classification revealed moderate inter-rater reliability. For the Kirchhoff classification, only fair inter-rater reliability was found for the non-expert group. Almost perfect intra-rater reliability was measured for all groups of the Wright & Cofield classification and the all-rater and expert groups of the UCPF. All groups of the Kirchhoff and Worland classifications and the group of non-experts for the UCPF had substantial intra-rater reliabilities. Regarding treatment recommendations, substantial inter-rater and moderate intra-rater reliabilities were found. Simple classification systems for PPSFx (Wright & Cofield, Worland) show the highest inter- and intra-observer reliability but lack comprehensiveness as they fail to describe scapula-sided fractures. The complex Kirchhoff classification shows limited reliability. The UCPF seems to offer an acceptable combination of comprehensiveness and reliability.
View lessIntroduction: Since cannabinoids were partially legalized as prescription medicines in Germany in 2017, they are mostly used when conventional therapies do not suffice. Ambiguities remain regarding use, benefits and risks. This web-based survey explored the perspectives of patients whose experiences are not well enough known to date.
Methods: In an anonymous, exploratory, cross-sectional, one-time web-based observational study, participants receiving cannabinoid therapy on prescription documented aspects of their medical history, diagnoses, attitudes toward cannabinoids, physical symptoms, and emotional states. Participants completed the questionnaires twice here: first regarding the time of the survey and then, retrospectively, for the time before their cannabinoid therapy. Participants were recruited in a stratified manner in three German federal states.
Results: N = 216 participants (48.1% female, aged 51.8 +/- 14.0) completed the survey, most of which (72%, n = 155) reported pain as their main reason for cannabinoid therapy. When comparing the current state with the retrospectively assessed state, participants reported greater satisfaction with their overall medical therapy (TSQM II: +47.9 +/- 36.5, p < 0.001); improved well-being (WHO-5: +7.8 +/- 5.9, p < 0.001) and fewer problems in PROMIS subscales (all p < 0.001). Patients suffering primarily from pain (72%, n = 155) reported a reduction of daily pain (NRS: -3.2 +/- 2.0, p < 0.001), while participants suffering mainly from spasticity (8%, n = 17) stated decreased muscle spasticity (MSSS: -1.5 +/- 0.6, p < 0.001) and better physical mobility (-0.8 +/- 0.8, p < 0.001). Data suggests clinically relevant effects for most scores. Participants' attitudes toward cannabinoids (on a 5-point scale) improved (+1.1 +/- 1.1, p < 0.001). Most patients (n = 146, 69%) did not report major difficulties with the cannabinoid prescription process, while (n = 27; 19%) had their cannabinoid therapy changed due to side effects.
Discussion: Most participants experienced their therapy with cannabinoids as more effective than their previous therapy. There are extensive limitations to this cross-sectional study: the originally intended representativeness of the dataset was not reached, partly due to the SARS-CoV-2 pandemic; the sample has a larger proportion of privately insured and self-paying patients. Results does not suggest that cannabinoid patients belong to a particular clientele. Effect sizes observed for pain reduction, quality of life, social participation, and other outcomes suggest a therapeutic potential, particularly in the treatment of chronic pain.
View lessIntroduction: Chronic pain is a growing worldwide health problem and complementary and integrative therapy options are becoming increasingly important. Multi-component yoga interventions represent such an integrative therapy approach with a promising body of evidence. Methods: The present study employed an experimental single-case multiple-baseline design. It investigated the effects of an 8-week yoga-based mind-body intervention, Meditation-Based Lifestyle Modification (MBLM), in the treatment of chronic pain. The main outcomes were pain intensity (BPI-sf), quality of life (WHO-5), and pain self-efficacy (PSEQ). Results: Twenty-two patients with chronic pain (back pain, fibromyalgia, or migraines) participated in the study and 17 women completed the intervention. MBLM proved to be an effective intervention for a large proportion of the participants. The largest effects were found for pain self-efficacy (TAU-U = 0.35), followed by average pain intensity (TAU-U = 0.21), quality of life (TAU-U = 0.23), and most severe pain (TAU-U = 0.14). However, the participants varied in their responses to the treatment. Conclusion: The present results point to relevant clinical effects of MBLM for the multifactorial conditions of chronic pain. Future controlled clinical studies should investigate its usefulness and safety with larger samples. The ethical and philosophical aspects of yoga should be further explored to verify their therapeutic utility.
View lessIntroduction: Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT).
Methods: We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials.
Results: We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm(3) were smaller tumors (pre-GTV < 15.0 cm(3)), whereas larger tumors greater than 25.0 cm(3) showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview.
Conclusion: Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.
View lessChronic granulomatous disease is an inborn error of immunity due to disrupted function of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This results in impaired respiratory burst of phagocytes and insufficient killing of bacteria and fungi. Patients with chronic granulomatous disease are at increased risk for infections, autoinflammation and autoimmunity. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only widely available curative therapy. While HSCT from human leukocyte antigen (HLA) matched siblings or unrelated donors are standard of care, transplantation from HLA-haploidentical donors or gene therapy are considered alternative options. We describe a 14-month-old male with X-linked chronic granulomatous disease who underwent a paternal HLA-haploidentical HSCT using T-cell receptor (TCR) alpha/beta(+)/CD19(+) depleted peripheral blood stem cells followed by mycophenolate graft versus host disease prophylaxis. Decreasing donor fraction of CD3(+) T cells was overcome by repeated infusions of donor lymphocytes from the paternal HLA-haploidentical donor. The patient achieved normalized respiratory burst and full donor chimerism. He remained disease-free off any antibiotic prophylaxis for more than three years after HLA-haploidentical HSCT. In patients with x-linked chronic granulomatous disease without a matched donor paternal HLA-haploidentical HSCT is a treatment option worth to consider. Administration of donor lymphocytes can prevent imminent graft failure.
View lessThree-dimensional higher-order topological insulators can have topologically protected chiral modes propagating on their hinges. Hinges with two copropagating chiral modes can serve as a “beam splitter” between hinges with only a single chiral mode. Here we show how such a crystal, with Ohmic contacts attached to its hinges, can be used to realize a Mach-Zehnder interferometer. We present concrete calculations for a lattice model of a first-order topological insulator in a magnetic field, which, for a suitable choice of parameters, is an extrinsic second-order topological insulator with the required configuration of chiral hinge modes.
View lessAims: Heart failure (HF) does not only reduce the life expectancy in patients, but their life is also often limited by HF symptoms leading to a reduced quality of life (QoL) and a diminished exercise capacity. Novel parameters in cardiac imaging, including both global and regional myocardial strain imaging, promise to contribute to better patient characterization and ultimately to better patient management. However, many of these methods are not part of clinical routine yet, their associations with clinical parameters have been poorly studied. An imaging parameters that also indicate the clinical symptom burden of HF patients would make cardiac imaging more robust toward incomplete clinical information and support the clinical decision process.
Methods and results: This prospective study conducted at two centers in Germany between 2017 and 2018 enrolled stable outpatient subjects with HF [n = 56, including HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and a control cohort (n = 19). Parameters assessed included measures for external myocardial function, for example, cardiac index and myocardial deformation measurements by cardiovascular magnetic resonance imaging, left ventricular global longitudinal strain (GLS), the global circumferential strain (GCS), and the regional distribution of segment deformation within the LV myocardium, as well as basic phenotypical characteristics including the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the 6-minute walk test (6MWT). If less than 80% of the LV segments are preserved in their deformation capacity the functional capacity by 6MWT (6 minutes walking distance: MyoHealth >= 80%: 579.8 +/- 177.6 m; MyoHealth 60-<80%: 401.3 +/- 121.7 m; MyoHealth 40-<60%: 456.4 +/- 68.9 m; MyoHealth < 40%: 397.6 +/- 125.9 m, overall p-value: 0.03) as well as the symptom burden are significantly impaired (NYHA class: MyoHealth >= 80%: 0.6 +/- 1.1 m; MyoHealth 60-p-value < 0.01). Differences were also observed in the perceived exertion assessed by on the Borg scale (MyoHealth >= 80%: 8.2 +/- 2.3 m; MyoHealth 60-p-value: 0.20) as well as quality of life measures (MLHFQ; MyoHealth >= 80%: 7.5 +/- 12.4 m; MyoHealth 60-p-value: 0.15)-while these differences were not significant.
Conclusion: The share of LV segments with preserved myocardial contraction promises to discriminate between symptomatic and asymptomatic subjects based on the imaging findings, even when the LV ejection fraction is preserved. This finding is promising to make imaging studies more robust toward incomplete clinical information.
View lessPressure overload hypertrophy of the left ventricle is a common result of many cardiovascular diseases. Androgens show anabolic effects in skeletal muscles, but also in myocardial hypertrophy. We carefully reviewed literature regarding possible effects of androgens on specific left ventricular hypertrophy in pressure overload conditions excluding volume overload conditions or generel sex differences.
This article interrogates the widely held, but rarely defended, view that states wield legitimate power over potential immigrants when and because they refrain from violating their human rights. I reconstruct a strong argument for this view, which turns on a claim about the limited power states claim over migrants. Drawing on recent empirical work, I show how this argument is inapplicable to the border regimes of a set of wealthy democracies. These regimes are characterized by a practice that is coordinated and extraterritorial in a way that undercuts the case for holding them to a minimal legitimacy standard. By participating in this practice, these states wield significant power over potential immigrants. I argue that this power exposes potential immigrants to novel risk, which in turn triggers a demand for the satisfaction of a higher standard of legitimation.
View lessBackground
Early negative life events (NLE) have long-lasting influences on neurodevelopment and psychopathology. Reduced orbitofrontal cortex (OFC) thickness was frequently associated with NLE and depressive symptoms. OFC thinning might mediate the effect of NLE on depressive symptoms, although few longitudinal studies exist. Using a complete longitudinal design with four time points, we examined whether NLE during childhood and early adolescence predict depressive symptoms in young adulthood through accelerated OFC thinning across adolescence.
Methods
We acquired structural MRI from 321 participants at two sites across four time points from ages 14 to 22. We measured NLE with the Life Events Questionnaire at the first time point and depressive symptoms with the Center for Epidemiologic Studies Depression Scale at the fourth time point. Modeling latent growth curves, we tested whether OFC thinning mediates the effect of NLE on depressive symptoms.
Results
A higher burden of NLE, a thicker OFC at the age of 14, and an accelerated OFC thinning across adolescence predicted young adults' depressive symptoms. We did not identify an effect of NLE on OFC thickness nor OFC thickness mediating effects of NLE on depressive symptoms.
Conclusions
Using a complete longitudinal design with four waves, we show that NLE in childhood and early adolescence predict depressive symptoms in the long term. Results indicate that an accelerated OFC thinning may precede depressive symptoms. Assessment of early additionally to acute NLEs and neurodevelopment may be warranted in clinical settings to identify risk factors for depression.
View less[Fe]-hydrogenase harbors the iron-guanylylpyridinol (FeGP) cofactor, in which the Fe(II) complex contains acyl-carbon, pyridinol-nitrogen, cysteine-thiolate and two CO as ligands. Irradiation with UV-A/blue light decomposes the FeGP cofactor to a 6-carboxymethyl-4-guanylyl-2-pyridone (GP) and other components. Previous in vitro biosynthesis experiments indicated that the acyl- and CO-ligands in the FeGP cofactor can scramble, but whether scrambling occurred during biosynthesis or photolysis was unclear. Here, we demonstrate that the [18O1-carboxy]-group of GP is incorporated into the FeGP cofactor by in vitro biosynthesis. MS/MS analysis of the 18O-labeled FeGP cofactor revealed that the produced [18O1]-acyl group is not exchanged with a CO ligand of the cofactor, indicating that the acyl and CO ligands are scrambled during photolysis rather than biosynthesis, which ruled out any biosynthesis mechanisms allowing acyl/CO ligands scrambling. Time-resolved infrared spectroscopy indicated that an acyl-Fe(CO)3 intermediate is formed during photolysis, in which scrambling of the CO and acyl ligands can occur. This finding also suggests that the light-excited FeGP cofactor has a higher affinity for external CO. These results contribute to our understanding of the biosynthesis and photosensitive properties of this unique H2-activating natural complex.
View lessFamilial cancer burden and genetics play an increasingly important role in the early detection and prevention of gynecological cancers. However, people with hereditary cancer risks are often identified late when they already have cancer. We aimed at developing and evaluating a training concept for primary care gynecologists—iKNOWgynetics—to improve their knowledge and awareness of genetic cancer syndromes and their ability to identify patients with increased familial cancer risks based on up-to-date evidence and current guidelines (in Germany, primary care includes all doctors treating patients on an outpatient basis without a clear separation of the expertise of the doctor or of their specialty). Starting off with a needs assessment among primary care gynecologists, we developed and evaluated an online training concept—using a web-based learning platform in combination with a live virtual seminar—to convey practice-relevant knowledge about familial cancer. After registration, participants get access to the web-based learning platform (www.iknowgynetics.de) to prepare for the virtual seminars and to use it as online reference to re-access the contents after the training. Evaluation included multiple-choice (MC) questions on knowledge and participants' self-efficacy to implement the acquired knowledge, which were administered in a pre-post design. Of 109 participants, 103 (94.5%) filled out pre- and post-questionnaires. Eighty-five participants were gynecologists in primary care from Berlin (81.2%) and Brandenburg (18.8%) and had an average of 24.1 years (SD = 8.5 years) of professional experience. After the training, participants answered significantly more knowledge questions correctly (M = 15.2 of 17, SD = 1.3) than before (M = 13.8 of 17, SD = 1.7) (p < 0.01) and felt more confident to be able to apply referral criteria for specialized counseling in practice (p < 0.001). The online-based training iKNOWgynetics considers the busy schedule of primary care gynecologists and supports them in acquiring practice-relevant information on familial cancer risks and on how to identify healthy persons at risk, which may ultimately help to improve the prevention of gynecological cancers. In future studies, the reported concept could be transferred to other entities.
View lessThe growth, morphology, and structure of MnxAu1-x films on Cu(001) and Ag(001) are studied by means of low-energy electron diffraction (LEED), medium-energy electron diffraction, Auger electron spectroscopy, and scanning tunnelling microscopy. Different concentrations x from about 0.5 to 1 and thicknesses from0.2 to 12.9 ML of MnxAu1-x are examined. For several values of x, MnxAu1-x exhibits a c(2 x 2) superstructure pattern on Cu(001) when the total thickness is around or above 0.5 ML. Above 1 ML, LEED patterns of MnxAu1-x can be only observed on Ag(001), but not on Cu(001). LEED-I(V) is employed to deduce the vertical interlayer distance for as-grown and post-annealed films on Ag(001). Above 500 K, Ag from the substrate segregates into thefilms.
View lessLunar impact basins are critical markers to understand the early bombardment history. This study focuses on isostatic compensation processes at 16 lunar farside basins, exploring how long-term alteration processes affect estimates of impactor sizes and timing. Using a lithospheric flexure model, we analyze the isostatically compensated gravity signature of these basins. Our approach is based on previously published basin formation models using the iSALE-2D shock physics code. Here we investigate how isostatic compensation processes alter the gravity signature using models of basin formation as initial conditions. We compare our results with the present day observed gravity data. We assume that isostatic compensation is the result of flexural deformation of the crust-mantle boundary with varying lithospheric elastic thicknesses. Our results indicate that the effect of isostatic compensation on the gravity signature varies depending on the thermal conditions at the time of impact. We find that despite this variability, the overall influence of isostatic compensation on the gravity signature is generally moderate to minor. Additionally, our analysis is consistent with previous studies that have shown that the elastic thickness varies across the Moon. Our findings contribute to our understanding of the relationship between basin formation and the thermal evolution of the Moon. The variations in elastic thickness found provide nuanced insights into lunar geological processes and improve our understanding of the early history of the Moon.
View lessThe study of environmental ancient DNA provides us with the unique opportunity to link environmental with ecosystem change over a millennial timescale. Paleorecords such as lake sediments contain genetic pools of past living organisms that are a valuable source of information to reconstruct how ecosystems were and how they changed in response to climate in the past. Here, we report on paleometagenomics of a sedimentary record in northern Siberia covering the past 6700 years. We integrated taxonomic with functional gene analysis, which enabled to shed light not only on community compositions but also on eco-physiological adaptations and ecosystem functioning. We reconstructed the presence of an open boreal forest 6700 years ago that over time was gradually replaced by tundra. This vegetation change had major consequences on the environmental microbiome, primarily enriching bacterial and archaeal ammonia oxidizers (e.g., Nitrospira, Nitrosopumilus, and Ca. Nitrosocosmicus) in the tundra ecosystem. We identified a core microbiome conserved through time and largely consisting of heterotrophic bacteria of the Bacteroidetes phylum (e.g., Mucilaginibacter) harboring numerous functional genes for degradation of plant-biomass and abiotic and biotic stress resistance. Archaea were also a key functional guild, involved in nitrogen and carbon cycling, not only methanogenesis but possibly also degradation of plant material via enzymes such as cellulases and amylases. Overall, the paleo-perspective offered by our study can have a profound impact on modern climate change biology, by helping to explain and predict the ecological interplay among multiple ecosystem levels based on past experiences.
View lessIn this work, we analyzed trifluoromethyl fluorosulfonate (CF3OSO2F) and trifluoromethoxy sulfur pentafluoride (CF3OSF5) regarding their potential use as dielectrics by investigating some of their intrinsic and extrinsic properties. Both compounds show a higher breakdown voltage than SF6 with averaged relative breakdown voltages of 1.3±0.2 for CF3OSO2F and 1.4±0.2 for CF3OSF5 compared to SF6 with 1.0. Like the dielectric (CF3)2CFCN, both compounds decompose during the breakdown process. The decomposition products were analyzed by IR spectroscopy and GCIR methods. Furthermore, the molecular structures of both gaseous compounds CF3OSO2F and CF3OSF5 have been determined by in situ crystallization, and their physical properties were determined as well.
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