Untrustworthy faces incur negative judgments across numerous domains. Existing work in this area has focused on situations in which the target's trustworthiness is relevant to the judgment (e.g., ...criminal verdicts and economic games). Yet in the present studies, we found that people also overgeneralized trustworthiness in criminal-sentencing decisions when trustworthiness should not be judicially relevant, and they did so even for the most extreme sentencing decision: condemning someone to death. In Study 1, we found that perceptions of untrustworthiness predicted death sentences (vs. life sentences) for convicted murderers in Florida (N = 742). Moreover, in Study 2, we found that the link between trustworthiness and the death sentence occurred even when participants viewed innocent people who had been exonerated after originally being sentenced to death. These results highlight the power of facial appearance to prejudice perceivers and affect life outcomes even to the point of execution, which suggests an alarming bias in the criminal-justice system.
Summary Background Health-care workers have been implicated in nosocomial outbreaks of Staphylococcus aureus , but the dearth of evidence from non-outbreak situations means that routine health-care ...worker screening and S aureus eradication are controversial. We aimed to determine how often S aureus is transmitted from health-care workers or the environment to patients in an intensive care unit (ICU) and a high-dependency unit (HDU) where standard infection control measures were in place. Methods In this longitudinal cohort study, we systematically sampled health-care workers, the environment, and patients over 14 months at the ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs were taken from health-care workers every 4 weeks, bed spaces were sampled monthly, and screening swabs were obtained from patients at admission to the ICU or HDU, weekly thereafter, and at discharge. Isolates were cultured and their whole genome sequenced, and we used the threshold of 40 single-nucleotide variants (SNVs) or fewer to define subtypes and infer recent transmission. Findings Between Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care workers, 40 environmental locations, and 1854 patients; 1819 isolates were sequenced. Median nasal carriage rate of S aureus in health-care workers at 4-weekly timepoints was 36·9% (IQR 35·7–37·3), and 115 (58%) health-care workers had S aureus detected at least once during the study. S aureus was identified in 8–50% of environmental samples. 605 genetically distinct subtypes were identified (median SNV difference 273, IQR 162–399) at a rate of 38 (IQR 34–42) per 4-weekly cycle. Only 25 instances of transmission to patients (seven from health-care workers, two from the environment, and 16 from other patients) were detected. Interpretation In the presence of standard infection control measures, health-care workers were infrequently sources of transmission to patients. S aureus epidemiology in the ICU and HDU is characterised by continuous ingress of distinct subtypes rather than transmission of genetically related strains. Funding UK Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, UK National Institute for Health Research, and Public Health England.
•Gait impairments are linked to deterioration of the brain.•Evidence suggests that specific brain regions relate to different gait components.•Future gait velocity decline may be predicted from ...measurements of white matter.•Cognition can mediate associations between gait and neuroimaging parameters.•Functional neuroimaging will aid further interpretation of neural-gait correlates.
Gait is complex, described by diverse characteristics underpinned by widespread central nervous system networks including motor and cognitive functions. Despite this, neural substrates of discrete gait characteristics are poorly understood, limiting understanding of gait impairment in ageing and disease. This structured review aims to map gait characteristics, defined from a pre-specified model reflecting independent gait domains, to brain imaging parameters in older adults. Fifty-two studies of 38,029 yielded were reviewed. Studies showed inconsistent approaches when mapping gait assessment to neural substrates, limiting conclusions. Gait impairments typically associated with brain deterioration, specifically grey matter atrophy and white matter integrity loss. Gait velocity, a global measure of gait control, was most frequently associated with these imaging markers within frontal and basal ganglia regions, and its decline predicted from white matter volume and integrity measurements. Fewer studies assessed additional gait measures or functional imaging parameters. Future studies mapping regional neuroanatomical and functional correlates of gait are needed, including those which take a multi-process network perspective to better understand mobility in health and disease.
Abstract
Background
Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger ...cohort “real life” safety and efficacy data including functional visual outcomes.
Methods
Children receiving bevacizumab-based treatments (BBT) for PLGG (2009–2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical–radiological correlation, survival outcomes and multivariate prognostic analysis.
Results
Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients’ best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients’ worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses.
Conclusions
BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.
Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal ...proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
: Gait disturbance is an early, cardinal feature of Parkinson's disease (PD) associated with falls and reduced physical activity. Progression of gait impairment in Parkinson's disease is not well ...characterized and a better understanding is imperative to mitigate impairment. Subtle gait impairments progress in early disease despite optimal dopaminergic medication. Evaluating gait disturbances over longer periods, accounting for typical aging and dopaminergic medication changes, will enable a better understanding of gait changes and inform targeted therapies for early disease. This study aimed to describe gait progression over the first 6 years of PD by delineating changes associated with aging, medication, and pathology.
: One-hundred and nine newly diagnosed PD participants and 130 controls completed at least two gait assessments. Gait was assessed at 18-month intervals for up to 6 years using an instrumented walkway to measure sixteen spatiotemporal gait characteristics. Linear mixed-effects models assessed progression.
: Ten gait characteristics significantly progressed in PD, with changes in four of these characteristics attributable to disease progression. Age-related changes also contributed to gait progression; changes in another two characteristics reflected both aging and disease progression. Gait impairment progressed irrespective of dopaminergic medication change for all characteristics except step width variability.
: Discrete gait impairments continue to progress in PD over 6 years, reflecting a combination of, and potential interaction between, disease-specific progression and age-related change. Gait changes were mostly unrelated to dopaminergic medication adjustments, highlighting limitations of current dopaminergic therapy and the need to improve interventions targeting gait decline.
Summary Background New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae . We used ...whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. Methods We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae , and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. Findings 1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. Interpretation We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. Funding Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.
Segmentation of the wrist bones in CT images has been frequently used in different clinical applications including arthritis evaluation, bone age assessment and image-guided interventions. The major ...challenges include non-uniformity and spongy textures of the bone tissue as well as narrow inter-bone spaces. In this work, we propose an automatic wrist bone segmentation technique for CT images based on a statistical model that captures the shape and pose variations of the wrist joint across 60 example wrists at nine different wrist positions. To establish the correspondences across the training shapes at neutral positions, the wrist bone surfaces are jointly aligned using a group-wise registration framework based on a Gaussian Mixture Model. Principal component analysis is then used to determine the major modes of shape variations. The variations in poses not only across the population but also across different wrist positions are incorporated in two pose models. An intra-subject pose model is developed by utilizing the similarity transforms at all wrist positions across the population. Further, an inter-subject pose model is used to model the pose variations across different wrist positions. For segmentation of the wrist bones in CT images, the developed model is registered to the edge point cloud extracted from the CT volume through an expectation maximization based probabilistic approach. Residual registration errors are corrected by application of a non-rigid registration technique. We validate the proposed segmentation method by registering the wrist model to a total of 66 unseen CT volumes of average voxel size of 0.38 mm. We report a mean surface distance error of 0.33 mm and a mean Jaccard index of 0.86.
Parkinson's disease (PD) is the fastest growing neurological condition worldwide. Recent theories suggest that symptoms of PD may arise due to spread of Lewy-body pathology where the process begins ...in the gut and propagate transynaptically via the vagus nerve to the central nervous system. In PD, gait impairments are common motor manifestations that are progressive and can appear early in the disease course. As therapies to mitigate gait impairments are limited, novel interventions targeting these and their consequences, i.e., reducing the risk of falls, are urgently needed. Non-invasive vagus nerve stimulation (nVNS) is a neuromodulation technique targeting the vagus nerve. We recently showed in a small pilot trial that a single dose of nVNS improved (decreased) discrete gait variability characteristics in those receiving active stimulation relative to those receiving sham stimulation. Further multi-dose, multi-session studies are needed to assess the safety and tolerability of the stimulation and if improvement in gait is sustained over time.
This will be an investigator-initiated, single-site, proof-of-concept, double-blind sham-controlled randomised pilot trial in 40 people with PD. Participants will be randomly assigned on a 1:1 ratio to receive either active or sham transcutaneous cervical VNS. All participants will undergo comprehensive cognitive, autonomic and gait assessments during three sessions over 24 weeks, in addition to remote monitoring of ambulatory activity and falls, and exploratory analyses of cholinergic peripheral plasma markers. The primary outcome measure is the safety and tolerability of multi-dose nVNS in PD. Secondary outcomes include improvements in gait, cognition and autonomic function that will be summarised using descriptive statistics.
This study will report on the proportion of eligible and enrolled patients, rates of eligibility and reasons for ineligibility. Adverse events will be recorded informing on the safety and device tolerability in PD. This study will additionally provide us with information for sample size calculations for future studies and evidence whether improvement in gait control is enhanced when nVNS is delivered repeatedly and sustained over time.
This trial is prospectively registered at www.isrctn.com/ISRCTN19394828 . Registered August 23, 2021.
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