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B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5’-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r –0·33, Plinear < 0·0001), serum amyloid A (SAA) (r –0·23, Plinear = 0·003), IL-6 (r –0·39, Plinear < 0·0001), IL-8 (r –0·20, Plinear = 0·02) and TNFα (r –0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r –0·14), SAA (r –0·14) and TNFα (r –0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
Three states and one county now allow Emergency Medical Services (EMS) providers to transport injured law enforcement K9s (LEK9s) as long as no human needs the ambulance at the time. Several other states either have pending legislation or are in discussions about this topic. As additional states ponder these laws, it is likely that the EMS transport of LEK9s will become legal in many states. In the wake of this legislation, a significant void was created. Currently, there are no published protocols for the safe transport of LEK9s by EMS providers. Additionally, the transport destination for these LEK9s is unlikely to be programmed into vehicle Global Positioning Systems. The authors of this report convened a Joint Task Force on Working Dog Care, consisting of veterinarians, EMS directors, EMS physicians, and LEK9 handlers, who met to develop a protocol for LEK9s being transported to a veterinary facility. The protocol covers the logistics of getting the LEK9 into the ambulance (eg, when the handler is or is not available), appropriate restraint, and the importance of prior arrangements with a veterinary emergency facility. A LEK9 hand-off form and a Transport Policy Form are provided, downloadable, and customizable for each EMS provider. This protocol provides essential information on safety and transport logistics for injured LEK9s. The hope is that this protocol will assist EMS providers to streamline the transport of an injured LEK9 to an appropriate veterinary facility.
This document is a resource for Emergency Medical Services (EMS) treating an injured law enforcement K9 (LEK9) in the field and/or during transport by ambulance to a veterinary hospital. A Joint Task Force on Working Dog Care was created, which included veterinarians, EMS directors, EMS physicians, and canine handlers, who met to develop a treatment protocol for injured LEK9s. The protocol covers many major life-threatening injuries that LEK9s may sustain in the line of duty, and also discusses personnel safety and necessary equipment. This protocol may help train EMS providers to save the life of an injured LEK9.
Critical to the development of improved HIV elimination efforts is a greater understanding of how social networks and their dynamics are related to HIV risk and prevention. In this paper, we examine network stability of confidant and sexual networks among young black men who have sex with men (YBMSM). We use data from uConnect (2013–2016), a population-based, longitudinal cohort study. We use an innovative approach to measure both sexual and confidant network stability at three time points, and examine the relationship between each type of stability and HIV risk and prevention behaviors. This approach is consistent with a co-evolutionary perspective in which behavior is not only affected by static properties of an individual's network, but may also be associated with changes in the topology of his or her egocentric network. Our results indicate that although confidant and sexual network stability are moderately correlated, their dynamics are distinct with different predictors and differing associations with behavior. Both types of stability are associated with lower rates of risk behaviors, and both are reduced among those who have spent time in jail. Public health awareness and engagement with both types of networks may provide new opportunities for HIV prevention interventions.
Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures
eV and electron densities
. The iron will be probed using continuum X-rays emitted in a
diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design,
of the NIF beams deliver 500 kJ to the
mm diameter hohlraum, and the remaining
directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.
To characterise and identify nationwide trends in suicide-related emergency department (ED) visits in the USA from 2006 to 2013.
We used data from the Nationwide Emergency Department Sample (NEDS) from 2006 to 2013. E-codes were used to identify ED visits related to suicide attempts and self-inflicted injury. Visits were characterised by factors such as age, sex, US census region, calendar month, as well as injury severity and mechanism. Injury severity and mechanism were compared between age groups and sex by chi-square tests and Wilcoxon rank-sum tests. Population-based rates were computed using US Census data.
Between 2006 and 2013, a total of 3 567 084 suicide attempt-related ED visits were reported. The total number of visits was stable between 2006 and 2013, with a population-based rate ranging from 163.1 to 173.8 per 100 000 annually. The frequency of these visits peaks during ages 15–19 and plateaus during ages 35–45, with a mean age at presentation of 33.2 years. More visits were by females (57.4%) than by males (42.6%); however, the age patterns for males and females were similar. Visits peaked in late spring (8.9% of all visits occurred in May), with a smaller peak in the fall. The most common mechanism of injury was poisoning (66.5%), followed by cutting and piercing (22.1%). Males were 1.6 times more likely than females to use violent methods to attempt suicide (OR = 1.64; 95% CI = 1.60–1.68; p < 0.001). The vast majority of patients (82.7%) had a concurrent mental disorder. Mood disorders were the most common (42.1%), followed by substance-related disorders (12.1%), alcohol-related disorders (8.9%) and anxiety disorders (6.4%).
The annual incidence of ED visits for attempted suicide and self-inflicted injury in the NEDS is comparable with figures previously reported from other national databases. We highlighted the value of the NEDS in allowing us to look in depth at age, sex, seasonal and mechanism patterns. Furthermore, using this large national database, we confirmed results from previous smaller studies, including a higher incidence of suicide attempts among women and individuals aged 15–19 years, a large seasonal peak in suicide attempts in the spring, a predominance of poisoning as the mechanism of injury for suicide attempts and a greater use of violent mechanisms in men, suggesting possible avenues for further research into strategies for prevention.
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
This paper discusses some of the criticisms recently raised by Rafael Dobado-González about our work on real wages in the Americas in the long run. Although addressing a series of issues, Dobado mainly questions our use of the welfare ratio methodology to assess standards of living in colonial Spanish America. In this article we explain how, despite its limitations, this methodology provides a solid, transparent metric to compare economic development across space and time. In particular, welfare ratios present more economically relevant information on living standards than the commodity wages that Dobado prefers (Dobado González and García Montero 2014). We argue that Dobado fails to offer convincing evidence against our findings; hence, we stand by these results, which suggest that the divergence between North and Latin America began early in the colonial period.
A synthesis of the upper Moscovian sedimentological and palaeontological record of terrestrial habitats across the Variscan foreland and adjacent intramontane basins (an area which is referred to here as Variscan Euramerica) suggests a contraction and progressive westward shift of the coal swamps. These changes can be correlated with pulses of tectonic activity (tectonic phases) resulting from the northwards migration of the Variscan Front. This tectonic activity caused disruption to the landscapes and drainage patterns where the coal swamps were growing, which became less suitable to growth of the dominant plants of the swamps, the arborescent lycopsids. They were progressively replaced by vegetation dominated by marattialean ferns, which through a combination of slower growth and larger canopies resulted in less evapo-transpiration. This in turn caused localised reductions in rainfall, which further affected the ability of the lycopsids to dominate the swamp vegetation. These changes were initially localised and where the coal swamps were able to survive the lycopsids and pteridosperms show little change in either species diversity or biogeography, indicating that at this time there was minimal regional-scale climate change taking place. By Asturian times, however, the process had accelerated and the swamps in Variscan Euramerica became progressively replaced by predominantly conifer and cordaite vegetation that favoured much drier substrates. Except in localised pockets in intramontane basins of the Variscan Mountains, the last development of coal swamps in Variscan Euramerica was of early Cantabrian age. Further west, lycopsid-dominated coal swamps persisted for a little longer. The last remnants of the lycopsid-dominated coal swamps in the Illinois Basin disappeared probably by middle-late Cantabrian times, as the cycle of contracting wetlands and regional reductions in rainfall generated its own momentum, and no longer needed the impetus of tectonic instability. This tectonically-driven decline in the Euramerican coal swamps was probably responsible for an annual increase in atmospheric CO2 of c. 0.37 ppm, and may have been implicated in the marked increase in global temperatures near the Moscovian – Kasimovian boundary, and the onset of the Late Pennsylvanian interglacial.
The Millimetre Astronomy Legacy Team 90 GHz (MALT90) survey aims to characterise the physical and chemical evolution of high-mass star-forming clumps. Exploiting the unique broad frequency range and on-the-fly mapping capabilities of the Australia Telescope National Facility Mopra 22 m single-dish telescope1, MALT90 has obtained 3′ × 3′ maps towards ~2 000 dense molecular clumps identified in the ATLASGAL 870 μm Galactic plane survey. The clumps were selected to host the early stages of high-mass star formation and to span the complete range in their evolutionary states (from prestellar, to protostellar, and on to
regions and photodissociation regions). Because MALT90 mapped 16 lines simultaneously with excellent spatial (38 arcsec) and spectral (0.11 km s−1) resolution, the data reveal a wealth of information about the clumps’ morphologies, chemistry, and kinematics. In this paper we outline the survey strategy, observing mode, data reduction procedure, and highlight some early science results. All MALT90 raw and processed data products are available to the community. With its unprecedented large sample of clumps, MALT90 is the largest survey of its type ever conducted and an excellent resource for identifying interesting candidates for high-resolution studies with ALMA.
The aim of this study was to determine the effect of butaphosphan and cyanocobalamin (BTPC) supplementation on plasma metabolites and milk production in postpartum dairy cows. A total of fifty-two Holstein cows were randomly assigned to receive either: (1) 10 ml of saline (NaCl 0.9%, control group); (2) 1000 mg of butaphosphan and 0.5 mg of cyanocobalamin (BTPC1 group); and (3) 2000 mg of butaphosphan and 1.0 mg of cyanocobalamin (BTPC2 group). All cows received injections every 5 days from calving to 20 days in milk (DIM). Blood samples were collected every 15 days from calving until 75 DIM to determine serum concentration of glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), cholesterol, urea, calcium (Ca), phosphorus (P), magnesium (Mg), aminotransferase aspartate (AST) and γ-glutamyltransferase (GGT). The body condition score (BCS) and milk production were evaluated from calving until 90 DIM. Increasing doses of BTPC caused a linear reduction in plasma concentrations of NEFA and cholesterol. Supplementation of BTPC also reduced concentrations of BHB but it did not differ between the two treatment doses. Milk yield and milk protein had a linear increase with increasing doses of BTPC. A quadratic effect was detected for milk fat and total milk solids according to treatment dose, and BTPC1 had the lowest mean values. Concentrations of glucose, urea, P, Mg, AST, GGT, milk lactose and BCS were not affected by treatment. These results indicate that injections of BTPC during the early postpartum period can reduce NEFA and BHB concentrations and increase milk production in Holstein cows.
This article introduces the Americas in the Great Divergence debate by measuring real wages in various North and South American cities between colonization and independence, and comparing them to Europe and Asia. We find that for much of the period, North America was the most prosperous region of the world, while Latin America was much poorer. We then discuss a series of hypotheses that can explain these results, including migration, the demography of the American Indian populations, and the various labor systems implemented in the continent.
National Security Technologies (NSTec) has developed calibration procedures for X-ray imaging systems. The X-ray sources that are used for calibration are both diode type and diode/fluorescer combinations. Calibrating the X-ray detectors is a key to accurate calibration of the X-ray sources. Both energy dispersive detectors and photodiodes measuring total flux were used. We have developed calibration techniques for the detectors using radioactive sources that are traceable to the National Institute of Standards and Technology (NIST). The German synchrotron at Physikalische Technische Bundestalt (PTB) was used to calibrate the silicon photodiodes over the energy range from 50 to 60 keV. The measurements on X-ray cameras made using the NSTec X-ray sources included quantum efficiency averaged over all pixels, camera counts per photon per pixel, and response variation across the sensor. The instrumentation required to accomplish the calibrations is described. The X-ray energies ranged from 720 to 22.7 keV. The X-ray sources produce narrow energy bands, allowing us to determine the properties as a function of X-ray energy. The calibrations were done for several types of imaging devices. There were back and front illuminated CCD (charge-coupled device) sensors, and a CID (charge injection device) type camera. The CCD and CID camera types differ significantly in some of their properties that affect the accuracy of the X-ray intensity measurements. All the cameras discussed here are silicon based. The measurements of the quantum efficiency variation with the X-ray energy are compared to the models for the sensor structure. The cameras that are not back-thinned are compared to those that are.
The Moncure microvertebrate locality in the Cumnock Formation, Sanford sub-basin, North Carolina, dramatically increases the known Late Triassic age vertebrate assemblage from the Deep River Basin. The ∼50,000 recovered microvertebrate fossils include osteichthyans, amphibians, and numerous lepidosauromorph, archosauriform, and synapsid amniotes. Actinopterygian fossils consist of thousands of scales, teeth, skull, and lower jaw fragments, principally of redfieldiids and semionotids. Non-tetrapod sarcopterygians include the dipnoan Arganodus sp., the first record of lungfish in the Newark Supergroup. Temnospondyls are comparatively rare but the preserved centra, teeth, and skull fragments probably represent small (juvenile) metoposaurids. Two fragmentary teeth are assigned to the unusual reptile Colognathus obscurus (Case). Poorly preserved but intriguing records include acrodont and pleurodont jaw fragments tentatively assigned to lepidosaurs. Among the archosauriform teeth is a taxon distinct from R. callenderi that we assign to Revueltosaurus olseni new combination, a morphotype best assigned to cf. Galtonia, the first Newark Supergroup record of Crosbysaurus sp., and several other archosauriform tooth morphotypes, as well as grooved teeth assigned to the recently named species Uatchitodon schneideri. Synapsids represented by molariform teeth include both “traversodontids” assigned to aff. Boreogomphodon and the “dromatheriid” Microconodon. These records are biogeographically important, with many new records for the Cumnock Formation and/or the Newark Supergroup. In particular, Colognathus, Crosbysaurus, and Uatchitodon are known from basins of Adamanian age in the southwestern U.S.A. These new records include microvertebrate taxa more typical of non-Newark basins (abundant archosauriforms, temnospondyls, lungfish) as well as more typical Newark osteichthyans and synapsid-rich faunal elements.
The aim of this study was to determine the effect of prepartum somatotropin injection in late-pregnant Holstein heifers on metabolism, milk production and resumption of postpartum ovulation. For this study, 31 late-pregnant Holstein heifers were used. The heifers were assigned randomly into two treatments: (1) 500 mg sc injections of somatotropin (somatotropin treatment, n = 15) at −35 and −21 days, and, if pertinent, at −7 days from expected calving date and (2) no treatment (control group, n = 16). Blood samples were collected weekly from −5 to 7 weeks after calving. Heifers with progesterone concentrations in plasma above 1 ng/ml in two consecutive postpartum samples were considered as having resumed ovarian activity. A higher proportion (P = 0.04) of heifers treated with somatotropin resumed ovarian activity in the first 7 weeks post partum (73.3%; 11/15) compared with the control group (37.5%; 6/16). A higher number (P = 0.02) of heifers in the somatotropin treatment group also ovulated during the first postpartum follicular wave (53.3%; 8/15) compared with the control group (12.5%; 2/16), as indicated by the number of heifers ovulating in the first 3 weeks post partum. Pregnancy rate was not affected by treatments (P > 0.10) and averaged 40.0% (6/15) in somatotropin-treated and 25.0% (4/16) in control heifers when evaluated up to 150 days in milk. Somatotropin treatment increased the average daily milk production by 2.8 kg/cow per day (P < 0.0001) and reduced the somatic cell count (P = 0.009). Plasma IGF-I was higher (P < 0.05) for somatotropin-treated heifers in the prepartum period. Insulin and body condition score were higher (P < 0.05) and non-esterified fatty acids were lower (P < 0.05) for somatotropin-treated cows in the early postpartum period. In conclusion, somatotropin injection during the prepartum period in late-pregnant Holstein heifers was able to increase the proportion of heifers resuming ovarian activity early post partum, inspite of higher milk production.