Visual outcomes and predictors in optic pathway glioma: a single centre study.

BACKGROUND/AIMS: Optic pathway gliomas (OPGs) may cause progressive visual loss despite chemotherapy. Newer, less toxic treatments might be given earlier, depending on visual prognosis. We aimed to investigate the prognostic value of visual evoked potentials (VEP) and optical coherence tomography (OCT). METHODS: A retrospective study of OPG patients (treated 2003-2017) was conducted. Primary outcome was PEDIG category visual acuity in better and worse eyes (good < = 0.2, moderate 0.3-0.6 and poor > = 0.7 logMAR). Binary logistic regression analysis was used to identify predictors of these outcomes. RESULTS: 60 patients (32 Neurofibromatosis type 1 [NF1] and 28 sporadic) had median presentation age 49 months (range 17-183) (NF1) and 27 months (range 4-92) (sporadic). Median follow up was 82 months (range 12-189 months). At follow up 24/32 (75%) of NF1 children and 14/28 (50%) of sporadic children had good better eye visual acuity and 11/32 (34%) of NF1 children and 15/28 (54%) of sporadics had poor worse eye acuity. Mean peripapillary retinal nerve fibre layer (RNFL) thickness predicted good better eye final acuity (OR 0.799, 95%CI 0.646-0.987, p = 0.038). Presenting with visual symptoms (OR 0.22 95% CI 0.001-0.508, p = 0.017) and poorer VEP scores (OR 2.35 95% CI 1.1-5.03, p = 0.027) predicted poor worse eye final acuity. 16 children had homonymous hemianopias at follow up, predicted by poor presenting binocular VEP score (OR 1.449 95%CI 1.052-1.995, p = 0.02). CONCLUSIONS: We found that both RNFL thickness on OCT and VEP were useful in predicting future visual acuity and vision and potentially in planning treatment. We had a high prevalence of homonymous hemianopia.

Effects of cyclooxygenase and soluble epoxide hydrolase inhibitors on apoptosis of cultured primary equine chondrocytes.

BACKGROUND: Apoptosis is an important mechanism underlying chondrocyte loss in osteoarthritis that could be affected by modulation of lipid signaling via inhibition of cyclooxygenases (COX) and soluble epoxide hydrolase (sEH). OBJECTIVE: To determine the impact of inhibiting COX and sEH alone or in combination on apoptosis of equine chondrocytes. METHODS: Cultured primary equine chondrocytes were subjected to serum deprivation or incubation with 1 µg/ml tunicamycin for 24 h to induce apoptosis via caspase activation and endoplasmic reticulum (ER) stress, respectively. Cells were treated with the non-selective COX inhibitor phenylbutazone, the COX-2 selective inhibitor firocoxib and the sEH inhibitor t-TUCB alone or in combination. The inhibitors were used at half-maximal (IC50), 80% of maximal (IC80) and 10-fold the 80% inhibitory concentration (10xIC80) for the equine enzymes. Apoptosis was quantified via ELISA technique. Data were analyzed with unpaired two-tailed t-test or one-way ANOVA followed by Bonferroni's post-hoc while correcting for multiple comparisons via statistical hypothesis testing. P < 0.05 was considered significant. RESULTS: In the caspase model, 10xIC80t-TUCB significantly decreased whereas 10xIC80 phenylbutazone significantly enhanced apoptosis. Apoptosis enhancement by phenylbutazone was significantly attenuated by concurrent 10xIC80t-TUCB. The remaining treatments and concentrations had no effect on apoptosis development. In the ER stress model, IC50 and IC80 phenylbutazone and firocoxib significantly enhanced apoptosis, which was fully prevented by concurrent 10xIC80t-TUCB. MAIN LIMITATIONS: In vitro findings that will need to be verified in vivo. CONCLUSIONS: Chondrocyte apoptosis caused by ER stress can be enhanced by COX inhibition but prevented by concurrent inhibition of sEH.

Land use and management effects on soil carbon in U.S. Lake States, with emphasis on forestry, fire, and reforestation.

There is growing need to quantify and communicate how land use and management activities influence soil organic carbon (SOC) at scales relevant to, and in the tangible control of landowners and forest managers. The continued proliferation of publications and growth of data sets, data synthesis and meta-analysis approaches allows the application of powerful tools to such questions at ever finer scales. In this analysis, we combined a literature review and effect-size meta-analysis with two large, independent, observational databases to assess how land use and management impact SOC stocks, primarily with regards to forest land uses. We performed this work for the (Great Lakes) U.S. Lake States, which comprise 6% of the land area, but 7% of the forest and 9% of the forest SOC in the United States, as the second in a series of ecoregional SOC assessments. Most importantly, our analysis indicates that natural factors, such as soil texture and parent material, exert more control over SOC stocks than land use or management. With that for context, our analysis also indicates which natural factors most influence management impacts on SOC storage. We report an overall trend of significantly diminished topsoil SOC stocks with harvesting, consistent across all three data sets, while also demonstrating how certain sites and soils diverge from this pattern, including some that show opposite trends. Impacts of fire grossly mirror those of harvesting, with declines near the top of the profile, but potential gains at depth and no net change when considering the whole profile. Land use changes showing significant SOC impacts are limited to reforestation on barren mining substrates (large and variable gains) and conversion of native forest to cultivation (losses). We describe patterns within the observational data that reveal the physical basis for preferential land use, e.g., cultivation of soils with the most favorable physical properties, and forest plantation establishment on the most marginal soils, and use these patterns to identify management opportunities and considerations. We also qualify our results with ratings of confidence, based on their degree of support across approaches, and offer concise, defensible tactics for adapting management operations to site-specific criteria and SOC vulnerability.

What best animal science teachers do.

Great teachers have the extraordinary ability to inspire and motivate even those students who resist learning. The top educators are knowledgeable not only about the content of the course they are teaching but also of the information, literature, and practice of instructional delivery to their audience. Many exemplary educators have been profiled and studied; however, there is a paucity of information pertaining to how the top animal science teachers teach. The objective of this study was to identify and describe characteristics of award-winning animal science teachers. The inclusion criterion for selecting faculty was being bestowed an excellence in teaching award through their professional organization. Each teacher answered a series of questions about themselves, their students, and the class being taught. Lecture was captured using a digital all-inclusive camera and later analyzed for pedagogical trends and instructor-student interactions. Despite a variety of topics being taught by award-winning teachers, there were multiple trends emerging from their classrooms. Common events included reviewing highlights of previous lectures, distributing something to students, posing questions during class, and calling on students by name. Each teacher taught differently, but they all understood their audience; they grasped the subject matter and most importantly, they valued students learning. Collectively, these findings can be utilized and applied by animal science teachers in their own environments in an attempt to foster improved student learning through excellent teaching.

One Health and antimicrobial resistance, a United States perspective.

Antimicrobial drugs are a precious resource, responsible for saving millions of lives since their discovery. Unfortunately, some antimicrobials are rapidly losing their effectiveness due to the development and spread of antimicrobial resistance (AMR), a multi-faceted and complex problem affecting humans, animals, plants and the environment. While AMR is a global problem, in this paper, the authors briefly highlight some ongoing efforts in the United States of America aimed at integrating a One Health approach into policies and programmes that address this important health threat.

Les antibiotiques sont des ressources de grande valeur qui ont sauvé des millions de vies depuis leur découverte. Malheureusement, certains agents antimicrobiens perdent rapidement leur efficacité en raison de l'apparition et propagation des résistances à ces agents, phénomène complexe et multidimensionnel qui affecte l'homme, les animaux, les plantes et l'environnement. La résistance aux agents antimicrobiens est un problème mondial ; dans cet article, les auteurs décrivent certaines initiatives actuellement mises en oeuvre aux États-Unis d'Amérique pour intégrer l'approche Une seule santé dans les politiques et les programmes conçus pour lutter contre cette menace sanitaire majeure.

Los fármacos antimicrobianos son un recurso valiosísimo, cuyo uso ha salvado millones de vidas desde que fueron descubiertos. Lamentablemente, algunos de ellos están perdiendo rápidamente eficacia debido a la aparición y propagación de resistencias, lo que plantea un problema tan complejo como poliédrico, que afecta a personas, animales, plantas y ecosistemas. Aunque la dimensión del problema es planetaria, los autores destacan aquí brevemente algunas de las iniciativas en curso en los Estados Unidos de América que tienen por objetivo integrar los planteamientos de Una sola salud en el conjunto de políticas y programas desde los cuales se aborda esta importante amenaza sanitaria.

Management of acute traumatic spinal cord injuries.

Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome.

Toward inventory-based estimates of soil organic carbon in forests of the United States.

Soil organic carbon (SOC) is the largest terrestrial carbon (C) sink on Earth; this pool plays a critical role in ecosystem processes and climate change. Given the cost and time required to measure SOC, and particularly changes in SOC, many signatory nations to the United Nations Framework Convention on Climate Change report estimates of SOC stocks and stock changes using default values from the Intergovernmental Panel on Climate Change or country-specific models. In the United States, SOC in forests is monitored by the national forest inventory (NFI) conducted by the Forest Inventory and Analysis (FIA) program within the U.S. Department of Agriculture, Forest Service. The FIA program has been consistently measuring soil attributes as part of the NFI since 2001 and has amassed an extensive inventory of SOC in forest land in the conterminous United States and southeast and southcentral coastal Alaska. That said, the FIA program has been using country-specific predictions of SOC based, in part, upon a model using SOC estimates from the State Soil Geographic (STATSGO) database compiled by the Natural Resources Conservation Service. Estimates obtained from the STATSGO database are averages over large map units and are not expected to provide accurate estimates for specific locations, e.g., NFI plots. To improve the accuracy of SOC estimates in U.S. forests, NFI SOC observations were used for the first time to predict SOC density to a depth of 100 cm for all forested NFI plots. Incorporating soil-forming factors along with observations of SOC into a new estimation framework resulted in a 75% (48 ± 0.78 Mg/ha) increase in SOC densities nationally. This substantially increases the contribution of the SOC pool, from approximately 44% (17 Pg) of the total forest ecosystem C stocks to 56% (28 Pg), in the forest C budget of the United States.

Attribution of net carbon change by disturbance type across forest lands of the conterminous United States.

BACKGROUND: Locating terrestrial sources and sinks of carbon (C) will be critical to developing strategies that contribute to the climate change mitigation goals of the Paris Agreement. Here we present spatially resolved estimates of net C change across United States (US) forest lands between 2006 and 2010 and attribute them to natural and anthropogenic processes. RESULTS: Forests in the conterminous US sequestered -460 ± 48 Tg C year-1, while C losses from disturbance averaged 191 ± 10 Tg C year-1. Combining estimates of net C losses and gains results in net carbon change of -269 ± 49 Tg C year-1. New forests gained -8 ± 1 Tg C year-1, while deforestation resulted in losses of 6 ± 1 Tg C year-1. Forest land remaining forest land lost 185 ± 10 Tg C year-1 to various disturbances; these losses were compensated by net carbon gains of -452 ± 48 Tg C year-1. C loss in the southern US was highest (105 ± 6 Tg C year-1) with the highest fractional contributions from harvest (92%) and wind (5%). C loss in the western US (44 ± 3 Tg C year-1) was due predominantly to harvest (66%), fire (15%), and insect damage (13%). The northern US had the lowest C loss (41 ± 2 Tg C year-1) with the most significant proportional contributions from harvest (86%), insect damage (9%), and conversion (3%). Taken together, these disturbances reduced the estimated potential C sink of US forests by 42%. CONCLUSION: The framework presented here allows for the integration of ground and space observations to more fully inform US forest C policy and monitoring efforts.

Monitoring Network Confirms Land Use Change is a Substantial Component of the Forest Carbon Sink in the eastern United States.

Quantifying forest carbon (C) stocks and stock change within a matrix of land use (LU) and LU change is a central component of large-scale forest C monitoring and reporting practices prescribed by the Intergovernmental Panel on Climate Change (IPCC). Using a region-wide, repeated forest inventory, forest C stocks and stock change by pool were examined by LU categories. In eastern US forests, LU change is a substantial component of C sink strength (~37% of forest sink strength) only secondary to that of C accumulation in forests remaining forest where their comingling with other LUs does not substantially reduce sink strength. The strongest sinks of forest C were study areas not completely dominated by forests, even when there was some loss of forest to agriculture/settlement/other LUs. Long-term LU planning exercises and policy development that seeks to maintain and/or enhance regional C sinks should explicitly recognize the importance of maximizing non-forest to forest LU changes and not overlook management and conservation of forests located in landscapes not currently dominated by forests.

Dental survey of the Falkland Islands' child population.

In November 2013 the first dental epidemiological survey of 5, 12 and 15 year old children was undertaken on The Falkland Islands. The census survey used the ICDAS II system and achieved an overall response rate of 87.4%. To allow international comparisons obvious decay experience is reported. The mean dmft of 5-year-olds was 1.2 teeth, the prevalence of decay experience was 34.6%. The mean DMFT of 12-year-old children was 0.9 teeth, the prevalence of decay experience was 36.7%. The mean DMFT of 15-year-olds was 1.78 teeth, and the prevalence of decay experience was 66.7%. This first dental survey showed that levels of child dental decay in the Falkland Islands are similar to western European countries. The results can now be used as a baseline and benchmark to follow future trends in dental health in this British Overseas Territory.

Increasing efficiency of BEAMnrc-simulated Co-60 beams using directional source biasing.

PURPOSE: This study describes the implementation of a directional source biasing (DSB) scheme for efficiently simulating Cobalt-60 treatment heads using the BEAMnrc Monte Carlo code. Previous simulation of Co-60 beams with BEAMnrc was impractical because of the time required to track photons not directed into the treatment field and to simulate secondary charged particles. METHODS: In DSB, efficiency is increased by splitting each photon emitted by the Co-60 source a user-defined number of times. Only those split primary photons directed into a user-defined splitting field (encompassing the treatment field) are sampled, yielding many low-weight photons directed into the field. Efficiency can be further increased by taking advantage of radial symmetry at the top of the treatment head to reduce the number of split primary photons tracked in this portion. There is also an option to generate contaminant electrons in DSB. RESULTS: The DSB scheme in BEAMnrc increases the photon fluence calculation efficiency in a 10 × 10 cm(2) Co-60 beam by a factor of 1800 with a concurrent increase in contaminant electron fluence calculation efficiency by a factor of 1200. Implementation of DSB in beampp, a C++ code for accelerator simulations based on EGSnrc and the C++ class library, egspp, increases photon fluence efficiency by a factor of 2800 and contaminant electron fluence efficiency by a factor of 1600. Optimum splitting numbers are in the range of 20,000-40,000. For dose calculations in a water phantom (0.5 × 0.5 × 0.5 cm(3) voxels) this translates into a factor of ∼400 increase in dose calculation efficiency (all doses > 0.5 × Dmax). An example calculation of the ratio of dose to water to dose to chamber (the basis of the beam quality correction factor) to within 0.2% in a realistic chamber using a full simulation of a Co-60 treatment head as a source indicates the practicality of Co-60 simulations with DSB. CONCLUSIONS: The efficiency improvement resulting from DSB makes Monte Carlo commissioning of Co-60 beams and calculation of beam quality correction factors feasible.

Building up and knocking down: an emerging role for epigenetics and proteasomal degradation in systems consolidation.

Memory formation is a protracted process in which recently acquired events are consolidated to produce stable and specific associations. Initially, newly acquired information undergoes cellular consolidation in the hippocampus, which transiently supports the storage of recently acquired memories. In contrast, remote, or "old" memories are maintained in the cortex and show almost complete independence from the hippocampus. Memories are transferred from the hippocampus to the cortex through a process termed systems consolidation. Emerging evidence suggests that recurrent activation, or "training" of the cortex by the hippocampus is vital to systems consolidation. This process involves prolonged waves of memory-related gene activity in the hippocampus and cortex long after the learning event has terminated. Indeed, molecular events occurring within hours and days of fear conditioning are essential for stabilizing and eventually transitioning the memory to the cortex. It is increasingly evident that molecular mechanisms that exhibit a capacity for prolonged activation may underlie systems consolidation. Processes that have the capacity to control protein abundance over long time scales, such as epigenetic modifications, are prime candidates for the molecular mechanism of systems consolidation. Indeed, recent work has established two types of epigenetic modifications as integral for systems consolidation. First, localized nucleosomal histone variant exchange and histone modifications are integral for early stages of systems consolidation, whereas DNA methylation appears to be utilized to form stable marks that support memory maintenance. Since systems consolidation also requires discrete and time-sensitive changes in protein abundance, additional mechanisms, such as protein degradation, need also be considered, although their role in systems consolidation has yet to be investigated. Here, we discuss the role of molecular mechanisms in systems consolidation and their implications for understanding how memories persist over time.

Net carbon flux of dead wood in forests of the Eastern US.

Downed dead wood (DDW) in forest ecosystems is a C pool whose net flux is governed by a complex of natural and anthropogenic processes and is critical to the management of the entire forest C pool. As empirical examination of DDW C net flux has rarely been conducted across large scales, the goal of this study was to use a remeasured inventory of DDW C and ancillary forest attributes to assess C net flux across forests of the Eastern US. Stocks associated with large fine woody debris (diameter 2.6-7.6 cm) decreased over time (-0.11 Mg ha(-1) year(-1)), while stocks of larger-sized coarse DDW increased (0.02 Mg ha(-1) year(-1)). Stocks of total DDW C decreased (-0.14 Mg ha(-1) year(-1)), while standing dead and live tree stocks both increased, 0.01 and 0.44 Mg ha(-1) year(-1), respectively. The spatial distribution of DDW C stock change was highly heterogeneous with random forests model results indicating that management history, live tree stocking, natural disturbance, and growing degree days only partially explain stock change. Natural disturbances drove substantial C transfers from the live tree pool (≈-4 Mg ha(-1) year(-1)) to the standing dead tree pool (≈3 Mg ha(-1) year(-1)) with only a minimal increase in DDW C stocks (≈1 Mg ha(-1) year(-1)) in lower decay classes, suggesting a delayed transfer of C to the DDW pool. The assessment and management of DDW C flux is complicated by the diversity of natural and anthropogenic forces that drive their dynamics with the scale and timing of flux among forest C pools remaining a large knowledge gap.

Strategies for directing the structure and function of three-dimensional collagen biomaterials across length scales.

Collagen type I is a widely used natural biomaterial that has found utility in a variety of biological and medical applications. Its well-characterized structure and role as an extracellular matrix protein make it a highly relevant material for controlling cell function and mimicking tissue properties. Collagen type I is abundant in a number of tissues, and can be isolated as a purified protein. This review focuses on hydrogel biomaterials made by reconstituting collagen type I from a solubilized form, with an emphasis on in vitro studies in which collagen structure can be controlled. The hierarchical structure of collagen from the nanoscale to the macroscale is described, with an emphasis on how structure is related to function across scales. Methods of reconstituting collagen into hydrogel materials are presented, including molding of macroscopic constructs, creation of microscale modules and electrospinning of nanoscale fibers. The modification of collagen biomaterials to achieve the desired structures and functions is also addressed, with particular emphasis on mechanical control of collagen structure, creation of collagen composite materials and crosslinking of collagenous matrices. Biomaterials scientists have made remarkable progress in rationally designing collagen-based biomaterials and in applying them both to the study of biology and for therapeutic benefit. This broad review illustrates recent examples of techniques used to control collagen structure and thereby to direct its biological and mechanical functions.

A simple scoring method using cardiometabolic risk measurements in pregnancy to determine 10-year risk of type 2 diabetes in women with gestational diabetes.

OBJECTIVE: To examine if clustering of cardiometabolic risk factors in pregnancy predicts type 2 diabetes and cardiovascular disease (CVD) risk at 10 years in women with gestational diabetes mellitus (GDM). STUDY DESIGN AND SUBJECTS: A prospective case-control study in 150 GDM and 72 overweight women with normal glucose tolerance (NGT) measured cardiometabolic risk factors (body mass index (BMI), systolic blood pressure (SBP), fasting glucose, insulin, and triglycerides and high-density lipoprotein (HDL) cholesterol) at 28 weeks gestation and 6 months and 10 years after pregnancy. Cluster analysis of cardiometabolic risk factors in pregnancy was used to stratify GDM as 'high' and 'low risk' for diabetes and CVD risk at 10 years. The data in pregnancy were used to determine a simple method for assessing risk of future diabetes. RESULTS: BMI in the 150 GDM at study entry was similar to NGT, but 35% of GDM fell into a 'high-risk cluster' with elevated BMI, SBP, glucose, insulin and triglycerides and lower HDL levels. At 10 years, type 2 diabetes was sixfold higher in 'high-risk' GDM (odds ratio (OR)=6.75, confidence interval (CI)=2.0, 22.7, P=0.002) compared with 'low-risk' GDM and was not reported in NGT. The 'high-risk' cluster predicted type 2 diabetes better than BMI>30 (OR=2.13, CI=0.71, 6.4, P=0.179) or fasting glucose >5.5 mmol l(-1), (OR=4.56, CI=1.50, 13.85, P=0.007). We determined that GDM with any four of the cardiometabolic risk factors (BMI>30 kg m(-2), fasting glucose>5.0 mmol l(-1), insulin>7.8 mU l(-1), triglycerides >2.4 mmol l(-1), HDL<1.6 mmol l(-1) or SBP>105 mm Hg) in pregnancy would be in a 'high-risk' cluster. CONCLUSIONS: A metabolic syndrome-like cluster in pregnant GDM identifies risk for type 2 diabetes providing an opportunity to focus on rigorous lifestyle interventions after delivery to reduce the burden of disease attributed to this condition.

Prevention of venous thromboembolism in patients admitted to Australian hospitals: summary of National Health and Medical Research Council clinical practice guideline.

Each year in Australia, about 1 in 1000 people develop a first episode of venous thromboembolism (VTE), which approximates to about 20,000 cases. More than half of these episodes occur during or soon after a hospital admission, which makes them potentially preventable. This paper summarises recommendations from the National Health and Medical Research Council's 'Clinical Practice Guideline for the Prevention of Venous Thromboembolism in Patients Admitted to Australian Hospitals' and describes the way these recommendations were developed. The guideline has two aims: to provide advice on VTE prevention to Australian clinicians and to support implementation of effective programmes for VTE prevention in Australian hospitals by offering evidence-based recommendations which local hospital guidelines can be based on. Methods for preventing VTE are pharmacological and/or mechanical, and they require appropriate timing, dosing and duration and also need to be accompanied by good clinical care, such as promoting mobility and hydration whilst in hospital. With some procedures or injuries, the risk of VTE is sufficiently high to require that all patients receive an effective form of prophylaxis unless this is contraindicated; in other clinical settings, the need for prophylaxis requires individual assessment. For optimal VTE prevention, all patients admitted to hospital should have early and formal assessments of: (i) their intrinsic VTE risk and the risks related to their medical conditions; (ii) the added VTE risks resulting from surgery or trauma; (iii) bleeding risks that would contraindicate pharmacological prophylaxis; (iv) any contraindications to mechanical prophylaxis, culminating in (v) a decision about prophylaxis (pharmacological and/or mechanical, or none). The most appropriate form of prophylaxis will depend on the type of surgery, medical condition and patient characteristics. Recommendations for various clinical circumstances are provided as summary tables with relevance to orthopaedic surgical procedures, other types of surgery and medical inpatients. In addition, the tables indicate the grades of supporting evidence for the recommendations (these range from Grade A which can be trusted to guide practice, to Grade D where there is more uncertainty; Good Practice Points are consensus-based expert opinions).

PP030. Cardiovascular disease and risk in a pregnant woman's father as a risk factor for preeclampsia.

INTRODUCTION: In women experiencing their first pregnancy the assessment of risk of developing a hypertensive disorder of pregnancy (HDP) including preeclampsia is imprecise. Identification of women at higher than normal risk of developing preeclampsia may improve pregnancy management and lead to better outcomes. Previous studies, mostly retrospective, have indicated a possible link between cardiovascular history and risk of preeclampsia. OBJECTIVES: To evaluate the self-reported family history of cardiovascular disease and risk (CVD/R) during an antenatal interview as a means of screening for risk of developing preeclampsia or other HDP. METHODS: Nulliparous women were recruited prospectively in early pregnancy before diagnosis of any HDP. Women reported on their maternal characteristics and the history of cardiovascular health in themselves, their parents and siblings and the father of the baby and his parents and siblings. Cardiovascular health was assessed as cardiovascular risk (high blood pressure, high cholesterol and diabetes) and cardiovascular disease (heart attack, stroke, angina and any major vascular surgery). Pregnancy outcomes were recorded after delivery, the diagnoses of gestational hypertension, preeclampsia and superimposed preeclampsia being assigned according to the criteria defined by SOMANZ, 2008. A nominal logistic regression analysis was used to evaluate the effects of family history on risk of developing HDP while adjusting for clinical risk factors known at the time of recruitment. RESULTS: Nine hundred and ninety-seven women completed the study. Median gestational age at recruitment was 31.3weeks (Interquartile range [IQR] 24.4-35.9, range 5.6-39.1). Median age was 27.0years (IQR 23.0-32.0, range 16.0-45.0), median BMI was 28.6 (IQR 24.8-36.4, range 16.7-64.4) and 76.4% of the women did not smoke during the pregnancy. Preeclampsia was diagnosed in 12.6% of the women (103/997 preeclampsia, 23/997 superimposed) and 6.2% developed gestational hypertension (62/997). CVD/R was reported by 22.3% of mothers (including 1.7% of CVD alone) and in 9.3% of the partners (including 1.7% of CVD alone). Women reported CVD/R in 39.1% of their mothers (including 6.5% CVD alone) and in 42.2% (including 13.3% CVD alone) of their fathers. Women reported CVD/R in 30.3% (including 6.1% CVD alone) of the partners' mothers and in 38.9% (including 15.0% CVD alone) of the partners' fathers. Women who knew of CVD/R in their fathers had increased risk of preeclampsia (16.2% vs. 10.1%; Odds Ratio [OR]=.66 95% Confidence Interval [CI] 1.16-2.36, p=.005) that remained elevated after adjustments for maternal age, BMI, smoking in pregnancy and maternal CVD/R. No similar increase in risk of gestational hypertension was evident (7.4% vs. 5.4%; OR=1.31 95% CI0.81-2.10,p=0.272). CVD/R reported for any other family member did not significantly alter the woman's risk of developing preeclampsia or any other HDP. CONCLUSION: The presence of a history of CVD/R in the father of the pregnant woman indicated an increased risk of developing preeclampsia. The possibility of a similar association between CVD/R in other family members and HDP may exist however women in their first pregnancy may not have sufficient knowledge of family history. This lack of comprehensive information may limit the potential value of family history in determining the risk of preeclampsia and other hypertensive disorders in pregnancy.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Dose to medium versus dose to water as an estimator of dose to sensitive skeletal tissue.

The purpose of this study is to determine whether dose to medium, D(m), or dose to water, D(w), provides a better estimate of the dose to the radiosensitive red bone marrow (RBM) and bone surface cells (BSC) in spongiosa, or cancellous bone. This is addressed in the larger context of the ongoing debate over whether D(m) or D(w) should be specified in Monte Carlo calculated radiotherapy treatment plans. The study uses voxelized, virtual human phantoms, FAX06/MAX06 (female/male), incorporated into an EGSnrc Monte Carlo code to perform Monte Carlo dose calculations during simulated irradiation by a 6 MV photon beam from an Elekta SL25 accelerator. Head and neck, chest and pelvis irradiations are studied. FAX06/MAX06 include precise modelling of spongiosa based on microCT images, allowing dose to RBM and BSC to be resolved from the dose to bone. Modifications to the FAX06/MAX06 user codes are required to score D(w) and D(m) in spongiosa. Dose uncertainties of approximately 1% (BSC, RBM) or approximately 0.5% (D(m), D(w)) are obtained after up to 5 days of simulations on 88 CPUs. Clinically significant differences (>5%) between D(m) and D(w) are found only in cranial spongiosa, where the volume fraction of trabecular bone (TBVF) is high (55%). However, for spongiosa locations where there is any significant difference between D(m) and D(w), comparisons of differential dose volume histograms (DVHs) and average doses show that D(w) provides a better overall estimate of dose to RBM and BSC. For example, in cranial spongiosa the average D(m) underestimates the average dose to sensitive tissue by at least 5%, while average D(w) is within approximately 1% of the average dose to sensitive tissue. Thus, it is better to specify D(w) than D(m) in Monte Carlo treatment plans, since D(w) provides a better estimate of dose to sensitive tissue in bone, the only location where the difference is likely to be clinically significant.

Skeletal dosimetry in cone beam computed tomography.

Cone beam computed tomography (CBCT) is a relatively new patient imaging technique that has proved invaluable for treatment target verification and patient positioning during image-guided radiotherapy (IGRT). It has been shown that CBCT results in additional dose to bone that may amount to 10% of the prescribed dose. In this study, voxelized human phantoms, FAX06 (adult female) and MAX06 (adult male), are used together with phase-space data collected from a realistic model of a CBCT imager to calculate dose in the red bone marrow (RBM) and bone surface cells (BSCs), the two organs at risk within the bone spongiosa, during simulated head and neck, chest and pelvis CBCT scans. The FAX06/MAX06 phantoms model spongiosa based on micro-CT images, filling the relevant phantom voxels, which are 0.12 x 0.12 x 0.12 cm3, with 17 x 17 x 17 microm3 microvoxels to form a micromatrix of trabecular bone and bone marrow. FAX06/ MAX06 have already been implemented in an EGSnrc-based Monte Carlo code to simulate radiation transport in the phantoms; however, this study required significant modifications of the code to allow use of phase-space data from a simulated CBCT imager as a source and to allow scoring of total dose, RBM dose and BSC dose on a voxel-by-voxel basis. In simulated CBCT scans, the BSC dose is significantly greater than the dose to other organs at risk. For example, in a simulated head and neck scan, the average BSC dose is 25% higher than the average dose to eye lens (approximately 8.3 cGy), and 80% greater than the average dose to brain (5.7 cGy). Average dose to RBM, on the other hand, is typically only approximately 50% of the average BSC dose and less than the dose to other organs at risk (54% of the dose to eye lens and 76% of dose to brain in a head and neck scan). Thus, elevated dose in bone due to CBCT results in elevated BSC dose. This is potentially of concern when using CBCT in conjunction with radiotherapy treatment.