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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Introduction: Prompt defibrillation is critical during paediatric cardiac arrest. The main objective of this systematic review was to determine the initial defibrillation energy dose for ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) that is associated with sustained return of spontaneous circulation (ROSC) during paediatric cardiac arrest. Associations between initial defibrillation energy dose with any ROSC, survival and defibrillation-induced complications were also assessed. Methods: A systematic review was performed using four databases (Medline, Embase, Web of Science, Cochrane Library) (PROSPERO: CRD42016036734). Human studies (cohort studies or controlled trials) and animal model studies (controlled trials) of pediatric cardiac arrest involving assessment of external defibrillation energy dosing were considered. The primary outcome was sustained ROSC. Two researchers independently reviewed all the titles and abstracts of the retrieved citations, selected the studies and extracted the data using a standardized template. Risk of bias of human non-randomised studies were assessed using the ROBIN-I tool (formerly ACROBAT-NRSI) tool proposed by the Cochrane Collaboration group. Results: The search strategy identified 14,471 citations of which 232 manuscripts were reviewed. Ten human and 10 animal model studies met the inclusion criteria. Human studies were prospective (n = 6) or retrospective (n = 4) cohort studies and included between 11 and 266 patients (median = 46 patients). Sustained ROSC rates ranged from 0 to 61% (n = 7). No studies reported a statistically significant association between the initial defibrillation energy dose and the rate of sustained ROSC (n = 7) or survival (n = 6). No human studies reported defibrillation-induced complications. Meta-analysis was not considered appropriate due to clinical heterogeneity. The overall risk of bias was moderate. All animal studies were randomized controlled trials with 8 and 52 (median = 27) piglets. ROSC was frequently achieved (more than 85%) with energy dose ranging from 2 to 7 joules/kg (n = 7). The defibrillation threshold varied according to the body weight and appears to be higher in infant models. Conclusion: Defibrillation energy doses and thresholds varied according to the body weight and trended higher for infants. No definitive association between initial defibrillation doses and the outcomes of sustained ROSC or survival could be demonstrated.
From 1565 to 1570, Spain established no fewer than three networks of presidios (fortified military settlements) across portions of its frontier territories in La Florida and New Spain. Juan Pardo's network of six forts, extending from the Atlantic coast over the Appalachian Mountains, was the least successful of these presidio systems, lasting only from late 1566 to early 1568. The failure of Pardo's defensive network has long been attributed to poor planning and an insufficient investment of resources. Yet recent archaeological discoveries at the Berry site in western North Carolina—the location of both the Native American town of Joara and Pardo's first garrison, Fort San Juan—warrants a reappraisal of this interpretation. While previous archaeological research at Berry concentrated on the domestic compound where Pardo's soldiers resided, the location of the fort itself remained unknown. In 2013, the remains of Fort San Juan were finally identified south of the compound, the first of Pardo's interior forts to be discovered by archaeologists. Data from excavations and geophysical surveys suggest that it was a substantial defensive construction. We attribute the failure of Pardo's network to the social geography of the Native South rather than to an insufficient investment of resources.
Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.
Reproductive performance of ewe lambs is lower than that of adult ewes (Quirke 1979). This is mainly the result of preimplantation losses, which can exceed 50% of fertilised eggs. Previous evidence from this laboratory suggests that these losses may be associated with abnormal ovarian hormone production (Davies and Beck 1993). Khan (1999) demonstrated that blood progesterone levels during the oestrous cycle and pregnancy were lower in ewe lambs than in ewes. Furthermore, both progesterone and oestradiol concentrations were lower in ewe lambs, than in ewes, following gonadotrophin stimulation (Khan, Beck and Khalid 1999). These results suggest that ewe lamb corpora lutea and follicles secrete less progesterone and oestradiol, respectively, than those of ewes. The aim of this study was to determine whether there is a difference in vitro steroid hormone production by corpora lutea and follicles, from ewe lambs and ewes.
This paper presents latest thinking from the Institute and Faculty of Actuaries’ Model Risk Working Party and follows on from their Phase I work, Model Risk: Daring to Open the Black Box. This is a more practical paper and presents the contributors’ experiences of model risk gained from a wide range of financial and non-financial organisations with suggestions for good practice and proven methods to reduce model risk. After a recap of the Phase I work, examples of model risk communication are given covering communication: to the Board; to the regulator; and to external stakeholders. We present a practical framework for model risk management and quantification with examples of the key actors, processes and cultural challenge. Lessons learned are then presented from other industries that make extensive use of models and include the weather forecasting, software and aerospace industries. Finally, a series of case studies in practical model risk management and mitigation are presented from the contributors’ own experiences covering primarily financial services.
The main objective of this report is to present the dating process routinely applied to different types of samples at the Laboratoire de Mesure du Carbone 14 (LMC14). All the results and protocols refer to our procedures over the last 5 years. A description of the sorting and chemical pretreatments of the samples as well as the extraction and graphitization of CO2 are reported. Our last study concerning the degradation of the blank level according to the storage time of the targets between graphitization and accelerator mass spectrometry (AMS) measurement is also presented. This article also provides information on how to submit a valid laboratory sample. We give details relating to sampling procedures on site as well as contamination issues relative to the 14C dating methodology.
Observational techniques with high angular and high spectral resolution have become available in recent years and have had a major impact on the study of Herbig-Haro outflows from very young stars. We discuss new results obtained using WFPC2, ACS and STIS onboard the Hubble Space Telescope, as well as spectroscopic data obtained at the Keck telescope and with the Integral Field Unit at the Gemini telescope. We also discuss centimeter radio continuum maps from the Very Large Array and their importance in testing scenarios for the formation of giant Herbig-Haro flows.
New radiocarbon calibration curves, IntCal04 and Marine04, have been constructed and internationally ratified to replace the terrestrial and marine components of IntCal98. The new calibration data sets extend an additional 2000 yr, from 0–26 cal kyr BP (Before Present, 0 cal BP = AD 1950), and provide much higher resolution, greater precision, and more detailed structure than IntCal98. For the Marine04 curve, dendrochronologically-dated tree-ring samples, converted with a box diffusion model to marine mixed-layer ages, cover the period from 0–10.5 cal kyr BP. Beyond 10.5 cal kyr BP, high-resolution marine data become available from foraminifera in varved sediments and U/Th-dated corals. The marine records are corrected with site-specific 14C reservoir age information to provide a single global marine mixed-layer calibration from 10.5–26.0 cal kyr BP. A substantial enhancement relative to IntCal98 is the introduction of a random walk model, which takes into account the uncertainty in both the calendar age and the 14C age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed here. The tree-ring data sets, sources of uncertainty, and regional offsets are presented in detail in a companion paper by Reimer et al. (this issue).
The radiocarbon calibration curve IntCal04 extends back to 26 cal kyr B P. While several high-resolution records exist beyond this limit, these data sets exhibit discrepancies of up to several millennia. As a result, no calibration curve for the time range 26–50 cal kyr BP can be recommended as yet, but in this paper the IntCal04 working group compares the available data sets and offers a discussion of the information that they hold.
The IntCal04 and Marine04 radiocarbon calibration curves have been updated from 12 cal kBP (cal kBP is here defined as thousands of calibrated years before AD 1950), and extended to 50 cal kBP, utilizing newly available data sets that meet the IntCal Working Group criteria for pristine corals and other carbonates and for quantification of uncertainty in both the 14C and calendar timescales as established in 2002. No change was made to the curves from 0–12 cal kBP. The curves were constructed using a Markov chain Monte Carlo (MCMC) implementation of the random walk model used for IntCal04 and Marine04. The new curves were ratified at the 20th International Radiocarbon Conference in June 2009 and are available in the Supplemental Material at www.radiocarbon.org.
We calibrated portions of the radiocarbon time scale with combined 230Th, 231Pa, 14C measurements of corals collected from Espiritu Santo, Vanuatu and the Huon Peninsula, Papua New Guinea. The new data map 14C variations ranging from the current limit of the tree-ring calibration [11,900 calendar years before present (cal BP), Kromer and Spurk 1998, now updated to 12,400 cal B P, see Kromer et al., this issue], to the 14C-dating limit of 50,000 cal BP, with detailed structure between 14 to 16 cal kyr BP and 19 to 24 cal kyr BP. Samples older than 25,000 cal BP were analyzed with high-precision 231Pa dating methods (Pickett et al. 1994; Edwards et al. 1997) as a rigorous second check on the accuracy of the 230Th ages. These are the first coral calibration data to receive this additional check, adding confidence to the age data forming the older portion of the calibration. Our results, in general, show that the offset between calibrated and 14C ages generally increases with age until about 28,000 cal BP, when the recorded 14C age is nearly 6800 yr too young. The gap between ages before this time is less; at 50,000 cal BP, the recorded 14C age is 4600 yr too young. Two major 14C-age plateaus result from a 130 drop in Δ14C between 14–15 cal kyr BP and a 700 drop in Δ14C between 22–25 cal kyr BP. In addition, a large atmospheric Δ14C excursion to values over 1000 occurs at 28 cal kyr BP. Between 20 and 10 cal kyr BP, a component of atmospheric Δ14C anti-correlates with Greenland ice δ18O, indicating that some portion of the variability in atmospheric Δ14C is related to climate change, most likely through climate-related changes in the carbon cycle. Furthermore, the 28-kyr excursion occurs at about the time of significant climate shifts. Taken as a whole, our data indicate that in addition to a terrestrial magnetic field, factors related to climate change have affected the history of atmospheric 14C.
A serosurvey of 349 military working horses and 231 military working dogs was conducted in ten sites in Morocco in 2012. This survey revealed a high level of exposure of these animals to flaviviruses: seroprevalence rates of 60% in horses and of 62% in dogs were observed using a competitive West Nile virus (WNV) enzyme-linked immunosorbent assay (cELISA). Seroneutralization test results showed that the majority of cELISA-positive results were due to exposure to WNV. Further assays conducted in vaccinated horses with a DIVA (Differentiating Infected from Vaccinated Animals) test indicated that anti-WNV antibodies had been stimulated through WNV natural infection. Moreover, in both species, seroneutralization tests suggested an exposure to Usutu virus (USUV). Data analysis did not show any significant difference of cELISA seropositivity risk between horses and dogs. Dogs may thus represent an interesting alternative to equines for the serological surveillance of WNV or USUV circulation, especially in areas where equine vaccination precludes passive surveillance (based on the detection of West Nile fever cases) in horses.
Beginning with Kathleen Deagan’s description of the St. Augustine Pattern, in which domestic relations between Spanish men and Native American women contributed to a pattern of mestizaje in Spanish colonies, gender has assumed a central role in archaeological perspectives on colonial encounters. This is especially true for those encounters that accompanied colonialism in the Americas during the sixteenth through the nineteenth centuries. Gender relations were essential to the creation of new cultural identities during this time, as indigenous communities encountered immigrant, European settler groups often comprised mostly or entirely of adult men. Yet as significant as gender is for understanding how an encounter unfolded in time and space, it can be a challenge to identify and evaluate the archaeological correlates of such relations through material culture patterns. In this article, we use the related domains of food and foodways, particularly in the social context of provisioning, to evaluate how gender relations changed during the occupation of Fort San Juan de Joara (1566–1568), located at the Berry site in western North Carolina. Our research contributes to reappraisals of the St. Augustine Pattern, which posits well-defined roles for Native American women and Spanish men, by likewise situating the agency of Native American men.
With the increasing use of complex quantitative models in applications throughout the financial world, model risk has become a major concern. Such risk is generated by the potential inaccuracy and inappropriate use of models in business applications, which can lead to substantial financial losses and reputational damage. In this paper, we deal with the management and measurement of model risk. First, a model risk framework is developed, adapting concepts such as risk appetite, monitoring, and mitigation to the particular case of model risk. The usefulness of such a framework for preventing losses associated with model risk is demonstrated through case studies. Second, we investigate the ways in which different ways of using and perceiving models within an organisation both lead to different model risks. We identify four distinct model cultures and argue that in conditions of deep model uncertainty, each of those cultures makes a valuable contribution to model risk governance. Thus, the space of legitimate challenges to models is expanded, such that, in addition to a technical critique, operational and commercial concerns are also addressed. Third, we discuss through the examples of proxy modelling, longevity risk, and investment advice, common methods and challenges for quantifying model risk. Difficulties arise in mapping model errors to actual financial impact. In the case of irreducible model uncertainty, it is necessary to employ a variety of measurement approaches, based on statistical inference, fitting multiple models, and stress and scenario analysis.
This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg−1, intraperitoneally [i.p.]) and C-LNCs (10 mg kg−1, i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0·05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.