Modular pipeline for reconstruction and localization of implanted intracranial ECoG and sEEG electrodes.

Implantation of electrodes in the brain has been used as a clinical tool for decades to stimulate and record brain activity. As this method increasingly becomes the standard of care for several disorders and diseases, there is a growing need to quickly and accurately localize the electrodes once they are placed within the brain. We share here a protocol pipeline for localizing electrodes implanted in the brain, which we have applied to more than 260 patients, that is accessible to multiple skill levels and modular in execution. This pipeline uses multiple software packages to prioritize flexibility by permitting multiple different parallel outputs while minimizing the number of steps for each output. These outputs include co-registered imaging, electrode coordinates, 2D and 3D visualizations of the implants, automatic surface and volumetric localizations of the brain regions per electrode, and anonymization and data sharing tools. We demonstrate here some of the pipeline's visualizations and automatic localization algorithms which we have applied to determine appropriate stimulation targets, to conduct seizure dynamics analysis, and to localize neural activity from cognitive tasks in previous studies. Further, the output facilitates the extraction of information such as the probability of grey matter intersection or the nearest anatomic structure per electrode contact across all data sets that go through the pipeline. We expect that this pipeline will be a useful framework for researchers and clinicians alike to localize implanted electrodes in the human brain.

Peptide Biomaterials for Tissue Regeneration.

Expanding the toolbox of therapeutic materials for soft tissue and organ repair has become a critical component of tissue engineering. While animal- and plant-derived proteins are the foundation for developing biomimetic tissue constructs, using peptides as either constituents or frameworks for the materials has gained increasing momentum in recent years. This mini review discusses recent advances in peptide-based biomaterials' design and application. We also discuss some of the future challenges posed and opportunities opened by peptide-based structures in the field of tissue engineering and regenerative medicine.

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.

Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.

The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication.

The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. We found that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed histone H3 lysine 27 monomethylation in plants depends on H3.1, TSK, and DNA polymerase theta (Pol θ). This work reveals an H3.1-specific function during replication and a common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone monomethyltransferases and reading of the H3.1 variant.

Nanoengineered Sprayable Therapy for Treating Myocardial Infarction.

We report the development, as well as the in vitro and in vivo testing, of a sprayable nanotherapeutic that uses surface engineered custom-designed multiarmed peptide grafted nanogold for on-the-spot coating of an infarcted myocardial surface. When applied to mouse hearts, 1 week after infarction, the spray-on treatment resulted in an increase in cardiac function (2.4-fold), muscle contractility, and myocardial electrical conductivity. The applied nanogold remained at the treatment site 28 days postapplication with no off-target organ infiltration. Further, the infarct size in the mice that received treatment was found to be <10% of the total left ventricle area, while the number of blood vessels, prohealing macrophages, and cardiomyocytes increased to levels comparable to that of a healthy animal. Our cumulative data suggest that the therapeutic action of our spray-on nanotherapeutic is highly effective, and in practice, its application is simpler than other regenerative approaches for treating an infarcted heart.

Mimicking biofilm formation and development: Recent progress in in vitro and in vivo biofilm models.

Biofilm formation in living organisms is associated to tissue and implant infections, and it has also been linked to the contribution of antibiotic resistance. Thus, understanding biofilm development and being able to mimic such processes is vital for the successful development of antibiofilm treatments and therapies. Several decades of research have contributed to building the foundation for developing in vitro and in vivo biofilm models. However, no such thing as an "all fit" in vitro or in vivo biofilm models is currently available. In this review, in addition to presenting an updated overview of biofilm formation, we critically revise recent approaches for the improvement of in vitro and in vivo biofilm models.

A low cost and open access system for rapid synthesis of large volumes of gold and silver nanoparticles.

Rapid synthesis of nanomaterials in scalable quantities is critical for accelerating the discovery and commercial translation of nanoscale-based technologies. The synthesis of metal nanogold and silver in volumes larger than 100 mL is not automatized and might require of the use of harsh conditions that in most cases is detrimental for the production of nanoparticles with reproducible size distributions. In this work, we present the development and optimization of an open-access low-cost NanoParticle Flow Synthesis System (NPFloSS) that allows for the rapid preparation of volumes of up to 1 L of gold and silver nanoparticle aqueous solutions.

Consensus on a video analysis framework of descriptors and definitions by the Rugby Union Video Analysis Consensus group.

Using an expert consensus-based approach, a rugby union Video Analysis Consensus (RUVAC) group was formed to develop a framework for video analysis research in rugby union. The aim of the framework is to improve the consistency of video analysis work in rugby union and help enhance the overall quality of future research in the sport. To reach consensus, a systematic review and Delphi method study design was used. After a systematic search of the literature, 17 articles were used to develop the final framework that described and defined key actions and events in rugby union (rugby). Thereafter, a group of researchers and practitioners with experience and expertise in rugby video analysis formed the RUVAC group. Each member of the group examined the framework of descriptors and definitions and rated their level of agreement on a 5-point agreement Likert scale (1: strongly disagree; 2: disagree; 3: neither agree or disagree; 4: agree; 5: strongly agree). The mean rating of agreement on the five-point scale (1: strongly disagree; 5: strongly agree) was 4.6 (4.3-4.9), 4.6 (4.4-4.9), 4.7 (4.5-4.9), 4.8 (4.6-5.0) and 4.8 (4.6-5.0) for the tackle, ruck, scrum, line-out and maul, respectively. The RUVAC group recommends using this consensus as the starting framework when conducting rugby video analysis research. Which variables to use (if not all) depends on the objectives of the study. Furthermore, the intention of this consensus is to help integrate video data with other data (eg, injury surveillance).

Self-Neglect in Older Populations: A Description and Analysis of Current Approaches.

Self-neglect in old age has severe effects on a person's health and quality of life and poses diverse challenges for primary caregivers and the community. The authors provide a narrative overview of the literature on self-neglect and summarize what is known to date about the main approaches for describing self-neglect, the factors that contribute to self-neglect, and the interventions that have been attempted. We found that answering the question about what factors led people into a state of self-neglect was extremely complex since many studies described a variety of interlinked factors, some of which are sociocultural and others medical. Our analysis suggested a need for a consolidated approach that focuses instead on the vulnerabilities affecting an older person and the factors that can improve resilience to adversity. Tackling vulnerability and resilience may hold the keys to successful multidisciplinary and person-centered management of self-neglect in older age.

Changes in mechanical properties of sprinting during repeated sprint in elite rugby sevens athletes.

This study aimed to analyse fatigue-induced changes in mechanical sprinting properties during a specific repeated-sprint test in elite rugby sevens athletes. Twenty elite rugby sevens players performed ten 40 m sprints on a 30 s cycle with participant's running back and forth in a marked lane. Radar was used to assess maximal overground sprint performance over each 40 m. Macroscopic mechanical properties (maximal horizontal force (F0), maximal horizontal power (Pmax), maximal ratio of horizontal force (RFpeak), decrease in the ratio of horizontal-to-total force (DRF), total force and maximal sprinting velocity (v0)) were drawn from horizontal force velocity relationships, using a validated method applied to the speed-time data. Fatigue-induced changes were analysed comparing the first sprint to an average of 2nd-4th, 5th-7th and 8th-10th. Repeated-sprint ability (RSA) testing induced substantial changes in the maximal velocity component, with a decrease (-15%) in v0 (effect size (ES) = -2.46 to -4.98), and to a lower extent (-5.9%) in the maximal force component F0 (ES = -0.59). DRF moderately decreased (14%; ES=-0.76-1.11), and RFpeak largely decreased in the later sprints (ES = -0.32 to -1.27). Fatigue observed in this RSA test appeared to have a greater effect on the technical ability to produce horizontal force at high velocities, likely due to an alteration in the ability to maintain horizontally oriented force application when velocity increases rather than during the initial acceleration phase, but also the overall force production capacity. The ability to maintain forward-oriented force at high velocities is of central importance for identifying fatigue and monitoring load.

High quality clinical grade human embryonic stem cell lines derived from fresh discarded embryos.

BACKGROUND: Human embryonic stem cells (hESCs) hold tremendous promise for cell replacement therapies for a range of degenerative diseases. In order to provide cost-effective treatments affordable by public health systems, HLA-matched allogeneic tissue banks of the highest quality clinical-grade hESCs will be required. However only a small number of existing hESC lines are suitable for clinical use; they are limited by moral and ethical concerns and none of them apply Good Manufacturing Practice (GMP) standards to the earliest and critical stages of gamete and embryo procurement. We thus aimed to derive new clinical grade hESC lines of highest quality from fresh surplus GMP grade human embryos. METHODS: A comprehensive screen was performed for suitable combinations of culture media with supporting feeder cells or feeder-free matrix, at different stages, to support expansion of the inner cell mass and to establish new hESC lines. RESULTS: We developed a novel two-step and sequential media system of clinical-grade hESC derivation and successfully generated seven new hESC lines of widely varying HLA type, carefully screened for genetic health, from human embryos donated under the highest ethical and moral standards under an integrated GMP system which extends from hESC banking all the way back to gamete and embryo procurement. CONCLUSIONS: The present study, for the first time, reports the successful derivation of highest-quality clinical-grade hESC lines from fresh poor-quality surplus human embryos generated in a GMP-grade IVF laboratory. The availability of hESC lines of this status represents an important step towards more widespread application of regenerative medicine therapies.

Medical and Assistive Health Technology: Meeting the Needs of Aging Populations.

PURPOSE OF THE STUDY: To identify policy gaps in the delivery and availability of assistive health technology (AHT) and medical devices (MD) for aging populations, particularly in low- and middle-income countries (LMICs). DESIGN AND METHODS: The findings presented in this paper are the results of several narrative overviews. They provide a contextual analysis of the conclusions and evidence from WHO commissioned research and expert consultations in 2013 and 2014, as well as a synthesis of literature reviews conducted on AHT and MD. RESULTS: Practical, life-enhancing support for older people through AHT, MD, and related health and social services is a neglected issue. This is particularly so in LMICs where the biggest increases in aging populations are occurring, and yet where there is commonly little or no access to these vital components of healthy aging. IMPLICATIONS: Health technologies, especially medical and assistive health technology, are essential to ensure older people's dignity and autonomy, but their current and potential benefits have received little recognition in LMICs. Viewing these technologies as relevant only to disabled people is an inadequate approach. They should be accessible to both older adults with disabilities and older adults with functional limitation. Many countries need much greater official awareness of older adults' needs and preferences. Such attitudinal changes should then be reflected in laws and regulations to address the specificities of care for older people.

A world of cities and the end of TB.

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB.

Metrics in Urban Health: Current Developments and Future Prospects.

The research community has shown increasing interest in developing and using metrics to determine the relationships between urban living and health. In particular, we have seen a recent exponential increase in efforts aiming to investigate and apply metrics for urban health, especially the health impacts of the social and built environments as well as air pollution. A greater recognition of the need to investigate the impacts and trends of health inequities is also evident through more recent literature. Data availability and accuracy have improved through new affordable technologies for mapping, geographic information systems (GIS), and remote sensing. However, less research has been conducted in low- and middle-income countries where quality data are not always available, and capacity for analyzing available data may be limited. For this increased interest in research and development of metrics to be meaningful, the best available evidence must be accessible to decision makers to improve health impacts through urban policies.

The achievement of public health services in pharmacy practice: A literature review.

BACKGROUND: It is known that pharmacists are currently contributing to public health; however, the extent of this contribution as reported in the literature has not been examined. Investigating the ways that pharmacists are currently participating in public health is critical for the profession of pharmacy, pharmacy educators, and the public health community. OBJECTIVES: The purpose of this study was to determine the reported contributions of pharmacy to each of the ten essential services of public health, and which of the five core competencies of public health were most frequently utilized in those contributions. METHODS: A PubMed search was used to extract references that included both the words pharmacy and services in the title or abstract, and the words public health in any part of the document. A total of 247 references were extracted and categorized into the essential services and core competencies. RESULTS: The essential services Inform, Educate, and Empower, and Link to/Provide Care were more frequently represented in the literature, and the core competency of Health Policy and Administration was most frequently utilized. CONCLUSION: To further contribute to and integrate their contributions within population health, pharmacists must consider ways to strategically contribute to the essential services of public health and seek to increase competency in public health.

Assistive technologies for ageing populations in six low-income and middle-income countries: a systematic review.

Despite the benefits derived from the use of assistive technologies (AT), some parts of the world have minimal or no access to AT. In many low-income and middle-income countries (LMIC), only 5-15% of people who require AT have access to them. Rapid demographic changes will exacerbate this situation as populations over 60 years of age, as well as functional limitations among older populations, in LMIC are expected to be higher than in high-income countries in the coming years. Given both these trends, AT are likely to be in high demand and provide many benefits to respond to challenges related to healthy and productive ageing. Multiple databases were searched for English literature. Three groups of keywords were combined: those relating to AT, ageing population and LMIC selected for this study, namely Brazil, Cambodia, Egypt, India, Turkey and Zimbabwe. These countries are expected to see the most rapid growth in the 65 and above population in the coming years. Results indicate that all countries had AT designed for older adults with existing impairment and disability, but had limited AT that are designed to prevent impairment and disability among older adults who do not currently have any disabilities. All countries have ratified the UN Convention on the Rights of Persons with Disabilities. The findings conclude that AT for ageing populations have received some attention in LMIC as attested by the limited literature results. Analysis of review findings indicate the need for a comprehensive, integrated health and social system approach to increase the current availability of AT for ageing populations in LMIC. These would entail, yet not be limited to, work on: (1) promoting initiatives for low-cost AT; (2) awareness raising and capacity building on AT; (3) bridging the gap between AT policy and practice; and (4) fostering targeted research on AT.

Prioritizing action on health inequities in cities: An evaluation of Urban Health Equity Assessment and Response Tool (Urban HEART) in 15 cities from Asia and Africa.

Following the recommendations of the Commission on Social Determinants of Health (2008), the World Health Organization (WHO) developed the Urban Health Equity Assessment and Response Tool (HEART) to support local stakeholders in identifying and planning action on health inequities. The objective of this report is to analyze the experiences of cities in implementing Urban HEART in order to inform how the future development of the tool could support local stakeholders better in addressing health inequities. The study method is documentary analysis from independent evaluations and city implementation reports submitted to WHO. Independent evaluations were conducted in 2011-12 on Urban HEART piloting in 15 cities from seven countries in Asia and Africa: Indonesia, Iran, Kenya, Mongolia, Philippines, Sri Lanka, and Vietnam. Local or national health departments led Urban HEART piloting in 12 of the 15 cities. Other stakeholders commonly engaged included the city council, budget and planning departments, education sector, urban planning department, and the Mayor's office. Ten of the 12 core indicators recommended in Urban HEART were collected by at least 10 of the 15 cities. Improving access to safe water and sanitation was a priority equity-oriented intervention in 12 of the 15 cities, while unemployment was addressed in seven cities. Cities who piloted Urban HEART displayed confidence in its potential by sustaining or scaling up its use within their countries. Engagement of a wider group of stakeholders was more likely to lead to actions for improving health equity. Indicators that were collected were more likely to be acted upon. Quality of data for neighbourhoods within cities was one of the major issues. As local governments and stakeholders around the world gain greater control of decisions regarding their health, Urban HEART could prove to be a valuable tool in helping them pursue the goal of health equity.

The match demands of international rugby sevens.

The purpose of this study was to quantify the global match demands of international rugby sevens and to compare the match demands of forwards and backs, and between tournament rounds. To assess the match demands, global positioning system (GPS) and video analysis were collected from 27 international rugby sevens players from the same team across an entire International Rugby Board Sevens World Series season. Differences in running demands and match activities between forwards and backs were mostly trivial and small (ES = 0.05-0.84) while differences in running demands and match activities between Pool and Cup rounds were trivial (ES = 0.001-0.12). Cup round matches showed an increase in long-duration ball-in-play sequences (proportion ratio 0.46). These findings suggest international rugby sevens forwards and backs experience similar match demands while overall match demands remain consistent across tournament rounds.