Search

It is well known that activity in, or coordination among, brain regions, can underlie movement, sensation, language, and cognition but there are observations that tasks unrelated to specific brain regions can nonetheless alter activity in those regions. These tasks might invoke activity in multiregional networks, but it also is possible that they are associated with changes beyond these networks. We therefore evaluated the possibility that more widespread, or even whole-cortical, mechanisms might complement or alter focal or multifocal cortical activity.We assessed the extent of electroencephalographic changes occurring outside areas with epileptiform activity, but that were associated with termination of the epileptiform activity. To do this, we measured the distribution of wavelet cross-coherence changes based on electrocorticography from 15 patients who showed regional afterdischarges in response to electrical brain stimulation prior to epilepsy surgery and in whom cognitive tasks were used in attempts to end the afterdischarges. There were 1276 electrodes implanted in these patients, and we analyzed a total of 55,494 electrode combinations. We compared recordings when cognitive effort was versus when it was not successful in ending afterdischarges.We found that when afterdischarges were suppressed there were changes in electrocorticographic coherence that were similar throughout cortex, regardless of the distance between sites.The similarity implies coordination of the changes, and the similarity regardless of distance or location implies a pan-cortical effect.Our results provide physical support for hypotheses that pan-cortical processes complement the well-known regional and multiregional networks. These processes may participate in, be recruited by, modify, or underlie the conative experiences of waking life.

The Exploring for the Future (EFTF) program is an Australian government initiative to boost investment in resource exploration and development in Australia, and is committed to supporting a strong economy, resilient society and sustainable environment for the benefit of Australians. There are a number of interrelated projects within the EFTF, including the Australia’s Resources Framework (ARF) project. The latter is a continental-scale project aimed at laying the foundations for a national view of Australia’s surface and subsurface geology, to underpin our understanding of the continent’s mineral, energy and groundwater potential. The ARF project involves new, large-scale data acquisition, advances in big data analytics and tailored resource assessments, to support the resource sector, agriculture, remote communities and the environment, and contribute to community safety. As part of ARF, Geoscience Australia has been undertaking studies of Australian basins that are prospective for, or have potential for, basin-hosted base metal mineral systems (Pb-Zn, Co-Cu), as part of the basins module. The first component of this module (2016-2020) investigated the Paleoproterozoic to Mesoproterozoic greater McArthur Basin system, Northern Territory and western Queensland (Champion et al., 2020 a, b, c; Huston et al. 2020). The 2020-2024 module is focusing on the Neoproterozoic part of the Stuart Shelf region of the Adelaide Superbasin, South Australia. The Paleo- to Mesoproterozoic sedimentary and volcanic sequences of the Mount Isa–McArthur Basin region of Northern Territory and Queensland are host to a range of world class mineral deposits (Hutton et al., 2012) and include the basin-hosted base metal deposits of the North Australian Zinc Belt, the world’s richest belt of zinc deposits (Huston et al., 2006; Large et al., 2005). These syngenetic (and epigenetic) basin-hosted mineral deposits include McArthur River (formerly HYC) and Century lead-zinc (Pb-Zn) deposits, the Walford Creek Zn-Pb-Cu-Ag deposit (Rohrlach et al., 1998; Large et al., 2005; Hutton et al. 2012) and the Redbank Cu deposit (Knutson et al. 1979). The Neoproterozoic sedimentary sequences of the Stuart Shelf, and their continuation into the Torrens Hinge Zone and Adelaide Rift Complex (Adelaide Superbasin), South Australia, are host to, or form an integral part of, a number of, often historically important, deposits, including the first copper mining region in Australia. These include, amongst others, the Kapunda, Mt Gunson, Cattle Grid, MG14, Windabout, Myall Creek, and Emmie Bluff copper deposits (Lambert et al. 1980, 1984, 1985 1987; Knutson et al. 1983; Coda Minerals 2020, 2021). These deposits are hosted within the Neoproterozoic sediments or along the basal unconformity with older Mesoproterozoic clastic sedimentary rocks (Lambert et al. 1987). This report contains reanalysed geochemical data, and associated sample metadata, for legacy samples collected by the Baas Becking laboratories in the 1970’s from deposits and surrounds in the MacArthur Basin and Stuart Shelf region. This includes samples (mafic igneous rocks, mineralised samples and sedimentary rocks) from the Redbank Cu deposit and surrounds in the McArthur Basin, partly documented in Knutson et al. (1979); samples (sediments, mafic igneous rocks including basement volcanic units (Gawler Range Volcanics), and mineralised samples) from the Mt Gunson deposit and surrounds (Mt Gunson-Lake Dutton area) documented in Knutson et al. (1983, 1992); and a small subset of five samples (sediments, variably mineralised) from the Myall Creek prospect, documented in Lambert et al. (1984). The great majority of these samples are from drill core, with the full list of samples analyses and metadata listed in Appendix A and summarised in Table 1. This data release also includes 52 samples from the Killi Killi Hills regions and surrounds, Tanami, Northern Territory (jobno 9004424), collected by the NTGS and GA, and originally analysed, in the early 1990’s and early 2000’s. These samples included a subset of P2O5-Sr-HREE-enriched Gardiner Sandstone samples from the Killi Killi Hills prospect. These samples are not directly related to the basins project but have been included as they were analysed at the same time as the Stuart Shelf and Redbank samples, and they increase the number of samples and the range of rock types analysed, and so help with statistics for QA/QC purposes. All geochemical data are provided in the appendices, listed by batch. The data can be downloaded via the Geoscience Australia EFTF portal (https://portal.ga.gov.au/persona/eftf).

Despite decades of effort toward reducing nitrogen and phosphorus flux to Chesapeake Bay, water-quality and ecological responses in surface waters have been mixed. Recent research, however, provides useful insight into multiple factors complicating the understanding of nutrient trends in bay tributaries, which we review in this paper, as we approach a 2025 total maximum daily load (TMDL) management deadline. Improvements in water quality in many streams are attributable to management actions that reduced point sources and atmospheric nitrogen deposition and to changes in climate. Nutrient reductions expected from management actions, however, have not been fully realized in watershed streams. Nitrogen from urban nonpoint sources has declined, although water-quality responses to urbanization in individual streams vary depending on predevelopment land use. Evolving agriculture, the largest watershed source of nutrients, has likely contributed to local nutrient trends but has not affected substantial changes in flux to the bay. Changing average nitrogen yields from farmland underlain by carbonate rocks, however, may suggest future trends in other areas under similar management, climatic, or other influences, although drivers of these changes remain unclear. Regardless of upstream trends, phosphorus flux to the bay from its largest tributary has increased due to sediment infill in the Conowingo Reservoir. In general, recent research emphasizes the utility of input reductions over attempts to manage nutrient fate and transport at limiting nutrients in surface waters. Ongoing research opportunities include evaluating effects of climate change and conservation practices over time and space and developing tools to disentangle and evaluate multiple influences on regional water quality.

Etherification of 5-hydroxymethylfurfural (HMF) and ethanol to yield ethoxymethylfurfural (EMF) is an important reaction for producing diesel blendstocks from biomass resources. This aqueous-phase ...

We report on the vapochromic behavior of a series of homo- and heterometallic copper(i) iodide/silver(i) iodide nanoparticles when exposed to dimethyl sulfide (DMS) vapor. These systems show remarkable colorimetric sensing behavior via emission color upon DMS exposure, shifting from pink to green emission. Kinetics measurements of CuI/AgI nanoparticle reactions with DMS show a significant rate increase with increasing Ag(i) content. However, luminescence spectroscopy and X-ray diffraction of the post-exposure samples with varying Ag(i) content reveal that the luminophore is identical in all cases and contains no Ag(i) ions. To rationalize the experimental observations and determine the vapochromic response mechanism, molecular dynamic calculations were performed on model (111) cation-terminated surfaces of copper iodide crystals doped with variable amounts of silver. Computational studies indicate that heterometallic Cu/Ag systems have a stronger binding affinity towards DMS vapor molecules than homometallic CuI and that embedding of the DMS molecules into the surface is the primary intermediate by which the vapochromic response occurs.

Background Individuals with quiescent inflammatory bowel diseases (IBD) can continue to have several symptoms. Physical activity (PA) can improve immunological response and psychological health. Purpose We performed a systematic review of trials investigating the safety and efficacy of PA as an adjunct therapy to manage persistent symptoms in quiescent or mildly active IBD. Method We searched for randomised controlled trials (RCTs) and nonrandomised non-controlled trials (non-RCTs) in eight databases, trial registries and conference proceedings, published in English between 2011 and 2021. We focused on trials in adults (>18 years) using any form of PA as an adjunct therapy to medical therapy. Outcomes of interest were health-related quality of life, fatigue, joint pain, abdominal pain, stress, anxiety, and depression. Result(s) From 10,862 retrieved citations, we identified seven RCTs and one non-RCT that met our inclusion criteria. All trials deemed PA safe for individuals with quiescent or mildly active IBD. Clinical heterogeneity was noted among the trials for all outcomes. Six RCTs utilized parallel-group design while one utilized a cross-over design. Seven trials provided partially or fully supervised PA interventions, and one provided no supervision. All trials used different types of PA, which varied between running, resistance training, yoga, and aerobic exercises. The trials used different parameters to measure PA intensity including Peak Power Output, Resistance Intensity Scale for Exercise, percentage of maximum heart rate, ability to talk while running. Heterogeneity was noted in the duration and frequency of PA. Conclusion(s) Even though PA is safe for individuals with quiescent or mildly active IBD, heterogeneity in available trials make it difficult to ascertain precise estimates of treatment effect. This also presents a challenge when determining the specific modes of PA that are beneficial for individuals with quiescent or mildly active IBD. This highlights the need for standardization of the definitions of parameters involved in PA in IBD research. Please acknowledge all funding agencies by checking the applicable boxes below CAG Disclosure of Interest None Declared

To determine whether mitigating the harmful effects of circulating microvesicle-associated inducible nitric oxide (MV-A iNOS) in vivo increases the survival of challenged mice in three different mouse models of sepsis, the ability of anti-MV-A iNOS monoclonal antibodies (mAbs) to rescue challenged mice was assessed using three different mouse models of sepsis. The vivarium of a research laboratory Balb/c mice were challenged with an LD80 dose of either lipopolysaccharide (LPS/endotoxin), TNFα, or MV-A iNOS and then treated at various times after the challenge with saline as control or with an anti-MV-A iNOS mAb as a potential immunotherapeutic to treat sepsis. Each group of mice was checked daily for survivors, and Kaplan–Meier survival curves were constructed. Five different murine anti-MV-A iNOS mAbs from our panel of 24 murine anti-MV-A iNOS mAbs were found to rescue some of the challenged mice. All five murine mAbs were used to genetically engineer humanized anti-MV-A iNOS mAbs by inserting the murine complementarity-determining regions (CDRs) into a human IgG1,kappa scaffold and expressing the humanized mAbs in CHO cells. Three humanized anti-MV-A iNOS mAbs were effective at rescuing mice from sepsis in three different animal models of sepsis. The effectiveness of the treatment was both time- and dose-dependent. Humanized anti-MV-A iNOS rHJ mAb could rescue up to 80% of the challenged animals if administered early and at a high dose. Our conclusions are that MV-A iNOS is a novel therapeutic target to treat sepsis; anti-MV-A iNOS mAbs can mitigate the harmful effects of MV-A iNOS; the neutralizing mAb’s efficacy is both time- and dose-dependent; and a specifically targeted immunotherapeutic for MV-A iNOS could potentially save tens of thousands of lives annually and could result in improved antibiotic stewardship.

ObjectiveTo determine if mitigating the harmful effects of circulating microvesicle-associated inducible nitric oxide (MV-A iNOS) in vivo increases the survival of challenged mice in three different mouse models of sepsis.DesignThe ability of anti-MV-A iNOS monoclonal antibodies (mAbs) to rescue challenged mice was assessed using three different mouse models of sepsis.SettingThe vivarium of a research laboratorySubjectsBalb/c miceInterventions: Mice were challenged with an LD80 dose of either lipopolysaccharide (LPS / endotoxin), TNFα, or MV-A iNOS and then treated at various times after the challenge with saline as control or with an anti-MV-A iNOS mAb as a potential immunotherapeutic to treat sepsis.Measurement and Main ResultsEach group of mice was checked daily for survivors, and Kaplan-Meier survival curves were constructed. Five different murine anti-MV-A iNOS mAbs from our panel of 24 murine anti-MV-A iNOS mAbs (1) were found to rescue some of the challenged mice. All five murine mAbs were used to genetically engineer humanized anti-MV-A iNOS mAbs by inserting the murine complementarity-determining regions (CDRs) into a human IgG1,kappa scaffold and expressing the humanized mAbs in CHO cells. Three humanized anti-MV-A iNOS mAbs were effective at rescuing mice from sepsis in three different animal models of sepsis. The effectiveness of the treatment was both time and dose dependent. Humanized anti-MV-A iNOS rHJ mAb could rescue up to 80% of the challenged animal if administered early and at a high dose.ConclusionsOur conclusions are MV-A iNOS is a novel therapeutic target to treat sepsis; anti-MV-A iNOS mAbs can mitigate the harmful effects of MV-A iNOS; the neutralizing mAb’s efficacy is both time and dose dependent; and a specifically targeted immunotherapeutic for MV-A iNOS could potentially save tens-of-thousands of lives annually and could result in improved antibiotic stewardship.

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 to 55 years were included. These factors were categorized and summed into a clinical CVH score ranging from 0 (worst) to 8 (best). Adjusted, segmented, linear mixed models were used to estimate the change in CVH over time. Among the 18,343 participants, 9,461 (52%) were female and 12,346 (67%) were White. The baseline mean (standard deviation) clinical CVH score was 6.9 (1.2) at an average age of 17.6 (8.1) years. Two inflection points were estimated: at 16.9 years (95% confidence interval: 16.4, 17.4) and at 37.2 years (95% confidence interval: 32.4, 41.9). Late adolescence and early middle age appear to be influential periods during which the loss of CVH accelerates.

A number of statistical approaches have been developed to quantify the overall trend in river water quality, but most approaches are not intended for reporting separate trends for different flow conditions. We propose an approach called FN2Q, which is an extension of the flow-normalization (FN) procedure of the well-established WRTDS (“Weighted Regressions on Time, Discharge, and Season”) method. The FN2Q approach provides a daily time series of low-flow and high-flow FN flux estimates that represent the lower and upper half of daily riverflow observations that occurred on each calendar day across the period of record. These daily estimates can be summarized into any time period of interest (e.g., monthly, seasonal, or annual) for quantifying trends. The proposed approach is illustrated with an application to a record of total nitrogen concentration (632 samples) collected between 1985 and 2018 from the South Fork Shenandoah River at Front Royal, Virginia (USA). Results show that the overall FN flux of total nitrogen has declined in the period of 1985–2018, which is mainly attributable to FN flux decline in the low-flow class. Furthermore, the decline in the low-flow class was highly correlated with wastewater effluent loads, indicating that the upgrades of treatment technology at wastewater treatment facilities have likely led to water-quality improvement under low-flow conditions. The high-flow FN flux showed a spike around 2007, which was likely caused by increased delivery of particulate nitrogen associated with sediment transport. The case study demonstrates the utility of the FN2Q approach toward not only characterizing the changes in river water quality but also guiding the direction of additional analysis for capturing the underlying drivers. The FN2Q approach (and the published code) can easily be applied to widely available river monitoring records to quantify water-quality trends under different flow conditions to enhance understanding of river water-quality dynamics. (Journal article: https://doi.org/10.1016/j.scitotenv.2020.143562; R code and data release: https://doi.org/10.5066/P9LBJEY1).

BackgroundThe current International Society of Clinical Densitometry (ISCD) recommendation for bone densitometry practice is that single hip measurement is sufficient in clinical practice, as there is overall a good correlation between the two hip bone mineral densities (BMD) (1) (2). However, discordance in individual T- scores and BMD between the 2 hips due to increasing age and osteoarthritis (3)-(5) is well recognised.ObjectivesWe aimed to identify whether discordant hip BMD values would lead to differences in the FRAX risk assessment score between the two hips, and thereby impact treatment decisions in clinical practice.MethodsWe looked at all DXA scans performed at our centre for 2 months between 23/7/21 and 23/9/21. Cases in which both hips were scanned and anti-resorptive treatment was advised were included in our study. The femoral neck with the lower BMD is used to calculate the FRAX score and this was referred to as the ‘reported’ hip. The FRAX score for ‘reported’ and ‘unreported’ hip were calculated and the T-score of the spine was also noted. Our local treatment threshold is set at 20% for a major osteoporotic fracture and 5% for hip fracture. Cases of difference in scores crossing the 20%/5% FRAX threshold were highlighted and reviewed in more detail.ResultsDXA scans were performed in 328 patients over the 2 month period, of which 201 patients had both of their hips scanned. Of these, 50 patients were advised to start anti-resorptive treatment. The majority of the treatment decisions (60%; 30/50 cases) were based on the hip/femoral neck BMD value, while 40% (20/50 cases) were based on the spine T-score.Where the treatment decision was based on hip/femoral neck BMD, 20% (6/30 cases) were found to have a FRAX risk above the treatment threshold at one hip only, meaning that treatment may not have been offered if both hips had not been scanned. Similarly, where treatment was advised based on spinal T-scores, 20% (4/20 cases) had a FRAX risk above treatment threshold at one hip only.Mean age across these 10 cases with a discordant FRAX risk between the two hips was 72 years (range 59 – 83); 80% (8/10) were female. Steroid use and chronic inflammatory co-morbidities were the predominant indications for these DXA Scans.ConclusionA significant proportion of patients in our cohort (20%; 10/50) may not have been offered treatment if only one hip was scanned. Scanning both hips does not require much additional time and can help mitigate the risk of undertreating patients. The recommendation for best practice for DXA BMD measurements should be reviewed to consider lumbar spine and dual hip BMD as standard of care.References[1]E. Michael Lewiecki, Nelson B. Watts, Michael R. McClung, Steven M. Petak, Laura K. Bachrach, John A. Shepherd, Robert W. Downs, Jr., Official Positions of the International Society for Clinical Densitometry, The Journal of Clinical Endocrinology & Metabolism, Volume 89, Issue 8, 1 August 2004, Pages 3651–3655, https://doi.org/10.1210/jc.2004-0124[2]Rao AD, Reddy S, Rao DS. Is there a difference between right and left femoral bone density? J Clin Densitom. 2000 Spring;3(1):57-61. doi: 10.1385/jcd:3:1:057. PMID: 10745302.[3]Chen W, Khan Z, Freund J, Pocock N. Dual Hip DXA. Is it Time to Change Standard Protocol? J Clin Densitom. 2021 Jul 24:S1094-6950(21)00060-3. doi: 10.1016/j.jocd.2021.07.006. Epub ahead of print. PMID: 34391641.[4]Mounach A, Rezqi A, Ghozlani I, Achemlal L, Bezza A, El Maghraoui A. Prevalence and Risk Factors of Discordance between Left- and Right-Hip Bone Mineral Density Using DXA. ISRN Rheumatol. 2012;2012:617535. doi: 10.5402/2012/617535. Epub 2012 Jun 17. PMID: 22778990; PMCID: PMC3384949.[5]Nishizawa K, Harato K, Morishige Y, Kobayashi S, Niki Y, Nagura T. Correlation between weight-bearing asymmetry and bone mineral density in patients with bilateral knee osteoarthritis. J Orthop Surg Res. 2021;16(1):102. Published 2021 Feb 2. doi:10.1186/s13018-021-02252-5.Disclosure of InterestsAishwarya Anilkumar: None declared, Sadaf Saeed: None declared, Ehsan Elsayed: None declared, Chandrin N. R. Jayatilleke: None declared, Stuart Webber: None declared, Mathew A. Roy Consultant of: Worked as a paid consultant for Kyowa Kirin.

A number of statistical approaches have been developed to quantify the overall trend in river water quality, but most approaches are not intended for reporting separate trends for different flow conditions. We propose an approach called FN2Q, which is an extension of the flow-normalization (FN) procedure of the well-established WRTDS ("Weighted Regressions on Time, Discharge, and Season") method. The FN2Q approach provides a daily time series of low-flow and high-flow FN flux estimates that represent the lower and upper half of daily riverflow observations that occurred on each calendar day across the period of record. These daily estimates can be summarized into any time period of interest (e.g., monthly, seasonal, or annual) for quantifying trends. The proposed approach is illustrated with an application to a record of total nitrogen concentration (632 samples) collected between 1985 and 2018 from the South Fork Shenandoah River at Front Royal, Virginia (USA). Results show that the overall FN flux of total nitrogen has declined in the period of 1985-2018, which is mainly attributable to FN flux decline in the low-flow class. Furthermore, the decline in the low-flow class was highly correlated with wastewater effluent loads, indicating that the upgrades of treatment technology at wastewater treatment facilities have likely led to water-quality improvement under low-flow conditions. The high-flow FN flux showed a spike around 2007, which was likely caused by increased delivery of particulate nitrogen associated with sediment transport. The case study demonstrates the utility of the FN2Q approach toward not only characterizing the changes in river water quality but also guiding the direction of additional analysis for capturing the underlying drivers. The FN2Q approach (and the published code) can easily be applied to widely available river monitoring records to quantify water-quality trends under different flow conditions to enhance understanding of river water-quality dynamics.

Introduction: This study examines sex differences in the prevalence of low clinical cardiovascular health (CVH) scores from ages 8-50 years old. Methods: Five cardiovascular cohorts (Bogalusa, Young Finns, HB!, CARDIA, and STRIP) were used to create a pooled cohort spanning from ages 8 to 50 years old. The American Heart Association criteria for poor, intermediate and ideal levels for 4 CVH factors (blood pressure, BMI, cholesterol, and glucose) were summed to calculate a clinical CVH score (range 0-8; higher being more ideal). Sex differences in the prevalence rates of low clinical CVH by age group (defined as a score ≤3) were estimated using logistic regression models. Results: Sex differences were examined among 9,386 participants with data on clinical CVH (56% female, 66% White and average follow-up time of 23 yrs). The prevalence of low clinical CVH increased for both men and women with age from 0.72% at age 8-14 yrs to 15% at 45-50 yrs of age in women and from 0.44% at ages 8-14 yrs to over 23% at ages 45-50 yrs in men. There were no significant sex differences in the prevalence of low clinical CVH at younger ages (8-20 years old, p>0.05). Between the ages of 21-26 years old, males were 2 times more likely to have low clinical CVH than women (odds ratio [OR] 2.2, 95% confidence interval [CI], 1.4-3.4). Sex differences in the prevalence of low clinical CVH persisted through adulthood and with only a slight decrease by ages 45-50 years old (OR 1.6, 95%CI 1.4-1.9). Conclusions: Sex differences in the prevalence of low clinical CVH change over the lifetime. In childhood the prevalence of low clinical CVH is similar. By young adulthood, men are more than twice more likely to have low clinical CVH than women; that sex difference is maintained throughout middle age. Understanding the reasons for the growing sex differences in the prevalence of low clinical CVH with age may help to identify targets for primordial prevention, especially prevention strategies to target young men.

Antibodies are immunoglobulin proteins secreted by activated B lymphocytes as part of the adaptive immune response. Antibodies of known binding specificity, including polyclonal antisera, monoclonal antibodies, and more recently recombinant antibodies, are widely used in biomedical research for a variety of immunological assays due to their highly specific antigen (analyte) recognition. Antibodies are the cornerstones on which much basic research, drug development, and clinical in vitro diagnostic tests are based. However, locating an existing antibody for a specific application is often difficult. In this chapter a step-by-step guide of how to find a suitable antibody for conducting research on traumatic brain injury is described. A flexible approach is presented for how to evaluate and characterize an antibody and how to validate the immunoassay using the antibody to detect or measure a specific TBI analyte for successful, repeatable, and reproducible biomarker analysis.

Down syndrome (DS), characterized by trisomy of human chromosome 21, is associated with a variety of endocrine disorders as well as profound skeletal abnormalities. The low bone mass phenotype in DS is defined by low bone turnover due to decreased osteoclast and osteoblast activity, decreasing the utility of antiresorptive agents in people with DS. Sclerostin antibody (SclAb) is a therapeutic candidate currently being evaluated as a bone anabolic agent. Scl, the product of the sclerostin gene (SOST), inhibits bone formation through its inhibition of Wnt signaling. SclAb increases bone mass by suppressing the action of the endogenous inhibitor of bone formation, Scl. To examine the effects of SclAb on the DS bone phenotype, 8‐week‐old male wild‐type (WT) andTs65Dn DS mice were treated with 4 weekly iv injections of 100 mg/kg SclAb. Dual‐energy X‐ray absorptiometry (DXA), microCT, and dynamic histomorphometry analyses revealed that SclAb had a significant anabolic effect on both age‐matched WT littermate controls and Ts65Dn DS mice that was osteoblast mediated, without significant changes in osteoclast parameters. SclAb treatment significantly increased both cortical and trabecular bone mass at multiple sites; SclAb treatment resulted in the normalization of Ts65Dn bone mineral density (BMD) to WT levels in the proximal tibia, distal femur, and whole body. Ex vivo bone marrow cultures demonstrated that SclAb increased the recruitment of the mesenchymal progenitors into the osteoblast lineage, as indicated by increased alkaline phosphatase–positive colonies, with no effect on osteoclast differentiation. Together, in the setting of a murine model of DS and decreased bone turnover, SclAb had a potent anabolic effect. SclAb stimulated bone formation and increased osteoblastogenesis without affecting osteoclastogenesis or bone resorption. These data suggest that SclAb is a promising new therapy to improve bone mass and reduce fracture risk in the face of the low bone mass and turnover prevalent in the DS population. © 2017 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Morphological imperfections of mixed-cellulose ester filters and their possible influence on sample preparation and analysis of asbestos were examined. Filters were identified with large regions of non-porous “dead zones” which could negatively affect fiber deposition and, therefore, fiber recovery and analysis by Transmission Electron Microscopy (TEM). As these imperfections are effectively erased during the preparation of the sample, they may not be readily observed by TEM. Un-collapsed filters as well as those collapsed using dimethylformamide (DMF) and two acetone techniques were examined. In order to minimize negative sampling and analytical bias, it is suggested that MCE samples be collapsed utilizing a 35% DMF solution, etched with a correctly calibrated low-temperature etcher, carbon coated using a rotating and tilted stage, and analyzed with a strong analyst-independent grid square opening randomization scheme.

To evaluate several adult diabetes risk calculation tools for predicting the development of incident diabetes and pre-diabetes in a bi-racial, young adult population.Surveys beginning in young adulthood (baseline age ≥18) and continuing across multiple decades for 2122 participants of the Bogalusa Heart Study were used to test the associations of five well-known adult diabetes risk scores with incident diabetes and pre-diabetes using separate Cox models for each risk score. Racial differences were tested within each model. Predictive utility and discrimination were determined for each risk score using the Net Reclassification Index (NRI) and Harrell's c-statistic.All risk scores were strongly associated (p.0001) with incident diabetes and pre-diabetes. The Wilson model indicated greater risk of diabetes for blacks versus whites with equivalent risk scores (HR=1.59; 95% CI 1.11-2.28; p=.01). C-statistics for the diabetes risk models ranged from 0.79 to 0.83. Non-event NRIs indicated high specificity (non-event NRIs: 76%-88%), but poor sensitivity (event NRIs: -23% to -3%).Five diabetes risk scores established in middle-aged, racially homogenous adult populations are generally applicable to younger adults with good specificity but poor sensitivity. The addition of race to these models did not result in greater predictive capabilities. A more sensitive risk score to predict diabetes in younger adults is needed.

Background The sepsis pathology remains an enormous medical problem globally because morbidity and mortality remain unacceptably high in septic patients despite intense research efforts. The economic and societal burden of sepsis makes it the most pressing patient care issue in the US and worldwide. Sepsis is a dysregulated immune response normally initiated by an infection. The need for an early, accurate, and reliable biomarker test to detect the onset of sepsis and for a targeted sepsis therapy is widely recognized in the biomedical community. Content This report reviews the published findings relevant to microvesicle-associated inducible nitric oxide synthase (MV-A iNOS) as a novel plasma biomarker for the onset of sepsis, including human clinical studies and animal studies. Plasma iNOS as both a standalone test and 1 of the components of a novel panel of biomarkers to stage the progression of sepsis is presented and discussed in comparison with other biomarkers and other proposed panels of biomarkers for sepsis. Summary The data strongly support the concept that extracellular plasma MV-A iNOS in circulating microvesicles is centrally involved in the initiation of sepsis, and a diagnostic test based on plasma iNOS can serve as an early presymptomatic warning signal for the onset of sepsis. A novel panel of plasma biomarkers comprising iNOS, pro-interleukin-18, pro-interleukin-33, and regenerating protein 1-α is proposed as a multianalyte presymptomatic method to stage the onset of sepsis for improved, prompt, data-driven patient care.

We have developed a small animal conformal radiation therapy device that provides a degree of geometrical/anatomical targeting comparable to what is achievable in a commercial animal irradiator. small animal conformal radiation therapy device is capable of producing precise and accurate conformal delivery of radiation to target as well as for imaging small animals. The small animal conformal radiation therapy device uses an X-ray tube, a robotic animal position system, and a digital imager. The system is in a steel enclosure with adequate lead shielding following National Council on Radiation Protection and Measurements 49 guidelines and verified with Geiger-Mueller survey meter. The X-ray source is calibrated following AAPM TG-61 specifications and mounted at 101.6 cm from the floor, which is a primary barrier. The X-ray tube is mounted on a custom-made “gantry” and has a special collimating assembly system that allows field size between 0.5 mm and 20 cm at isocenter. Three-dimensional imaging can be performed to aid target localization using the same X-ray source at custom settings and an in-house reconstruction software. The small animal conformal radiation therapy device thus provides an excellent integrated system to promote translational research in radiation oncology in an academic laboratory. The purpose of this article is to review shielding and dosimetric measurement and highlight a few successful studies that have been performed to date with our system. In addition, an example of new data from an in vivo rat model of breast cancer is presented in which spatially fractionated radiation alone and in combination with thermal ablation was applied and the therapeutic benefit examined.

SummaryBackground Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. Methods Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. Results At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04–1.77) and 1.47 (1.11–1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1–4 years, 5–8 years, and 8+ years were 0.96 (0.44–2.09), 1.20 (0.70–2.04) and 1.52 (1.22–1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). Conclusions These results suggest that childhood OW is associated with a high risk of OSA in middle age.

Economic and racial segregation are major challenges to the United States. Without concerted government action to reduce segregation, however, little progress is likely. The chapters in this volume recommend three major strategies for government action. First is promoting integration in high-opportunity neighborhoods by supporting the movement of poor minorities into affluent, usually majority-white areas. Second is redeveloping areas of concentrated poverty as mixed-race, mixed-income neighborhoods. Third is encouraging the maintenance and expansion of existing, economically diverse middle neighborhoods. All of these steps are challenging and require significant changes in federal or local public policy. This concluding chapter conveys the importance of tackling these challenges and the need to build a political movement for reducing segregation.