Chemically Recyclable and Biodegradable Vulcanized Rubber.

The cross-linked nature of vulcanized rubbers as used in tire and many other applications prohibits an effective closed-loop mechanical or chemical recycling. Moreover, vulcanization significantly retards the material's biodegradation. Here, we report a recyclable and biodegradable rubber that is generated by the vulcanization of amorphous, unsaturated polyesters. The elastic material can be broken down via solvolysis into the underlying monomers. After removal of the vulcanized repeat units, the saturated monomers, constituting the major share of the material, can be recovered in overall recycling rates exceeding 90%. Respirometric biodegradation experiments by 13CO2 tracking under environmental conditions via the polyesters' diol monomer indicated depolymerization and partial mineralization of the vulcanized polyester rubbers.

Synthesis and Deconstruction of Polyethylene-type Materials.

Polyethylene deconstruction to reusable smaller molecules is hindered by the chemical inertness of its hydrocarbon chains. Pyrolysis and related approaches commonly require high temperatures, are energy-intensive, and yield mixtures of multiple classes of compounds. Selective cleavage reactions under mild conditions (

A New Look at P Values for Randomized Clinical Trials.

BACKGROUND: We have examined the primary efficacy results of 23,551 randomized clinical trials from the Cochrane Database of Systematic Reviews. METHODS: We estimate that the great majority of trials have much lower statistical power for actual effects than the 80 or 90% for the stated effect sizes. Consequently, "statistically significant" estimates tend to seriously overestimate actual treatment effects, "nonsignificant" results often correspond to important effects, and efforts to replicate often fail to achieve "significance" and may even appear to contradict initial results. To address these issues, we reinterpret the P value in terms of a reference population of studies that are, or could have been, in the Cochrane Database. RESULTS: This leads to an empirical guide for the interpretation of an observed P value from a "typical" clinical trial in terms of the degree of overestimation of the reported effect, the probability of the effect's sign being wrong, and the predictive power of the trial. CONCLUSIONS: Such an interpretation provides additional insight about the effect under study and can guard medical researchers against naive interpretations of the P value and overoptimistic effect sizes. Because many research fields suffer from low power, our results are also relevant outside the medical domain. (Funded by the U.S. Office of Naval Research.)

Clinical prediction model for prognosis in kidney transplant recipients (KIDMO): study protocol.

BACKGROUND: Many potential prognostic factors for predicting kidney transplantation outcomes have been identified. However, in Switzerland, no widely accepted prognostic model or risk score for transplantation outcomes is being routinely used in clinical practice yet. We aim to develop three prediction models for the prognosis of graft survival, quality of life, and graft function following transplantation in Switzerland. METHODS: The clinical kidney prediction models (KIDMO) are developed with data from a national multi-center cohort study (Swiss Transplant Cohort Study; STCS) and the Swiss Organ Allocation System (SOAS). The primary outcome is the kidney graft survival (with death of recipient as competing risk); the secondary outcomes are the quality of life (patient-reported health status) at 12 months and estimated glomerular filtration rate (eGFR) slope. Organ donor, transplantation, and recipient-related clinical information will be used as predictors at the time of organ allocation. We will use a Fine & Gray subdistribution model and linear mixed-effects models for the primary and the two secondary outcomes, respectively. Model optimism, calibration, discrimination, and heterogeneity between transplant centres will be assessed using bootstrapping, internal-external cross-validation, and methods from meta-analysis. DISCUSSION: Thorough evaluation of the existing risk scores for the kidney graft survival or patient-reported outcomes has been lacking in the Swiss transplant setting. In order to be useful in clinical practice, a prognostic score needs to be valid, reliable, clinically relevant, and preferably integrated into the decision-making process to improve long-term patient outcomes and support informed decisions for clinicians and their patients. The state-of-the-art methodology by taking into account competing risks and variable selection using expert knowledge is applied to data from a nationwide prospective multi-center cohort study. Ideally, healthcare providers together with patients can predetermine the risk they are willing to accept from a deceased-donor kidney, with graft survival, quality of life, and graft function estimates available for their consideration. STUDY REGISTRATION: Open Science Framework ID: z6mvj.

Biodegradable High-Density Polyethylene-like Material.

We report a novel polyester material generated from readily available biobased 1,18-octadecanedicarboxylic acid and ethylene glycol possesses a polyethylene-like solid-state structure and also tensile properties similar to high density polyethylene (HDPE). Despite its crystallinity, high melting point (Tm =96 °C) and hydrophobic nature, polyester-2,18 is subject to rapid and complete hydrolytic degradation in in vitro assays with isolated naturally occurring enzymes. Under industrial composting conditions (ISO standard 14855-1) the material is biodegraded with mineralization above 95 % within two months. Reference studies with polyester-18,18 (Tm =99 °C) reveal a strong impact of the nature of the diol repeating unit on degradation rates, possibly related to the density of ester groups in the amorphous phase. Depolymerization by methanolysis indicates suitability for closed-loop recycling.

Functional connectivity directionality between large-scale resting-state networks across typical and non-typical trajectories in children and adolescence.

Mental disorders often emerge during adolescence and have been associated with age-related differences in connection strengths of brain networks (static functional connectivity), manifesting in non-typical trajectories of brain development. However, little is known about the direction of information flow (directed functional connectivity) in this period of functional brain progression. We employed dynamic graphical models (DGM) to estimate directed functional connectivity from resting state functional magnetic resonance imaging data on 1143 participants, aged 6 to 17 years from the healthy brain network (HBN) sample. We tested for effects of age, sex, cognitive abilities and psychopathology on estimates of direction flow. Across participants, we show a pattern of reciprocal information flow between visual-medial and visual-lateral connections, in line with findings in adults. Investigating directed connectivity patterns between networks, we observed a positive association for age and direction flow from the cerebellar to the auditory network, and for the auditory to the sensorimotor network. Further, higher cognitive abilities were linked to lower information flow from the visual occipital to the default mode network. Additionally, examining the degree networks overall send and receive information to each other, we identified age-related effects implicating the right frontoparietal and sensorimotor network. However, we did not find any associations with psychopathology. Our results suggest that the directed functional connectivity of large-scale resting-state brain networks is sensitive to age and cognition during adolescence, warranting further studies that may explore directed relationships at rest and trajectories in more fine-grained network parcellations and in different populations.

Right Inferior Frontal Activation During Alcohol-Specific Inhibition Increases With Craving and Predicts Drinking Outcome in Alcohol Use Disorder.

Alcohol use disorder (AUD) is characterized by enhanced cue-reactivity and the opposing control processes being insufficient. The ability to inhibit reactions to alcohol-related cues, alcohol-specific inhibition, is thus crucial to AUD; and trainings strengthening this ability might increase treatment outcome. The present study investigated whether neurophysiological correlates of alcohol-specific inhibition (I) vary with craving, (II) predict drinking outcome in AUD and (III) are modulated by alcohol-specific inhibition training. A total of 45 recently abstinent patients with AUD and 25 controls participated in this study. All participants underwent functional magnetic resonance imaging (fMRI) during a Go-NoGo task with alcohol-related as well as neutral conditions. Patients with AUD additionally participated in a double-blind RCT, where they were randomized to either an alcohol-specific inhibition training or an active control condition (non-specific inhibition training). After the training, patients participated in a second fMRI measurement where the Go-NoGo task was repeated. Percentage of days abstinent was assessed as drinking outcome 3 months after discharge from residential treatment. Whole brain analyses indicated that in the right inferior frontal gyrus (rIFG), activation related to alcohol-specific inhibition varied with craving and predicted drinking outcome at 3-months follow-up. This neurophysiological correlate of alcohol-specific inhibition was however not modulated by the training version. Our results suggest that enhanced rIFG activation during alcohol-specific (compared to neutral) inhibition (I) is needed to inhibit responses when craving is high and (II) fosters sustained abstinence in patients with AUD. As alcohol-specific rIFG activation was not affected by the training, future research might investigate whether potential training effects on neurophysiology are better detectable with other methodological approaches.

Strong evidence for age as the single most dominant predictor of medically supervised driving test-mini mental status test outcomes provide only weak but significant moderate additional predictive value.

BACKGROUND: With age, medical conditions impairing safe driving accumulate. Consequently, the risk of accidents increases. To mitigate this risk, Swiss law requires biannual assessments of the fitness to drive of elderly drivers. Drivers may prove their cognitive and physical capacity for safe driving in a medically supervised driving test (MSDT) when borderline cases, as indicated by low performance in a set of four cognitive tests, including e.g. the mini mental status test (MMST). Any prognostic, rather than indicative, relations for MSDT outcomes have neither been confirmed nor falsified so far. In order to avoid use of unsubstantiated rules of thumb, we here evaluate the predictive value for MSDT outcomes of the outcomes of the standard set of four cognitive tests, used in Swiss traffic medicine examinations. METHODS: We present descriptive information on age, gender and cognitive pretesting results of all MSDTs recorded in our case database from 2017 to 2019. Based on these retrospective cohort data, we used logistic regression to predict the binary outcome MSDT. An exploratory analysis used all available data (model 1). Based on the Akaike Information Criterion (AIC), we then established a model including variables age and MMST (model 2). To evaluate the predictive value of the four cognitive assessments, model 3 included cognitive test outcomes only. Receiver operating characteristics (ROC) and area under the curve (AUC) allowed evaluating discriminative performance of the three different models using independent validation data. RESULTS: Using N = 188 complete data sets of a total of 225 included cases, AIC identified age (p < 0.0008) and MMST (p = 0.024) as dominating predictors for MSDT outcomes with a median AUC of 0.71 (95%-CI 0.57-0.85) across different training and validation splits, while using the four cognitive test results exclusively yielded a median AUC of 0.55 (95%-CI 0.40-0.71). CONCLUSIONS: Our analysis provided strong evidence for age as the single most dominant predictor of MSDT outcomes. Adding MMST provides only weak additional predictive value for MSDT outcomes. Combining the results of four cognitive test used as standard screen in Swiss traffic medicine alone, proved to be of poor predictive value. This highlights the importance of MSDTs for balancing between the mitigation of risks by and the right to drive for the elderly.

Assessing treatment effects and publication bias across different specialties in medicine: a meta-epidemiological study.

OBJECTIVES: To assess the prevalence of statistically significant treatment effects, adverse events and small-study effects (when small studies report more extreme results than large studies) and publication bias (over-reporting of statistically significant results) across medical specialties. DESIGN: Large meta-epidemiological study of treatment effects from the Cochrane Database of Systematic Reviews. METHODS: We investigated outcomes from 57 162 studies from 1922 to 2019, and overall 98 966 meta-analyses and 5534 large meta-analyses (≥10 studies). Egger's and Harbord's tests to detect small-study effects, limit meta-analysis and Copas selection models to bias-adjust effect estimates and generalised linear mixed models were used to analyse one of the largest collections of evidence in medicine. RESULTS: Medical specialties showed differences in the prevalence of statistically significant results of efficacy and safety outcomes. Treatment effects from primary studies published in high ranking journals were more likely to be statistically significant (OR=1.52; 95% CI 1.32 to 1.75) while randomised controlled trials were less likely to report a statistically significant effect (OR=0.90; 95% CI 0.86 to 0.94). Altogether 19% (95% CI 18% to 20%) of the large meta-analyses showed evidence for small-study effects, but only 3.9% (95% CI 3.4% to 4.4%) showed evidence for publication bias after further assessment of funnel plots. Adjusting treatment effects resulted in overall less evidence for efficacy. CONCLUSIONS: These results suggest that reporting of large treatment effects from small studies may cause greater concern than publication bias. Incentives should be created so that studies of the highest quality become more visible than studies that report more extreme results.

The statistical properties of RCTs and a proposal for shrinkage.

We abstract the concept of a randomized controlled trial as a triple (ß,b,s) , where ß is the primary efficacy parameter, b the estimate, and s the standard error ( s>0 ). If the parameter ß is either a difference of means, a log odds ratio or a log hazard ratio, then it is reasonable to assume that b is unbiased and normally distributed. This then allows us to estimate the joint distribution of the z-value z=b/s and the signal-to-noise ratio SNR=ß/s from a sample of pairs (bi,si) . We have collected 23 551 such pairs from the Cochrane database. We note that there are many statistical quantities that depend on (ß,b,s) only through the pair (z,SNR) . We start by determining the estimated distribution of the achieved power. In particular, we estimate the median achieved power to be only 13%. We also consider the exaggeration ratio which is the factor by which the magnitude of ß is overestimated. We find that if the estimate is just significant at the 5% level, we would expect it to overestimate the true effect by a factor of 1.7. This exaggeration is sometimes referred to as the winner's curse and it is undoubtedly to a considerable extent responsible for disappointing replication results. For this reason, we believe it is important to shrink the unbiased estimator, and we propose a method for doing so. We show that our shrinkage estimator successfully addresses the exaggeration. As an example, we re-analyze the ANDROMEDA-SHOCK trial.

3D Printed Sand Tools for Thermoforming Applications of Carbon Fiber Reinforced Composites-A Perspective.

Tooling, especially for prototyping or small series, may prove to be very costly. Further, prototyping of fiber reinforced thermoplastic shell structures may rely on time-consuming manual efforts. This perspective paper discusses the idea of fabricating tools at reduced time and cost compared to conventional machining-based methods. The targeted tools are manufactured out of sand using the Binder Jetting process. These molds should fulfill the demands regarding flexural and compressive behavior while allowing for vacuum thermoforming of fiber reinforced thermoplastic sheets. The paper discusses the requirements and the challenges and presents a perspective study addressing this innovative idea. The authors present the idea for discussion in the additive manufacturing and FRP producing communities.

Brainhack: Developing a culture of open, inclusive, community-driven neuroscience.

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.

Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer's Disease.

BACKGROUND: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer's disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia. OBJECTIVE: To unravel mutual and divergent functional alterations in Alzheimer's disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer's disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17). METHODS: In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series from 66 regions for correlation analysis. RESULTS: Apart from differing connections between Alzheimer's disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes. CONCLUSION: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain's functional disconnectivity in Alzheimer's disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures.

Differences in directed functional brain connectivity related to age, sex and mental health.

Functional interconnections between brain regions define the "connectome" which is of central interest for understanding human brain function. Resting-state functional magnetic resonance (rsfMRI) work has revealed changes in static connectivity related to age, sex, cognitive abilities and psychiatric symptoms, yet little is known how these factors may alter the information flow. The commonly used approach infers functional brain connectivity using stationary coefficients yielding static estimates of the undirected connection strength between brain regions. Dynamic graphical models (DGMs) are a multivariate model with dynamic coefficients reflecting directed temporal associations between nodes, and can yield novel insight into directed functional connectivity. Here, we leveraged this approach to test for associations between edge-wise estimates of direction flow across the functional connectome and age, sex, intellectual abilities and mental health. We applied DGM to investigate patterns of information flow in data from 984 individuals from the Human Connectome Project (HCP) and 10,249 individuals from the UK Biobank. Our analysis yielded patterns of directed connectivity in independent HCP and UK Biobank data similar to those previously reported, including that the cerebellum consistently receives information from other networks. We show robust associations between information flow and age and sex for several connections, with strongest effects of age observed in the sensorimotor network. Visual, auditory and sensorimotor nodes were also linked to mental health. Our findings support the use of DGM as a measure of directed connectivity in rsfMRI data and provide new insight into the shaping of the connectome during aging.

Glucocorticoids and cortical decoding in the phobic brain.

Glucocorticoids reduce phobic fear in anxiety disorders and enhance psychotherapy, possibly by reducing the retrieval of fear memories and enhancing the consolidation of new corrective memories. Glucocorticoid signaling in the basolateral amygdala can influence connected fear and memory-related cortical regions, but this is not fully understood. Previous studies investigated specific pathways moderated by glucocorticoids, for example, visual-temporal pathways; however, these analyses were limited to a-priori selected regions. Here, we performed whole-brain pattern analysis to localize phobic stimulus decoding related to the fear-reducing effect of glucocorticoids. We reanalyzed functional magnetic resonance imaging (fMRI) data from a previously published study with spider-phobic patients and healthy controls. The patients received glucocorticoids or a placebo before the exposure to spider images. There was moderate evidence that patients with phobia had higher decoding of phobic content in the anterior cingulate cortex (ACC) and the left and right anterior insula compared to controls. Decoding in the ACC and the right insula showed strong evidence for correlation with experienced fear. Patients with cortisol reported a reduction of fear by 10-13%; however, there was only weak evidence for changes in neural decoding compared to placebo which was found in the precuneus, the opercular cortex, and the left cerebellum.

Science After Covid-19: Faster, Better, Stronger?

The novel coronavirus has dramatically affected our daily lives in the short term. But will the pandemic change research for the better over the longer term? By Simon Schwab and Leonhard Held.

Rescuers at Risk: Posttraumatic Stress Symptoms Among Police Officers, Fire Fighters, Ambulance Personnel, and Emergency and Psychiatric Nurses.

Emergency personnel and rescue workers may be at a risk of posttraumatic stress symptoms (PTSS) due to exposure to trauma and work-related stressors. Though rescuers of different professions are often engaged in the same type of emergency, they have different tasks and responsibilities and receive different training in coping with traumatic events and stress; hence, we speculated that the salience of identified risk factors for PTSS vary across their respective professions. The present cross-sectional survey aimed to identify influencing variables on PTSS, well-being, and suicidal ideation that can act differently across professions of rescue workers and emergency personnel. In this anonymous online study, data from 1,002 rescue workers and emergency personnel in Switzerland, were collected: 499 police officers, 239 firefighters, 97 ambulance personnel, and 85 emergency and 82 psychiatric nurses. PTSS, coping strategies, well-being, suicidal ideation, previously experienced and work-related trauma, and self-efficacy were measured and analyzed using multiple regression and structural equation modeling (SEM). The prevalence of suspected posttraumatic stress disorder varied across the professions, ranged from 8% (firefighters) to 22% (psychiatric nurses), and was associated with psychological strain and suicidal ideation. The SEM showed that dysfunctional coping strategies, self-efficacy, previously experienced and work-related trauma, years on job, and female sex explained up to 78% of PTSS and that PTSS itself explained up to 68% of the psychological strain experienced in the different professions. Independent of the profession, dysfunctional coping such as alcohol use, avoidance, and distraction, as well as work-related trauma were the most robust predictors of PTSS. However, while self-efficacy was a risk factor for police officers, firefighters and ambulance personnel, it was a protective factor for emergency and psychiatric nurses. Furthermore, female sex was only a risk factor for ambulance personnel and emergency nurses. In agreement with prior research, emergency personnel and rescuers exhibited enhanced prevalence of PTSS and suspected PTSD, leading to significant psychological strain and suicidal ideation. However, risk factors varied across the professions. Thus, the development of profession-specific trainings to improve self-efficacy and coping with work-related stressors to reduce PTSS, and enhance quality of life, is needed for individuals in such high-risk professions. Clinical Trial Registration: ClinicalTrials.gov Nr. NCT03842553.

Attempted suicide short intervention program influences coping among patients with a history of attempted suicide.

BACKGROUND: The development of individual coping strategies for suicidal crises is essential for suicide prevention. However, the influence of a brief intervention and the effect on coping strategies is largely unknown. This study aimed to investigate the influence of the Attempted Suicide Short Intervention Program on the development of coping strategies, in comparison to a control group. METHOD: In this secondary analysis of a 24-month follow-up randomised controlled study, 120 patients (55% female; mean age of 36) with a history of suicide attempts were randomly allocated to either the ASSIP group or to a control group, in addition to treatment as usual. RESULTS: The present study identified 11% less dysfunctional coping in the ASSIP group and 6% more problem-focussed coping compared to the control group after 24-months. The analysis of broader strategies showed a statistically significant group difference regarding self-distraction (after 12-months) and self-blame (after 24-months). In regard to the long-term association between coping strategies and suicidal ideation, active coping and substance use were negatively associated with suicidal ideation in the ASSIP group. Whereas, in the control group, behavioural disengagement and positive reframing were positively and self-distraction was negatively related to suicidal ideation. LIMITATION: The receipt of a clinical interview and suicide risk assessment in the control group could have potentially had an effect on participants' coping mechanisms. CONCLUSION: These results indicate that ASSIP may have an impact on the development of problem-focussed coping strategies. Although a reduction in dysfunctional coping seems to be essential in overcoming suicidal crises.

Glucocorticoid administration restores salience network activity in patients with spider phobia.

BACKGROUND: Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli. METHODS: We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20 mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points. RESULTS: Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo-treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol- versus placebo-treated patients to a level that was similar to that observed in healthy controls. CONCLUSIONS: Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.