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In evaluative conditioning, a neutral conditional stimulus (CS) acquires the valence of a pleasant or unpleasant unconditional stimulus (US) after the CS and US are paired (acquisition). Valence acquired by the CS can generalise to other stimuli from the same category. Presenting the CS alone can reduce evaluative conditioning (extinction), but evaluations can return after the US is presented alone (reinstatement). The current research investigated whether extinction and reinstatement generalise to other category members (generalisation stimuli, GS). In Experiment 1, evaluations generalised in acquisition after conditioning with one category exemplar, but GS evaluations were unaffected by extinction and reinstatement. In Experiment 2, we aimed to enhance generalisation by presenting multiple category exemplars during conditioning. This strengthened the generalisation of evaluations in extinction but not reinstatement. In Experiment 3, conditioning with multiple exemplars caused explicit and implicit evaluations (measured using an affective priming task) to generalise in acquisition but not in extinction or reinstatement. The acquisition and extinction of US expectancy generalised in all experiments, but the reinstatement generalised in Experiment 3 only. Overall, we found partial evidence of evaluative generalisation during extinction (but not reinstatement) and demonstrated that the extinction and reinstatement of US expectancy generalises in evaluative conditioning. [ABSTRACT FROM AUTHOR]

Ageing has become a ubiquitous concern in European policy. Critics have bemoaned that such policies are not so much about older people but rather about finding justification for other policy aims, such as economic growth or technological innovation. However, such critiques do not capture the co-constitutive relationship between ageing and innovation shaping one another. Using the example of the Silver Economy discourse, we show that ageing has not only been reframed under the imperatives of economic and innovation policies, but that ageing itself can also affect those policies. In its formative stages, the Silver Economy was characterised by a number of tensions between, on the one hand, common ageist assumptions about old age and, on the other hand, alternative visions of what ageing could mean as a policy field. However, these potentials have later been domesticated within the broader field of Active and Healthy Ageing. In this Forum Article, we therefore hypothesise what it would mean to take ageing more seriously as a driver of progressive politics as indicated in those formative years of the Silver Economy. Such a speculative take on current old-age policy, we hold, opens up a number of fruitful avenues and new interfaces between critical researchers, practitioners and policy makers interested in driving progressive politics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Automated sorting of mixed municipal solid waste in material recovery facilities. • Average recovery potential of plastic packaging in Austria 83,000 t/a. • Average increase in plastic packaging recycling rate from currently 25% to 35% Austria must recycle more packaging materials. Especially for plastic packaging waste, significant increases are necessary to reach the EU recycling targets for 2025 and 2030. In addition to improving separate collection and introducing a deposit system for specific fractions, the share of plastic packaging in mixed municipal solid waste (MSW) could be utilized. In Austria, about 1.8 million tonnes of mixed MSW are generated. This includes about 110,000 t/a of plastic packaging waste. Most of the mixed MSW (94 %) is sent directly or via residues from pre-treatment, such as mechanical–biological treatment or waste sorting, to waste incineration. While materials such as glass and metals can also be recovered from the bottom ash, combustible materials such as plastics must be recovered before incineration. This work aims to evaluate the recovery potential of plastic packaging waste in mixed MSW with automated waste sorting. For this purpose, two of the largest Austrian waste sorting plants, with a total annual throughput of about 280,000 t/a, were investigated. The investigation included regular sampling of selected output streams and sorting analysis. The results show that the theoretical recovery potential of plastic packaging from these two plants is 6,500 t/a on average. An extrapolation to Austria results in a potential of about 83,000 t/a. If losses due to further treatment, such as sorting and recycling, are considered, about 30,000 t/a of recyclate could be returned to plastic production. This would correspond to an increase in plastic packaging recycling rate from 25 % to 35 %. [ABSTRACT FROM AUTHOR]

The present study examines an understudied potential warning sign of school shootings: violence against women (VAW). Utilizing the social–ecological model of violence prevention, we employed directed content analysis to determine the prevalence of acts and social–ecological features of VAW among profiles of 59 boys/men who perpetrated school shootings between 1966 and 2018. The majority of shootings profiled occurred in the United States (47, 79.7%), followed by Canada (five, 8.5%), Finland (two, 3.4%), Germany (two, 3.4%), Brazil (one, 1.7%), Scotland (one, 1.7%), and Ukraine (one, 1.7%). Results demonstrated a strong presence of VAW among profiled school shooters, with almost 70% perpetrating VAW and the identification of frequent features of VAW that cut across the social–ecological levels, most notably (the enactment of and failure to meet expectations of) hegemonic masculinity and normalization of violence. Implications for research and intervention are discussed. Public Significance Statement: Nearly 70% of profiled school shooters perpetrated acts of violence against women, including intimate partner violence and sexual assault. Thus, violence against women and its related social–ecological features, including hegemonic masculinity (e.g., expectations of toughness, antifemininity, and status among men, as well as the failure to meet these expectations) and normalization of violence (e.g., ignoring everyday acts of violence), are critical avenues for intervention in the prevention of school shootings. [ABSTRACT FROM AUTHOR]

Roboticists are faced with a striking discrepancy between vision and demonstration of care with robots. On the one hand, research funders, policy makers, and entrepreneurs expect robots to become a panacea to impending demographic change. On the other hand, efforts to demonstrate that vision in care practice have largely remained unfulfilled. In this article, I investigate how roboticists manage and deal with this discrepancy between high expectations toward robotics research and what robots are capable of doing in practice. I will offer an extensive analysis of the efforts by roboticists and others to install, repair, stage, and, surprisingly, suspend robot dramas. Robot dramas comprise an ambivalent mix of experimental practices that seek to stage visions of care robotics while at the same time testing precarious phenomena of human–robot interaction. This relates two prominent but still largely disconnected strands of research in Science and Technology Studies: works on techno-scientific demonstrations, and on high and low expectations. Here, robot dramas are a crucial site for studying the conflicting interrelation between the theatrical performativity of demonstrations and the interplay of high and low expectations. [ABSTRACT FROM AUTHOR]

Pairing a conditional stimulus (CS) with an aversive unconditional stimulus (US) causes negative valence and US expectancy to generalize to stimuli that are perceptually and/or conceptually similar to the CS. Past research has shown that instructing participants that the US is more likely to follow stimuli that are dissimilar to the CS reversed the generalization of US expectancy but left generalized valence unchanged. Here, we examined whether instructions about the relationship between stimuli that are perceptually similar would affect the generalization of valence. A picture of an alien (CS+) was paired with an electric stimulus, while a perceptually different alien stimulus (CS–) was presented alone. After conditioning, valence, US expectancy, and electrodermal responses generalized to different aliens that were perceptually similar (by color and shape) to the CS+ and CS–. Participants were then instructed that aliens perceptually similar to the CS+ belonged to the same group as the CS‐ and that aliens perceptually similar to the CS– belonged to the same group as the CS+. The instructions caused an elimination (but not a reversal) of generalized expectancy and valence but did not affect generalized electrodermal responses. This suggests that evaluations of generalization stimuli are sensitive to instructions about their relationship to the CS and that dissociations reported in the literature between valence and expectancy after instructions may occur due to the type of instruction used. Past research has shown that instructions about the likelihood of the unconditional stimulus occurrence affect unconditional stimulus expectancy ratings during perceptually similar generalization stimuli but do not influence evaluations. In the current study, we demonstrate that instructions that change how the conditional and generalization stimuli are related affected generalized unconditional stimulus expectancy ratings and evaluations but did not affect electrodermal responding. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative accurate localization of tumors in the lower gastrointestinal tract is essential to ensure oncologic radicality. In minimally invasive colon surgery, tactile identification of tumors is challenging due to diminished or absent haptics. In clinical practice, preoperative endoscopic application of a blue dye (ink) to the tumor site has become the standard for marking and identification of tumors in the colon. However, this method has the major limitation that accidental intraperitoneal spillage of the dye can significantly complicate the identification of anatomical structures and surgical planes. In this work, we describe a new approach of NIR fluorescent tattooing using a near-infrared (NIR) fluorescent marker instead of a blue dye (ink) for endoscopic tattooing. Methods: AFS81x is a newly developed NIR fluorescent marker. In an experimental study with four domestic pigs, the newly developed NIR fluorescent marker (AFS81x) was used for endoscopic tattooing of the colon. 7–12 endoscopic submucosal injections of AFS81x were placed per animal in the colon. On day 0, day 1, and day 10 after endoscopic tattooing with AFS81x, the visualization of the fluorescent markings in the colon was evaluated during laparoscopic surgery by two surgeons and photographically documented. Results: The detection rate of the NIR fluorescent tattoos at day 0, day 1, and day 10 after endoscopic tattooing was 100%. Recognizability of anatomical structures during laparoscopy was not affected in any of the markings, as the markings were not visible in the white light channel of the laparoscope, but only in the NIR channel or in the overlay of the white light and the NIR channel of the laparoscope. The brightness, the sharpness, and size of the endoscopic tattoos did not change significantly on day 1 and day 10, but remained almost identical compared to day 0. Conclusion: The new approach of endoscopic NIR fluorescence tattooing using the newly developed NIR fluorescence marker AFS81x enables stable marking of colonic sites over a long period of at least 10 days without compromising the recognizability of anatomical structures and surgical planes in any way. [ABSTRACT FROM AUTHOR]

The Robot Orthodontic Measurement and Simulation System (ROSS) is a novel biomechanical, dynamic, self-regulating setup for the simulation of tooth movement. The intrusion of the front teeth with forces greater than 0.5 N poses a risk for orthodontic-induced inflammatory root resorption (OIIRR). The aim was to investigate forces and moments during simulated tooth intrusion using ROSS. Five specimens of sixteen unmodified NiTi archwires and seven NiTi archwires with intrusion steps from different manufacturers (Forestadent, Ormco, Dentsply Sirona) with a 0.012″/0.014″/0.016″ wire dimension were tested. Overall, a higher wire dimension correlated with greater intrusive forces Fz (0.012″: 0.561–0.690 N; 0.014″: 0.996–1.321 N; 0.016″: 1.44–2.254 N) and protruding moments Mx (0.012″: −2.65 to −3.922 Nmm; 0.014″: −4.753 to −7.384 Nmm; 0.016″: −5.556 to −11.466 Nmm) during the simulated intrusion of a 1.6 mm-extruded upper incisor. However, the 'intrusion efficiency' parameter was greater for smaller wire dimensions. Modification with intrusion steps led to an overcompensation of the intrusion distance; however, it led to a severe increase in Fz and Mx, e.g., the Sentalloy 0.016″ medium (Dentsply Sirona) exerted 2.891 N and −19.437 Nmm. To reduce the risk for OIIRR, 0.014″ NiTi archwires can be applied for initial aligning (without vertical challenges), and intrusion steps for the vertical levelling of extruded teeth should be bent in the initial archwire, i.e., 0.012″ NiTi. [ABSTRACT FROM AUTHOR]

The transformation of carbon monoxide (CO) from a molecular liquid to a polymeric solid under isothermal compression at room temperature is investigated using first principles theory. We report structural and thermodynamic properties from ambient density up to 2.45 g/cc obtained using density functional theory molecular dynamics simulations, including hybrid exchange corrections. The theoretical results are compared with newly obtained polymeric CO samples, synthesized in a large volume press. The explosive performance of polymeric CO is predicted and discussed. Under most favorable assumptions, it is found to be comparable to trinitrotoluene. [ABSTRACT FROM AUTHOR]

We measured the atomic volume of Ag in a toroidal diamond anvil cell to a maximum pressure of 416 GPa and calculated the atomic volume and elastic constants of Ag up to 750 and 460 GPa, respectively. Our density functional theory calculations at 0 K utilize an all-electron fully relativistic method and agree well with our volume measurements, particularly at pressures above ∼75 GPa. We corrected our experimental results for non-hydrostaticity using a line shift analysis, and the resulting Vinet equation of state (EOS) parameters are reported. We find that the uniaxial stress sustained by Ag increases linearly up to 4.5 GPa at a pressure of 416 GPa. Our experimental results indicate that the fcc structure of Ag remains stable to at least 416 GPa at room temperature. Our theoretical results show that C44 increases as pressure increases and reaches a maximum at ∼100 GPa above which it begins to decrease, a sign that the fcc structure of Ag is becoming unstable, and at V/V0 = 0.30, the bcc structure is lower in energy than fcc. [ABSTRACT FROM AUTHOR]

Modern X-ray free-electron lasers (XFELs) produce intense femtosecond X-ray pulses able to cause significant damage to irradiated targets. Energetic photoelectrons created upon X-ray absorption, and Auger electrons emitted after relaxation of core-hole states trigger secondary electron cascades, which contribute to the increasing transient free electron density on femtosecond timescales. Further evolution may involve energy and particle diffusion, creation of point defects, and lattice heating. This long-timescale (up to a microsecond) X-ray-induced dynamics is discussed on the example of silicon in two-dimensional geometry. For modeling, we apply an extended Two-Temperature model with electron density dynamics, nTTM, which describes relaxation of an irradiated sample between two successive X-ray pulses, emitted from XFEL at MHz pulse repetition rate. It takes into account ambipolar carrier diffusion, electronic and atomic heat conduction, as well as electron-ion coupling. To solve the nTTM system of equations in two dimensions, we developed a dedicated finite-difference integration algorithm based on Alternating Direction Implicit method with an additional predictor-corrector scheme. We show first results obtained with the model and discuss its possible applications for XFEL optics, detectors, and for diagnostics tools. In particular, the model can estimate the timescale of material relaxation relevant for beam diagnostic applications during MHz operation of contemporary and future XFELs. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer (PC) is infamous for its silent and lethal nature, making it one of the leading causes of cancer-related deaths worldwide. The early detection of PC is critical to achieve a favorable prognosis, as it typically goes unnoticed until advanced stages. Fatty pancreas (FP) is often associated with PC, but the causal relationship has not been clearly defined. With this systematic review and meta-analysis, we aim to strengthen the connection and emphasize the potential risks of FP to the development of PC. Based on our analysis, our findings exhibit a clear risk of PC in the presence of FP, advocating for future prospective studies to be performed in order to solidify the relationship. Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case–control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42–4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61–14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42–0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended. [ABSTRACT FROM AUTHOR]

Care robots promise to assist older people in an ageing society. This article investigates the socio-material conditions of care with robots by focusing on the usually invisible practices of human-machine interfacing. I define human-machine interfacing as the activities by roboticists and others to render interaction between robots and people possible in the first place. This includes, efforts to render prototypical arrangements of care 'robot-friendly'. In my video-assisted ethnography of human-robot interaction (HRI) experiments. I identify four types of interfacing practices, where care comes to matter: integrating the ephemeral entity that is 'a robot', helping it by way of mundane courtesies, making users 'fit' for interacting with it, and establishing corridors of interaction between the robot and people's bodies. I show that robots do not so much care for (older) people but rather, the other way around – people need to care for robots. Hence, care robots are not simply agents of care but also objects of care, rendering necessary a symmetrical analysis of human-machine interfacing. Furthermore, these practices do not merely reflect the prototypical state of the art in robotics. Rather, they indicate a more general mode of how robots and people interface. I argue that care with robots requires us to re-consider the exclusive focus on the human and at least complement it with care for the non-human and, incidentally, the robotic, too. [ABSTRACT FROM AUTHOR]

Modern X-ray free-electron lasers (XFELs) produce intense femtosecond X-ray pulses able to cause significant damage to irradiated targets. Energetic photoelectrons created upon X-ray absorption, and Auger electrons emitted after relaxation of core-hole states trigger secondary electron cascades, which contribute to the increasing transient free electron density on femtosecond timescales. Further evolution may involve energy and particle diffusion, creation of point defects, and lattice heating. This long-timescale (up to a microsecond) X-ray-induced dynamics is discussed on the example of silicon in two-dimensional geometry. For modeling, we apply an extended Two-Temperature model with electron density dynamics, nTTM, which describes relaxation of an irradiated sample between two successive X-ray pulses, emitted from XFEL at MHz pulse repetition rate. It takes into account ambipolar carrier diffusion, electronic and atomic heat conduction, as well as electron-ion coupling. To solve the nTTM system of equations in two dimensions, we developed a dedicated finite-difference integration algorithm based on Alternating Direction Implicit method with an additional predictor-corrector scheme. We show first results obtained with the model and discuss its possible applications for XFEL optics, detectors, and for diagnostics tools. In particular, the model can estimate the timescale of material relaxation relevant for beam diagnostic applications during MHz operation of contemporary and future XFELs. [ABSTRACT FROM AUTHOR]

The understanding of cell–cell and cell–matrix interactions via receptor and ligand binding relies on our ability to study the very first events of their contact. Of particular interest is the interaction between a T cell receptor and its cognate peptide–major histocompatibility complex. Indeed, analyzing their binding kinetics and cellular avidity in large-scale low-cost and fast cell sorting would largely facilitate the access to cell-based cancer immunotherapies. We thus propose a microfluidic tool able to independently control two types of micro-sized objects, put them in contact for a defined time and probe their adhesion state. The device consists of hydrodynamic traps holding the first type of cell from below against the fluid flow, and a dielectrophoretic system to force the second type of object to remain in contact with the first one. First, the device is validated by performing an adhesion frequency assay between fibroblasts and fibronectin coated beads. Then, a study is conducted on the modification of the cellular environment to match the dielectrophoretic technology requirements without modifying the cell viability and interaction functionalities. Finally, we demonstrate the capability of the developed device to put cancer cells and a population of T cells in contact and show the discrimination between specific and non-specific interactions based on the pair lifetime. This proof-of-concept device lays the foundations for the development of next generation fast cell–cell interaction technologies. [ABSTRACT FROM AUTHOR]

Extricating histories of uplift and erosion from landscapes is crucial for many branches of the Earth sciences. An objective way to calculate such histories is to identify calibrated models that minimize misfit between observations (e.g., topography) and predictions (e.g., synthetic landscapes). In the presence of natural or computational noise, widely used Euclidean measures of similarity can have complicated objective functions, obscuring the search for optimal models. Instead, we introduce the Wasserstein distance as a means to measure misfit between observed and theoretical landscapes. Our results come in two parts. First, we show that this approach can generate much smoother objective functions than Euclidean measures, simplifying the search for optimal models. Second, we show how locations and amplitudes of uplift can be accurately recovered from synthetic landscapes even when seeded with different noisy initial conditions. We suggest that this approach holds promise for inverting real landscapes for their histories. Plain Language Summary: The shapes of Earth's landscapes tell us about how they were formed by processes like tectonic uplift and erosion. Mathematical models are used to predict how landscapes change over time due to these processes. However, identifying models that produce theoretical landscapes that resemble reality can be challenging. One way to do so is by comparing model predictions to actual landscapes we observe. To make this comparison, we need a way to measure how similar or different predicted and observed landscapes are. One common approach is to compare heights of land from both cases. However, this method can struggle because a small shift in the position of a theoretical valley, say, can dramatically change the outcome of a comparison. In this paper, we introduce an alternative approach that uses a metric called the Wasserstein distance from the field of "Optimal Transport." The Wasserstein distance is a measure of how different two probability distributions are from each other by considering how much "work" is needed to transform one distribution into the other. We show that this metric is effective for finding models to understand how landscapes were shaped by uplift over time. Key Points: The use of the Wasserstein distance for identifying optimal landscape evolution models is demonstratedThis approach can produce simple objective functions, simplifying the search for models that minimize data misfitAccurate amplitudes and locations of uplift can be retrieved from synthetic landscapes generated using different initial conditions [ABSTRACT FROM AUTHOR]

The article discusses the issue of "futility" in therapy and sheds light on specific treatment situations at the end of life, with incapacitated adults and with a desire for maximal therapy. Ineffective measures have no effect in favor of the treatment goal, contraindicated measures harm the patient, and measures with an unfavorable benefit-risk ratio do not need to be included in the decision-making process unless the patient asks for them. Doctors must explain their assessments transparently and inform the patient unless there is no reasonable doubt about the evaluation. In end-of-life situations, life-sustaining measures should be replaced by palliative measures. In the case of incapacitated patients, a patient representative should be involved in the decision-making process. [Extracted from the article]

Initial evidence suggests that rates of intimate partner violence (IPV) increased at the beginning of the COVID‐19 pandemic. However, much of the prevalence research has focused on survivors' experiences of IPV during the initial lockdown period from March to June 2020. The current study adds to this initial research by centering the experience of a domestic violence agency located in the United States, 3‐months prior to, during, and after the COVID‐19 lockdown. The results suggest a similar pattern across service utilization (e.g., total clients served, calls, safe house capacity) and survivor demographics (e.g., race/ethnicity, cisgender women and men), with an initial decrease in service utilization from pre‐lockdown to lockdown and an increase, surpassing pre‐lockdown, post‐lockdown. The only deviations from this pattern of service utilization were for sexual minority individuals, whose service utilization continued to decline post‐lockdown and Asian American/Pacific Islander and trans/gender‐nonbinary survivors who rarely utilized services across the time period. Additionally, the domestic violence agency relied heavily on their existing finances, well‐rounded staff training, and staff wellbeing throughout the pandemic. The unique challenges that COVID‐19 provided demanded flexibility, increased technological utilization, and additional funding particularly for safe housing. Implications for future research, intervention, and policy change are provided below. [ABSTRACT FROM AUTHOR]

The author discusses his experiences in online teaching of the Reformation. He mentions his usual storytelling technique and his desire to retain that online, his use of podcasts and short documentary films to enhance his lectures, and how he hopes to continue including such techniques after the return to the classroom.

Generalisation in evaluative conditioning occurs when the valence acquired by a conditional stimulus (CS), after repeated pairing with an unconditional stimulus (US), spreads to stimuli that are similar to the CS (generalisation stimuli, GS). CS evaluations can be updated via CS instructions that conflict with prior conditioning (negative conditioning + positive instruction). We examined whether CS instructions can update GS evaluations after conditioning. We used alien stimuli where one alien (CSp) from a fictional group was paired with pleasant US images and another alien (CSu) from a different group was paired with unpleasant US images. The other members from the two groups were used as GSs. After conditioning, participants received negative CSp instructions and positive CSu instructions. In Experiment 1, explicit and implicit GS evaluations were measured before and after the instructions. In Experiment 2, we used a between-participants design where one group received positive/negative CS instructions while a control group received neutral instructions. In both experiments, the positive/negative CS instructions caused a reversal of explicit GS evaluations and an elimination of implicit GS evaluations. The findings suggest that generalised evaluations can change after CS instructions which may have implications for interventions aimed at reducing negative group attitudes. [ABSTRACT FROM AUTHOR]

First offers play a significant role in negotiations as they anchor negotiators' perceptions and influence negotiation outcomes in favor of the first-offer proposer. However, negotiation is a joint decision-making process in which a first offer is typically succeeded by a counteroffer. The impact of a counteroffer has not yet been systematically researched. We propose that a counteroffer influences negotiation outcomes like a first offer. In addition, we conceptualize the "anchor zone" as the distance between the first offer and the counteroffer. We theorize that the anchor zone influences negotiation outcomes because it captures additional information compared to a single offer. To test our hypotheses, we conducted two studies: Study 1 was a vignette study (n = 190) in which participants reacted to a counteroffer that they received based on their first offer as part of a simulated negotiation. Study 2 was an online experiment (n = 212) in which participants negotiated by exchanging offers with no further communication. Our analysis suggests that the counteroffer is a significant predictor of economic outcomes. Thus, it works like a first offer, but with a lower impact. In addition, the anchor zone predicted how far the final agreement was from the first offer. Furthermore, we found that the third offer, the average concessions, and the number of offers mediated the effects of the counteroffer and anchor zone on economic outcomes. Finally, we discovered that a more aggressive counteroffer reduced the subjective value of both negotiators. [ABSTRACT FROM AUTHOR]

Low self-efficacy for threatening stimuli and situations has been proposed as an important etiological factor in the development and maintenance of specific phobias. The present study examined the relationships between general self-efficacy (GSE), specific self-efficacy (SSE) and specific fears in a representative sample (n = 717). While GSE was associated with higher self-reported fear and avoidance, SSE (e.g. SSE in the presence of animal-related fear) was more related to specific fears. SSE turned out to be a significant predictor of specific fear even after controlling for trait anxiety, age and gender. Interestingly, the association between SSE and specific fear differed across the different fear categories. Fear and avoidance of blood/injection/injuries showed the highest associations with SSE. In contrast, the association between natural environment-related fear and avoidance and GSE or SSE together was only modest. Exploratory analyses revealed a gender-specific effect on the strength of the association between SSE and specific fears. Women scored higher in animal-related fears and SSE. Our findings support the self-efficacy hypothesis of anxiety disorder development and provide a more detailed insight into the role of GSE and SSE in specific fears and phobias. [ABSTRACT FROM AUTHOR]

The article "Limits of Therapy and 'Futility': Children and Adolescents (Part 1)" addresses the question of the limits of medical therapy in children and adolescents. The discussion about the so-called "futility" issue is taken up by the Swiss Academy of Medical Sciences (SAMW) and the German Central Ethics Committee at the Federal Medical Association (ZEKO). The article suggests examining the various case scenarios more closely, determining criteria for dealing with them, and investigating the consequences for the treatment of patients. Part 1 of the article deals with general aspects and focuses on children and adolescents, while Part 2 in the next issue addresses end-of-life case scenarios, incapacitated adults, and the desire for maximal therapy. The text discusses different approaches to determining the futility of a medical treatment measure. It is pointed out that there is no consensus on how this should be determined. The approaches range from objective criteria to subjective evaluations by doctors or patients. Medical indication plays an important role in assessing the futility of a treatment. The decision is based on a comprehensive risk-benefit assessment, which also takes into account the goals, values, and personal circumstances of the patient. In special treatment situations, additional challenges arise. The article examines the peculiarities of treating children and adolescents as well as scarce treatment resources ("triage") in connection with the concept of "futility". Minor patients cannot enter into a treatment contract and are usually represented by their legal guardians. As they grow older and more mature, children should be involved in the decision-making process. In Austria, decision-making capacity for consenting to medical treatments is presumed from the age of 14, but for serious treatments, the consent of a legal guardian is also required. The debate about "triage decisions" has experienced a renaissance due to the COVID-19 pandemic, and it differs from the "futility" issue, although both decisions ultimately determine whether a treatment is initiated or continued. The text discusses the limits of therapy and the handling of "futility" in the medical context. It emphasizes that a decision to refuse treatment is only necessary if a treatment is medically indicated. The discussion focuses on the distinction between ineffectiveness, contraindication, and a very unfavorable risk-benefit ratio. It is also noted that the risk-benefit assessment should not only be based on purely medical criteria but should also take into account the goals, values, and personal circumstances of the patient. However, the discussion is not yet concluded, and further questions, such as the influence of economic factors, still need to be investigated. [Extracted from the article]

Presenting unpaired unconditional stimuli (US) during extinction training reduces the renewal of conditional fear due to context change. The present study investigated whether this reduced return of fear is specific to the aversive US presented during acquisition or can also be observed after extinction with unpaired presentations of another aversive or of a non-aversive US. Using an ABA renewal paradigm that trained extinction in a context different from that of the acquisition, renewal and re-acquisition test phases, participants received five unpaired presentations of either the aversive US used during acquisition (Group Aversive-Same), an aversive US not presented during acquisition (Group Aversive-Different) or a non-aversive US (Group Non-aversive) during extinction training. Renewal of electrodermal conditional responses was observed in group Non-aversive, but not in groups Aversive-Same or Aversive-Different. Re-acquisition did not differ across the groups. These results are consistent with a valenced arousal account to explain the effects of unpaired presentations of the US during extinction training which would suggest that extinction learning is enhanced under conditions of increased aversive arousal. • Return of fear after successful treatment is a major problem. • Human fear conditioning experiments test interventions to reduce return of fear. • Unpaired unconditional stimuli (USs) during extinction reduce fear renewal. • This is also observed with aversive USs not used during acquisition. • Increased unpleasant arousal seems to strengthen extinction learning. [ABSTRACT FROM AUTHOR]

Significant amounts of research have been devoted to treatment of post-traumatic stress disorder (PTSD) and the understanding of its fear and stress-related symptoms. However, current interventions are only effective in 60 % of the patient population. Allopregnanolone has become a topic of interest for PTSD due to its influences on inhibitory neurotransmission and the physiological stress response. This review explores available literature that suggests that allopregnanolone has an influence on (a) chronic stress and anxiety-like symptoms, (b) fear conditioning and contextual fear, and (c) intrusive and emotional memories. A relationship between allopregnanolone and PTSD is suggested, postulating that allopregnanolone is a potential target for the treatment of PTSD. This very exciting prospect calls for the expansion of research investigating a direct relationship between allopregnanolone and PTSD. • Allopregnanolone may have a role in stress, fear and intrusive memories. • Allopregnanolone potentially influences intrusive memory development. • Allopregnanolone is a potential target for the treatment of PTSD. [ABSTRACT FROM AUTHOR]

Jeremy Greene's book, "The doctor who wasn't there: technology, history, and the limits of telehealth," explores the history of telemedicine and its failures and limitations. The book highlights how different technologies, such as the telephone and cable television, were initially seen as revolutionary tools for healthcare but ultimately fell short of their promises. Greene argues that the success or failure of telemedicine is not solely determined by technology but by human choices and political agendas. The book emphasizes the importance of considering social context and the role of individuals in shaping the future of telemedicine. [Extracted from the article]

• Specification of ECM at the murine MTJ depended on muscle contraction. • Knockout of Tbx3 resulted in an ectopic muscle that inserted into an MTJ. • Ectopic MTJ formation was not dependent on insertion into an enthesis. • Deposition of ECM at the MTJ was also influenced by static loading. The myotendinous junction (MTJ) contributes to the generation of motion by connecting muscle to tendon. At the adult MTJ, a specialized extracellular matrix (ECM) is thought to contribute to the mechanical integrity of the muscle-tendon interface, but the factors that influence MTJ formation during mammalian development are unclear. Here, we combined 3D imaging and proteomics with murine models in which muscle contractility and patterning are disrupted to resolve morphological and compositional changes in the ECM during MTJ development. We found that MTJ-specific ECM deposition can be initiated via static loading due to growth; however, it required cyclic loading to develop a mature morphology. Furthermore, the MTJ can mature without the tendon terminating into cartilage. Based on these results, we describe a model wherein MTJ development depends on mechanical loading but not insertion into an enthesis. [ABSTRACT FROM AUTHOR]

Co-creation has become a major concern in science and public policy. It aims to give a more central role to end users in producing (public sector) innovation outcomes. This leads to a new variety of end user roles in innovation activities and poses challenges for both practitioners and policy makers. We offer an in-depth, comparative analysis of such end user roles in three cases of co-creative public sector innovation across Europe. We argue that the definition of particular end user roles is crucial in shaping both the inclusiveness and outcomes of co-creative innovation. We offer a typology of end user roles and their respective limits and potentials with regard to co-creation. Our analysis suggests that, for co-creation to produce useful and legitimate outcomes, the process by which roles are assigned to and negotiated with end users must be part of the co-creative process itself. [ABSTRACT FROM AUTHOR]

Based on a prior demonstration of the high activity of a homogeneous tungstosilicic acid catalyst for the esterification of acetic acid as bio-oil model compound, a further study has been undertaken in an attempt to heterogenize the catalyst. Tungsten oxide was supported on amorphous silica (W/A150) using incipient wetness impregnation and incorporated into the structure of structured silica (W-KIT-5) via a one-step hydrothermal synthesis. The catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), physisorption (BET), and temperature-programmed desorption of ammonia (NH3-TPD). Both series were evaluated for the esterification of acetic acid with ethanol and compared with the homogeneous 12-tungstosilicic acid catalyst. The result of XRD analysis suggests the average crystallite size of the W oxide nanoparticles on both supports to be less than 2 nm, while XPS analysis revealed that all W existed in the W 6+ oxidation state. From the BET and NH3-TPD analyses, it was shown that the KIT-5 series had higher surface area and acidity than the W/A150 catalyst. The 10% W-KIT-5 was shown to be the best heterogeneous catalyst with the highest activity and acid conversion of about 20% and 93% of the homogeneous catalyst. Significant leaching of tungsten from both the supports occurred and will have to be solved in the future. [ABSTRACT FROM AUTHOR]

Effective interaction potentials suitable for Cu/δ–Ni2Si and Cu/β–Ni3Si are developed. We optimise the potential parameters of an embedded atom method potential to reproduce forces, energies, and stresses obtained from ab initio calculations. Details of the potential generation are given, and its validation is demonstrated. The potentials are used in molecular dynamics simulations of shear tests to study the interactions of edge dislocations with coherent δ–Ni2Si and β–Ni3Si precipitates embedded in a copper matrix. In spite of significantly different crystallographic structures of copper and δ–Ni2Si which usually result in circumvention of dislocations, we also observed cutting processes in our simulations. Dislocations cut for a specific orientation of the δ–Ni2Si precipitate and in some cases where dislocation loops originating from previous circumvention processes are present in the glide plane. It is found that β–Ni3Si precipitates have a similar effect on precipitation strengthening as δ–Ni2Si. Dislocations usually cut β–Ni3Si but increased coherency strain can lead to circumvention processes. [ABSTRACT FROM AUTHOR]

Past research has shown that Intolerance of Uncertainty (IU) affects Pavlovian fear conditioning processes. In particular, extinction of learned fear is delayed in those reporting high IU. Reports of differences during acquisition are less consistent with most of the studies reporting no evidence for effects of IU. This may be due to past studies' focus on first interval electrodermal responses or fear potentiated startle, rather than on indices that may better capture uncertainty – like the response to the absence of a probabilistic unconditional stimulus. The current analysis combined data across three experiments that employed a 50 % reinforcement schedule and assessed electrodermal responses and (in two experiments) ratings of conditional stimulus pleasantness. Participants scoring high on IU showed overall larger electrodermal first interval responses during habituation and acquisition but did not differ from those scoring low on IU in differential conditioning (the difference between CS+ and CS-), as indicated by electrodermal first or second interval responses or ratings of CS pleasantness. However, participants high in IU showed larger differential third interval electrodermal responses to the omission of the electro-tactile unconditional stimulus during acquisition. Some evidence for this difference emerged in each experiment, supporting the reliability of the result. The current results suggest that effects of IU emerge in conditions of high uncertainty in Pavlovian fear learning tasks, such as during the omission of probabilistic unconditional stimuli. • Intolerance of Uncertainty (IU) has been shown to affect fear conditioning in particular during extinction. • Past research has yielded mixed effects for IU during fear acquisition. • Participants high in IU show larger electrodermal responses to the omission of a probabilistic unconditional stimulus. [ABSTRACT FROM AUTHOR]

Objectives: Colistimethate sodium and tobramycin are important systemic antibiotics for treatment of cystic fibrosis (CF) pulmonary exacerbations but can induce acute kidney injury (AKI). We characterize the rate of AKI in CF patients treated with systemic colistimethate sodium compared with tobramycin.Methods: This single-centre, retrospective cohort study included hospitalized CF patients treated with IV colistimethate sodium or tobramycin. The primary outcome was AKI defined using the RIFLE criteria. Multivariate logistic regression using a mixed model was performed to identify variables that were independently associated with AKI.Results: Overall, 156 patients representing 507 care encounters were included. The OR of AKI was not increased with IV colistimethate sodium relative to IV tobramycin after adjusting for other potential predictor variables (aOR 1.00; 95% CI 0.16-6.03). The frequency of AKI was 9.5% across all encounters, 6.9% with IV colistimethate sodium and 9.9% with IV tobramycin, with RIFLE category R (risk) being the most common stage, accounting for 4.2% of encounters with IV colistimethate sodium and 9.2% with IV tobramycin. The concomitant use of another nephrotoxin (aOR 2.51; 95% CI 1.27-4.95) or the combination of vancomycin and piperacillin/tazobactam (aOR 5.95; 95% CI 2.05-17.3) were both associated with increased odds of AKI.Conclusions: Systemic treatment with colistimethate sodium or tobramycin in the CF patient population is associated with a similar rate of nephrotoxicity. However, clinicians should be mindful of the increased risk for AKI in patients treated with either IV colistimethate sodium or IV tobramycin when used concurrently with other nephrotoxic agents, particularly the combination of vancomycin and piperacillin/tazobactam. [ABSTRACT FROM AUTHOR]

The loss of olfactory function has a profound impact on quality of life, affecting not only sensory perception but also memory, emotion, and overall well-being. Despite this, advancements in olfactory prostheses have lagged significantly behind those made for vision and hearing restoration. This review offers a comprehensive analysis of the current state of devices for electrical stimulation of the olfactory system. We begin by providing an overview of the olfactory system's structure and function, emphasizing the neural pathways involved in smell perception. Following this, we explore the key challenges associated with chronic implantation and electrical stimulation, material biocompatibility, inflammation risks, and ensuring long-term functionality and durability. A detailed analysis of existing neural stimulation devices—including ECoG, intracortical, and depth electrodes—is presented, assessing their potential for application in olfactory stimulation. We also discuss the limitations and pitfalls of current approaches and explore new emerging technologies aimed at overcoming these obstacles. A comprehensive literature review about the olfactory system electrical stimulation is reported, and results are analyzed to identify the most promising routes. Finally, the review highlights emerging technologies, ongoing research, and the ethical considerations associated with olfactory implants, along with future directions for developing more effective, safe, and durable solutions to restore the sense of smell for individuals with olfactory disorders. [ABSTRACT FROM AUTHOR]

Presenting unpaired unconditional stimuli (US) during extinction training reduces the renewal of conditional fear due to context change and slows re-acquisition. The present study investigated whether this reduced return of fear is mediated by Pavlovian inhibitory conditioning to the conditional stimulus paired with the US during acquisition (CS+) that is acquired when this stimulus is presented without the US in an excitatory extinction context. Using an ABA renewal paradigm that trained extinction in a context different from acquisition and renewal test, participants either received no USs (Standard), five unsignalled US presentations (Unsignalled) or five presentations of the US preceded by a novel, third CS (Signalled) during extinction training. Extinction was followed by tests for renewal and re-acquisition. Replicating previous results, renewal of electrodermal conditional responses was observed in group Standard, but not in group Unsignalled. Signalling the additional USs, and thus reducing context conditioning and the potential for inhibitory conditioning, did not reduce their effect in that renewal was absent in group Signalled. These results are inconsistent with an inhibitory conditioning account of the effects of unpaired US presentations during extinction. A trial sequence learning account or an arousal account may explain the effects of unpaired presentations of the US during extinction. • Unpaired unconditional stimuli (USs) during extinction reduce fear renewal. • The current study tested an inhibitory conditioning account of this finding. • Signalling the USs should reduce inhibitory conditioning during extinction. • Both signalled and unsignalled USs reduced renewal of fear. • An arousal account may provide an explanation for this result. [ABSTRACT FROM AUTHOR]

Conceptual generalisation occurs when conditional responses generalise to novel stimuli from the same category. Past research demonstrates that physiological fear responses generalise across categories, however, conceptual generalisation of stimulus valence evaluations during fear conditioning has not been examined. We investigated whether conceptual generalisation, as indexed by electrodermal responses and stimulus evaluations, would occur, and differ after training with single or multiple conditional stimuli (CSs). Stimuli from two of four categories (vegetables, farm animals, clothing, and office supplies) were used as the CS+ (followed by an electric stimulus) or CS- (presented alone). Generalisation was assessed by presenting novel stimuli from the CS categories after acquisition, extinction, and reinstatement. One category exemplar was used as the CS+ and CS- in the single group, whereas three exemplars were used as the CS+ and CS- in the multiple group. Electrodermal responses generalised in acquisition and extinction but did not differ between groups. In the multiple group, CS evaluations generalised in acquisition and extinction, whereas generalisation was not evident in the single group. Training with multiple CSs also resulted in the extinction of stimulus valence. The current findings have implications for future research examining the generalisation of valence and for exposure-based treatments of anxiety. [ABSTRACT FROM AUTHOR]

Treatment of tracheal stenosis is occasionally performed in combination with wound healing modulators to manipulate new extracellular matrix (ECM) formation and prevent fibrosis. Hyaluronic acid (HA) and collagen-polyvinylpyrrolidone (collagen-PVP) decrease fibrosis in experimental tracheal healing. However, they have not been used clinically as their effect on ECM components, which modify tracheal scarring, has not been described. Objective. To evaluate the effect of the application of HA, collagen-PVP, a mixture of HA and collagen-PVP (HA+collagen-PVP), and mitomycin C on the expression of decorin, matrix metalloproteinase 1 (MMP1), and MMP9, as well as the type of collagen and deposits formed in the scar after resection and end-to-end anastomosis (REEA) of the cervical trachea using an experimental model. Materials and Methods. Thirty dogs underwent REEA of the cervical trachea and were treated with different wound healing modulators: group I (n = 6), control; group II (n = 6), HA; group III (n = 6), collagen-PVP; group IV (n = 6), HA+collagen-PVP; and group V (n = 6), mitomycin C. The dogs were evaluated clinically and endoscopically for 4 weeks. Subsequently, macroscopic and microscopic changes, expression of ECM proteins, and collagen deposition in tracheal scars were analysed. Results. Groups II, III, and IV showed reduced endoscopic, macroscopic, and microscopic inflammation, improved neovascularization, high decorin expression (p < 0.01 , analysis of variance (ANOVA)), and moderate expression of MMP1 (p < 0.003 , ANOVA) and type I and III collagen (p < 0.05 , Kruskal–Wallis). Groups IV and V developed fewer collagen deposits (p < 0.001 , ANOVA). Conclusion. Treatment with HA and collagen-PVP improved post-REEA healing by increasing neovascularization, stimulating the expression of decorin, and regulating the expression of MMP1, as well as type I and III collagen and their deposition. [ABSTRACT FROM AUTHOR]

Many college students experience the death of someone close to them and could be at risk for complicated grieving. Their primary sources of support may be unavailable as family members may live far away and their peers may be unprepared to respond to their grief. In addition, college students are exposed to a variety of stressors that could result in maladaptive coping. Furthermore, although most college-aged students use social media, little is known about its impact on grieving. The purpose of this study was to examine the degree to which social support, coping, continuing bonds, and social media use predicted complicated grief and posttraumatic growth in a sample of college students who had experienced an interpersonal loss. Participants (N = 258; 77.5% female, M age = 19.98, SD = 1.41) completed an online survey assessing the aforementioned constructs using Likert-type scales. Findings from two hierarchical regressions indicated that coping variables accounted for the greatest percentage of variance in grieving outcomes with avoidant-emotional coping being the most robust predictor of complicated grief and problem-focused coping accounting for considerable variance in posttraumatic growth (both were associated positively with the outcomes). As hypothesized, continuing bonds explained variance in both grieving outcomes with externalized continuing bonds and maintaining continuing bonds on social media predicting complicated grief and internalized continuing bonds contributing to posttraumatic growth (also all positively associated). Social support from family also was predictive of posttraumatic growth in the positive direction. Future research directions and implications for practice are discussed with the hope that this research might inform the development of interventions to assist college students who are grieving. [ABSTRACT FROM AUTHOR]

Technology takes an unprecedented position in contemporary society. In particular, it has become part and parcel of governmental attempts to manufacture life in new ways. Such ideas concerning the (self-)governance of life organize around the same contention: that technology and life are, in fact, highly interconnectable. This is surprising because if one enters the sites of techno-scientific experimentation, those visions turn out to be much frailer and by no means "in place" yet. Rather, they afford or enforce constant interfacing work, a particular mode of manufacturing life, rendering disparate, sturdy, and often surprisingly incompatible things available for one another. Here, we contend that both of those aspects, pervasive rationalities of interconnectability and practices of interfacing mark the cornerstones of what we call a new(ly articulated) techno-bio-politics of life. In order to grasp the government of life under the technological condition, we must understand how both human and non-human entities are being rendered interconnectable and re-worked through practices of interfacing. We take neuro-technology and care robotics as two illustrative cases. Our analysis shows that the contemporary government of life is not primarily concerned with life itself in its biological re-constitution but rather with life as it is interfaced with and through technology. [ABSTRACT FROM AUTHOR]

Studying electron‐ and X‐ray‐induced electron cascades in solids is essential for various research areas at free‐electron laser facilities, such as X‐ray imaging, crystallography, pulse diagnostics or X‐ray‐induced damage. To better understand the fundamental factors that define the duration and spatial size of such cascades, this work investigates the electron propagation in ten solids relevant for the applications of X‐ray lasers: Au, B4C, diamond, Ni, polystyrene, Ru, Si, SiC, Si3N4 and W. Using classical Monte Carlo simulation in the atomic approximation, we study the dependence of the cascade size on the incident electron or photon energy and on the target parameters. The results show that an electron‐induced cascade is systematically larger than a photon‐induced cascade. Moreover, in contrast with the common assumption, the maximal cascade size does not necessarily coincide with the electron range. It was found that the cascade size can be controlled by careful selection of the photon energy for a particular material. Photon energy, just above an ionization potential, can essentially split the absorbed energy between two electrons (photo‐ and Auger), reducing their initial energy and thus shrinking the cascade size. This analysis suggests a way of tailoring the electron cascades for applications requiring either small cascades with a high density of excited electrons or large‐spread cascades with lower electron densities. [ABSTRACT FROM AUTHOR]

Many contemporary studies of human fear conditioning exclude participants who fail to show differential electrodermal responding during late stages of acquisition training, deeming them to be non‐Learners. The current study examined whether non‐Learners, defined as those who fail to show larger electrodermal first interval responses to CS+ than to CS− in the second half of acquisition, show differential electrodermal responding early during acquisition or during extinction or evidence of fear‐learning on other measures, including rated CS valence and contingency report. In a sample of 351 participants who completed a standard differential fear‐conditioning paradigm that employed electrodermal first and second interval responses (FIR, SIR), continuous CS evaluations, and post‐experimental contingency reports to assess fear‐learning, 74 participants were identified as non‐Learners. These non‐Learners displayed overall smaller electrodermal responses but showed evidence for differential conditioning during acquisition in electrodermal FIR (block1) and SIR (blocks 2–3) and in CS evaluations during acquisition (blocks 2–4) and extinction (blocks 1–4). Fifty‐nine non‐Learners correctly reported the contingencies. A lack of differential electrodermal first interval responding during the second half of acquisition does not indicate the absence of fear‐learning. Rather, this criterion appears to capture participants who exhibit low physiological arousal and performance decrements toward the end of acquisition. Applying criteria based on "end of acquisition" electrodermal responding to determine "non‐learning" results in the exclusion of participants who display fear‐learning at other experimental stages or in other measures. A lack of differential electrodermal responding late during acquisition training is frequently taken to indicate a failure to acquire conditioned fear. We show that such non‐Learners display evidence for fear conditioning in stimulus evaluations and contingency reports, but also in electrodermal responses recorded in different latency windows or earlier during acquisition. Given its link to overall stimulus‐driven electrodermal responsiveness, a lack of differential responding seems to reflect a deficit in performance, not in learning. [ABSTRACT FROM AUTHOR]

The effect of millisecond flash lamp annealing (FLA) on aluminumdopedZnO (AZO) films and their interface with Si have been studied. The AZO films were deposited by magnetron sputtering on Si (100) substrates. The electrical and structural properties of the film and AZO/Si structures were characterized by current-voltage, capacitance-voltage, and deep level transient spectroscopy measurements, X-ray diffraction, and secondary ion mass spectrometry. The resistivity of the AZO film is reduced to a close to state-of-the-art value of 2 × 10-4 Ω cm after FLA for 3 ms with an average energy density of 29 J/cm2. In addition, most of the interfacial defects energy levels are simultaneously annealed out, except for one persisting shallow level, tentatively assigned to the vacancy-oxygen complex in Si, which was not affected by FLA. Subsequent to the FLA, the samples were treated in N2 or forming gas (FG) (N2/H2, 90/10%mole) ambient at 200-500 °C. The latter samples maintained the low resistivity achieved after the FLA, but not the former ones. The interfacial defect level persisting after the FLA is removed by the FG treatment, concurrently as another level emerges at ~0.18 eV below the conduction band. The electrical data of the AZO films are discussed in term of point defects controlling the resistivity, and it is argued that the FLA promotes formation of electrically neutral clusters of Zink vacancies (VZn's) rather than passivating/compensating complexes between the Al donors and VZn's. [ABSTRACT FROM AUTHOR]

Background Outpatient clinics treating neuro-oncology patients are becoming more multidisciplinary. Utilization of all team members is critical for the holistic care of these complex patients. Specifically, the role of clinical pharmacist (CP) in the ambulatory clinic remains undefined and will likely evolve as more therapeutics are developed for CNS malignancies. We queried the Society for Neuro-Oncology (SNO) membership about the availability of a CP in their ambulatory setting and, if present, the role of that CP. Methods In an IRB-exempt study, we surveyed the SNO community and analyzed responses to queries about CPs in the ambulatory setting. Results Of the 65 SNO members who responded, 52 were clinical members. Of these 52 clinicians, the majority were physicians (88.5%, n = 46). Of these physicians, most were in academic practices (93.5%, n = 43). Over half of the 52 clinical respondents (51.9%, n = 27) reported that they saw ≥30 primary brain tumor patients per month, thus typifying busy clinics. Despite having busy clinics, only 12 (28.6%) of 42 providers with access to a CP reported that their CP was solely dedicated to neuro-oncology patients. For the respondents who had access to a CP, only ~two-thirds of those CPs had direct patient interaction. The top 3 roles of the CP included medication review, chemotherapy dosing/modifications, and practice guideline development; none of which involve direct patient interaction. Conclusions We found that while our surveyed population of SNO clinical members have demanding outpatient practices, most do not have the support or expertise of dedicated neuro-oncology CPs. [ABSTRACT FROM AUTHOR]

Intense X-ray pulses from free-electron lasers can trigger ultrafast electronic, structural and magnetic transitions in solid materials, within a material volume which can be precisely shaped through adjustment of X-ray beam parameters. This opens unique prospects for material processing with X rays. However, any fundamental and applicational studies are in need of computational tools, able to predict material response to X-ray radiation. Here we present a dedicated computational approach developed to study X-ray induced transitions in a broad range of solid materials, including those of high chemical complexity. The latter becomes possible due to the implementation of the versatile density functional tight binding code DFTB+ to follow band structure evolution in irradiated materials. The outstanding performance of the implementation is demonstrated with a comparative study of XUV induced graphitization in diamond. [ABSTRACT FROM AUTHOR]

Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells. We purified and characterized tumorinfiltrating lymphocytes (TILs) and their patient-matched non-tumor counterparts from treatmentnaïve NSCLC patient biopsies to evaluate the effect of PD1 expression on the functional and molecular profiles of tumor-resident T cells. We show that PD1+ CD8+ TILs have elevated expression of the transcriptional regulator ID3 and that the cytotoxic potential of CD8 T cells can be improved by knocking down ID3, defining it as a potential regulator of T cell effector function. PD1+ CD4 + memory TILs display transcriptional patterns consistent with both helper and regulator function, but can robustly facilitate B cell activation and expansion. Furthermore, we show that expanding ex vivo-prepared TILs in vitro broadly preserves their functionality with respect to tumor cell killing, B cell help, and TCR repertoire. Although purified PD1+ CD8+ TILs generally maintain an exhausted phenotype upon expansion in vitro, transcriptional analysis reveals a downregulation of markers of T-cell dysfunction, including the co-inhibitory molecules PD1 and CTLA-4 and transcription factors ID3, TOX and TOX2, while genes involved in cell cycle and DNA repair are upregulated. We find reduced expression of WNT signaling components to be a hallmark of PD1+ CD8+ exhausted T cells in vivo and in vitro and demonstrate that restoring WNT signaling, by pharmacological blockade of GSK3β, can improve effector function. These data unveil novel targets for tumor immunotherapy and have promising implications for the development of a personalized TIL-based cell therapy for lung cancer. [ABSTRACT FROM AUTHOR]