Comparative quasi-static mechanical characterization of fresh and stored porcine trachea specimens

Abstract: Tissues of the upper airways of critically ill patients are particularly vulnerable to mechanical damage associated with the use of ventilators. Ventilation is known to disrupt the structural integrity of respiratory tissues and their function. This damage contributes to the vulnerability of these tissues to infection. We are currently developing tissue models of damage and infection to the upper airways. As part of our studies, we have compared how tissue storage conditions affect mechanical properties of excised respiratory tissues using a quasi-static platform. Data presented here show considerable differences in mechanical responses of stored specimens compared to freshly excised specimens. These data indicate that implementation of storage and maintenance procedures that minimize rapid degradation of tissue structure are essential for retaining the material properties in our tissue trauma models

Electrical stimulation devices for the prevention of venous thromboembolism: Preliminary studies of physiological efficacy and user satisfaction.

Introduction: Electrical stimulation could provide an alternative method for preventing venous thromboembolism in stroke patients. The purpose of this preliminary study was to explore the effects of electrical stimulation and intermittent pneumatic compression on enhancing lower limb venous return in healthy and chronic stroke patients and also to evaluate patient and nurse satisfaction. Methods: We investigated the effectiveness of two electrical stimulation devices: Geko (Firstkind Ltd, High Wycombe, UK) and Orthopaedic Microstim 2V2 (Odstock Medical Ltd, Salisbury, UK); and one intermittent pneumatic compression device: Huntleigh Flowstron Universal (Huntleigh Healthcare Ltd, Cardiff, UK). We recruited 12 healthy and 5 chronic stroke participants. The devices were fitted sequentially, and Doppler ultrasound measurements were taken. Eight patients and nurses were also recruited for a separate usability evaluation. Results: The electrical stimulation devices emulated the blood flow characteristics of intermittent pneumatic compression in both healthy and stroke participants provided that the intensity of electrical stimulation was sufficient. Patients and nurses also felt that the electrical stimulation devices were acceptable. Conclusions: Electrical stimulation may offer benefit as an alternative method for venous thromboembolism prevention in stroke patients. The apparent benefit is sufficient to warrant further investigation in a full powered randomised controlled trial

The influence of parents and the home environment on preschoolers' physical activity behaviours: A qualitative investigation of childcare providers' perspectives

<p>Abstract</p> <p>Background</p> <p>Physical activity offers numerous physiological and psychological benefits for young children; however, many preschool-aged children are not engaging in sufficient activity. The home environment, inclusive of parent role modeling, has been identified as influencing preschoolers' physical activity. This study sought to examine childcare providers' perspectives of the importance of parents and the home environment for supporting the physical activity behaviours of preschool-aged children (aged 2.5-5 years) attending childcare.</p> <p>Methods</p> <p>A heterogeneous sample of childcare providers (<it>n </it>= 84; response rate 39%) working at childcare facilities in London, Ontario participated. Thirteen semi-structured focus groups were conducted in London centres between February 2009 and February 2010. Focus groups were audio recorded and transcribed verbatim and inductive content analysis was used to code and classify themes. A number of strategies were used to verify the trustworthiness of the data.</p> <p>Results</p> <p>Childcare providers acknowledged their reliance on parents/guardians to create a home environment that complements the positive physical activity messaging children may receive in childcare. Moreover, childcare staff highlighted the need for positive parent role modeling and parent support to encourage active healthy lifestyles among young children.</p> <p>Conclusion</p> <p>This study's findings highlight the need for increased parent-caregiver partnering in terms of communication and cooperation in service of promoting appropriate amounts of physical activity among London preschoolers.</p

MadingleyR: An R package for mechanistic ecosystem modelling

Abstract: Aim: Mechanistic general ecosystem models are used to explore fundamental ecological dynamics and to assess possible consequences of anthropogenic and natural disturbances on ecosystems. The Madingley model is a mechanistic general ecosystem model (GEM) that simulates a coherent global ecosystem, consisting of photo‐autotrophic and heterotrophic life, based on fundamental ecological processes. The C++ implementation of the Madingley model delivers fast computational performance, but it (a) limits the userbase to researchers that are familiar with the intricacies of C++ programming, (b) has limited possibility to change model settings and provide model outputs required to address specific research questions, and (c) has limited reproducibility of simulation experiments. The aim of this paper is to present an R package of the Madingley model to aid with increasing the accessibility and flexibility of the model. Innovation: The MadingleyR R package streamlines the installation procedure and supports all major operating systems. MadingleyR enables users to combine multiple consecutive simulations, making case study specific modifications to MadingleyR objects along the way. Default input files are available from the package and study‐specific inputs can be easily loaded from the R environment. MadingleyR also provides functions to plot and summarize MadingleyR outputs. We provide a comprehensive description of the MadingleyR functions and workflow. We also demonstrate the applicability of the MadingleyR package using three case studies: (a) simulating the cascading effects of the loss of mega‐herbivores on food‐web structure, (b) simulating the impacts of increased land‐use intensity on the total biomass of different feeding guilds by restricting the total vegetation biomass available for feeding and (c) simulating the impacts of an intensive land‐use scenario on a continental scale. Main conclusions: The MadingleyR package provides direct accessibility to simulations with the mechanistic ecosystem model Madingley and is flexible in its application without a loss in performance

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

The effects of knee joint angle on neuromuscular activity during electrostimulation in healthy older adults

Introduction Electrostimulation devices stimulate the common peroneal nerve, producing a calf muscle-pump action to promote venous circulation. Whether knee joint angle influences calf neuromuscular activity remains unclear. Our aim was to determine the effects of knee joint angle on lower limb neuromuscular activity during electrostimulation. Methods Fifteen healthy, older adults underwent 60 min of electrostimulation, with the knee joint at three different angles (0°, 45° or 90° flexion; random order; 20 min each). Outcome variables included electromyography of the peroneus longus, tibialis anterior and gastrocnemius medialis and lateralis and discomfort. Results Knee angle did not influence tibialis anterior and peroneus longus neuromuscular activity during electrostimulation. Neuromuscular activity was greater in the gastrocnemius medialis (p = 0.002) and lateralis (p = 0.002) at 90°, than 0° knee angle. Electrostimulation intensity was positively related to neuromuscular activity for each muscle, with a knee angle effect for the gastrocnemius medialis (p = 0.05). Conclusion Results suggest that during electrostimulation, knee joint angle influenced gastrocnemii neuromuscular activity; increased gastrocnemius medialis activity across all intensities (at 90°), when compared to 0° and 45° flexion; and did not influence peroneus longus and tibialis anterior activity. Greater electrostimulation-evoked gastrocnemii activity has implications for producing a more forceful calf muscle-pump action, potentially further improving venous flow

Plastic Pollution and Small Juvenile Marine Turtles: A Potential Evolutionary Trap

The ingestion of plastic by marine turtles is now reported for all species. Small juvenile turtles (including post-hatchling and oceanic juveniles) are thought to be most at risk, due to feeding preferences and overlap with areas of high plastic abundance. Their remote and dispersed life stage, however, results in limited access and assessments. Here, stranded and bycaught specimens from Queensland Australia, Pacific Ocean (PO;n = 65; 1993–2019) and Western Australia, Indian Ocean (IO; n = 56; 2015–2019) provide a unique opportunity to assess the extent of plastic (> 1mm) ingestion in five species [green (Chelonia mydas), loggerhead (Caretta caretta), hawksbill (Eretmochelys imbricata), olive ridley (Lepidochelys olivacea), and flatback turtles (Natator depressus)]. In the Pacific Ocean, high incidence of ingestion occurred in green (83%; n = 36), loggerhead (86%; n = 7), flatback (80%; n = 10) and olive ridley turtles (29%; n = 7). There was an overall lower incidence in IO; highest being in the flatback (28%; n = 18), the loggerhead (21%; n = 14) and green (9%; n = 22). No macroplastic debris ingestion was documented for hawksbill turtles in either site although sample sizes were smaller for this species (PO n = 5; IO n = 2). In the Pacific Ocean, the majority of ingested debris was made up of hard fragments (mean of all species 52%; species averages 46–97%), whereas for the Indian Ocean these were filamentous plastics (52%; 43–77%). The most abundant colour for both sites across all species was clear (PO: 36%; IO: 39%), followed by white for PO (36%) then green and blue for IO (16%; 16%). The polymers most commonly ingested by turtles in both oceans were polyethylene (PE; PO-58%; IO-39%) and polypropylene (PP; PO-20.2%; IO-23.5%). We frame the high occurrence of ingested plastic present in this marine turtle life stage as a potential evolutionary trap as they undertake their development in what are now some of the most polluted areas of the global oceans

Phenotype Prediction Using Regularized Regression on Genetic Data in the DREAM5 Systems Genetics B Challenge

A major goal of large-scale genomics projects is to enable the use of data from high-throughput experimental methods to predict complex phenotypes such as disease susceptibility. The DREAM5 Systems Genetics B Challenge solicited algorithms to predict soybean plant resistance to the pathogen Phytophthora sojae from training sets including phenotype, genotype, and gene expression data. The challenge test set was divided into three subcategories, one requiring prediction based on only genotype data, another on only gene expression data, and the third on both genotype and gene expression data. Here we present our approach, primarily using regularized regression, which received the best-performer award for subchallenge B2 (gene expression only). We found that despite the availability of 941 genotype markers and 28,395 gene expression features, optimal models determined by cross-validation experiments typically used fewer than ten predictors, underscoring the importance of strong regularization in noisy datasets with far more features than samples. We also present substantial analysis of the training and test setup of the challenge, identifying high variance in performance on the gold standard test sets.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Defense Science and Engineering Graduate Fellowshi

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

BACKGROUND: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. METHODS AND FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. CONCLUSIONS: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions