Interceptive Actions in Adults and Children

Interceptive actions refer to goal directed movements in which people attempt to make a controlled collision with a moving object (e.g. catching a ball). Because interceptive actions often take place under severe temporal constraints, movements need to be executed with exquisite temporal accuracy and precision. To achieve this the sensorimotor system needs to: (i) accurately predict the motion of the target object, and (ii) move the intercepting effector (e.g. hand, bat) to a location through which the object will pass at just the right time. This presents the sensorimotor system with numerous computational challenges. Examining interceptive timing in adults provides insights into how these challenges are overcome in the developed sensorimotor system, while studying children can reveal how these abilities are acquired and how they are related to the development of other sensorimotor and cognitive processes. The first part of this thesis investigates the control of interceptive timing behaviours in adults. Chapter 3 provides evidence that online sensory information is combined with a-priori knowledge, using Bayesian integration, to optimise movement timing. Chapter 4 demonstrates that adults optimally time their movements to exploit a physical relationship between the speed and temporal precision of their movements. The second part of this thesis then examines interceptive timing abilities in children. Chapter 5 documents the developmental trajectory of interceptive timing abilities over childhood, revealing that performance is still far from adult levels by the time children finish primary school (age 11 years). Chapter 6 tests a common taxonomy of motor skills, revealing that interceptive timing tasks measure a somewhat distinct ‘motor construct’ from that measured by ‘fine’ and ‘gross’ motor tasks. Finally, chapter 7 reveals a relationship between interceptive timing abilities and academic attainment in mathematics, even after controlling for motor skills in other taxonomic domains. Together these experiments shed light on how humans are able to exquisitely time interceptive actions, and provide key insights into the ontogeny of this fundamental motor ability

Variable-Drift Diffusion Models of Pedestrian Road-Crossing Decisions

Peer reviewe

A new topological insulator built from quasi one-dimensional atomic ribbons

A novel topological insulator with orthorhombic crystal structure is demonstrated. It is characterized by quasi one-dimensional, conducting atomic chains instead of the layered, two-dimensional sheets known from the established Bi2(Se,Te)3 system. The Sb-doped Bi2Se3 nanowires are grown in a TiO2-catalyzed process by chemical vapor deposition. The binary Bi2Se3 is transformed from rhombohedral to orthorhombic by substituting Sb on ∼38% of the Bi sites. Pure Sb2Se3 is a topologically trivial band insulator with an orthorhombic crystal structure at ambient conditions, and it is known to transform into a topological insulator at high pressure. Angle-resolved photoemission spectroscopy shows a topological surface state, while Sb doping also tunes the Fermi level to reside in the bandgap

Understanding and tackling snakebite envenoming with transdisciplinary research

Snakebite envenoming (SBE) is a neglected tropical disease (NTD) of high global impact. The World Health Organization (WHO) estimates 4.5 to 5.4 million people are bitten by snakes annually, resulting in 1.8 to 2.7 million envenomings, 81,000 to 138,000 deaths, and at least 400,000 people suffering from physical or psychological sequelae. SBE mostly affects impoverished rural populations in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, thus fueling a vicious cycle of poverty and illness. SBE not only affects humans, but also domestic animals, including livestock, with negative social and economic consequences. This requires a better understanding of the complex social, cultural, and ecological contexts where SBE occurs, within the conceptual frame of One Health, an integrated approach that recognizes the health of humans, animals, and the environment as closely linked and interdependent. Such complexity demands more integrative approaches for better understanding and confronting this disease. SBE has unique features that make its prevention and control challenging. Unlike many infectious diseases, SBE cannot be eradicated, but its incidence and impact can be reduced through effective programs aimed at better prevention and rapid access to treatment. This in turn demands the engagement of communities to improve the cohabitation of humans, domestic animals, and snakes in rural agroecosystems. In 2019, the WHO launched a strategy for the prevention and control of SBE, aimed at halving the deaths and disabilities caused by this NTD by the year 2030. This strategy is based on 4 pillars, i.e., empower and engage communities; ensure safe, effective treatment; strengthen health systems; and increase partnerships, coordination, and resources. Building on previous ideas and publications, this article discusses and advocates for transdisciplinary research on SBE and for promoting dialogue and collaboration between sectors, particularly by engaging communities affected by SBE at all levels of the research process

Understanding and tackling snakebite envenoming with transdisciplinary research

Snakebite envenoming (SBE) is a neglected tropical disease (NTD) of high global impact. The World Health Organization (WHO) estimates 4.5 to 5.4 million people are bitten by snakes annually, resulting in 1.8 to 2.7 million envenomings, 81,000 to 138,000 deaths, and at least 400,000 people suffering from physical or psychological sequelae. SBE mostly affects impoverished rural populations in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, thus fueling a vicious cycle of poverty and illness. SBE not only affects humans, but also domestic animals, including livestock, with negative social and economic consequences. This requires a better understanding of the complex social, cultural, and ecological contexts where SBE occurs, within the conceptual frame of One Health, an integrated approach that recognizes the health of humans, animals, and the environment as closely linked and interdependent. Such complexity demands more integrative approaches for better understanding and confronting this disease. SBE has unique features that make its prevention and control challenging. Unlike many infectious diseases, SBE cannot be eradicated, but its incidence and impact can be reduced through effective programs aimed at better prevention and rapid access to treatment. This in turn demands the engagement of communities to improve the cohabitation of humans, domestic animals, and snakes in rural agroecosystems. In 2019, the WHO launched a strategy for the prevention and control of SBE, aimed at halving the deaths and disabilities caused by this NTD by the year 2030. This strategy is based on 4 pillars, i.e., empower and engage communities; ensure safe, effective treatment; strengthen health systems; and increase partnerships, coordination, and resources. Building on previous ideas and publications, this article discusses and advocates for transdisciplinary research on SBE and for promoting dialogue and collaboration between sectors, particularly by engaging communities affected by SBE at all levels of the research process

Red clover (Trifolium pratense L.) draft genome provides a platform for trait improvement

Red clover (Trifolium pratense L.) is a globally significant forage legume in pastoral livestock farming systems. It is an attractive component of grassland farming, because of its high yield and protein content, nutritional value and ability to fix atmospheric nitrogen. Enhancing its role further in sustainable agriculture requires genetic improvement of persistency, disease resistance, and tolerance to grazing. To help address these challenges, we have assembled a chromosome-scale reference genome for red clover. We observed large blocks of conserved synteny with Medicago truncatula and estimated that the two species diverged ~23 million years ago. Among the 40,868 annotated genes, we identified gene clusters involved in biochemical pathways of importance for forage quality and livestock nutrition. Genotyping by sequencing of a synthetic population of 86 genotypes show that the number of markers required for genomics-based breeding approaches is tractable, making red clover a suitable candidate for association studies and genomic selection

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research