EffEctiveness of Prophylactic fOam dressings in the prevention of saCral pressure injuries in at-risk hospitalised patients: the EEPOC trial.

BACKGROUND: Prophylactic dressings are increasingly used to prevent pressure injuries in hospitalised patients. However, evidence regarding the effectiveness of these dressings is still emerging. This trial aims to determine the clinical and cost-effectiveness of a prophylactic silicone foam border dressing in preventing sacral pressure injuries in medical-surgical patients. METHODS: This is a multicentre, pragmatic, parallel group, randomised controlled trial. A sample size of 1320 was calculated to have >90% power to detect a 5% difference in the primary outcome at an alpha of 0.05. Adult patients admitted to participating medical-surgical wards are screened for eligibility: ≥18 years, admitted to hospital within the previous 36 h, expected length of stay of ≥24 h, and assessed high risk for hospital-acquired pressure injury. Consenting participants are randomly allocated to either prophylactic silicone foam dressing intervention or usual care without any dressing as the control group via a web-based randomisation service independent of the trial. Patients are enrolled across three Australian hospitals. The primary outcome is the cumulative incidence of patients who develop a sacral pressure injury. Secondary outcomes include the time to sacral pressure injury, incidence of severity (stage) of sacral pressure injury, cost-effectiveness of dressings, and process evaluation. Participant outcomes are assessed daily for up to 14 days by blinded independent outcome assessors using de-identified, digitally modified sacral photographs. Those who develop a sacral pressure injury are followed for an additional 14 days to estimate costs of pressure injury treatment. Analysis of clinical outcomes will be based on intention-to-treat, per-protocol, and sensitivity analyses. DISCUSSION: This trial aims to provide definitive evidence on the effect prophylactic dressings have on the development of hospital-acquired sacral pressure injuries in medical-surgical patients. A parallel economic evaluation of pressure injury prevention and treatment will enable evidence-informed decisions and policy. The inclusion of a process evaluation will help to explain the contextual factors that may have a bearing on trial results including the acceptability of the dressings to patients and staff. The trial commenced 5 March 2020 and has been significantly delayed due to COVID-19. TRIAL REGISTRATION: ANZCTR ACTRN12619000763145. Prospectively registered on 22 May 2019.

Radioactivity concentration measurements in fish and shellfish samples from the west coast of Canada after the Fukushima nuclear accident (2011-2018).

Radioactive contamination of the Pacific Ocean following the Fukushima nuclear accident has raised public concern about seafood safety, particularly in coastal Indigenous communities. To address this, Health Canada and partners have collected and analyzed a total of 621 samples of commonly consumed salmon, ground fish, and shellfish from the Canadian west coast from 2011 to 2018. While the vast majority of the 137Cs and 134Cs levels were below the Minimum Detectable Concentration (MDC, typically 0.7-1.0 Bq kg-1 fw for a 6 h counting), further examination of 19 fish samples revealed 137Cs concentrations of 0.17-0.53 Bq kg-1 fw with an average value and uncertainty (k = 1) of 0.29 ± 0.02 Bq kg-1 fw. Of these, only two samples were found to have trace levels of 134Cs likely derived from the Fukushima accident. The global fallout contribution from atmospheric nuclear weapons testing to the observed 137Cs in these two samples was determined to be 0.26 ± 0.08 Bq kg-1 fw (49 ± 14%) and 0.12 ± 0.02 Bq kg-1 fw (24 ± 4%) for collection years 2015 and 2016, respectively. The annual average level of 137Cs in fish and shellfish was also determined by spectral summation for collection years 2014-2018. In fish, 137Cs levels determined through spectral summation were relatively constant (0.18-0.25 Bq kg-1 fw) with an average value and uncertainty of 0.21 ± 0.02 Bq kg-1 fw. By contrast, 38 shellfish samples (bivalves) were measured and revealed no radiocesium or other anomalies in either tissue or shell. In all, measurements over eight years showed that the radioactivity in fish and shellfish was dominated by natural radionuclides and that the level of anthropogenic radionuclides, as indicated by the radioactive cesium content, remained small. An upper bound for ingested dose from 137Cs was determined to be approximately 0.26 µSv per year, far below the worldwide average annual effective dose of 2400 µSv from exposure to natural background radiation. We can therefore conclude that fish, such as salmon, ground fish, and shellfish from the Canadian west coast are of no radiological health concern despite the Fukushima Dai-ichi nuclear accident of 2011.

Genome-wide association analysis for susceptibility to infection by Mycobacterium avium ssp. paratuberculosis in US Holsteins.

Paratuberculosis, or Johne's disease, is a chronic, granulomatous, gastrointestinal tract disease of cattle and other ruminants caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). Control of Johne's disease is based on programs of testing and culling animals positive for infection with MAP and concurrently modifying management to reduce the likelihood of infection. The current study was motivated by the hypothesis that genetic variation in host susceptibility to MAP infection can be dissected and quantifiable associations with genetic markers identified. Two separate GWAS analyses were conducted, the first using 897 genotyped Holstein artificial insemination sires with phenotypes derived from incidence of MAP infection among daughters based on milk ELISA testing records. The second GWAS analysis was a case-control design using US Holstein cows phenotyped for MAP infection by serum ELISA or fecal culture tests. Cases included cows positive for either serum ELISA, fecal culture, or both. Controls consisted of animals negative for all tests conducted. A total of 376 samples (70 cases and 306 controls) from a University of Minnesota Johne's management demonstration project and 184 samples (76 cases and 108 controls) from a Michigan State University study were used. Medium-density (sires) and high-density (cows) genotype data were imputed to full genome sequence for the analyses. Marker-trait associations were analyzed using the single-step (ss)GWAS procedure implemented in the BLUPF90 suite of programs. Evidence of significant genomic contributions for susceptibility to MAP infection were observed on multiple chromosomes. Results were combined across studies in a meta-analysis, and increased support for genomic regions on BTA7 and BTA21 were observed. Gene set enrichment analysis suggested pathways for antigen processing and presentation, antimicrobial peptides and natural killer cell-mediated cytotoxicity are relevant to variation in host susceptibility to MAP infection, among others. Genomic prediction was evaluated using a 5-fold cross-validation, and moderate correlations were observed between genomic breeding value predictions and daughter averages (∼0.43 to 0.53) for MAP infection in testing data sets. These results suggest that genomic selection against susceptibility to MAP infection is feasible in Holstein cattle.

Pedi-R-MAPP: The development of a nutritional awareness tool for use in remote paediatric consultations using a modified Delphi consensus.

BACKGROUND & AIMS: The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation. METHODS: A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool. RESULTS: The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations. Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised. CONCLUSION: The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.

Safety, immunogenicity, and efficacy of NDV-3A against Staphylococcus aureus colonization: A phase 2 vaccine trial among US Army Infantry trainees.

BACKGROUND: Military trainees are at increased risk for Staphylococcus aureus colonization and infection. Disease prevention strategies are needed, but a S. aureus vaccine does not currently exist. METHODS: We enrolled US Army Infantry trainees (Fort Benning, GA) in a phase 2, randomized, double-blind, placebo-controlled trial of NDV-3A, a vaccine containing a recombinant adhesin/invasion protein of Candida albicans that has structural similarity to the S. aureus protein clumping factor A. Study participants received one intramuscular dose of NDV-3A or placebo (adjuvant alone) within 72 h of arrival on base. Longitudinal nasal and oral (throat) swabs were collected throughout the 14-week Infantry training cycle. Safety, immunogenicity, and efficacy of NDV-3A against S. aureus nasal / oral acquisition were the endpoints. RESULTS: The NDV-3A candidate had minimal reactogenicity and elicited robust antigen-specific B- and T-cell responses. During the 56-day post-vaccination period, there was no difference in the incidence of S. aureus nasal acquisition between those who were randomized to receive NDV-3A vs. placebo (25.6% vs. 29.1%; vaccine efficacy [VE]: 12.1%; p = 0.31). In time-to-event analysis, there was no difference between study groups with respect to the S. aureus colonization-free interval (VE: 13%; p = 0.29). Similarly, the efficacy of NDV-3A against S. aureus oral acquisition was poor (VE: 2.4%; p = 0.52). CONCLUSIONS: A single dose of NDV-3A did not prevent nasal nor oral acquisition of S. aureus in a population of military trainees at high risk for colonization.

The role of competition on invader colonization along stress gradients in the Fuegian steppe.

Competition exerted by native plant communities is an important component of biotic resistance against the spread and impact of non-indigenous plant species in novel habitats. However, how the role of biotic resistance varies along environmental gradients to delay invasions is less clear. We conducted two field experiments to determine how competition from native communities affects colonization of a recognized invader of grasslands, Hieracium pilosella L., in the Fuegian steppe along different environmental gradients at regional and landscape scale. We assessed the role of competition on invader survival and growth along a climate gradient at regional scale (4.7-6.6 °C and 270-450 mm year-1), and across four major plant communities (i.e. meadows, grasslands, scrublands, and heathlands) along a topographic catena. At regional scale, the climate gradient showed a 33% reduction in H. pilosella survival at the coldest and wettest extreme, while reduced its biomass in 41% at the warmest and driest site, in the opposite extreme of the gradient. Competition caused a 34% decrease of the invader biomass, similarly along the climate gradient. At landscape scale, the topographic gradient had a stronger effect on invader survival reaching a 67% reduction in lowland meadows due to flooding events, while competition reduced in 29-39% the invader biomass only in grasslands or scrublands with negligible effects on low-resource heathlands. These results suggest that biotic resistance plays a significant and similar role along the climate gradient to delay invasion at regional scale, but at landscape scale is only determinant for rich-resource communities in absence of abiotic stresses.

Printing bone in a gel: using nanocomposite bioink to print functionalised bone scaffolds.

Free-form printing offers a novel biofabrication approach to generate complex shapes by depositing hydrogel materials within a temporary supportive environment. However, printed hydrogels typically lack the requisite mechanical properties and functionality of the desired tissue, limiting application and, more importantly, safety and efficacy of the implant. The study authors have developed an innovative nanoclay-based bioink to print high shape fidelity functional constructs for potential skeletal application. Laponite® (LAP) nanoclay was combined with gellan gum (GG) to generate a printable hydrogel that was highly stable in vitro, displayed limited swelling ability compared with the silicate-free control and remained stable over time. An agarose fluid gel was found to provide the requisite support for the deposition of the material ink and preservation of the printed structure before crosslinking. Printed C2C12 myoblasts remained viable and displayed extensive proliferation over 21 days in culture. Cell-laden scaffolds demonstrated functionality within 1 day of culture in vitro and that was preserved over 3 weeks. Analysis of absorption and release mechanisms from LAP-GG using model proteins (lysozyme and bovine serum albumin) demonstrated the retention capability of the clay-based materials for compound localisation and absence of burst release. Vascular endothelial growth factor â€‹was loaded within the agarose fluid gel and absorbed by the material ink via absorption during deposition. The 3D-printed constructs were implanted on the chorioallantoic membrane of a 10-day-old developing chick. Extensive and preferential vasculature infiltration was observed in LAP-GG-loaded vascular endothelial growth factor constructs compared with controls (p<0.01 and p<0.0001) after only 7 days of incubation. The current studies demonstrate, for the first time, the application of innovative LAP-GG 3D constructs in the generation of growth factor-loaded 3D constructs for potential application in skeletal tissue repair.

A review of the use of high-flow nasal cannula oxygen therapy in hospitalised children at a regional hospital in the Cape Town Metro, South Africa.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen is a non-invasive alternative to nasal continuous positive airway pressure (CPAP) therapy for infants and children requiring respiratory support. There is a paucity of data to support its use in children, with no published data from sub-Saharan Africa. OBJECTIVES: To describe the outcomes of and adverse events related to HFNC in the first year of its use in a level 2 (L2) general paediatric ward, and to compare these outcomes with those of a historical cohort when this intervention was unavailable. METHODS: This retrospective descriptive study included children aged <13 years who received HFNC in the first 12 months after its introduction (HFNC-availability group, n=66). Demographic data, clinical characteristics and outcomes (death, treatment failure, length of HFNC and HFNC-related adverse events) were assessed. A comparative description of children who required transfer to level 3 (L3) for any form of respiratory support (other than the available standard low-flow oxygen) during the 12-month period prior to HFNC availability (pre-HFNC group, n=54) was made. All analyses were performed in the paediatric wards, New Somerset Hospital, Cape Town, South Africa. Outcomes were compared using standard descriptive and comparative statistics. RESULTS: The median age of the cohort was 5 months (interquartile range (IQR) 1.9 - 14.6). Sixteen children (13.3%) were malnourished, 10 (8.3%) were HIV-infected, and 30 (25.0%) had been born prematurely. The most common diagnoses were pneumonia, bronchiolitis and asthma. Asthma, anaemia and cardiac abnormalities were the most prevalent underlying comorbidities. Two children died in each group. All 54 children in the pre-HFNC group were transferred to L3; 38 (70.4%) needed CPAP or invasive ventilation. In the HFNC-availability period, 85 children were assessed as needing more than standard low-flow oxygen therapy: of the 19 immediately transferred to L3, 17 (89.4%) received CPAP or invasive ventilation; of the 66 who received HFNC at L2, 16 (24.2%) subsequently required transfer to L3 for CPAP or invasive ventilation. The median duration of HFNC was 46.3 hours (IQR 19.5 - 93.5) overall, and it was 12 hours (IQR 4 - 28) and 58.5 hours (IQR 39.5 - 106) for those who failed or were successfully managed on HFNC, respectively. No HFNC-related serious adverse events were recorded. CONCLUSIONS: HFNC is a safe, effective, feasible option for non-invasive ventilation of children with respiratory illnesses in a resource-limited L2 setting. A greater proportion of children with lower respiratory tract infections in the HFNC-availability group than in the pre-HFNC group required support, but the intervention reduced the bed pressure on L3. Improved ways to identify HFNC failures would be beneficial.

Radical fluoroalkylation reactions of (hetero)arenes and sulfides under red light photocatalysis.

Fluoroalkylation reactions of (hetero)aromatics have been accomplished through the low-power illumination from red LEDs (λmax = 635 nm) of commercially available perfluoroalkyl iodides RF-I and phthalocyanine zinc salt as photocatalyst in MeCN : DMF solvent mixture. This methodology has been extended to the perfluorobutylation of sulfides. As far as we are concerned, this is the first report on a perfluoroalkylation reaction of (hetero)aromatics and sulfides under red-light photocatalysis.

210Po in Pacific Salmon from the West Coast of Canada and its Contribution to Dose by Ingestion.

In response to public concern in Canada regarding health impacts attributable to the Fukushima Daiichi nuclear accident, oceanic seawater samples from the north Pacific and Arctic oceans, coastal seawater samples from 16 locations along the British Columbia coastline, and seafood samples (salmon, steelhead trout, and shellfish) from British Columbia coastal waters were collected and analyzed. This paper reports radiological analysis results of Pacific salmon samples (Oncorhynchus species) obtained from summer 2013 to fall 2016. While radioactive cesium from the Fukushima disaster was not detectable in most salmon samples, naturally occurring Po was measured in almost all individual samples in varying activity concentrations, from below the detection limit of 0.2 Bq kg fresh weight up to 4.7 Bq kg fresh weight. The average Po concentration among 297 salmon samples was 0.73 Bq kg fresh weight. The average ingested radiation dose per kilogram of salmon from Po is estimated to be 0.88 µSv, and the average dose from Cs is estimated to be 0.0026 µSv. The annual dose from ingested salmon would be only a fraction of the worldwide average annual effective dose from exposure to natural background radiation (2,400 µSv y) (). The measurement results showed clearly that radiation doses to people consuming fish (such as salmon) from the Canadian west coast pose no health concern.

The role of subchondral bone, and its histomorphology, on the dynamic viscoelasticity of cartilage, bone and osteochondral cores.

OBJECTIVE: Viscoelastic properties of articular cartilage have been characterised at physiological frequencies. However, studies investigating the interaction between cartilage and subchondral bone and the influence of underlying bone histomorphometry on the viscoelasticity of cartilage are lacking. METHOD: Dynamic Mechanical Analysis (DMA) has been used to quantify the dynamic viscoelasticity of bovine tibial plateau osteochondral cores, over a frequency sweep from 1 to 88 Hz. Specimens (approximately aged between 18 and 30 months) were neither osteoarthritic nor otherwise compromised. A maximum nominal stress of 1.7 MPa was induced. Viscoelastic properties of cores have been compared with that of its components (cartilage and bone) in terms of the elastic and viscous components of both structural stiffness and material modulus. Micro-computed tomography scans were used to quantify the histomorphological properties of the subchondral bone. RESULTS: Opposing frequency-dependent loss stiffness, and modulus, trends were witnessed for osteochondral tissues: for cartilage it increased logarithmically (P < 0.05); for bone it decreased logarithmically (P < 0.05). The storage stiffness of osteochondral cores was logarithmically frequency-dependent (P < 0.05), however, the loss stiffness was typically frequency-independent (P > 0.05). A linear relationship between the subchondral bone plate (SBP) thickness and cartilage thickness (P < 0.001) was identified. Cartilage loss modulus was linearly correlated to bone mineral density (BMD) (P < 0.05) and bone volume (P < 0.05). CONCLUSION: The relationship between the subchondral bone histomorphometry and cartilage viscoelasticity (namely loss modulus) and thickness, have implications for the initiation and progression of osteoarthritis (OA) through an altered ability of cartilage to dissipate energy.

Bimorph material/structure designs for high sensitivity flexible surface acoustic wave temperature sensors.

A fundamental challenge for surface acoustic wave (SAW) temperature sensors is the detection of small temperature changes on non-planar, often curved, surfaces. In this work, we present a new design methodology for SAW devices based on flexible substrate and bimorph material/structures, which can maximize the temperature coefficient of frequency (TCF). We performed finite element analysis simulations and obtained theoretical TCF values for SAW sensors made of ZnO thin films (~5 µm thick) coated aluminum (Al) foil and Al plate substrates with thicknesses varied from 1 to 1600 µm. Based on the simulation results, SAW devices with selected Al foil or plate thicknesses were fabricated. The experimentally measured TCF values were in excellent agreements with the simulation results. A normalized wavelength parameter (e.g., the ratio between wavelength and sample thickness, λ/h) was applied to successfully describe changes in the TCF values, and the TCF readings of the ZnO/Al SAW devices showed dramatic increases when the normalized wavelength λ/h was larger than 1. Using this design approach, we obtained the highest reported TCF value of -760 ppm/K for a SAW device made of ZnO thin film coated on Al foils (50 µm thick), thereby enabling low cost temperature sensor applications to be realized on flexible substrates.

A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC. Methods: This exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC. Results: The study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B- and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). The analysis of evaluable patients, which combined patients aged <40 years (77%) and ≥40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099). Conclusions: In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged <40 years. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC. Clinical Trials Registration: NCT01926028.

The British Services Dhaulagiri Medical Research Expedition 2016: a unique military and civilian research collaboration.

INTRODUCTION: High-altitude environments lead to a significant physiological challenge and disease processes which can be life threatening; operational effectiveness at high altitude can be severely compromised. The UK military research is investigating ways of mitigating the physiological effects of high altitude. METHODS: The British Service Dhaulagiri Research Expedition took place from March to May 2016, and the military personnel were invited to consent to a variety of study protocols investigating adaptation to high altitudes and diagnosis of high-altitude illness. The studies took place in remote and austere environments at altitudes of up to 7500 m. RESULTS: This paper gives an overview of the individual research protocols investigated, the execution of the expedition and the challenges involved. 129 servicemen and women were involved at altitudes of up to 7500 m; 8 research protocols were investigated. CONCLUSIONS: The outputs from these studies will help to individualise the acclimatisation process and inform strategies for pre-acclimatisation should troops ever need to deploy at high altitude at short notice.

The effect of high altitude on central blood pressure and arterial stiffness.

Central arterial systolic blood pressure (SBP) and arterial stiffness are known to be better predictors of adverse cardiovascular outcomes than brachial SBP. The effect of progressive high altitude (HA) on these parameters has not been examined. Ninety healthy adults were included. Central BP and the augmentation index (AI) were measured at the level of the brachial artery (Uscom BP+ device) at <200 m and at 3619, 4600 and 5140 m. The average age of the subjects (70% men) were 32.2±8.7 years. Compared with central arterial pressures, brachial SBP (+8.1±6.4 mm Hg; P<0.0001) and pulse pressure (+10.9±6.6 mm Hg; P<0.0001) were significantly higher and brachial diastolic BP was lower (-2.8±1.6 mm Hg; P<0.0001). Compared with <200 m, HA led to a significant increase in brachial and central SBP. Central SBP correlated with AI (r=0.50; 95% confidence interval (CI): 0.41-0.58; P<0.0001) and age (r=0.32; 95% CI: 21-0.41; P<0.001). AI positively correlated with age (r=0.39; P<0.001) and inversely with subject height (r=-0.22; P<0.0001), weight (r=-0.19; P=0.006) and heart rate (r=-0.49; P<0.0001). There was no relationship between acute mountain sickness scores (Lake Louis Scoring System (LLS)) and AI or central BP. The independent predictors of central SBP were male sex (coefficient, t=4.7; P<0.0001), age (t=3.6; P=0.004) and AI (t=7.5; P<0.0001; overall r2=0.40; P<0.0001). Subject height (t=2.4; P=0.02), age (7.4; P<0.0001) and heart rate (t=11.4; P<0.0001) were the only independent predictors of AI (overall r2=0.43; P<0.0001). Central BP and AI significantly increase at HA. This rise was influenced by subject-related factors and heart rate but not independently by altitude, LLS or SpO2.

Secondary osteons scale allometrically in mammalian humerus and femur.

Intra-cortical bone remodelling is a cell-driven process that replaces existing bone tissue with new bone tissue in the bone cortex, leaving behind histological features called secondary osteons. While the scaling of bone dimensions on a macroscopic scale is well known, less is known about how the spatial dimensions of secondary osteons vary in relation to the adult body size of the species. We measured the cross-sectional area of individual intact secondary osteons and their central Haversian canals in transverse sections from 40 stylopodal bones of 39 mammalian species (body mass 0.3-21 000 kg). Scaling analysis of our data shows that mean osteonal resorption area (negative allometry, exponent 0.23,R2 0.54,p<0.005) and Haversian canal area (negative allometry, exponent 0.31,R2 0.45,p<0.005) are significantly related to body mass, independent of phylogeny. This study is the most comprehensive of its kind to date, and allows us to describe overall trends in the scaling behaviour of secondary osteon dimensions, supporting the inference that the osteonal resorption area may be limited by the need to avoid fracture in smaller mammalian species, but the need to maintain osteocyte viability in larger mammalian species.

Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3.

Chitinase 3-like 1, otherwise known as YKL-40, is a secreted glycoprotein purported to have a role in extracellular matrix metabolism. The first mammalian cell type found to express YKL-40 was the human osteosarcoma-derived osteoblast, MG63. In that first study the active vitamin D3 metabolite, 1,25-dihydroxycholecalciferol (1,25D), stimulated YKL-40 expression, thereby indicating that a vital factor for skeletal health promoted YKL-40 synthesis by bone forming cells. However, when these MG63 cells were exposed to 1,25D they were also exposed to serum, a rich source of the pleiotropic lipid mediator, lysophosphatidic acid (LPA). Given that 1,25D is now known to co-operate with selected growth factors, including LPA, to influence human osteoblast differentiation we hypothesised that 1,25D and LPA may work together to stimulate osteoblast YKL-40 expression. Herein we report that 1,25D and LPA synergistically promote YKL-40 expression by MG63 cells. Inhibitors targeting AP1, MEK, Sp1 and STAT3 blunted the expression of both alkaline phosphatase and YKL-40 by MG63 cells in response to co-stimulation with 1,25D and LPA. Other ligands of the vitamin D receptor also co-operated with LPA in driving YKL-40 mobilisation. Collectively our findings highlight another important role of 1,25D and LPA in the regulation of human osteoblast function.