A CNN cascade for landmark guided semantic part segmentation

This paper proposes a CNN cascade for semantic part segmentation guided by pose-specifc information encoded in terms of a set of landmarks (or keypoints). There is large amount of prior work on each of these tasks separately, yet, to the best of our knowledge, this is the first time in literature that the interplay between pose estimation and semantic part segmentation is investigated. To address this limitation of prior work, in this paper, we propose a CNN cascade of tasks that firstly performs landmark localisation and then uses this information as input for guiding semantic part segmentation. We applied our architecture to the problem of facial part segmentation and report large performance improvement over the standard unguided network on the most challenging face datasets. Testing code and models will be published online at http://cs.nott.ac.uk/~psxasj/

A Third Copy of the Down Syndrome Cell Adhesion Molecule ( Dscam ) Causes Synaptic and Locomotor Dysfunction in Drosophila

Down syndrome (DS) is caused by triplication of chromosome 21 (HSA21). It is characterised by intellectual disability and impaired motor coordination that arise from changes in brain volume, structure and function. However, the contribution of each HSA21 gene to these various phenotypes and to the causal alterations in neuronal and synaptic structure and function are largely unknown. Here we have investigated the effect of overexpression of the HSA21 gene DSCAM (Down syndrome cell adhesion molecule), on glutamatergic synaptic transmission and motor coordination, using Drosophila expressing three copies of Dscam1. Electrophysiological recordings of miniature and evoked excitatory junction potentials at the glutamatergic neuromuscular junction of Drosophila larvae showed that the extra copy of Dscam1 changed the properties of spontaneous and electrically-evoked transmitter release and strengthened short-term synaptic depression during high-frequency firing of the motor nerve. Behavioural analyses uncovered impaired locomotor coordination despite preserved gross motor function. This work identifies DSCAM as a candidate causative gene in DS that is sufficient to modify synaptic transmission and synaptic plasticity and cause a DS behavioural phenotype

Impaired Pre-Motor Circuit Activity and Movement in a Drosophila Model of KCNMA1-Linked Dyskinesia

BACKGROUND: Paroxysmal dyskinesias (PxDs) are characterized by involuntary movements and altered pre-motor circuit activity. Causative mutations provide a means to understand the molecular basis of PxDs. Yet in many cases, animal models harboring corresponding mutations are lacking. Here we utilize the fruit fly, Drosophila, to study a PxD linked to a gain-of-function (GOF) mutation in the KCNMA1/hSlo1 BK potassium channel. OBJECTIVES: We aimed to recreate the equivalent BK (big potassium) channel mutation in Drosophila. We sought to determine how this mutation altered action potentials (APs) and synaptic release in vivo; to test whether this mutation disrupted pre-motor circuit function and locomotion; and to define neural circuits involved in locomotor disruption. METHODS: We generated a knock-in Drosophila model using homologous recombination. We used electrophysiological recordings and calcium-imaging to assess AP shape, neurotransmission, and the activity of the larval pre-motor central pattern generator (CPG). We used video-tracking and automated systems to measure movement, and developed a genetic method to limit BK channel expression to defined circuits. RESULTS: Neuronal APs exhibited reduced width and an enhanced afterhyperpolarization in the PxD model. We identified calcium-dependent reductions in neurotransmitter release, dysfunction of the CPG, and corresponding alterations in movement, in model larvae. Finally, we observed aberrant locomotion and dyskinesia-like movements in adult model flies, and partially mapped the impact of GOF BK channels on movement to cholinergic neurons. CONCLUSION: Our model supports a link between BK channel GOF and hyperkinetic movements, and provides a platform to dissect the mechanistic basis of PxDs. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Diagnostic Impact of Repeated Expert Review & Long‐Term Follow‐Up in Determining Etiology of Idiopathic Cardiac Arrest

Background: Recognizing the etiology of sudden cardiac arrest (SCA) has an enormous impact on the management of victims and their immediate families. A significant proportion of SCA survivors with a structurally normal heart are not offered a diagnosis and there is no clear consensus on the type and duration of follow‐up. We aimed to assess the utility of a multidisciplinary approach in optimizing diagnosis of cardiac arrest etiology during follow‐up. Methods and Results: We retrospectively assessed 327 consecutive SCA survivors (mean age 61.9±16.2 years, 80% men) who underwent secondary prevention implantable cardioverter defibrillators between May 2015 and November 2018. The initial diagnosis was recorded at the time of admission and follow‐up diagnosis was deduced from subsequent clinic records, investigations, and outcomes of multidisciplinary team meetings. Structural heart disease accounted for 282 (86%) of SCAs. Forty‐five (14%) patients had a structurally normal heart and underwent comprehensive testing and follow‐up (mean duration 93±52 weeks). On initial evaluation, 14/45 (31%) of these received a diagnosis, rising to 29/45 (64%) with serial reviews during follow‐up. Discussion in multidisciplinary team meetings and imaging reassessment accounted for 47% of new diagnoses. No additional diagnoses were made beyond 96 weeks. Nineteen (5.8%) fatalities occurred in the entire cohort, exclusively in patients with structural heart disease. Conclusions: Systematic comprehensive testing combined with multidisciplinary expert team review of SCA survivors without structural heart disease improves the yield and time to diagnosis compared with previously published studies. This approach has positive implications in the management of SCA survivors and their families

Spatial connectivity in mosquito-borne disease models: a systematic review of methods and assumptions

This is the final version. Available from The Royal Society via the DOI in this record.Data extracted from the studies included in this systematic review are available from https://github.com/sophie-a-lee/mbd_connectivity_review and archived in a permanent repository on Zenodo (http://doi.org/10.5281/zenodo.4706866).Spatial connectivity plays an important role in mosquito-borne disease transmission. Connectivity can arise for many reasons, including shared environments, vector ecology and human movement. This systematic review synthesizes the spatial methods used to model mosquito-borne diseases, their spatial connectivity assumptions and the data used to inform spatial model components. We identified 248 papers eligible for inclusion. Most used statistical models (84.2%), although mechanistic are increasingly used. We identified 17 spatial models which used one of four methods (spatial covariates, local regression, random effects/fields and movement matrices). Over 80% of studies assumed that connectivity was distance-based despite this approach ignoring distant connections and potentially oversimplifying the process of transmission. Studies were more likely to assume connectivity was driven by human movement if the disease was transmitted by an Aedes mosquito. Connectivity arising from human movement was more commonly assumed in studies using a mechanistic model, likely influenced by a lack of statistical models able to account for these connections. Although models have been increasing in complexity, it is important to select the most appropriate, parsimonious model available based on the research question, disease transmission process, the spatial scale and availability of data, and the way spatial connectivity is assumed to occur.Engineering and Physical Sciences Research Council (EPSRC)The Royal Societ

Decolonising violence against women research: a study design for co-developing violence prevention interventions with communities in low and middle income countries (LMICs)

BACKGROUND: There has been substantial progress in research on preventing violence against women and girls (VAWG) in the last 20 years. While the evidence suggests the potential of well-designed curriculum-based interventions that target known risk factors of violence at the community level, this has certain limitations for working in partnership with communities in low- and middle-income (LMIC) countries, particularly when it comes to addressing the power dynamics embedded within north-south research relationships. METHODS: As an alternative approach, we outline the study design for the EVE Project: a formative research project implemented in partnership with community-based researchers in Samoa and Amantaní (Peru) using a participatory co-design approach to VAWG prevention research. We detail the methods we will use to overcome the power dynamics that have been historically embedded in Western research practices, including: collaboratively defining and agreeing research guidelines before the start of the project, co-creating theories of change with community stakeholders, identifying local understandings of violence to inform the selection and measurement of potential outcomes, and co-designing VAWG prevention interventions with communities. DISCUSSION: Indigenous knowledge and ways of thinking have often been undermined historically by Western research practices, contributing to repeated calls for better recognition of Southern epistemologies. The EVE Project design outlines our collective thinking on how to address this gap and to further VAWG prevention through the meaningful participation of communities affected by violence in the research and design of their own interventions. We also discuss the significant impact of the COVID-19 pandemic on the project in ways that have both disrupted and expanded the potential for a better transfer of power to the communities involved. This article offers specific strategies for integrating Southern epistemologies into VAWG research practices in four domains: ethics, theories of change, measurement, and intervention design. Our aim is to create new spaces for engagement between indigenous ways of thinking and the evidence that has been established from the past two decades of VAWG prevention research and practice

Effect of climate change, connectivity, and socioeconomic factors on the expansion of the dengue virus transmission zone in 21st century Brazil: an ecological modelling study

This is the final version. Available on open access from Elsevier via the DOI in this record.2021 Planetary Health Annual Meeting and Festival, 25 - 30 April 2021. VirtualBackground Globally, incidence of dengue fever has increased more than 30-times in the past 50 years, with outbreaks becoming frequent in tropical and subtropical countries. This rapid emergence has been attributed to increased urbanisation, globalisation, international mobility, and climate change. Brazil is endemic to all four dengue virus serotypes with outbreaks occurring in every region of the country. Previous studies identified geographical barriers to dengue diffusion, with some regions of Brazil being relatively protected from outbreaks. These regions included areas in the south of the country where seasonal temperatures were too cold for vectors to efficiently transmit the virus, regions of the western Amazon that were isolated from infectious hosts and vectors, and mountainous regions of southeast Brazil. Methods In this ecological modelling study, we used a Bayesian spatiotemporal model to understand the effect of climate variation, connectivity between cities, and socioeconomic factors, such as urbanisation, on the expansion of the permanent dengue virus transmission zone in Brazil. We obtained monthly dengue fever case data from 5560 municipalities in Brazil for 2001–19 from the Notifiable Diseases Information System (SINAN) surveillance system. The model was fitted to an outbreak indicator defined as exceeding 300 cases per 100 000 inhabitants per year. Fixed effects included climate suitability and hydrometeorological variables obtained from the Climate Research Unit (University of East Anglia, Norwich, UK), the level of influence of a city from the Brazilian Regiōes de Influência das Cidades study, and socioeconomic factors, such as urbanisation, from census data. Spatiotemporal random effects were included to account for unobserved heterogeneity, spatial autocorrelation, and temporal trends. Findings Data from the past 10 years showed that pre-identified geographical barriers to dengue virus transmission are being eroded or destroyed completely. The emergence of dengue fever outbreaks in south Brazil coincided with an increase in the number of months per year with temperatures suitable for transmission. Interpretation Understanding the factors that lead to the erosion of barriers to dengue virus transmission will help identify regions at risk of future outbreaks, and improve public health preparedness to emerging and re-emerging diseases.Royal Societ

Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.

Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME

Biometrics in forensic science: challenges, lessons and new technologies

Biometrics has historically found its natural mate in Forensics. The first applications found in the literature and over cited so many times, are related to biometric measurements for the identification of multiple offenders from some of their biometric and anthropometric characteristics (tenprint cards) and individualization of offender from traces found on crime-scenes (e.g. fingermarks, earmarks, bitemarks, DNA). From sir Francis Galton, to the introduction of AFIS systems in the scientific laboratories of police departments, Biometrics and Forensics have been "dating" with alternate results and outcomes. As a matter of facts there are many technologies developed under the "Biometrics umbrella" which may be optimised to better impact several Forensic scenarios and criminal investigations. At the same time, there is an almost endless list of open problems and processes in Forensics which may benefit from the introduction of tailored Biometric technologies. Joining the two disciplines, on a proper scientific ground, may only result in the success for both fields, as well as a tangible benefit for the society. A number of Forensic processes may involve Biometric-related technologies, among them: Evidence evaluation, Forensic investigation, Forensic Intelligence, Surveillance, Forensic ID management and Verification.\ud The COST Action IC1106 funded by the European Commission, is trying to better understand how Biometric and Forensics synergies can be exploited within a pan-European scientific alliance which extends its scope to partners from USA, China and Australia.\ud Several results have been already accomplished pursuing research in this direction. Notably the studies in 2D and 3D face recognition have been gradually applied to the forensic investigation process. In this paper a few solutions will be presented to match 3D face shapes along with some experimental results