Probabilistic U-Net model observer for the DDC method in CT scan protocol optimization.

Optimizing complex imaging procedures within Computed Tomography, considering both dose and image quality, presents significant challenges amidst rapid technological advancements and the adoption of machine learning (ML) methods. A crucial metric in this context is the Difference-Detailed Curve, which relies on human observer studies. However, these studies are labor-intensive and prone to both inter- and intra-observer variability. To tackle these issues, a ML-based model observer utilizing the U-Net architecture and a Bayesian methodology is proposed. In order to train a model observer unaffected by the spatial arrangement of low-contrast objects, the image preprocessing incorporates a Gaussian Process-based noise model. Additionally, gradient-weighted class activation mapping is utilized to gain insights into the model observer's decision-making process. By training on data from a diverse group of observers, well-calibrated probabilistic predictions that quantify observer variability are achieved. Leveraging the principles of Beta regression, the Bayesian methodology is used to derive a model observer performance metric, effectively gauging the model observer's strength in terms of an 'effective number of observers'. Ultimately, this framework enables to predict the DDC distribution by applying thresholds to the inferred probabilities (Part of this work has been presented at: Stocker D, Sommer C, Gueng S, Stäuble J, Özden I, Griessinger J, Weyland M S, Lutters G, Scheidegger S (2023). Probabilistic U-Net Model Observer for the DDC Method in CT Scan Protocol Optimization. The 56th SSRMP Annual Meeting 2023, November 30. - December 1., 2023, Luzern, Switzerland).

Estimation of Electrostatic Interaction Energies on a Trapped-Ion Quantum Computer.

We present the first hardware implementation of electrostatic interaction energies by using a trapped-ion quantum computer. As test system for our computation, we focus on the reduction of NO to N2O catalyzed by a nitric oxide reductase (NOR). The quantum computer is used to generate an approximate ground state within the NOR active space. To efficiently measure the necessary one-particle density matrices, we incorporate fermionic basis rotations into the quantum circuit without extending the circuit length, laying the groundwork for further efficient measurement routines using factorizations. Measurements in the computational basis are then used as inputs for computing the electrostatic interaction energies on a classical computer. Our experimental results strongly agree with classical noise-less simulations of the same circuits, finding electrostatic interaction energies within chemical accuracy despite hardware noise. This work shows that algorithms tailored to specific observables of interest, such as interaction energies, may require significantly fewer quantum resources than individual ground state energies would require in the straightforward supermolecular approach.

The ROCEEH Out of Africa Database (ROAD): A large-scale research database serves as an indispensable tool for human evolutionary studies.

Large scale databases are critical for helping scientists decipher long-term patterns in human evolution. This paper describes the conception and development of such a research database and illustrates how big data can be harnessed to formulate new ideas about the past. The Role of Culture in Early Expansions of Humans (ROCEEH) is a transdisciplinary research center whose aim is to study the origins of culture and the multifaceted aspects of human expansions across Africa and Eurasia over the last three million years. To support its research, the ROCEEH team developed an online tool named the ROCEEH Out of Africa Database (ROAD) and implemented its web-based applications. ROAD integrates geographical data as well as archaeological, paleoanthropological, paleontological and paleobotanical content within a robust chronological framework. In fact, a unique feature of ROAD is its ability to dynamically link scientific data both spatially and temporally, thereby allowing its reuse in ways that were not originally conceived. The data stem from published sources spanning the last 150 years, including those generated by the research team. Descriptions of these data rely on the development of a standardized vocabulary and profit from online explanations of each table and attribute. By synthesizing legacy data, ROAD facilitates the reuse of heritage data in novel ways. Database queries yield structured information in a variety of interoperable formats. By visualizing data on maps, users can explore this vast dataset and develop their own theories. By downloading data, users can conduct further quantitative analyses, for example with Geographic Information Systems, modeling programs and artificial intelligence. In this paper, we demonstrate the innovative nature of ROAD and show how it helps scientists studying human evolution to access datasets from different fields, thereby connecting the social and natural sciences. Because it permits the reuse of "old" data in new ways, ROAD is now an indispensable tool for researchers of human evolution and paleogeography.

The impact of plasmonic electrodes on the photocarrier extraction of inverted organic bulk heterojunction solar cells.

Nano-patterning the semiconducting photoactive layer/back electrode interface of organic photovoltaic devices is a widely accepted approach to enhance the power conversion efficiency through the exploitation of numerous photonic and plasmonic effects. Yet, nano-patterning the semiconductor/metal interface leads to intertwined effects that impact the optical as well as the electrical characteristic of solar cells. In this work we aim to disentangle the optical and electrical effects of a nano-structured semiconductor/metal interface on the device performance. For this, we use an inverted bulk heterojunction P3HT:PCBM solar cell structure, where the nano-patterned photoactive layer/back electrode interface is realized by patterning the active layer with sinusoidal grating profiles bearing a periodicity of 300 nm or 400 nm through imprint lithography while varying the photoactive layer thickness (L PAL ) between 90 and 400 nm. The optical and electrical device characteristics of nano-patterned solar cells are compared to the characteristics of control devices, featuring a planar photoactive layer/back electrode interface. We find that patterned solar cells show for an enhanced photocurrent generation for a L PAL above 284 nm, which is not observed when using thinner active layer thicknesses. Simulating the optical characteristic of planar and patterned devices through a finite-difference time-domain approach proves for an increased light absorption in presence of a patterned electrode interface, originating from the excitation of propagating surface plasmon and dielectric waveguide modes. Evaluation of the external quantum efficiency characteristic and the voltage dependent charge extraction characteristics of fabricated planar and patterned solar cells reveals, however, that the increased photocurrents of patterned devices do not stem from an optical enhancement but from an improved charge carrier extraction efficiency in the space charge limited extraction regime. Presented findings clearly demonstrate that the improved charge extraction efficiency of patterned solar cells is linked to the periodic surface corrugation of the (back) electrode interface. Supplementary Information: The online version contains supplementary material available at 10.1007/s00339-023-06492-6.

The impact of pharmacists' interventions within the Closed Loop Medication Management process on medication safety: An analysis in a German university hospital.

Background: Single elements of the Closed Loop Medication Management process (CLMM), including electronic prescribing, involvement of clinical pharmacists (CPs), patient individual logistics and digital administration/documentation, have shown to improve medication safety and patient health outcomes. The impact of the complete CLMM on patient safety, as reflected in pharmacists' interventions (PIs), is largely unknown. Aim: To evaluate the extent and characterization of routine PIs performed by hospital-wide CPs at a university hospital with an implemented CLMM. Methods: This single-center study included all interventions documented by CPs on five self-chosen working days within 1 month using the validated online-database DokuPIK (Documentation of Pharmacists' Interventions in the Hospital). Based on different workflows, two groups of CPs were compared. One group operated as a part of the CLMM, the "Closed Loop Clinical Pharmacists" (CL-CPs), while the other group worked less dependent of the CLMM, the "Process Detached Clinical Pharmacists" (PD-CPs). The professional experience and the number of medication reviews were entered in an online survey. Combined pseudonymized datasets were analyzed descriptively after anonymization. Results: A total of 1,329 PIs were documented by nine CPs. Overall CPs intervened in every fifth medication review. The acceptance rate of PIs was 91.9%. The most common reasons were the categories "drugs" (e.g., indication, choice of formulation/drug and documentation/transcription) with 42.7%, followed by "dose" with 29.6%. One-quarter of PIs referred to the therapeutic subgroup "J01 antibacterials for systemic use." Of the 1,329 underlying PIs, 1,295 were classified as medication errors (MEs) and their vast majority (81.5%) was rated as "error, no harm" (NCC MERP categories B-D). Among PIs performed by CL-CPs (n = 1,125), the highest proportion of errors was categorized as B (56.5%), while in the group of PIs from PD-CPs (n = 170) errors categorized as C (68.2%) dominated (p < 0.001). Conclusion: Our study shows that a structured CLMM enables CPs to perform a high number of medication reviews while detecting and solving MEs at an early stage before they can cause harm to the patient. Based on key quality indicators for medication safety, the complete CLMM provides a suitable framework for the efficient medication management of inpatients.

A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles.

Although new genes can arrive from modes other than duplication, few examples are well characterized. Given high expression in some human brain subregions and a putative link to psychological disorders [e.g., schizophrenia (SCZ)], suggestive of brain functionality, here we characterize piggyBac transposable element-derived 1 (PGBD1). PGBD1 is nonmonotreme mammal-specific and under purifying selection, consistent with functionality. The gene body of human PGBD1 retains much of the original DNA transposon but has additionally captured SCAN and KRAB domains. Despite gene body retention, PGBD1 has lost transposition abilities, thus transposase functionality is absent. PGBD1 no longer recognizes piggyBac transposon-like inverted repeats, nonetheless PGBD1 has DNA binding activity. Genome scale analysis identifies enrichment of binding sites in and around genes involved in neuronal development, with association with both histone activating and repressing marks. We focus on one of the repressed genes, the long noncoding RNA NEAT1, also dysregulated in SCZ, the core structural RNA of paraspeckles. DNA binding assays confirm specific binding of PGBD1 both in the NEAT1 promoter and in the gene body. Depletion of PGBD1 in neuronal progenitor cells (NPCs) results in increased NEAT1/paraspeckles and differentiation. We conclude that PGBD1 has evolved core regulatory functionality for the maintenance of NPCs. As paraspeckles are a mammal-specific structure, the results presented here show a rare example of the evolution of a novel gene coupled to the evolution of a contemporaneous new structure.

Sustainable human population density in Western Europe between 560.000 and 360.000 years ago.

The time period between 560 and 360 ka (MIS14 to MIS11) was critical for the evolution of the Neanderthal lineage and the appearance of Levallois technology in Europe. The shifts in the distribution of the human populations, driven by cyclical climate changes, are generally accepted to have played major roles in both processes. We used a dataset of palaeoclimate maps and a species distribution model to reconstruct the changes in the area of Western Europe with suitable environmental conditions for humans during 11 time intervals of the MIS14 to MIS 11 period. Eventually, the maximum sustainable human population within the suitable area during each time interval was estimated by extrapolating the relationship observed between recent hunter-gatherer population density and net primary productivity and applying it to the past. Contrary to common assumptions, our results showed the three Mediterranean Peninsulas were not the only region suitable for humans during the glacial periods. The estimated total sustainable population of Western Europe from MIS14 to MIS11 oscillated between 13,000 and 25,000 individuals. These results offer a new theoretical scenario to develop models and hypotheses to explain cultural and biological evolution during the Middle Pleistocene in Western Europe.

[Arterial Hypertension]. / Arterielle Hypertonie ­ Eine Übersicht für den ärztlichen Alltag.

Arterial hypertension affects about one third of the German population with a prevalence increasing with age up to 60 %. Globally, more than a quarter gedoppelt of the population are considered hypertensive, resulting in a total of more than one billion people. Not only due to such high prevalence, but also because of its multiple cardiovascular, renal, ocular, and cognitive complications, arterial hypertension is a leading contributor to the global burden of disease and responsible for up to 10 million deaths worldwide. Contrary to the great importance of arterial hypertension resulting from such high prevalence and immense impact on health worldwide, awareness of disease is low in affected people. Less than every second patient knows about his or her disease status and less than 40 % of patients in Europe show adequate blood pressure control with a treatment target of < 140/90 mmHg despite antihypertensive treatment. This overview of arterial hypertension, its etiology, diagnostic tools, and therapeutic options aims to improve the understanding of arterial hypertension and to facilitate the diagnostic and therapeutic approach, eventually resulting in a better and more successful handling of patients with arterial hypertension.

Origination of free-form micro-optical elements using one- and two-photon grayscale laser lithography.

We discuss and describe the development of an origination process for planar free-form micro-optical elements from a given optical design. The targeted masters serve as origination structures for a roll-to-roll mass fabrication process. Specifically targeted are complex, optically smooth, surface relief structures with variable structure heights in the range of 1-20 µm, with typical lateral sizes of more than 5 µm. The area of the targeted masters is in the range of 1cm2. The main part of the paper is devoted to the description of a self-developed grayscale laser direct-write platform enabling one- and two-photon absorption lithography, also in combination on one and the same sample. In the following, we describe both methods and show that both lead to excellent structural quality of surface micro-relief structures. As a showcase of what the system can do in principle, we designed and fabricated free-form micro-optical elements to project light from an LED as a defined light pattern onto a wall. The proper optical functionality of the fabricated element was shown within a demonstrator setup.

Feasibility of a method for low contrast CT image quality assessment using difference detail curves for abdominal scans.

This work describes a measurement method for assessing dose-related image-quality of CT scans based on the difference detail curve (DDC) method, and showcases its use in a low contrast setting. The method is based on a phantom consisting of elliptical slices of different sizes into which contrast object modules can be inserted. These modules contain contrast objects based on (synthetic) resin mixtures with sucrose (native) or sodium iodine (contrast medium). Mixing ratios are provided to achieve a range of clinically relevant CT-numbers with these materials. The phantom is characterized in terms of contrast accuracy, energy dependency and long-term drift with satisfying results. Contrast accuracy and energy dependency are similar to that of water or soft tissue. Image quality of 655 scans of the phantom acquired at 30 different clinical institutions and with 16 different CT scanner models from 4 manufacturers was assessed by calculating a difference detail curve (DDC) from evaluation of up to 5 human observers using a custom-made software (RadiVates) described in this work. Based on these measurements, inter-observer variability was quantified using a bootstrap method and was shown to be a large contributor to the overall variability. This work demonstrates that assessment of CT image quality is feasible with the aforementioned phantom and DDC method.

Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis.

Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-independent endocytic pathway (CLIC-GEEC, CG pathway) is considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. While the core molecular players of CG-endocytosis have been recently defined, evidence of cargo-specific adaptors or selective uptake of proteins for the pathway are lacking. Here we identify the actin-binding protein Swiprosin-1 (Swip1, EFHD2) as a cargo-specific adaptor for CG-endocytosis. Swip1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery-Arf1, IRSp53 and actin-and is critical for integrin endocytosis. Through this function, Swip1 supports integrin-dependent cancer-cell migration and invasion, and is a negative prognostic marker in breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG pathway and a role for specific adaptors in recruitment into this endocytic route.

Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence.

BACKGROUND: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian-instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. METHODS: Using a PIT task, we examined three independent samples: young healthy subjects (N = 161), detoxified alcohol-dependent patients (N = 186) and age-matched healthy controls (N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. RESULTS: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. CONCLUSION: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

Rapid glacier retreat and downwasting throughout the European Alps in the early 21st century.

Mountain glaciers are known to be strongly affected by global climate change. Here we compute temporally consistent changes in glacier area, surface elevation and ice mass over the entire European Alps between 2000 and 2014. We apply remote sensing techniques on an extensive database of optical and radar imagery covering 93% of the total Alpine glacier volume. Our results reveal rapid glacier retreat across the Alps (-39 km² a-1) with regionally variable ice thickness changes (-0.5 to -0.9 m a-1). The strongest downwasting is observed in the Swiss Glarus and Lepontine Alps with specific mass change rates up to -1.03 m.w.e. a-1. For the entire Alps a mass loss of 1.3 ± 0.2 Gt a-1 (2000-2014) is estimated. Compared to previous studies, our estimated mass changes are similar for the central Alps, but less negative for the lower mountain ranges. These observations provide important information for future research on various socio-economic impacts like water resource management, risk assessments and tourism.

Prospects of reinforcement learning for the simultaneous damping of many mechanical modes.

We apply adaptive feedback for the partial refrigeration of a mechanical resonator, i.e. with the aim to simultaneously cool the classical thermal motion of more than one vibrational degree of freedom. The feedback is obtained from a neural network parametrized policy trained via a reinforcement learning strategy to choose the correct sequence of actions from a finite set in order to simultaneously reduce the energy of many modes of vibration. The actions are realized either as optical modulations of the spring constants in the so-called quadratic optomechanical coupling regime or as radiation pressure induced momentum kicks in the linear coupling regime. As a proof of principle we numerically illustrate efficient simultaneous cooling of four independent modes with an overall strong reduction of the total system temperature.

A multimodal neuroimaging classifier for alcohol dependence.

With progress in magnetic resonance imaging technology and a broader dissemination of state-of-the-art imaging facilities, the acquisition of multiple neuroimaging modalities is becoming increasingly feasible. One particular hope associated with multimodal neuroimaging is the development of reliable data-driven diagnostic classifiers for psychiatric disorders, yet previous studies have often failed to find a benefit of combining multiple modalities. As a psychiatric disorder with established neurobiological effects at several levels of description, alcohol dependence is particularly well-suited for multimodal classification. To this aim, we developed a multimodal classification scheme and applied it to a rich neuroimaging battery (structural, functional task-based and functional resting-state data) collected in a matched sample of alcohol-dependent patients (N = 119) and controls (N = 97). We found that our classification scheme yielded 79.3% diagnostic accuracy, which outperformed the strongest individual modality - grey-matter density - by 2.7%. We found that this moderate benefit of multimodal classification depended on a number of critical design choices: a procedure to select optimal modality-specific classifiers, a fine-grained ensemble prediction based on cross-modal weight matrices and continuous classifier decision values. We conclude that the combination of multiple neuroimaging modalities is able to moderately improve the accuracy of machine-learning-based diagnostic classification in alcohol dependence.

Dysfunctional approach behavior triggered by alcohol-unrelated Pavlovian cues predicts long-term relapse in alcohol dependence.

We demonstrated that alcohol-dependent patients who relapsed within 1 year after detoxification showed stronger PIT effects compared with abstainers and controls. Relapsers particularly failed to correctly perform in trials where an instrumental stimulus required inhibition while a Pavlovian background cue indicated a monetary gain. Under that condition, relapsers approached the instrumental stimulus, independent of the expected punishment. The failure of inhibiting an aversive stimulus in favor of approaching an appetitive context cue reflects dysfunctional altered learning mechanisms in relapsers.

Dissociating neural learning signals in human sign- and goal-trackers.

Individuals differ in how they learn from experience. In Pavlovian conditioning models, where cues predict reinforcer delivery at a different goal location, some animals-called sign-trackers-come to approach the cue, whereas others, called goal-trackers, approach the goal. In sign-trackers, model-free phasic dopaminergic reward-prediction errors underlie learning, which renders stimuli 'wanted'. Goal-trackers do not rely on dopamine for learning and are thought to use model-based learning. We demonstrate this double dissociation in 129 male humans using eye-tracking, pupillometry and functional magnetic resonance imaging informed by computational models of sign- and goal-tracking. We show that sign-trackers exhibit a neural reward prediction error signal that is not detectable in goal-trackers. Model-free value only guides gaze and pupil dilation in sign-trackers. Goal-trackers instead exhibit a stronger model-based neural state prediction error signal. This model-based construct determines gaze and pupil dilation more in goal-trackers.

Partial Optomechanical Refrigeration via Multimode Cold-Damping Feedback.

We provide a fully analytical treatment for the partial refrigeration of the thermal motion of a quantum mechanical resonator under the action of feedback. As opposed to standard cavity optomechanics where the aim is to isolate and cool a single mechanical mode, the aim here is to extract the thermal energy from many vibrational modes within a large frequency bandwidth. We consider a standard cold-damping technique, where homodyne readout of the cavity output field is fed into a feedback loop that provides a cooling action directly applied on the mechanical resonator. Analytical and numerical results predict that low final occupancies are achievable independent of the number of modes addressed by the feedback, as long as the cooling rate is smaller than the intermode frequency separation. For resonators exhibiting a few nearly degenerate pairs of modes, cooling is less efficient and a weak dependence on the number of modes is obtained. These scalings hint toward the design of frequency-resolved mechanical resonators, where efficient refrigeration is possible via simultaneous cold-damping feedback.