Establishing harmonised screening limits and detection times in greyhound racing - A considered approach.

An outline of the approach taken by international greyhound regulators to establish internationally harmonised screening limits and detection times in greyhound racing, which included a program of administration studies and an extensive and recognised risk assessment process, to ensure delivery of an effective anti-doping and medication control program.

Statistical primer: Composite endpoints and competing risks analysis.

Composite end-points are common primary outcomes in clinical trials. Their main benefit of utilizing a composite outcome is increasing the number of primary outcome events meaning fewer participants are required to deliver an adequately powered trial. By combining multiple important end-points in the primary outcome rather than having to select only one, composite end-points potentially make clinically meaningful benefits easier to detect and avoid ranking outcomes hierarchically. However there are a number of important considerations when designing and interpreting clinical trials that utilize composite end-points. In this Statistical Primer, issues with composite end-points such as competing events, halo effect, risk of bias, time to event limitations and the win ratio are discussed in the context of real world clinical trials.

Intraindividual Variability in Attention-Deficit/Hyperactivity Disorder: An Ex-Gaussian Approach.

Higher intraindividual variability (IIV) of response times is consistently noted in children with attention-deficit/hyperactivity disorder (ADHD). The current study investigated whether an ex-Gaussian estimate of IIV in children ages 6-13 years-old could differentiate between children with and without ADHD. Children completed a computerized go/no-go task to estimate trial-by-trial IIV and a continuous performance test (CPT) to estimate inattention and hyperactivity/impulsivity. Parents completed questionnaires assessing inattention and hyperactive/impulsive behaviors. IIV, commission errors, and attention problems as rated by parents were significantly greater in the ADHD group. Groups did not differ on errors of omission, but IIV was predictive of omission errors and parent ratings of inattention and hyperactivity/impulsivity. IIV predicted group membership (ADHD vs Control) whereas errors of omission did not. However, IIV did not improve diagnostic accuracy when parent ratings were used, such that parent ratings were superior at determining diagnosis. Current results support the use of IIV, based on the ex-Gaussian approach, as an objective measure of attention problems over omission errors on sustained attention CPT-type tasks. Additionally, while parent ratings of attention impairment remain the best predictor of ADHD diagnostic status, IIV may be helpful in determining when further assessment is required in the absence of those ratings.

An environmental scan of tools that help individuals living with mild cognitive impairment or neurocognitive disorders (NCD) achieve their preferred health or well-being.

BACKGROUND AND OBJECTIVES: Older adults experiencing neurocognitive disease (NCD) contend with complex care often characterized by high emotional strain. Mitigating complex care with decision support tools can clarify options. When used in conjunction with the practice of Shared Decision Making (SDM) these tools can improve satisfaction and confidence in treatment. Use of these tools for cognitive health has increased but more is needed to understand how these tools incorporate social needs into treatment plans. RESEARCH DESIGN AND METHODS: We conducted an environmental scan using a MEDLINE informed search strategy and feedback from an expert steering committee to characterize current tools and approaches for engaging older adults experiencing NCD. We assessed their application and development, incorporation of social determinants, goals or preferences, and inclusion of caregivers in their design. RESULTS: We identified eleven articles, seven of which show that SDM helps guide tool development and that all tools center on clinical decision making. Types of tools varied by clinical site and those differences reflected patient need. A collective value across tools was their use to forge meaningful conversations. No tool appeared designed with the explicit goal to elicit patient social needs or incorporate non-clinical strategies into treatment plans. DISCUSSION AND IMPLICATIONS: Several challenges and opportunities that centered on strategies to engage patients in the design and testing of tools that support conversations with clinicians about cognitive health. Future work should focus on building and testing adaptable tools that support patient and family social care needs beyond clinical care settings.

Illuminating the nanostructure of diffuse interfaces: Recent advances and future directions in reflectometry techniques.

Diffuse soft matter interfaces take many forms, from end-tethered polymer brushes or adsorbed surfactants to self-assembled layers of lipids. These interfaces play crucial roles across a multitude of fields, including materials science, biophysics, and nanotechnology. Understanding the nanostructure and properties of these interfaces is fundamental for optimising their performance and designing novel functional materials. In recent years, reflectometry techniques, in particular neutron reflectometry, have emerged as powerful tools for elucidating the intricate nanostructure of soft matter interfaces with remarkable precision and depth. This review provides an overview of selected recent developments in reflectometry and their applications for illuminating the nanostructure of diffuse interfaces. We explore various principles and methods of neutron and X-ray reflectometry, as well as ellipsometry, and discuss advances in their experimental setups and data analysis approaches. Improvements to experimental neutron reflectometry methods have enabled greater time resolution in kinetic measurements and elucidation of diffuse structure under shear or confinement, while innovation in analysis protocols has significantly reduced data processing times, facilitated co-refinement of reflectometry data from multiple instruments and provided greater-than-ever confidence in proposed structural models. Furthermore, we highlight some significant research findings enabled by these techniques, revealing the organisation, dynamics, and interfacial phenomena at the nanoscale. We also discuss future directions and potential advancements in reflectometry techniques. By shedding light on the nanostructure of diffuse interfaces, reflectometry techniques enable the rational design and tailoring of interfaces with enhanced properties and functionalities.

The Ring-Closing Reaction of Cyclopentadiene Probed with Ultrafast X-ray Scattering.

The dynamics of cyclopentadiene (CP) following optical excitation at 243 nm was investigated by time-resolved pump-probe X-ray scattering using 16.2 keV X-rays at the Linac Coherent Light Source (LCLS). We present the first ultrafast structural evidence that the reaction leads directly to the formation of bicyclo[2.1.0]pentene (BP), a strained molecule with three- and four-membered rings. The bicyclic compound decays via a thermal backreaction to the vibrationally hot CP with a time constant of 21 ± 3 ps. A minor channel leads to ring-opened structures on a subpicosecond time scale.

Pre-Operative Measures of Systemic Inflammation Predict Survival After Surgery for Primary Lung Cancer.

BACKGROUND: Measures of systemic inflammation (MSIs) have been developed and shown to help predict prognosis in patients with lung cancer. However, studies investigating the impact of MSIs on outcomes solely in cohorts of patients undergoing curative-intent resection of NSCLC are lacking. In the era of individualized therapies, targeting inflammatory pathways could represent a novel addition to the armamentarium of lung cancer treatment. METHODS: A multicentre retrospective review of patients who underwent primary lung cancer resection between 2012 and 2018 was undertaken. MSIs assessed were neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII), advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI) and haemoglobin albumin lymphocyte platelet (HALP) score. Cox regression analysis was performed to assess the impact of MSIs on overall survival. RESULTS: A total of 5029 patients were included in the study. Overall 90-day mortality was 3.7% (n = 185). All MSIs were significantly associated with overall survival on univariable analysis. After multivariable Cox regression analyses, lower ALI (expressed as a continuous variable) (HR 1.000, 95% CI 1.000-1.000, P = .049) and ALI <366.43 (expressed as a dichotomous variable) (HR 1.362, 95% CI 1.137-1.631, P < .001) remained independently associated with reduced overall survival. CONCLUSIONS: MSIs have emerged in this study as potentially important factors associated with survival following lung resection for NSCLC with curative intent. In particular, ALI has emerged as independently associated with long-term outcomes. The role of MSIs in the clinical management of patients with primary lung cancer requires further investigation.

Bed rest impairs the vestibular control of balance.

Prolonged bed rest impairs standing balance but the underlying mechanisms are uncertain. Previous research suggests strength loss is not the cause, leaving impaired sensorimotor control as an alternative. Here we examine vestibular control of posture in 18 male volunteers before and after 60 days of bed rest. Stochastic vestibular stimulation (SVS) was used to evoke sway responses before, 1 and 6 days after bed rest under different head yaw orientations. The directional accuracy and precision of these responses were calculated from ground reaction force vectors. Bed rest caused up to 63% increases in spontaneous standing sway and 31% reductions in leg strength, changes which were uncorrelated. The increase in sway was exacerbated when the eyes were closed. Mean directions of SVS-evoked sway responses were unaffected, being directed towards the anodal ear and rotating in line with head orientation in the same way before and after bed rest. However, individual trial analysis revealed 25%-30% increases in directional variability, which were significantly correlated with the increase in spontaneous sway (r = 0.48-0.71; P ≤ 0.044) and were still elevated on day 6 post-bed rest. This reveals that individual sway responses may be inappropriately oriented, a finding masked by the averaging process. Our results confirm that impaired balance following prolonged bedrest is not related to loss of strength. Rather, they demonstrate that the sensorimotor transformation process which converts vestibular feedback into appropriately directed balance responses is impaired. KEY POINTS: Prolonged inactivity impairs balance but previous research suggests this is not caused by loss of strength. Here we investigated vestibular control of balance before and after 60 days of bed rest using electrical vestibular stimulation (EVS) to evoke sway responses. Spontaneous sway significantly increased and muscle strength reduced following bed rest, but, in keeping with previous research, these two effects were not correlated. While the overall accuracy of EVS-evoked sway responses was unaffected, their directional variability significantly increased following bed rest, and this was correlated with the increases in spontaneous sway. We have shown that the ability to transform head-centred vestibular feedback into an appropriately directed body sway response is negatively affected by prolonged inactivity; this may contribute to the impaired balance commonly observed following bed rest.

Demographic, socioeconomic and life-course risk factors for internalized weight stigma in adulthood: evidence from an English birth cohort study.

Background: Obesity is highly stigmatized, with negative obesity-related stereotypes widespread across society. Internalized weight stigma (IWS) is linked to negative outcomes including poor mental health and disordered eating. Previous evidence examining population groups at higher risk of experiencing IWS comes from small, nonrepresentative samples. Here, we re-assess previously reported associations of IWS with demographic, socioeconomic, and wider social factors in a large general population birth cohort study for the first time. Methods: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we explored differences in IWS at age 31 years by sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences, using confounder-adjusted multivariable regression. Findings: In models adjusted for potential confounders and BMI in childhood, adolescence, and adulthood (N = 4060), IWS was higher for females (standardized beta: 0.56, 95% CI: 0.50, 0.61), sexual minorities (0.17 S.D. higher, 95% CI: 0.09, 0.24), and less socioeconomically advantaged individuals (e.g., 0.16 S.D. higher (95% CI: 0.08, 0.24) for participants whose mothers had minimum or no qualifications, compared to a university degree). The social environment during adolescence and young adulthood was important: IWS was higher for people who at age 13 years felt pressure to lose weight from family (by 0.13 S.D., 95% CI: 0.03, 0.23), and the media (by 0.17, 95% CI: 0.10, 0.25), or had experienced bullying (e.g., 0.25 S.D., 95% CI: 0.17, 0.33 for bullying at age 23 years). Interpretation: Internalized weight stigma differs substantially between demographic groups. Risk is elevated for females, sexual minorities, and socioeconomically disadvantaged adults, and this is not explained by differences in BMI. Pressure to lose weight from family and the media in adolescence may have long-lasting effects on IWS. Funding: The ESRC, MRC, NIHR, and Wellcome Trust.

Foodborne bacterial pathogens: genome-based approaches for enduring and emerging threats in a complex and changing world.

Foodborne illnesses pose a substantial health and economic burden, presenting challenges in prevention due to the diverse microbial hazards that can enter and spread within food systems. Various factors, including natural, political and commercial drivers, influence food production and distribution. The risks of foodborne illness will continue to evolve in step with these drivers and with changes to food systems. For example, climate impacts on water availability for agriculture, changes in food sustainability targets and evolving customer preferences can all have an impact on the ecology of foodborne pathogens and the agrifood niches that can carry microorganisms. Whole-genome and metagenome sequencing, combined with microbial surveillance schemes and insights from the food system, can provide authorities and businesses with transformative information to address risks and implement new food safety interventions across the food chain. In this Review, we describe how genome-based approaches have advanced our understanding of the evolution and spread of enduring bacterial foodborne hazards as well as their role in identifying emerging foodborne hazards. Furthermore, foodborne hazards exist in complex microbial communities across the entire food chain, and consideration of these co-existing organisms is essential to understanding the entire ecology supporting pathogen persistence and transmission in an evolving food system.

Comparison of two carbonaceous supported Fe-rich adsorbents for arsenate removal: A functionalisation and mechanistic study with applicability to groundwater treatment.

The presence of arsenic in groundwater, and through this in drinking water, has been shown to present a serious risk to public health in many regions of the world. In this study, two iron-rich carbonous adsorbents were compared for the removal of arsenate (As(V)) from groundwater. Biochars (FeO-biochar and FeO-pyrochar) derived from biomass waste were functionalised in two different ways with iron chloride for comparation. Batch and dynamic parameters were optimised to achieve >99% As(V) removal efficiency. Experimental data were best described by the pseudo-second order kinetic model, while multi-stage diffusion appeared to limit mass transfer of As(V). Among the isotherm models evaluated, the Freundlich model best described the experimental results with high correlation coefficients (R2 ≥ 0.94) for both adsorbents. Monolayer adsorption capacities were found to be 4.34 mg/g and 8.66 mg/g for FeO-biochar and FeO-pyrochar, respectively. Batch studies followed by instrumental characterisation of the materials indicated the removal mechanisms involved to be electrostatic interactions (outer-sphere), OH- ligand exchange (inner-sphere complexation) and hydrogen bonding with functional groups. Higher pHpzc (9.1), SBET (167.2 m2/g), and iron/elemental content for the FeO-pyrochar (compared with the FeO-biochar) suggested that both surface chemistry and porosity/surface area were important in adsorption. Dynamic studies showed FeO-pyrochar can be used to remove As(V) from groundwater even at low 'environmental' concentrations relevant to legislative limits (<10 µg/L), whereby 7 g of FeO-pyrochar was able to treat 5.4 L groundwater.

"Modernism with a Soul": Designing and Building Communities for Corporate and Civic Life.

This essay explores how film, feature and documentary, can offer a new perspective on modernist architecture, industrial design, and urban planning. Through the lens of two young directors, Kogonada and Davide Maffei, it traces the histories of two twentieth-century company towns: Ivrea, Italy, headquarters of Italian business machine giant Olivetti, and Columbus, Indiana, U.S.A., home to Cummins Inc., a global leader in diesel engine design and manufacturing. Adriano Olivetti and J. Irwin Miller shared the conviction that modernist architecture and design had a decisive role to play not just in the economic health of their respective firms but in the civic health of their surrounding communities. These companies have long abandoned the corporate idealism of their founding patrons. In film, Ivrea and Columbus have become architectural time capsules that raise important questions about the transformative power of architecture and design in the face of an increasingly competitive global economy.

A systematic review of cardiac surgery clinical prediction models that include intra-operative variables.

BACKGROUND: Most cardiac surgery clinical prediction models (CPMs) are developed using pre-operative variables to predict post-operative outcomes. Some CPMs are developed with intra-operative variables, but none are widely used. The objective of this systematic review was to identify CPMs with intra-operative variables that predict short-term outcomes following adult cardiac surgery. METHODS: Ovid MEDLINE and EMBASE databases were searched from inception to December 2022, for studies developing a CPM with at least one intra-operative variable. Data were extracted using a critical appraisal framework and bias assessment tool. Model performance was analysed using discrimination and calibration measures. RESULTS: A total of 24 models were identified. Frequent predicted outcomes were acute kidney injury (9/24 studies) and peri-operative mortality (6/24 studies). Frequent pre-operative variables were age (18/24 studies) and creatinine/eGFR (18/24 studies). Common intra-operative variables were cardiopulmonary bypass time (16/24 studies) and transfusion (13/24 studies). Model discrimination was acceptable for all internally validated models (AUC 0.69-0.91). Calibration was poor (15/24 studies) or unreported (8/24 studies). Most CPMs were at a high or indeterminate risk of bias (23/24 models). The added value of intra-operative variables was assessed in six studies with statistically significantly improved discrimination demonstrated in two. CONCLUSION: Weak reporting and methodological limitations may restrict wider applicability and adoption of existing CPMs that include intra-operative variables. There is some evidence that CPM discrimination is improved with the addition of intra-operative variables. Further work is required to understand the role of intra-operative CPMs in the management of cardiac surgery patients.

Exploring the ultrafast and isomer-dependent photodissociation of iodothiophenes via site-selective ionization.

C-I bond extension and fission following ultraviolet (UV, 262 nm) photoexcitation of 2- and 3-iodothiophene is studied using ultrafast time-resolved extreme ultraviolet (XUV) ionization in conjunction with velocity map ion imaging. The photoexcited molecules and eventual I atom products are probed by site-selective ionization at the I 4d edge using intense XUV pulses, which induce multiple charges initially localized to the iodine atom. At C-I separations below the critical distance for charge transfer (CT), charge can redistribute around the molecule leading to Coulomb explosion and charged fragments with high kinetic energy. At greater C-I separations, beyond the critical distance, CT is no longer possible and the measured kinetic energies of the charged iodine atoms report on the neutral dissociation process. The time and momentum resolved measurements allow determination of the timescales and the respective product momentum and kinetic energy distributions for both isomers, which are interpreted in terms of rival 'direct' and 'indirect' dissociation pathways. The measurements are compared with a classical over the barrier model, which reveals that the onset of the indirect dissociation process is delayed by ∼1 ps relative to the direct process. The kinetics of the two processes show no discernible difference between the two parent isomers, but the branching between the direct and indirect dissociation channels and the respective product momentum distributions show isomer dependencies. The greater relative yield of indirect dissociation products from 262 nm photolysis of 3-iodothiophene (cf. 2-iodothiophene) is attributed to the different partial cross-sections for (ring-centred) π∗ ← π and (C-I bond localized) σ∗ ← (n/π) excitation in the respective parent isomers.

The aetiology of fracture and nonunion in the hook of the hamate.

Fractures of the hook of the hamate are traditionally thought to be caused by direct trauma. A review of the anatomy and function of the hamate hook suggests that fracture is more likely as a result of a fatigue response that develops in the hook from repetitive load applied by the adjacent deep flexor tendons. Additional vascular compromise, from direct pressure of the tendons on critical local vessels, reduces blood flow leading to both mechanical and vascular effects that create pathological osseous change and weakening. These changes are likely to predispose to stress fracture and nonunion in repetitive gripping activities and are consistent with radiological findings.

Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe hereditary arrhythmia syndrome predominantly affecting children and young adults. It manifests through bidirectional or polymorphic ventricular arrhythmia, often culminating in syncope triggered by physical exertion or emotional stress which can lead to sudden cardiac death. Most cases stem from mutations in the gene responsible for encoding the cardiac ryanodine receptor (RyR2), or in the Calsequestrin 2 gene (CASQ2), disrupting the handling of calcium ions within the cardiac myocyte sarcoplasmic reticulum. Diagnosing CPVT typically involves unmasking the arrhythmia through exercise stress testing. This diagnosis emerges in the absence of structural heart disease by cardiac imaging and with a normal baseline electrocardiogram. Traditional first-line treatment primarily involves ß-blocker therapy, significantly reducing CPVT-associated mortality. Adjunctive therapies such as moderate exercise training, flecainide, left cardiac sympathetic denervation and implantable cardioverter-defibrillators have been utilized with reasonable success. However, the spectrum of options for managing CPVT has expanded over time, demonstrating decreased rates of arrhythmic events. Furthermore, ongoing research into potential new therapies including gene therapies has the potential to further enhance treatment paradigms. This review aims to succinctly encapsulate the contemporary understanding of the clinical characteristics, diagnostic approach, established therapeutic interventions and the promising future directions in managing CPVT.

Premorbid personality traits as predictors for incident predementia syndromes: a multistate model approach.

OBJECTIVE: Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. METHODS: Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. RESULTS: Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. CONCLUSIONS: FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

What works in radiology education for medical students: a systematic review and meta-analysis.

BACKGROUND: Medical imaging related knowledge and skills are widely used in clinical practice. However, radiology teaching methods and resultant knowledge among medical students and junior doctors is variable. A systematic review and meta-analysis was performed to compare the impact of different components of radiology teaching methods (active versus passive teaching, eLearning versus traditional face-to-face teaching) on radiology knowledge / skills of medical students. METHODS: PubMed and Scopus databases were searched for articles published in English over a 15-year period ending in June 2021 quantitatively comparing the effectiveness of undergraduate medical radiology education programs regarding acquisition of knowledge and/or skills. Study quality was appraised by the Medical Education Research Study Quality Instrument (MERSQI) scoring and analyses performed to assess for risk of bias. A random effects meta-analysis was performed to pool weighted effect sizes across studies and I2 statistics quantified heterogeneity. A meta-regression analysis was performed to assess for sources of heterogeneity. RESULTS: From 3,052 articles, 40 articles involving 6,242 medical students met inclusion criteria. Median MERSQI score of the included articles was 13 out of 18 possible with moderate degree of heterogeneity (I2 = 93.42%). Thematic analysis suggests trends toward synergisms between radiology and anatomy teaching, active learning producing superior knowledge gains compared with passive learning and eLearning producing equivalent learning gains to face-to-face teaching. No significant differences were detected in the effectiveness of methods of radiology education. However, when considered with the thematic analysis, eLearning is at least equivalent to traditional face-to-face teaching and could be synergistic. CONCLUSIONS: Studies of educational interventions are inherently heterogeneous and contextual, typically tailored to specific groups of students. Thus, we could not draw definitive conclusion about effectiveness of the various radiology education interventions based on the currently available data. Better standardisation in the design and implementation of radiology educational interventions and design of radiology education research are needed to understand aspects of educational design and delivery that are optimal for learning. TRIAL REGISTRATION: Prospero registration number CRD42022298607.

Risk Prediction Models for Long-Term Survival after Cardiac Surgery: A Systematic Review.

BACKGROUND: The reporting of alternative postoperative measures of quality after cardiac surgery is becoming increasingly important as in-hospital mortality rates continue to decline. This study aims to systematically review and assess risk models designed to predict long-term outcomes after cardiac surgery. METHODS: The MEDLINE and Embase databases were searched for articles published between 1990 and 2020. Studies developing or validating risk prediction models for long-term outcomes after cardiac surgery were included. Data were extracted using checklists for critical appraisal and systematic review of prediction modeling studies. RESULTS: Eleven studies were identified for inclusion in the review, of which nine studies described the development of long-term risk prediction models after cardiac surgery and two were external validation studies. A total of 70 predictors were included across the nine models. The most frequently used predictors were age (n = 9), peripheral vascular disease (n = 8), renal disease (n = 8), and pulmonary disease (n = 8). Despite all models demonstrating acceptable performance on internal validation, only two models underwent external validation, both of which performed poorly. CONCLUSION: Nine risk prediction models predicting long-term mortality after cardiac surgery have been identified in this review. Statistical issues with model development, limited inclusion of outcomes beyond 5 years of follow-up, and a lack of external validation studies means that none of the models identified can be recommended for use in contemporary cardiac surgery. Further work is needed either to successfully externally validate existing models or to develop new models. Newly developed models should aim to use standardized long-term specific reproducible outcome measures.