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The physicist, psychophysicist, physician, and philosopher Gustav Theodor Fechner – an intellectual force occupying Mahler from his student years in Vienna through the composition of Das Lied von der Erde – is often described as a “mystic” or a “speculative thinker” whose fantastical philosophical system attempts to reconcile mechanistic science with an “animistic non-rational world-view.” Accordingly, his theories are usually dismissed today as curiosities. But though Fechner’s views may appear strange, on closer examination they are not mere arbitrary convictions; rather, they have a rational foundation. Furthermore, it can be demonstrated that Fechner, unorthodox thoughts notwithstanding, made important contributions to the natural sciences: particularly in the notions of “psychophysical parallelism” of the “day view,” a response to contemporaneous materialist and mechanistic orientations. The basic details of these Fechnerian ideas are presented here, along with an account of his early reception.
Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.
Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.
A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.
Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.
To develop a scale to assess health motivation influencing food choices and to explore its performance in the associations with food intakes and nutritional biomarkers.
Psychometric study using cross-sectional self-report questionnaires and nutritional biomarkers.
Multi-centre investigation conducted in ten European cities.
2954 adolescents who were included in the HELENA study and completed the Food Choices and Preferences (FCP) questionnaire.
Nineteen out of 124 items of the FCP questionnaire were in the same dimension. Sixteen presented adequate parameters for the Scale of evaluatiOn of Food choIcEs (SOFIE). The scores were positively associated with the intakes of cereals, dairy products, meats and eggs, and fish, as well as with blood concentrations of vitamin C, β-carotene, n-3 fatty acids, cobalamin, holo-transcobalamin and folate; scores were negatively associated with the intake of alcohol.
SOFIE can improve the assessment of motivation influencing food choices based on items with the best performance and is proposed as a new measure to health-related studies.
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
In October 2017, the American Association of Blood Bankers (AABB; Bethesda, Maryland USA) approved a petition to allow low-titer group O whole blood as a standard product without the need for a waiver. Around that time, a few Texas, USA-based Emergency Medical Services (EMS) systems incorporated whole blood into their ground ambulances. The purpose of this project was to describe the epidemiology of ground ambulance patients that received a prehospital whole blood transfusion. The secondary aim of this project was to report an accounting analysis of these ground ambulance prehospital whole blood programs.
The dataset came from the Harris County Emergency Service District 48 Fire Department (HCESD 48; Harris County, Texas USA) and San Antonio Fire Department (SAFD; San Antonio, Texas USA) whole blood Quality Assurance/Quality Improvement (QA/QI) databases from September 2017 through December 2018. The primary outcome of this study was the prehospital transfusion indication. The secondary outcome was the projected cost per life saved during the first 10 years of the prehospital whole blood initiative.
Of 58 consecutive prehospital whole blood administrations, the team included all 58 cases. Hemorrhagic shock from a non-traumatic etiology accounted for 46.5% (95% CI, 34.3%-59.2%) of prehospital whole blood recipients. In the non-traumatic hemorrhagic shock cohort, gastrointestinal hemorrhage was the underlying etiology of hemorrhagic shock in 66.7% (95% CI, 47.8%-81.4%) of prehospital whole blood transfusion recipients. The projected average cost to save a life in Year 10 was US$5,136.51 for the combined cohort, US$4,512.69 for HCESD 48, and US$5,243.72 for SAFD EMS.
This retrospective analysis of ground ambulance patients that receive prehospital whole blood transfusion found that non-traumatic etiology accounted for 46.5% (95% CI, 34.3%-59.2%) of prehospital whole blood recipients. Additionally, the accounting analysis suggests that by Year 10 of a ground ambulance whole blood transfusion program, the average cost to save a life will be approximately US$5,136.51.
Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic option for major depressive disorder (MDD) in adults. Alternative third-line treatments for MDD in adolescents are scarce. Here we aimed to assess the effects of acute tVNS on emotion recognition in adolescents with MDD.
Adolescents (14–17 years) with MDD (n = 33) and non-depressed controls (n = 30) received tVNS or sham-stimulation in a cross-sectional, case–control, within-subject cross-randomized controlled trial, while performing different tasks assessing emotion recognition. Correct responses, response times, and errors of omission and commission on three different computerized emotion recognition tasks were assessed as main outcomes. Simultaneous recordings of electrocardiography and electro dermal activity, as well as sampling of saliva for the determination of α-amylase, were used to quantify the effects on autonomic nervous system function.
tVNS had no effect on the recognition of gradually or static expressed emotions but altered response inhibition on the emotional Go/NoGo-task. Specifically, tVNS increased the likelihood of omitting a response toward sad target-stimuli in adolescents with MDD, while decreasing errors (independent of the target emotion) in controls. Effects of acute tVNS on autonomic nervous system function were found in non-depressed controls only.
Acute tVNS alters the recognition of briefly presented facial expressions of negative valence in adolescents with MDD while generally increasing emotion recognition in controls. tVNS seems to specifically alter early visual processing of stimuli of negative emotional valence in MDD. These findings suggest a potential therapeutic benefit of tVNS in adolescent MDD that requires further evaluation within clinical trials.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
It is estimated that about half of all innovations, such as innovations in mechatronic product-service systems (PSS), fail to deliver the expected benefits to the adopting organization. Different studies point out that one of the main reasons for this is an ineffective implementation process.
In this paper, we argue that, apart from several organizational challenges, insufficient integration of technical and social aspects is one of the reasons for ineffective innovation implementation in the environment of mechatronic PSS.
In order to remedy this weakness, this paper builds on the work of interdisciplinary research collaboration. Experts from technical, socio-technical, and management fields integrate their work within a conceptual innovation implementation management system (IIMS). This IIMS is capable of capturing various methods and models that foster the socio-technical integration in mechatronic PSS. The approach is assessed in a lab-scale demonstration case that is representative of industrial environments.
The presented approach supports an effective innovation implementation process, while the IIMS facilitates individual alignments for future practitioners.
There is accumulating evidence that the error-related negativity (ERN), an event-related potential elicited after erroneous actions, is altered in different psychiatric disorders and may help to guide treatment options. Thus, the ERN is a promising candidate as a psychiatric biomarker. Basic methodological requirements for a biomarker are that their measurements are standardised and reliable. The aim of the present study was to establish ERN acquisition in a reliable, time-efficient and patient-friendly way for use in clinical practice.
Healthy subjects performed a speeded Eriksen Flanker Task that increases the number of errors. In a test–retest design (N = 14) with two sessions separated by 28 days we assessed the reliability of the ERN. To ensure external validity, we aimed to replicate previously reported correlation patterns of ERN amplitude with (A) number of errors and (B) negative affect. In order to optimise the clinical use of the task, we determined to which extent the task can be shortened while keeping reliability >0.80.
We found excellent reliability of the ERN (intraclass correlation coefficients = 0.806–0.947) and replicated ERN correlation patterns. The task can be halved to a patient-friendly length of 200 trials (recorded in 8 min) keeping reliability >0.80.
The modified task provides reliable and efficient recording of the ERN, facilitating its use as a psychiatric biomarker.
Treatment for hoarding disorder is typically performed by mental health professionals, potentially limiting access to care in underserved areas.
We aimed to conduct a non-inferiority trial of group peer-facilitated therapy (G-PFT) and group psychologist-led cognitive–behavioural therapy (G-CBT).
We randomised 323 adults with hording disorder 15 weeks of G-PFT or 16 weeks of G-CBT and assessed at baseline, post-treatment and longitudinally (≥3 months post-treatment: mean 14.4 months, range 3–25). Predictors of treatment response were examined.
G-PFT (effect size 1.20) was as effective as G-CBT (effect size 1.21; between-group difference 1.82 points, t = −1.71, d.f. = 245, P = 0.04). More homework completion and ongoing help from family and friends resulted in lower severity scores at longitudinal follow-up (t = 2.79, d.f. = 175, P = 0.006; t = 2.89, d.f. = 175, P = 0.004).
Peer-led groups were as effective as psychologist-led groups, providing a novel treatment avenue for individuals without access to mental health professionals.
Declaration of interest
C.A.M. has received grant funding from the National Institutes of Health (NIH) and travel reimbursement and speakers’ honoraria from the Tourette Association of America (TAA), as well as honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. K.D. receives research support from the NIH and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. R.S.M. receives research support from the National Institute of Mental Health, National Institute of Aging, the Hillblom Foundation, Janssen Pharmaceuticals (research grant) and the Alzheimer's Association. R.S.M. has also received travel support from the National Institute of Mental Health for Workshop participation. J.Y.T. receives research support from the NIH, Patient-Centered Outcomes Research Institute and the California Tobacco Related Research Program, and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. All other authors report no conflicts of interest.
OBJECTIVES/SPECIFIC AIMS: The objective of this study was to determine if trimethylamine N-oxide (TMAO) alone could acutely alter cardiac contractile function on a beat-to-beat basis. METHODS/STUDY POPULATION: CD1 adult mouse hearts were extracted, attached to a force transducer, oxygenated, and paced within an organ bath. Changes in contractility were measured after pipetting or reverse perfusing TMAO through the aorta via a modified Langendorff apparatus to facilitate TMAO delivery into the myocardium. To determine if our findings translated to the human heart, we performed contractility experiments using human right atrial appendage biopsy tissue retrieved during cardiopulmonary bypass procedures. To investigate whether TMAO alters contractile rate, in a separate series of experiments, the atria and sinoatrial node of isolated hearts were kept intact to allow for spontaneous beating without artificial pacing and were treated with TMAO or vehicle. In addition, intracellular calcium measurements were performed on spontaneously beating embryonic rat cardiomyocytes after TMAO or vehicle treatment. RESULTS/ANTICIPATED RESULTS: We found acute exposure to TMAO, diluted into the organ bath, increased average contraction amplitude 20% and 41% at 300 µM and 3000 µM, respectively (p<0.05, n=6). Langendorff reverse perfusion of mouse hearts ex vivo with 300 µM TMAO generated an even greater response than nonperfusion peripheral exposure and increased isometric force 32% (p<0.05, n=3). Consistent with what we observed in mouse hearts, incubation of human atrial muscle tissue with TMAO at 3000 µM increased isometric tension 31% compared with vehicle (p<0.05, n=4). TMAO treatment (3000 µM) also increased average beating frequency of ex vivo mouse hearts by 27% compared with vehicle (p<0.05, n=3) and increased the spontaneous beating frequency of primary rat cardiomyocytes by 13% compared with vehicle treatment (p<0.05, n=4). DISCUSSION/SIGNIFICANCE OF IMPACT: TMAO, at pathological concentrations, directly increases the force and rate of cardiac contractility. Initially, these inotropic and chronotropic effects may be adaptive during CKD; however, chronic increases in isometric tension and beating frequency can promote cardiac remodeling and heart failure. Further translational studies are needed to understand the intricate relationship between the microbiome, kidneys, and heart and to examine if TMAO represents a therapeutic target for reducing cardiovascular mortality in CKD patients.
Fee-for-service payment may motivate physicians to see more patients and achieve higher productivity. In 2015, emergency physicians at one Vancouver hospital switched to fee-for-service payment, while those at a sister hospital remained on contract, creating a natural experiment where the compensation method changed, but other factors remained constant. Our hypothesis was that fee-for-service payment would increase physician efficiency and reduce patient wait times.
This interrupted time series with concurrent control analysed emergency department (ED) performance during a 42-week period, encompassing the intervention (fee for service). Data were aggregated by week and plotted in a time series fashion. We adjusted for autocorrelation and developed general linear regression models to assess level and trend changes. Our primary outcome was the wait time to physician.
Data from 142,361 ED visits were analysed. Baseline wait times rose at both sites during the pre-intervention phase. Immediately post-intervention, the median wait time increased by 2.4 minutes at the control site and fell by 7.2 minutes at the intervention site (difference=9.6 minutes; 95% confidence interval, 2.9-16.4; p=0.007). The wait time trend (slope) subsequently deteriorated by 0.5 minutes per week at the intervention site relative to the expected counterfactual (p for the trend difference=0.07). By the end of the study, cross-site differences had not changed significantly from baseline.
Fee-for-service payment was associated with a 9.6-minute (24%) reduction in wait time, compatible with an extrinsic motivational effect; however, this was not sustained, and the intervention had no impact on other operational parameters studied. Physician compensation is an important policy issue but may not be a primary determinant of ED operational efficiency.
We add comments to a recent series of publications in peer-reviewed journals concerning the distribution of large Antarctic toothfish (Dissostichus mawsoni) found over the inner shelf of the Ross Sea. We note that earlier fish ecologists advanced innovative hypotheses invoking physical–biological interactions with life history, and that these, far from being disproved, have been relegated by more immediately pressing management concerns. We argue that, despite the considerable advances achieved by research groups working on D. mawsoni, an understanding of distribution and abundance is incomplete without reference to the physical structure that supports their life history. We briefly consider hypotheses highlighted by the recent literature in the context of major features of the shelf circulation in the Ross Sea, in particular intrusions of modified Circumpolar Deep Water along trough systems. We suggest physical–biological interactions that may be involved and call for improvements in the monitoring programme that can help test between the competing hypotheses.
Low resting respiratory sinus arrhythmia (RSA), and to a lesser extent excessive RSA reactivity to emotion evocation, are observed in many psychiatric disorders characterized by emotion dysregulation, including syndromes spanning the internalizing and externalizing spectra, and other conditions such as nonsuicidal self-injury. Nevertheless, some inconsistencies exist. For example, null outcomes in studies of RSA–emotion dysregulation relations are sometimes observed among younger participants. Such findings may derive from use of age inappropriate frequency bands in calculating RSA. We combine data from five published samples (N = 559) spanning ages 4 to 17 years, and reanalyze RSA data using age-appropriate respiratory frequencies. Misspecifying respiratory frequencies results in overestimates of resting RSA and underestimates of RSA reactivity, particularly among young children. Underestimates of developmental shifts in RSA and RSA reactivity from preschool to adolescence were also observed. Although correlational analyses revealed weak negative associations between resting RSA and aggression, those with clinical levels of externalizing exhibited lower resting RSA than their peers. No associations between RSA reactivity and externalizing were observed. Results confirm that age-corrected frequency bands should be used when estimating RSA, and that literature-wide overestimates of resting RSA, underestimates of RSA reactivity, and underestimates of developmental shifts in RSA and RSA reactivity may exist.
To investigate dietary sources of Ca and vitamin D (VitD) intakes, and the associated sociodemographic and lifestyle factors, among European adolescents.
Linear regression mixed models were used to examine sex-specific associations of Ca and VitD intakes with parental education, family affluence (FAS), physical activity and television (TV) watching while controlling for age, Tanner stage, energy intake and diet quality.
The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA)Cross-Sectional Study.
Adolescents aged 12·5–17·5 years (n 1804).
Milk and cheese were the main sources of Ca (23 and 19 % contribution to overall Ca intake, respectively). Fish products were the main VitD source (30 % contribution to overall VitD intake). Ca intake was positively associated with maternal education (β=56·41; 95 % CI 1·98, 110·82) and negatively associated with TV viewing in boys (β=–0·43; 95 % CI −0·79, −0·07); however, the significance of these associations disappeared when adjusting for diet quality. In girls, Ca intake was positively associated with mother’s (β=73·08; 95 % CI 34·41, 111·74) and father’s education (β=43·29; 95 % CI 5·44, 81·14) and FAS (β=37·45; 95 % CI 2·25, 72·65). This association between Ca intake and mother’s education remained significant after further adjustment for diet quality (β=41·66; 95 % CI 0·94, 82·38). Girls with high-educated mothers had higher Ca intake.
Low-educated families with poor diet quality may be targeted when strategizing health promotion programmes to enhance dietary Ca.
When using bifunctional core@shell catalysts, the stability of both the shell and core–shell interface is crucial for catalytic applications. In the present study, we elucidate the stability of a CuO/ZnO/Al2O3@ZSM-5 core@shell material, used for one-stage synthesis of dimethyl ether from synthesis gas. The catalyst stability was studied in a hierarchical manner by complementary environmental transmission electron microscopy (ETEM), scanning electron microscopy (SEM) and in situ hard X-ray ptychography with a specially designed in situ cell. Both reductive activation and reoxidation were applied. The core–shell interface was found to be stable during reducing and oxidizing treatment at 250°C as observed by ETEM and in situ X-ray ptychography, although strong changes occurred in the core on a 10 nm scale due to the reduction of copper oxide to metallic copper particles. At 350°C, in situ X-ray ptychography indicated the occurrence of structural changes also on the µm scale, i.e. the core material and parts of the shell undergo restructuring. Nevertheless, the crucial core–shell interface required for full bifunctionality appeared to remain stable. This study demonstrates the potential of these correlative in situ microscopy techniques for hierarchically designed catalysts.
St Andrews was of tremendous significance in medieval Scotland. Its importance remains readily apparent in the buildings which cluster the rocky promontory jutting out into the North Sea: the towers and walls of cathedral, castle and university provide reminders of the status and wealth of the city in the Middle Ages. As a centre of earthly and spiritual government, as the place of veneration forScotland's patron saint and as an ancient seat of learning, St Andrews was the ecclesiastical capital of Scotland. This volume provides the first full study of this special and multi-faceted centre throughout its golden age. The fourteen chapters use St Andrews as a focus for the discussion of multiple aspects of medieval life in Scotland. They examine church, spirituality, urban society andlearning in a specific context from the seventh to the sixteenth century, allowing for the consideration of St Andrews alongside other great religious and political centres of medieval Europe.
Michael Brown is Professor of Medieval Scottish History, University of St Andrews; Katie Stevenson is Keeper of Scottish History and Archaeology, National Museums Scotland and Senior Lecturer in Late Medieval History, University of St Andrews.
Contributors: Michael Brown, Ian Campbell, David Ditchburn, Elizabeth Ewan, Richard Fawcett, Derek Hall, Matthew Hammond, Julian Luxford, Roger Mason, Norman Reid, Bess Rhodes, Catherine Smith, Katie Stevenson, Simon Taylor, Tom Turpie.