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Today, the construction industry is continuously looking for lighter and high strength concrete (HSC) beams especially for high rise building. This research reported the effect of different positions of hollow section on the HSC beam containing eggshell powder (ESP) as partial cement replacement and tire crumb (TC) as partial sand replacement. Sustainable and high strength concrete is now widely used as a structural component like beam, slab and wall due to environmental impact. The hollow section also can reduce the dead loads which contribute to seismic effect in high rise buildings. Furthermore, eggshell is an agricultural waste that is generally considered worthless and is mostly disposed of because it leads to pollution, but it has similar properties as lime that used to be raw material to produce cement. In this study, 10% TC is used as partial sand replacement to produce a green concrete to make it more sustainable in construction. The experimental program consists of casting and testing high strength concrete beams of size 150 x 200 x 1500 mm with different positions of circular hollow sections. To study the flexural behaviour, all beams are tested after 28 days of curing subjected to four-points bending test in order to analyse the effect of different position of hollow section on the strength, deflection and mode of failure of HSC beam. Based on the experimental result, solid beam (SB) exhibits the higher strength with maximum loading of 156.45kN and flexural strength up to 39.11N/mm2. Besides, one hollow beam (OHB) and two vertical hollow beams (TVHB) show a better result in deflection compared to solid beam (SB). However, the two horizontal hollow beam (THHB) exhibits better performance in strength, with nearly 6.5% less than the SB. Conclusively, the position of the hollow beam affects the strength and deflection of the beam. All the beams experienced shear crack and flexural crack. The two horizontal hollow beams (THHB) can be used as a light structure beam of a building especially for the roof beam which receives less loading from the roof.

The emission of carbon dioxide by cement manufacturing has caused a negative impact on society and environment such as the greenhouse effect. Disposal of eggshell has created a lot of environmental problems due to its reusability of material is low in many industries. Recent years, researchers have found the value of eggshell due to its high content of calcium carbonate. Consequently, it has encouraged the researchers to incorporate the eggshell as cement replacement for concrete production hence contributing to sustainable development of building materials. This experimental study is aimed to investigate the optimum percentage of eggshell as cement replacement for high strength concrete (HSC) and the effect on HSC were studied in terms of workability, compressive strength and rebound hammer test as well as ultrasonic pulse velocity (UPV). Four types of mix proportion of HSC were prepared namely 0% ESP, 5% ESP, 10% ESP and 15% ESP. Based on the experiment results, the workability of the fresh concrete mixtures decreases as the percentage of eggshell replacement increases. Mix containing 10% eggshell specimen achieved the highest compressive strength of 68.4 MPa at 28 days. Furthermore, the 10% eggshell specimen also achieved the highest value of rebound number of 42.1 and pulse velocity of 6.50km/s at 28 days. Correlation between actual compressive strength and UPV was more reliable and had accurate expression through regression analysis compared to rebound hammer test. Conclusively, the concrete containing 10% eggshell as partial cement replacement exhibits higher compressive strength than control concrete has the potential to be used as construction material.

Redundancy is generally considered in the computer room air conditioners (CRACs) of the data center room. The position of the CRAC in the on state and the operating air volume have a great influence on the temperature distribution. The temperature distribution of the data center room will affect the failure rate of the servers and the energy consumption of the air-conditioning system. Taking a typical data center room as an example, this paper uses numerical simulation to study the influence of the on/off state and air volume of CRACs on the temperature distribution of the hot and cold aisles and energy consumption. The calculation results show that we should preferably turn off the staggered CRACs on the opposite side and close to the middle position under the partial load. When the IT load is unevenly distributed, it is irrational to use the setting method of even distribution of the air volume of each CRAC. The air volume of each CRAC should be appropriately adjusted based on the distribution characteristic of IT load to reduce the energy consumption.

Sustainable concrete is currently a widely studied topic in order to reduce the environmental impact of cement. Substitute materials are usually industrial and municipal wastes. Eggshell powder as cement replacement is a viable option to produce green concrete. At the same time, it improves the disposal of eggshell, which is thrown away as household waste and mostly ends up in the landfill. This paper reviews the constituents, production techniques and properties of eggshell concrete (ESC). The paper presents the chemical compound of eggshell and the suitability of the waste as cement replacement. This is followed by a discussion of the fresh, hardened and durability properties based on a variety of previous studies. At the optimal content of 10%, ESC has various advantages compared to conventional concrete. The advantages are associated with the high calcium content and good filling effect of eggshell powder. This includes improved hardened properties, reduced setting time, and increased resistance to water penetration and carbonation. Eggshell is also an accelerator to the hydration process. However, ESC shows weakness in chloride and sulphate environment due to the vulnerability of eggshell to these compounds. While studies on the material are available significantly, researches on durability properties of ESC should be enhanced.

Purpose To determine the prevalence of reticular pseudodrusen (RPD) and its association with age-related macular degeneration (AMD) and AMD risk factors in a large sample. Design Community-based cohort study in Melbourne, Victoria, Australia. Participants A total of 21130 participants 48 to 86 years of age available for ophthalmic assessment at follow-up from 2003 through 2007. Methods Lifestyle, diet, and anthropometric measurements were obtained at baseline and follow-up. At follow-up, digital macular color photographs were graded for early, intermediate, and late AMD as well as the presence of RPD. Data were analyzed using multinomial logistic regression controlling for age, gender, smoking, country of birth, and diet. Main Outcome Measures Detection of RPD based on color fundus photographs. Results Prevalence of RPD was 0.41% (87 of 21130 participants), with 51% having bilateral RPD. Patients with RPD were older compared with patients with large drusen (>125 μm; 76±4 vs. 68±9 years; P 125 μm) were associated with a higher prevalence of RPD. Presence of geographic atrophy (GA) was associated with the highest odds of having RPD (odds ratio [OR], 153; 95% confidence interval [CI], 53–442), followed by choroidal neovascularization (CNV; OR, 90; 95% CI, 26–310), intermediate AMD (OR, 33; 95% CI, 14–77), and early AMD (OR, 12; 95% CI, 5–31) compared with those with no AMD. The ARMS2 single nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs393955, rs1061170, and rs2274700 were associated with increased prevalence of RPD (all P Conclusions Reticular pseudodrusen are highly concurrent with AMD and have similar associations with known AMD risk factors such as age, gender, smoking, and genetic risk factors. Reticular pseudodrusen are associated more strongly with GA than with CNV. Although RPD are not specific to AMD, they are likely to be a strong risk factor for progression to late-stage AMD, similar to focal pigmentary abnormalities and large drusen.

This study aims at improving osseo-integration at the bone-implant interface of polyetheretherketone (PEEK) by water (H2O) and ammonia (NH3) plasma immersion ion implantation (PIII). The pertinent surface characteristics including surface energy, roughness, morphology, and chemical composition are investigated systematically and the in vitro biological performance is evaluated by cell adhesion and proliferation, alkaline phosphatase (ALP) activity, real-time RT-PCR evaluation, and mineralization tests. In vivo osseo-integration is examined via implanting samples into the distal femur of the rats. The hydrophilicity, surface roughness, cell adhesion, and proliferation, ALP activity, and osteogenic differentiation after H2O PIII or NH3 PIII are improved significantly. Furthermore, substantially enhanced osseo-integration is achieved in vivo. Nonline-of-sight plasma surface functionalization, which is particularly suitable for biomedical implants with an irregular geometry, does not alter the bulk compressive yield strength and elastic modulus of the materials. Consequently, the favorable bulk attributes of PEEK are preserved while the surface biological properties are enhanced thus boding well for wider orthopedic application of the biopolymer.

Cataract surgery in high myopes is challenging. Using third-generation intraocular lens (IOL) formulas, without adjustments, hyperopic refractive outcomes are common. We discuss these issues, focusing on the various lens formulas and transformations that have improved postoperative accuracy.Axial length measurement error has been largely overcome by the use of optical interferometry. Despite this, consistent hyperopic errors are still reported. We reviewed the postoperative refraction results compared with the predicted refractions using: standard formulas (Holladay 1, SRK/T, Hoffer Q, and Haigis) with manufacturers' optical lens constants, the User Group for Laser Interference Biometry (ULIB) constants, manufacturers' constants with axial length adjustment method, and fourth-generation IOL formulas (Barrett Universal II, Holladay 2, and Olsen).Improved predictive results is obtained with the Barrett Universal II (software constants), Haigis (ULIB), SRK/T, Holladay 2 (software constants), and Olsen (software constants) formulas in eyes with axial lengths greater than 26.0 mm and IOL powers greater than 6.0 D. In eyes with axial lengths greater than 26.0 mm and IOL less than 6.0 D, the Barrett Universal II formula (software constants) and the Haigis (axial length adjusted) and Holladay 1 formulas (axial length-adjusted) should be used.

We examine SMEs’ attitudes towards e-Business adoption from a multi-dimensional perspective to provide an understanding of the challenges and barriers to e-Business adoption in the SMEs context. We derive a framework containing the interaction among various elements that influence e-Business adoption. The framework was analysed with data from case studies involving Indonesian SMEs. Prior findings have shown the importance of e-Business for companies’ growth. However, we have extended this evidence by providing an understanding of issues that are important for e-Business adoption in the SMEs context. We have empirically established that e-Business adoption occurs through an interaction of various internal and external factors with owner-manager-related factors having the greatest influence on the outcome. The understanding of issues identified by this study will help policy makers, business owners, industry institutions, and other stakeholders to influence the uptake of e-Business among SMEs in Indonesia and elsewhere. Theoretical and practical implications are discussed.

Vegetation phenology and productivity play a crucial role in surface energy balance, plant and animal distribution, and animal movement and habitat use and can be measured with remote sensing metrics including start of season (SOS), peak instantaneous rate of green-up date (PIRGd), peak of season (POS), end of season (EOS), and integrated vegetation indices. However, for most metrics, we do not yet understand the agreement of remotely sensed data products with near-surface observations. We also need summaries of changes over time, spatial distribution, variability, and consistency in remote sensing dataset metrics for vegetation timing and quality. We compare metrics from 10 leading remote sensing datasets against a network of PhenoCam near-surface cameras throughout the western United States from 2002 to 2014. Most phenology metrics representing a date (SOS, PIRGd, POS, and EOS), rather than a duration (length of spring, length of growing season), better agreed with near-surface metrics but results varied by dataset, metric, and land cover, with absolute value of mean bias ranging from 0.38 (PIRGd) to 37.92 days (EOS). Datasets had higher agreement with PhenoCam metrics in shrublands, grasslands, and deciduous forests than in evergreen forests. Phenology metrics had higher agreement than productivity metrics, aside from a few datasets in deciduous forests. Using two datasets covering the period 1982–2016 that best agreed with PhenoCam metrics, we analyzed changes over time to growing seasons. Both datasets exhibited substantial spatial heterogeneity in the direction of phenology trends. Variability of metrics increased over time in some areas, particularly in the Southwest. Approximately 60% of pixels had consistent trend direction between datasets for SOS, POS, and EOS, with the direction varying by location. In all ecoregions except Mediterranean California, EOS has become later. This study comprehensively compares remote sensing datasets across multiple growing season metrics and discusses considerations for applied users to inform their data choices.

Objectives Chronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking. Methods We prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012–2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA. Results A total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L (milligrams of antigen-specific antibodies per liter) as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR 1.73; 95% CI 1.07–2.80), female sex (OR 1.49; 95% CI 1.14–1.95), old TB (OR 1.59; 1.05–2.42) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and four (2.1%) old TB patients developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942). Discussion Geographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using prespecified cut-off level.

To assess differences in the exposure, teaching, knowledge, appreciation, and interest in interventional radiology (IR) between male and female doctors prior to specialisation and to identify potential predisposing factors to the gender inequality in interventional radiology.A prospective cross-sectional multicentre study was conducted using in-person and web-based distribution of a voluntary, anonymous questionnaire to junior doctors yet to commence specialisation at 11 health services across two Australian states.Complete responses were provided by 333 junior doctors (21.9% response rate). Women were significantly less likely than men to consider a career in IR (13.1% versus 29.7%, p 0.001). No other statistically significant gender disparities were identified, as both men and women reported low levels of prior teaching and exposure to IR, strong belief in the importance of IR, and suboptimal knowledge of IR.The gender gap amongst practising Australian interventional radiologists is perpetuated by a consistent gender gap in upcoming junior doctors' desire to pursue IR. This disparity exists despite junior doctors receiving the same exposure and opportunities in interventional radiology, possibly suggesting that preconceived stereotypes or psychosocial factors deter females from pursuing this procedural, male-dominated subspecialty. Future qualitative studies are required to confirm this hypothesis, in conjunction with prospective, experimental trials to determine whether changes in education, mentorship, and advocacy can promote gender equality.

Keloids are abnormal scar formation that extends beyond the confines of the original injury. Immune cell infiltration is associated with keloid pathogenesis, but the exact mechanisms remain unknown. We aim to characterize the immune profile of keloid skin compared to normal skin in order to further understand the role of specific immune subsets in keloid formation. One abdominal normal skin sample and five keloid samples (four ear and one shoulder) were obtained from the Plastic Surgery clinics and the University of Colorado Biorepository Core Facility. Paraffin-embedded samples were stained with CD19+, CD20+, CD3+, CD8+ and FoxP3+ by the Human Immunology and Immunotherapy Initiative. The multiplex immunohistochemistry slides were scanned using Vectra 3 (PerkinElmer, MA, US) and captured images were analyzed with InForm Tissue Finder, phenotpr, and phenoptrReports (Akoya Biosciences, CA, US). CD20+ and CD19+ B cells were significantly increased in keloid tissue compared to normal skin (14.50% and 14.20% vs 6.47% and 7.56%), respectively. In contrast, no significant difference was observed in the percentage of CD3+ and CD8+ cell subsets in keloids compared to normal skin (12.92% and 4.98% vs 8.19% and 4.04%), respectively. Moreover, there was a significant increase in FoxP3+ positive cells found in keloid scars (9.68%) compared to normal skin (2.89%). Further studies examining the role of B cells and FoxP3+ cells in keloid pathogenesis are warranted.

Supplemental Digital Content is available in the text., Background: During reconstructive breast surgery, intraoperative assessment of tissue perfusion has been solely based on subjective clinical judgment. However, in the last decade, intraoperative indocyanine green angiography (ICGA) has become an influential tool to visualize blood flow to the tissue of interest. This angiography technique produces real-time blood flow information to provide an objective assessment of tissue perfusion. Methods: A comprehensive literature search of articles pertaining to ICGA in breast reconstruction surgery was performed. The overall findings of the articles are outlined here by surgical procedure: skin-sparing and nipple-sparing mastectomy, implant-based reconstruction, and autologous reconstruction. Results: Overall, there were 133 articles reviewed, describing the use of ICGA in breast reconstruction surgery. We found that ICGA can provide valuable information that aids in flap design, anastomotic success, and perfusion assessment. We also included example photographs and videos of ICGA use at our institution. Conclusions: ICGA can reduce postoperative tissue loss and aid in intraoperative flap design and inset. Despite the benefits of ICGA, its technical use and interpretation have yet to be standardized, limiting its widespread acceptance.

Hollow section is introduced on beam to reduce a dead load of the structure, which can ease the usage of IBS and hence minimize construction cost. It can also act as a pathing for mechanical and electrical works. Lightweight concrete produced by replacing 30% cement with PSBE with a density of 1600 kg/m³. Processed Spent Bleaching Earth (PSBE) is a residue from an oil-refining process that can be used to replace cement in the concrete mix. The study is conducted to analyse the best shape and position of the hollow section using ANSYS software. The study will also verify the results of previous experimental studies. Four-point bending test simulated on six beams samples. Beam S1, S2 and S3 have a square opening of size 50mm while beam C1, C2, and C3 have a circular opening of 50mm diameter. Samples Number 1 has opened right on the neutral axis. Samples Number 2 has opening above neutral axis while samples Number 3 have opening below the neutral axis. The size of all six beams is 150mm x 200mm x 1500mm. Finite element analysis performed on the samples with the usage of ANSYS software. The failure load and maximum total deformation are determined. From the result, beams with circular hollow section could withstand higher loading and had smaller deflection compared to its square hollow section counterpart. Also, the best position of the hollow is located above the neutral axis, while beams with hollow below the neutral axis were the weakest. Beam C2 produced the highest load among all sample, which was 4.015kN. The lowest beam was S3, which failed at 3.338kN. For beams with square hollow section, the beam produced a 1% increase in loading when the hollow section was above the neutral axis, but a strength loss of 15.3% observed when the hollow section was below the neutral axis. For beams with circular section, the hollow section above the neutral axis produced a 0.65% increase in loading, while the hollow section below neutral axis caused a strength loss of 3.79%. The resulting pattern agreed with experimental results. Concrete is weak in tension, so in unreinforced beams, the beam loses significant strength when the hollow section is below the neutral axis, which is the tension zone. Shifting the hollow section to above neutral axis strengthened the beams because concrete is good in compression and hollow section at the compression zone has little effect on the performance of the beams. The research aims to provide an understanding of the best shape and position of the hollow for a foamed concrete beam. It also verifies the ability of Finite Element Analysis to predict the performance of the hollow structure in the potential full-scale study.

Nowadays construction industry continuously looking for new, better and efficient construction material and method due to environmental impact. This research reported the effect of reinforced foamed concrete square hollow beam in order to reduce the effect of the application of concrete materials. Foamed concrete with density of 1600kg/m³ is now widely used as a structural component like slab and wall due to it lighter than the normal concrete. Meantime, it helps in saving cost and reduce the use of formwork. The hollow section also can reduce the dead loads which contribute to seismic effect in high rise buildings. In addition, the Processed Spent Bleaching Earth (PSBE) is an industry waste which possess a good pozzolanic reaction is used as partial cement replacement in order to make it more environmentally friendly. The experimental program consists of casting and testing of foamed concrete beams of size 150 x 200 x 1500 mm with and without square hollow section. To study the flexural behaviour, all beams are tested after 28 days of curing subjected to four-points bending test in order to analyse the effect of the reinforcement of hollow section on the strength, deflection and mode of failure of foamed concrete beam. The performance of reinforced foamed concrete hollow square beam (RHB) under flexural shows better when compared with conventional solid beam (CSB) and hollow square beam without reinforcement (HB). The RHB exhibited greater strength with lesser deflection and cracking.

A dietary fibre prepared from sugarcane stalk was compared with psyllium husk and wheat dextrin. In contrast to the other dietary fibres, sugarcane fibre was found to contain significant amounts of insoluble dietary fibre (73–86%), lignin (18.66–20.23%), and rare minerals such as chromium (0.67–2.54 mg/100 g) and manganese (1.07–2.34 mg/100 g). Analysis of the ethanol extract also detected compounds with antioxidant activity. Characterisation of five sugarcane fibres prepared from selected strains, harvest periods (growth or storage phase), and processing conditions showed these factors influenced the final composition. Furthermore, using in vitro digestion, we found that potassium, magnesium, chromium, and zinc in were bioaccessible in sugarcane samples. Also, sodium was shown to bind to the sugarcane fibre potentially indicating bile salt binding activity. Results from this study support the use of sugarcane as a source of dietary fibre in functional foods.

Introduction Sizing flow diverters (FDs) can be challenging during cerebral aneurysm pre-treatment planning. FDs can differ from their labelled lengths by 30% after deployment because of changes in vessel curvature and diameter. 1 Current FD sizing tools do not account for vessel shape or predict device apposition. We present a pilot study to evaluate the use of computational modelling for FD sizing. The modelling software is based on the finite element approach and has been shown to simulate FD deployments that closely match clinical deployments. 2 Methods Twenty-four patient cases in three hospitals were selected for treatment with the pipeline embolization device. Twelve of the cases were pre-planned using the SurgicalPreView computational modeling software, while the remaining cases were conventionally planned. In the computationally modeled cases, each patient’s CT image data were uploaded to SurgicalPreView and re-constructed before treatment. The principal physician simulated deployment of 1–3 different FDs on the software and evaluated simulation results before treatment. After treatment, the physician filled out a questionnaire on the usefulness of the simulation results. Further, post-treatment image data for the 12 cases were used to compare simulated and clinical deployments. Results According to physician responses, computational modeling was useful for all cases and it improved confidence in device selection. In 58% of cases, simulation results changed the physician’s original device selection. In most cases, the physician selected a longer length device or a larger device diameter after evaluating simulation results. Limited effect was observed on operative time and the number of endovascular devices used. An example comparison between simulated and clinical deployments is shown in figure 1. Conclusion Overall, the pilot study showed improvements in FD pre-treatment planning using computational modeling. Simulation results helped physicians predict the behavior of FDs in tortuous vessels and with maximizing apposition. Pretreatment planning may reduce costs by shortening operative time and reducing the number of devices used. Improvements to FD selection can potentially lead to better patient outcomes. References Fernandez H, Macho J, Andaluz J, Serra L, Larrabide I. Braided device foreshortening. presented at the Computer Assisted Radiology and Surgery, 2014. Babiker H, et al. Clinical validations of simulated neurovascular braided stent deployments . presented at the Frontiers in Medical Devices Conference – Innovations in Modeling and Simulation: Patient-Centered Healthcare, Washington, DC, 2016. Disclosures B. Chong: 4; C; Endovantage LLC. B. Bendok: None. C. Krishna: None. M. Sattur: None. B. Brown: None. R. Tawk: None. D. Miller: None. L. Rangel-Castilla: None. G. Lanzino: None.

To gain insight into the influence of coils on aneurysmal hemodynamics, computational fluid dynamics (CFD) can be used. Conventional methods of modeling coils consider the explicit geometry of the deployed devices within the aneurysm and discretize the fluid domain. However, the complex geometry of a coil mass leads to cumbersome domain discretization along with a significant number of mesh elements. These problems have motivated a homogeneous porous medium coil model, whereby the explicit geometry of the coils is greatly simplified, and relevant homogeneous porous medium parameters are approximated. Unfortunately, since the coils are not distributed uniformly in the aneurysm, the homogeneity assumption is no longer valid. In this paper, a novel heterogeneous porous medium approach is introduced. To verify the model, we performed CFD simulations to calculate the pressure drop caused by actual deployed coils in a straight cylinder. Next, we considered three different anatomical aneurysm geometries virtually treated with coils and studied the hemodynamics using the presented heterogeneous porous medium model. We show that the blood kinetic energy predicted by the heterogeneous model is in strong agreement with the conventional approach. The homogeneity assumption, on the other hand, significantly over-predicts the blood kinetic energy within the aneurysmal sac. These results indicate that the benefits of the porous medium assumption can be retained if a heterogeneous approach is applied. Implementation of the presented method led to a substantial reduction in the total number of mesh elements compared to the conventional method, and greater accuracy was enabled by considering heterogeneity compared to the homogenous approach.

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB.

Arteriovenous malformations (AVMs) are a subset of congenital vascular malformations (CVMs). They comprise abnormal connections between arterial and venous circulation; treatment approaches are dependent on the angioarchitecture of the AVM, specifically the number and arrangement of the feeder arteries and outflow veins. Various imaging modalities can be used to diagnose and plan treatment. Here we will review the use of transarterial approaches to treat AVMs.

There is growing public interest in the use of fiber supplements as a way of increasing dietary fiber intake and potentially improving the gut microbiota composition and digestive health. However, currently there is limited research into the effects of commercially available fiber supplements on the gut microbiota. Here we used an in vitro human digestive and gut microbiota model system to investigate the effect of three commercial fiber products; NutriKane™, Benefiber® and Psyllium husk (Macro) on the adult gut microbiota. The 16S rRNA gene amplicon sequencing results showed dramatic fiber-dependent changes in the gut microbiota structure and composition. Specific bacterial OTUs within the families Bacteroidaceae, Porphyromonadaceae, Ruminococcaceae, Lachnospiraceae, and Bifidobacteriaceae showed an increase in the relative abundances in the presence of one or more fiber product(s), while Enterobacteriaceae and Pseudomonadaceae showed a reduction in the relative abundances upon addition of all fiber treatments compared to the no added fiber control. Fiber-specific increases in SCFA concentrations showed correlation with the relative abundance of potential SCFA-producing gut bacteria. The chemical composition, antioxidant potential and polyphenolic content profiles of each fiber product were determined and found to be highly variable. Observed product-specific variations could be linked to differences in the chemical composition of the fiber products. The general nature of the fiber-dependent impact was relatively consistent across the individuals, which may demonstrate the potential of the products to alter the gut microbiota in a similar, and predictable direction, despite variability in the starting composition of the individual gut microbiota.

To assess outcomes of the treat-and-extend (TE) injection regimen for neovascular age-related macular degeneration (AMD) as compared to either a monthly or a pro re nata (PRN) treatment strategy.Systematic review and meta-analysis.Studies that compared the TE regimen with either monthly or PRN dosing for treatment-naïve AMD were included. Trial eligibility, data extraction, and risk of bias were assessed according to Cochrane review methods. Estimates were pooled using random-effects meta-analysis.Four eligible studies were identified, all using ranibizumab (total N = 940 eyes), including 2 randomized controlled trials comparing TE to monthly and 2 retrospective reviews comparing TE to PRN. No studies evaluating aflibercept were identified. Improvements in vision and central retinal thickness were similar between TE and monthly at 12 months, with a mean difference of -1.79 letters (95% confidence interval [CI]: 3.70, 0.13) and 3.76 μm (95% CI: -13.78, 21.30) in favor of monthly injections. In contrast, visual gains were higher in the TE compared to the PRN group (difference of +6.18 letters, 95% CI: 3.28, 9.08). Fewer injections were required using the TE regimen when compared to monthly (mean of -1.6 and -6.9 injections at 12 and 24 months, respectively). A mean of 1.44 more injections was required for the TE compared to PRN regimen at 12 months; however, this was achieved with fewer visits.Despite the growing preference for the TE regimen, there is limited head-to-head evidence comparing dosing strategies. The evidence available, however, suggests that at 12 months, TE is comparable to monthly and superior to PRN dosing for both efficacy and safety outcomes when using ranibizumab.

Background Pyogenic vertebral osteomyelitis (PVO) is rising in incidence, but optimal methods of investigation and duration of antibiotic therapy remain controversial. Methods We conducted a single-center retrospective cohort study of PVO at an Australian teaching hospital. We included all adults with a first episode of PVO between 2006 and 2015. PVO was defined based on the presence of prespecified clinical and radiological criteria. The main exposures of interest were investigation strategy and antibiotic treatment. The main outcome measures were duration of hospital admission, mortality during index admission, symptom resolution during index admission, and attributable readmission within 2 years. Results Of 129 included patients, 101 (78%) had a causative organism identified. Patients with an identified pathogen were more likely to be febrile (75% compared with 29%, P < .001) and had a higher mean admission C-reactive protein (207 vs 54, P < .001) compared with patients without an identified pathogen. However, they were less likely to experience an adverse outcome (death or attributable readmission within 2 years; adjusted odds ratio, 0.36; 95% confidence interval, 0.13–0.99; P = .04). Open biopsy of vertebral tissue had a higher diagnostic yield (70%) than fine needle aspirate (41%) or core biopsy (30%). Despite receiving a median of 6 weeks of intravenous antibiotics, only 15% of patients had a full recovery on discharge from index admission. Conclusions Clinical outcomes for patients with PVO were poor. Obtaining a microbiological diagnosis is associated with a better outcome. However, prospective and randomized studies are essential to establishing optimal investigation and treatment pathways.

There is growing public interest in the use of fiber supplements as a way of increasing dietary fiber intake and potentially improving the gut microbiota composition and digestive health. However, currently there is limited research into the effects of commercially available fiber supplements on the gut microbiota. Here we used an in vitro human digestive and gut microbiota model system to investigate the effect of three commercial fiber products; NutriKane™, Benefiber® and Psyllium husk (Macro) on the adult gut microbiota. The 16S rRNA gene amplicon sequencing results showed dramatic fiber-dependent changes in the gut microbiota structure and composition. Specific bacterial OTUs within the families Bacteroidaceae, Porphyromonadaceae, Ruminococcaceae, Lachnospiraceae, and Bifidobacteriaceae showed an increase in the relative abundances in the presence of one or more fiber product(s), while Enterobacteriaceae and Pseudomonadaceae showed a reduction in the relative abundances upon addition of all fiber treatments compared to the no added fiber control. Fiber-specific increases in SCFA concentrations showed correlation with the relative abundance of potential SCFA-producing gut bacteria. The chemical composition, antioxidant potential and polyphenolic content profiles of each fiber product were determined and found to be highly variable. Observed product-specific variations could be linked to differences in the chemical composition of the fiber products. The general nature of the fiber-dependent impact was relatively consistent across the individuals, which may demonstrate the potential of the products to alter the gut microbiota in a similar, and predictable direction, despite variability in the starting composition of the individual gut microbiota. Refereed/Peer-reviewed

For older adults, managing medications can be a burden and could lead to medication non-adherence. To decrease risks associated with medication non-adherence, healthcare providers may recommend medication reminder apps as an assistive tool. However, these apps are often not designed with consideration of older adults’ needs, capabilities, and limitations. To identify whether available apps are suitable for older adults, we conducted an in-depth cognitive walkthrough and a heuristic evaluation of the most commonly downloaded medication reminder app. Findings revealed three main issues: 1) difficulty in navigation, 2) poor visibility, and 3) a lack of transparency. We also selected the top five downloaded medication reminder apps and categorized user reviews to assess app functionality and usability problems. The results of our analysis provide guidance for app design for older adult users to provide effective tools for managing medications and supporting patient/user health.

Background: Seven isoforms of histone deacetylase Class III have been reported - Sirtuin (SIRT) 1-7. We recently demonstrated that EX-527, an inhibitor of SIRT1, reduces mortality in a mouse model of lethal-cecal-ligation-and-puncture (CLP)-induced septic shock. Our present study was aimed at determining whether selective inhibition of SIRT2, with AGK2, would decrease animal death and attenuate the inflammatory response in a septic model. Methods: Experiment I: C57BL/6J mice were intraperitoneally given either AGK2 (82 mg/kg) in dimethyl sulfoxide (DMSO) or DMSO alone, and 2 h later subjected to CLP. Survival was monitored for 240 hours. Experiment II: mice treated the same way as Experiment I, were grouped into (i) DMSO vehicle, and (ii) AGK2, with sham mice (operating but without any treatment) serving as controls. Peritoneal fluid and peripheral blood were examined at 24 and 48 hours for cytokine production. Samples of blood at 48 h were also allocated to assess coagulability using Thrombelastography (TEG). Morphological changes of bone marrow were evaluated from long bones (femurs and tibias) with hematoxylin and eosin (H&E) staining. Bone marrow atrophy was quantified by a blinded pathologist. Experiment III: cytokines in supernatant of the cultured normal primary splenocytes were measured after the cells were stimulated by lipopolysaccharide and treated with or without AGK2 (10 μM) for 6 hours. Results: AGK2 significantly reduced mortality and decreased levels of cytokines in blood (TNF-α: 298.3±24.6 vs 26.8±2.8 pg/ml, p=0.0034; IL-6: 633.4±82.8 vs 232.6±133.0 pg/ml, p=0.0344) and peritoneal fluid (IL-6: 704.8±67.7 vs 391.4±98.5 pg/ml, p=0.033) compared to vehicle control. Also, AGK2 suppressed the TNF-α and IL-6 production in the cultured splenocytes (TNF-α: 68.1±6.4 vs 23.9±2.8 pg/ml, p=0.0009; IL-6: 73.1±4.2 vs 49.6±3.0 pg/ml; p=0.0051). The TEG data showed that the mice subjected to CLP displayed prolonged fibrin formation and fibrin cross-linkage time, slower clot formation, decreased platelet function, and clot rigidity. AGK2 treatment was associated with dramatic improvements in fibrin cross-linkage and clot formation times, without a significant impact on the clot initiation parameters or platelet function. Additionally, AGK2 significantly attenuated the bone marrow atrophy (58.3±6.5 vs 30.0±8.2%, p=0.0262). Conclusion: Selective inhibition of SIRT2 significantly improves survival, and attenuates sepsis-associated “cytokine storm”, coagulopathy, and bone marrow atrophy in a mouse model of lethal septic shock.

Intravenous recombinant tissue plasminogen activator continues to be first-line therapy for patients with acute ischemic stroke presenting within the appropriate time window, but one potential limitation is the low rate of recanalization in the setting of large artery occlusions. Intra-arterial (IA) treatment is effective for emergency revascularization of proximal intracranial arterial occlusions, but proof of benefit has been lacking until recently. Our goal is to outline the history of endovascular therapy and review both IA thrombolysis and mechanical interventions. In addition, we will discuss the impact of important trials such as the Third Interventional Management of Stroke (IMS3) trial, and the more recent trials Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) on acute stroke management and the implications for the practicing neurohospitalist.

Aim Studies of fire activity along environmental gradients have been undertaken, but the results of such studies have yet to be integrated with fire-regime analysis. We characterize fire-regime components along climate gradients and a gradient of human influence. Location We focus on a climatically diverse region of north-western North America extending from northern British Columbia, Canada, to northern Utah and Colorado, USA. Methods We used a multivariate framework to collapse 12 climatic variables into two major climate gradients and binned them into 73 discrete climate domains. We examined variation in fire-regime components (frequency, size, severity, seasonality and cause) across climate domains. Fire-regime attributes were compiled from existing databases and Landsat imagery for 1897 large fires. Relationships among the fire-regime components, climate gradients and human influence were examined through bivariate regressions. The unique contribution of human influence was also assessed. Results A primary climate gradient of temperature and summer precipitation and a secondary gradient of continentality and winter precipitation in the study area were identified. Fire occupied a distinct central region of such climate space, within which fire-regime components varied considerably. We identified significant interrelations between fire-regime components of fire size, frequency, burn severity and cause. The influence of humans was apparent in patterns of burn severity and ignition cause. Main conclusions Wildfire activity is highest where thermal and moisture gradients converge to promote fuel production, flammability and ignitions. Having linked fire-regime components to large-scale climate gradients, we show that fire regimes – like the climate that controls them – are a part of a continuum, expanding on models of varying constraints on fire activity. The observed relationships between fire-regime components, together with the distinct role of climatic and human influences, generate variation in biotic communities. Thus, future changes to climate may lead to ecological changes through altered fire regimes.

Ozone at the tropospheric level is considered as pollutants and harms the human health. As the chemistry of tropospheric ozone is sensitive to solar radiation and temperature, one may expect significant changes to the tropospheric ozone variability due to climate change. In this study, the authors have explored the impact of regional climate change to the tropospheric ozone in a number of urban, rural and remote areas in Malaysia. This paper aims to develop a climate change scenario for A2 emissions over Malaysia using RCM PRECIS model and used the climate output as input to CiTTyCAT, a tropospheric chemistry model. At the end of this century, the surface temperature and precipitation were found to increase both during wet season (winter monsoon) and dry season (summer monsoon). In response to climate change relative to the observed ozone concentrations in year 2008, tropospheric ozone concentrations have been found to increase in urban areas (Kuala Lumpur, Sg. Petani and Kota Kinabalu), while in rural and remote areas (Kapit and Danum Valley) concentrations have been found to decrease. These projections were observed in both seasons. This study has suggested that tropospheric ozone sensitivity to climate change shows a degree of response variability.

Background The main aims of the 16th ISBT Platelet Immunology workshop were as follows: (i) to test the ability of the laboratories in the identification of platelet alloantibodies, (ii) to compare the detection of HPA-1a alloantibodies in serum and plasma, (iii) to quantify HPA-1a alloantibodies, (iv) to measure platelet-bound HPA-1a alloantibodies in lysates, (v) to evaluate a new bead-based assay for anti-HPA-1a and anti-HPA-1b detection, (vi) to evaluate the efficiency of a human monoclonal antibody for HPA-5a phenotyping and (vii) to test the ability to genotype for HPA-1, HPA-2, HPA-3, HPA-4, HPA-5, HPA-6, HPA-9, HPA-12w, HPA-13w and HPA-15. Materials and methods Seven exercises were developed to encompass the aims of this workshop. All materials and procedures were distributed for 34 laboratories from 20 countries. Results The platelet alloantibodies identification exercise presented good results compared with previous workshops. Comparison between serum and plasma in titration study showed comparable results for HPA-1a and HPA-5b alloantibodies. For the quantitative determination of HPA-1a alloantibodies, most of the laboratories could reliably assign a similar concentration. It was also possible to identify bound anti-HPA-1a alloantibodies in cell lysates within 2 weeks. The bead assay demonstrated good reproducibility between laboratories although some anti-HPA-1a samples remain an issue. Phenotyping of HPA-5b showed high false-negative error (6%). DNA typing presented excellent results, demonstrating that DNA tests for HPA are very well established in all laboratories. Conclusions This workshop presented high complexity exercises with very good results achieved in most of the exercises and approximately 100% consensus among the participants.

Myringotomy is a commonly performed procedure amongst otolaryngologists. Hemorrhage during myringotomy, albeit rare, can be devastating. Because bleeding during myringotomy is typically minimal if at all, otolaryngologists must be suspicious of a vascular injury if hemorrhage during myringotomy is encountered. Knowledge of vascular anatomy and potential variations is critical for prompt recognition of injury and timely management if injury should occur. Appropriate treatment includes initial control of bleeding followed by imaging to evaluate for vascular anomaly and/or injury. This will guide further treatment which may include embolization, surgical ligation, or bypass grafting.

The introduction of different nutrient and energy sources during weaning leads to significant changes in the infant gut microbiota. We used an in vitro infant digestive and gut microbiota model system to investigate the effect of four commercially available cereal products based on either wheat, sorghum, rice or oats, on the gut microbiota of six infants. Our results indicated cereal additions induced numerous changes in the gut microbiota composition. The relative abundance of bacterial families associated with fibre degradation, Bacteroidaceae, Bifidobacteriaceae, Lactobacillaceae, Prevotellaceae, Ruminococcaceae and Veillonellaceae increased, whilst the abundance of Enterobacteriaceae decreased with cereal additions. Corresponding changes in the production of SCFAs showed higher concentrations of acetate following all cereal additions, whilst, propionate and butyrate varied between specific cereal additions. These cereal-specific variations in the concentrations of SCFAs showed a moderate correlation with the relative abundance of potential SCFA-producing bacterial families. Overall, our results demonstrated clear shifts in the abundance of bacterial groups associated with weaning and an increase in the production of SCFAs following cereal additions.

The benefits of adult stem cells for repair of the heart have been attributed to the repertoire of salutary paracrine activities they appear to exert. We previously isolated human W8B2+ cardiac stem cells (CSCs) and found they powerfully influence cardiomyocytes and endothelial cells to collectively promote cardiac repair and regeneration. Here, the complexity of the W8B2+ CSC secretomes was characterised and examined in more detail. Using ion exchange chromatography to separate soluble proteins based on their net surface charge, the secreted factors responsible for the pro-survival activity of W8B2+ CSCs were found within the low and medium cation fractions. In addition to the soluble proteins, extracellular vesicles generated from W8B2+ CSCs not only exhibited pro-survival and pro-angiogenic activities, but also promoted proliferation of neonatal cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA and primary microRNA precursors that are enriched in exosomes and are capable of modulating collectively many of the cellular pathways involved in protein metabolism, cell growth, as well as cellular responses to stress and organisation of the extracellular matrix. Thus the W8B2+ CSC secretome contains a multitude of bioactive paracrine factors we have now characterised, that might well be harnessed for therapeutic application for cardiac repair and regeneration.

Malignant large artery stroke is associated with high mortality of 70% to 80% with best medical management. Decompressive craniectomy (DC) is a highly effective tool in reducing mortality. Convincing evidence has accumulated from several randomized trials, in addition to multiple retrospective studies, that demonstrate not only survival benefit but also improved functional outcome with DC in appropriately selected patients. This article explores in detail the evidence for DC, nuances regarding patient selection, and applicability of DC for supratentorial intracerebral hemorrhage and posterior fossa ischemic and hemorrhagic stroke.

The following telestroke guidelines were developed to assist practitioners in providing assessment, diagnosis, management, and/or remote consultative support to patients exhibiting symptoms and signs consistent with an acute stroke syndrome, using telemedicine communication technologies. Although telestroke practices may include the more broad utilization of telemedicine across the entire continuum of stroke care, with some even consulting on all neurologic emergencies, this document focuses on the acute phase of stroke, including both pre- and in-hospital encounters for cerebrovascular neurological emergencies. These guidelines describe a network of audiovisual communication and computer systems for delivery of telestroke clinical services and include operations, management, administration, and economic recommendations. These interactive encounters link patients with acute ischemic and hemorrhagic stroke syndromes with acute care facilities with remote and on-site healthcare practitioners providing access to expertise, enhancing clinical practice, and improving quality outcomes and metrics. These guidelines apply specifically to telestroke services and they do not prescribe or recommend overall clinical protocols for stroke patient care. Rather, the focus is on the unique aspects of delivering collaborative bedside and remote care through the telestroke model.

ObjectivesLinkage of “big data” can provide the answers to a variety of health questions that benefit the delivery of patient care, impact of policies, system planning and evaluation. In some jurisdictions, legal and operational barriers may prevent data linkage for research and system evaluation. Collaboration between international research institutions in Canada, Australia and Wales was formed at the Farr Institute International Conference in 2015. This partnership will test privacy-preserving record linkage (PPRL) techniques for linkage accuracy on real datasets held in a Canadian data repository. ApproachBloom filter PPRL techniques have been incorporated into a prototype linkage system. Evaluations on probabilistic linkage using Bloom filters method have shown potential for large-scale record linkage, performing both accurately and efficiently under experimental conditions. The prototype will be used to evaluate the Bloom filter PPRL techniques in 3 phases. Phase 1: 3 tests using simulated data relating to 20 million individuals will be matched to a sub-cohort of 1 million individuals. Phase 2: 100,000 people from hospital inpatient records will be matched to 18 million people in a health system registration file. These tests will inform whether the method can achieve high levels of privacy protection without negatively impacting performance and linkage quality. Performance indicators include match rate and processing efficiency based on record volumes. ResultsLinkage quality will be assessed by the number of true matches and non matches identified as links and non-links. This method will be evaluated using synthetic and real-world datasets, where the true match status is known. Initial performance testing linked a file of 3,000 records to 30,000 with a 100% match result. Subsequent test phases as above will continue to be evaluated and these results will be presented. ConclusionCompletion of the phased tests will confirm the ability to link datasets while preserving privacy. This international collaboration will expand the utility of this prototype linkage system and expand the global knowledge bank focusing on PPRL methods in general. It will also inform how to adapt to local requirements by providing a solution to many common legal and administrative challenges.