The effect of image fractal properties and its interaction with visual discomfort on gait kinematics.

Exposure to images of urban environments affords higher cognitive processing demands than exposure to images of nature scenes; an effect potentially related to differences in low-level image statistics such as fractals. The aim of the current study was to investigate whether the fractal dimensions of an abstract scene affect cognitive processing demands, using gait kinematics as a measure of cognitive demand. Participants (n = 40) were asked to walk towards different types of synthetic images which were parametrically varied in their fractal dimensions. At the end of each walk, participants rated each image for its visual discomfort (n = 20) or for its likability (n = 20) as potential confounding factors. Fractal dimensions were predictors of walking speed. Moreover, the interaction between fractal dimensions and subjective visual discomfort but not liking predicted velocity. Overall, these data suggest that fractal dimensions indeed contribute to environmentally induced cognitive processing demands.

Human locomotion over obstacles reveals real-time prediction of energy expenditure for optimized decision-making.

Despite decades of evidence revealing a multitude of ways in which animals are adapted to minimize the energy cost of locomotion, little is known about how energy expenditure shapes adaptive gait over complex terrain. Here, we show that the principle of energy optimality in human locomotion can be generalized to complex task-level locomotor behaviours requiring advance decision-making and anticipatory control. Participants completed a forced-choice locomotor task requiring them to choose between discrete multi-step obstacle negotiation strategies to cross a 'hole' in the ground. By modelling and analysing mechanical energy cost of transport for preferred and non-preferred manoeuvres over a wide range of obstacle dimensions, we showed that strategy selection was predicted by relative energy cost integrated across the complete multi-step task. Vision-based remote sensing was sufficient to select the strategy associated with the lowest prospective energy cost in advance of obstacle encounter, demonstrating the capacity for energetic optimization of locomotor behaviour in the absence of online proprioceptive or chemosensory feedback mechanisms. We highlight the integrative hierarchic optimizations that are required to facilitate energetically efficient locomotion over complex terrain and propose a new behavioural level linking mechanics, remote sensing and cognition that can be leveraged to explore locomotor control and decision-making.

Visuomotor control of leaping over a raised obstacle is sensitive to small baseline displacements.

The limb kinematics used for stepping or leaping over an obstacle are determined primarily by visual sensing of obstacle position and geometry. In this study, we demonstrate that changes are induced in limb kinematics even when obstacle geometry is manipulated in a way that does not introduce a mechanical requirement for a change of limb trajectory nor increase risk of collision. Human participants performed a running leap over a single raised obstacle bar. Kinematic changes were measured when an identical second bar was introduced at a ground level underneath the obstacle and displaced by a functionally insignificant distance along the axis of travel. The presence or absence of a baseline directly beneath the highest extremity had no significant effect on limb kinematics. However, displacing the baseline horizontally induced a horizontal translation of limb trajectory in the direction of the displacement. These results show that systematic changes to limb trajectories can occur in the absence of a change in sensed mechanical constraints or optimization. The nature of visuomotor control of human leaping may involve a continuous mapping of sensory input to kinematic output rather than one responsive only to information perceived to be mechanically relevant.

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender.

BACKGROUND: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.

The nature effect in motion: visual exposure to environmental scenes impacts cognitive load and human gait kinematics.

Prolonged exposure to urban environments requires higher cognitive processing resources than exposure to nature environments, even if only visual cues are available. Here, we explored the moment-to-moment impact of environment type on visual cognitive processing load, measuring gait kinematics and reaction times. In Experiment 1, participants (n = 20) walked toward nature and urban images projected in front of them, one image per walk, and rated each image for visual discomfort. Gait speed and step length decreased for exposure to urban as compared with nature scenes in line with gait changes observed during verbal cognitive load tasks. We teased apart factors that might contribute to cognitive load: image statistics and visual discomfort. Gait changes correlated with subjective ratings of visual discomfort and their interaction with the environment but not with low-level image statistics. In Experiment 2, participants (n = 45) performed a classic shape discrimination task with the same environmental scenes serving as task-irrelevant distractors. Shape discrimination was slower when urban scenes were presented, suggesting that it is harder to disengage attention from urban than from nature scenes. This provides converging evidence that increased cognitive demands posed by exposure to urban scenes can be measured with gait kinematics and reaction times even for short exposure times.

Neuropathological and biochemical investigation of Hereditary Ferritinopathy cases with ferritin light chain mutation: Prominent protein aggregation in the absence of major mitochondrial or oxidative stress.

AIMS: Neuroferritinopathy (NF) or hereditary ferritinopathy (HF) is an autosomal dominant movement disorder due to mutation in the light chain of the iron storage protein ferritin (FTL). HF is the only late-onset neurodegeneration with brain iron accumulation disorder and study of HF offers a unique opportunity to understand the role of iron in more common neurodegenerative syndromes. METHODS: We carried out pathological and biochemical studies of six individuals with the same pathogenic FTL mutation. RESULTS: CNS pathological changes were most prominent in the basal ganglia and cerebellar dentate, echoing the normal pattern of brain iron accumulation. Accumulation of ferritin and iron was conspicuous in cells with a phenotype suggesting oligodendrocytes, with accompanying neuronal pathology and neuronal loss. Neurons still survived, however, despite extensive adjacent glial iron deposition, suggesting neuronal loss is a downstream event. Typical age-related neurodegenerative pathology was not normally present. Uniquely, the extensive aggregates of ubiquitinated ferritin identified indicate that abnormal FTL can aggregate, reflecting the intrinsic ability of FTL to self-assemble. Ferritin aggregates were seen in neuronal and glial nuclei showing parallels with Huntington's disease. There was neither evidence of oxidative stress activation nor any significant mitochondrial pathology in the affected basal ganglia. CONCLUSIONS: HF shows hallmarks of a protein aggregation disorder, in addition to iron accumulation. Degeneration in HF is not accompanied by age-related neurodegenerative pathology and the lack of evidence of oxidative stress and mitochondrial damage suggests that these are not key mediators of neurodegeneration in HF, casting light on other neurodegenerative diseases characterized by iron deposition.

Meeting report from the joint IARC-NCI international cancer seminar series: a focus on colorectal cancer.

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low- and middle-income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute and the International Agency for Research on Cancer, which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.

A simple model predicts energetically optimised jumping in dogs.

It is generally accepted that animals move in a way that minimises energy use during regular gait and there is evidence that the principle might extend more generally to locomotor behaviour and manoeuvres. Jumping during locomotion is a useful manoeuvre that contributes to the versatility of legged locomotion and is within the repertoire of many terrestrial animals. We describe a simple ballistic model that can be used to identify a single unique trajectory of the body's centre of mass that minimises the mechanical work to initiate a jump, regardless of the approach velocity or take-off position. The model was used to show that domestic dogs (Canis lupus familiaris) demonstrate complex anticipatory control of locomotor behaviour by systematically using jump trajectories close to those that minimised the mechanical energy of jumps over raised obstacles. It is unclear how the dogs acquired the complex perception and control necessary to exhibit the observed behaviour. The model may be used to investigate whether animals adopt energetically optimised behaviour in any similarly constrained ballistic task.

Improvement in Functioning and Psychological Distress in Adolescents With Postural Orthostatic Tachycardia Syndrome Following Interdisciplinary Treatment.

Significant functional impairment and psychological distress have been observed in adolescent patients with postural orthostatic tachycardia syndrome (POTS). Interdisciplinary rehabilitation programs have been shown to be beneficial in the treatment of chronic pain in adults and adolescents. Only preliminary data have examined interdisciplinary rehabilitation efforts in patients with POTS. This study evaluated the impact of an interdisciplinary rehabilitation program on the functional impairment and psychological distress in 33 adolescents diagnosed with POTS. Patients included in the study were adolescents ages 11 to 18 diagnosed with POTS. Measures completed at admission and discharge from the program included the Functional Disability Index, Center for Epidemiological Studies-Depression-Child scale, and the Pain Catastrophizing Scale for Children. After participation in the 3-week program, adolescents with POTS demonstrated a significant increase in overall functional ability and significant reductions in depression and catastrophizing.

Estimates of benefits and harms of prophylactic use of aspirin in the general population.

BACKGROUND: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. METHODS: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. RESULTS: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. CONCLUSIONS: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis.

Effect of procedure volume on outcomes after iliac artery angioplasty and stenting.

BACKGROUND: Service reorganization to concentrate complex vascular services in hospitals with high caseload volume aims to reduce mortality and complication rates. The present study assessed the relationship between caseload volume and outcome for iliac artery angioplasty and stenting in England using a routinely available national data set (Hospital Episode Statistics, HES). METHODS: Routine administrative data for iliac artery angioplasty and stent procedures performed in England between 2007 and 2011 were analysed. Associations between centre volume and outcomes (death, complications and duration of hospital stay) were tested and compared for two methods of stratification (quartiles and quintiles) and two statistical tests (odds ratios and the Cochran-Armitage test for trend). Multivariable analysis was also performed. RESULTS: There were 23,308 episodes of care recorded in HES with Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, fourth revision, codes L54.1 or L54.4 corresponding to iliac artery intervention. There was a gradual increase year by year in number of procedures performed. Univariable and multivariable analysis showed no association between centre volume and either death or complications (multivariable odds ratio, OR 1.00, 95 per cent confidence interval 1.00 to 1.00) for elective and non-elective procedures. Age was associated with higher mortality and complication rates in elective procedures, and with mortality in non-elective procedures. The risk of death after elective iliac angioplasty or stenting was significantly higher in women (multivariable OR 4.98, 2.09 to 13.26). CONCLUSION: There was no association between the outcomes of endovascular iliac artery intervention and centre volume, but outcomes were significantly worse with increasing age and female sex.

Cardiac transplantation in a pediatric patient with systemic sclerosis.

INTRODUCTION: Diffuse cutaneous systemic sclerosis (SSc) is rare in children, but has a poor prognosis when cardiomyopathy is present. METHODS: We reviewed the case of a 14-year-old female with progressive skin thickening/tightness and dyspnea on exertion who was diagnosed with SSc. RESULTS: Our patient was found to have severe restrictive cardiomyopathy with poor left ventricular systolic function (ejection fraction = 20%), unresponsive to the immunosuppression used to treat her SSc. There was no evidence of pulmonary fibrosis. The patient underwent orthotopic cardiac transplantation, with improvement in systemic symptoms. Two years after transplantation, she had elevated filling pressures during a surveillance catheterization, with no evidence of cellular rejection or coronary artery vasculopathy. Four months later, she developed severe ventricular dysfunction and dyspnea, despite a negative biopsy and negative C4d immunofluorescence staining. Her immunosuppression was intensified with improvement of cardiac function. Despite this, 1 month later she had sudden pulseless cardiac arrest from which she could not be revived. The family declined an autopsy. DISCUSSION: We report a 14-year-old female with SSc who had cardiac transplantation. The etiology behind her recurrent restrictive physiology, cardiac dysfunction, and subsequent cardiac arrest remains unclear.

Ischaemic Preconditioning and Intermittent Clamping Does not Influence Mediators of Liver Regeneration in a Human Liver Sinusoidal Endothelial Cell Model of Ischaemia-Reperfusion Injury.

BACKGROUND: The role of surgical technique on liver regeneration following surgery remains inconclusive. The aim of the study was to assess the effect of ischaemic preconditioning (IPC) and intermittent clamping (IC) on mediators of regeneration produced by human liver sinusoidal endothelial cells (SECs), using an in vitro hypoxia-reoxygenation model to mimic ischaemia-reperfusion injury (IRI). METHODS: Following extraction from samples obtained from liver resection (n = 5), confluent culture flasks of SECs were subjected to IRI (1 hour hypoxia + 1 hour reoxygenation), IPC prior to IRI (10 minutes hypoxia + 10 minutes reoxygenation + 1 hour hypoxia + 1 hour reoxygenation), IC (15 minutes hypoxia + 5 minutes reoxygenation x 3 + 1 hour reoxygenation) and compared to controls. The production of various mediators was determined over 48 hours. RESULTS: Interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor (G-CSF) and hepatocyte growth factor (HGF) were produced by SECs. Both IPC and IC did not significantly influence the profile of IL-6, IL-8, G-CSF and HGF by SECs compared to IRI over the study period. CONCLUSION: IPC and IC did not influence the production of pro-regenerative mediators in a SECs model of IRI. The role of surgical technique on liver regeneration remains to be determined.

An in vitro model of warm hypoxia-reoxygenation injury in human liver endothelial cells.

BACKGROUND: Ischemia-reperfusion or hypoxia-reoxygenation (H-R) injury adversely affects hepatic function following transplantation and major resection; the death of human sinusoidal endothelial cells (SECs) by apoptosis may play a central role in this process. Caspase-3 is an important intracellular protease in the intrinsic and extrinsic pathways of apoptosis. MATERIALS AND METHODS: SECs and EAhy926 cells were exposed to warm hypoxia at 37°C, followed by reoxygenation at 37°C. Activity of caspase-3 was quantified using Western blotting and colorimetric kinase assays. RESULTS: H-R caused a significant increase in caspase-3 activity compared with controls in both cell types. CONCLUSIONS: Warm H-R injury causes apoptotic cell death of SECs and immortalized cells, but with differing patterns of caspase activity.