Associated SM Higgs boson searches with ATLAS

The associated SM Higgs production channels are those with the lowest production cross sections at the LHC. Nevertheless, in the low Higgs mass range up to ~ 130 GeV, production together with a pair of t-quarks is the most promising channel to detect a Higgs boson that decays into a pair of b-quarks, due to the distinct signature of the tt system. Furthermore, all associated production channels can contribute to measurements of the Higgs boson's Yukawa and gauge couplings. The talk presents a Monte Carlo study of the channel ttH, H->bb in the semi-leptonic final state at the ATLAS experiment. In addition, the results of feasibility studies that have been performed for ttH / WH, H-> WW are briefly summarized

Familien in der Coronapandemie: Was hat belastet, was hat geholfen und was kann man für zukünftige Krisenstrategien lernen?

In der Pandemie ist die Lebenszufriedenheit deutlich gesunken, vor allem in Zeiten von Kontaktbeschränkungen. Nach Lockerung der Restriktionen ist die Lebenszufriedenheit wieder etwas angestiegen. Um gut durch Krisen zu kommen, sind u.a. drei Dinge wichtig: Gute Beziehungen in der Familie, finanzielle Sicherheit und die Fähigkeit zu Optimismus. Familie zu haben, und dabei vor allem eine gute Beziehungsqualität in der Partnerschaft und zu den Kindern, war in der Pandemie zentral für das Wohlbefinden. Familienpolitik ist in Krisenzeiten besonders wichtig. Dies umfasst verlässliche, ganztägige Kita- und Schulbetreuung, niederschwellige psychosoziale Beratungsangebote für Kinder und Jugendliche sowie familienfreundlichere Arbeitsplätze. Etwa ein Drittel der Menschen im mittleren Alter hatte ernsthafte finanzielle Sorgen in der Pandemie, was mit einer niedrigeren Lebenszufriedenheit verbunden war. Politische Maßnahmen wie Kurzarbeit (oder bei der Energiekrise die Gaspreisbremse), die finanzielle Risiken schnell abfedern, sind hier hilfreich. Die Fähigkeit, auch in Krisen positive Seiten zu sehen, hängt eng mit einer höheren Lebenszufriedenheit zusammen. Eine Prise Optimismus und ein Blick auf andere Lebensaspekte können in Krisen zu Resilienz beitragen. Politik sollte die Chancen, die sich aus Krisen ergeben, angehen und unterstützende Maßnahmen breit kommunizieren

Sensing dot with high output swing for scalable baseband readout of spin qubits

A key requirement for quantum computing, in particular for a scalable quantum computing architecture, is a fast and high-fidelity qubit readout. For semiconductor based qubits, one limiting factor is the output swing of the charge sensor. We demonstrate GaAs and Si/SiGe asymmetric sensing dots (ASDs), which exceed the response of a conventional charge sensing dot by more than ten times, resulting in a boosted output swing of $3\,\text{mV}$. This substantially improved output signal is due to a device design with a strongly decoupled drain reservoir from the sensor dot, mitigating negative feedback effects of conventional sensors. The large output signal eases the use of very low-power readout amplifiers in close proximity to the qubit and will thus render true scalable qubit architectures with semiconductor based qubits possible in the future.Comment: 8 pages, 7 figure

Tailoring potentials by simulation-aided design of gate layouts for spin qubit applications

Gate-layouts of spin qubit devices are commonly adapted from previous successful devices. As qubit numbers and the device complexity increase, modelling new device layouts and optimizing for yield and performance becomes necessary. Simulation tools from advanced semiconductor industry need to be adapted for smaller structure sizes and electron numbers. Here, we present a general approach for electrostatically modelling new spin qubit device layouts, considering gate voltages, heterostructures, reservoirs and an applied source-drain bias. Exemplified by a specific potential, we study the influence of each parameter. We verify our model by indirectly probing the potential landscape of two design implementations through transport measurements. We use the simulations to identify critical design areas and optimize for robustness with regard to influence and resolution limits of the fabrication process.Comment: 10 pages, 6 figure

Personalised depression forecasting using mobile sensor data and ecological momentary assessment

Introduction Digital health interventions are an effective way to treat depression, but it is still largely unclear how patients’ individual symptoms evolve dynamically during such treatments. Data-driven forecasts of depressive symptoms would allow to greatly improve the personalisation of treatments. In current forecasting approaches, models are often trained on an entire population, resulting in a general model that works overall, but does not translate well to each individual in clinically heterogeneous, real-world populations. Model fairness across patient subgroups is also frequently overlooked. Personalised models tailored to the individual patient may therefore be promising. Methods We investigate different personalisation strategies using transfer learning, subgroup models, as well as subject-dependent standardisation on a newly-collected, longitudinal dataset of depression patients undergoing treatment with a digital intervention (N=65 patients recruited). Both passive mobile sensor data as well as ecological momentary assessments were available for modelling. We evaluated the models’ ability to predict symptoms of depression (Patient Health Questionnaire-2; PHQ-2) at the end of each day, and to forecast symptoms of the next day. Results In our experiments, we achieve a best mean-absolute-error (MAE) of 0.801 (25% improvement) for predicting PHQ-2 values at the end of the day with subject-dependent standardisation compared to a non-personalised baseline (MAE=1.062). For one day ahead-forecasting, we can improve the baseline of 1.539 by 12% to a MAE of 1.349 using a transfer learning approach with shared common layers. In addition, personalisation leads to fairer models at group-level. Discussion Our results suggest that personalisation using subject-dependent standardisation and transfer learning can improve predictions and forecasts, respectively, of depressive symptoms in participants of a digital depression intervention. We discuss technical and clinical limitations of this approach, avenues for future investigations, and how personalised machine learning architectures may be implemented to improve existing digital interventions for depression

Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial

Introduction: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients. Methods: In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20 mg. Frequent sNfL sampling (14 time points over 12 weeks) and monthly MRI scans enabled key analyses including assessment of the group-level temporal relationship of sNfL levels with on-study subclinical development of gadolinium-enhancing (Gd +)T1 lesions. Prognostic value of baseline sNfL ("high" vs. "low") level for subsequent on-study clinical relapse or Gd + T1 activity was assessed. Individual patient-level development of on-study Gd + T1 lesions wascompared across three predictors: baseline Gd + T1 lesion number, baseline sNfL ("high" vs. "low"), and time-matched sNfL. Results: In patients developing Gd + T1 lesions at week 4 (absent at baseline), sNfL levels increased during the month preceding the week-4 MRI scan and then gradually decreased back to baseline. High versus low baseline sNfL conferred increased risk of subsequent on-study clinical relapse or Gd + T1 activity (HR, 2.81; p < 0.0001) in the overall population and, notably, also in the patients without baseline Gd + T1 lesions (HR, 2.48; p = 0.0213). Individual patient trajectories revealed a marked difference in Gd + T1 lesions between patients with the ten highest vs. lowest baseline sNfL levels (119 vs. 19 lesions). Prognostic value of baseline or time-matched sNfL for on-study Gd + T1 lesions was comparable to that of the number of baseline MRI Gd + T1 lesions. Conclusions: sNfL measurement may have utility in capturing and monitoring subclinical disease activity in RMS patients. sNfL assessments could complement regular MRI scans and may provide an alternative when MRI assessment is not feasible. ClinicalTrials.gov: NCT03560739. Classification of Evidence: This study provides class I evidence that serum neurofilament light may be used as a biomarker for monitoring subclinical disease activity in relapsing multiple sclerosis patients, as shown by its elevation in the weeks preceding the development of new gadolinium-enhancing T1 lesion activity

Immune Suppressive Effects of Plasma-Derived Exosome Populations in Head and Neck Cancer

Plasma-derived exosomes of head and neck squamous cell carcinoma (HNSCC) patients carry inhibitory factors mediating immune suppression. Separation of tumor-derived exosomes (TEX) and non-TEX may assist in a better understanding of their respective parental cells. Here, we evaluate the impact of TEX or hematopoietic-derived exosomes on immune suppression. We evaluated apoptosis in CD8+ T cells, conversion of CD4+ T cells to regulatory T cells (Treg), and adenosine production by TEX, non-TEX, or total exosomes. Exosome protein cargo was significantly higher in total and CD45(−) exosomes from high stage compared to low stage patients. Furthermore, total and CD45(−) exosomes of high stage patients induced more apoptosis in CD8+ T cells than their low stage counterparts. CD69 suppression, a marker of reduced CD8+ T cell activation, was only mediated by CD45(−) exosomes. All fractions induced Treg differentiation, defined by CD39 expression, but only CD45(−) exosomes showed a stage-dependent conversion. CD45(−) exosomes produced higher adenosine concentrations than CD45(+) exosomes, concluding that adenosine production measured in total exosomes mainly derives from TEX. The presented results show significant induction of immune suppression by TEX in HNSCC. This immunosuppressive effect supports the potential role of exosomes as liquid biomarkers for disease stage and level of immune suppression

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion

Genome-Wide Association Study Identifies Two Novel Regions at 11p15.5-p13 and 1p31 with Major Impact on Acute-Phase Serum Amyloid A

Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20×10−111) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22×10−11) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins