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The themes of sedentarisation, urbanisation and state formation are fundamental ones in the archaeology of many diverse parts of the world but have been little explored in relation to early societies of the Saharan zone. Moreover, the possibility has rarely been considered that the precocious civilisations bordering this vast desert were interconnected by long-range contacts and knowledge networks. The orthodox opinion of many of the key oasis zones within the Sahara is that they were not created before the early Medieval period and the Islamic conquest of Mediterranean North Africa. Major claims of this volume are that the ultimate origins of oasis settlements in many parts of the Sahara were considerably earlier, that by the first millennium AD some of these oasis settlements were of a size and complexity to merit the categorisation 'towns' and that a few exceptional examples were focal centres within proto-states or early state-level societies.
We designed two practical, user-friendly, low-cost, aesthetically pleasing resources, with the goal of introducing residents and observers to a new Competence by Design assessment system based on entrustable professional activities. They included a set of rotation- and stage-specific entrustable professional activities reference cards for bedside use by residents and observers and a curriculum board to organize the entrustable professional activities reference cards by stages of training based on our program's curriculum map. A survey of 14 emergency medicine residents evaluated the utilization and helpfulness of these resources. They had a positive impact on our program's transition to Competence by Design and could be successfully incorporated into other residency programs to support the introduction of entrustable professional activities-based Competence by Design assessment systems.
Recent literature on philanthropy and business has focused on the returns to businesses and entrepreneurs from giving. In this article, we show how historical context impacts the motivations and organizational forms created over time in philanthropic giving that effect and affect such returns. We do this through the prism of the changing ownership structures in the Scotch whisky industry in the twentieth century using an institutional theory lens. In doing so, we capture the story of three sisters who inherited a Scotch whisky business in the 1940s and transformed it into a hybrid philanthropic-commercial vehicle that remains in operation today. We present an extended theoretical model illustrating the interplay of context, motivation, and organizational structure over time on exchanges of capital in entrepreneurial philanthropy.
In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Twin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FST values) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.
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.
Feed represents a substantial proportion of production costs in the dairy industry and is a useful target for improving overall system efficiency and sustainability. The objective of this study was to develop methodology to estimate the economic value for a feed efficiency trait and the associated methane production relevant to Canada. The approach quantifies the level of economic savings achieved by selecting animals that convert consumed feed into product while minimizing the feed energy used for inefficient metabolism, maintenance and digestion. We define a selection criterion trait called Feed Performance (FP) as a 1 kg increase in more efficiently used feed in a first parity lactating cow. The impact of a change in this trait on the total lifetime value of more efficiently used feed via correlated selection responses in other life stages is then quantified. The resulting improved conversion of feed was also applied to determine the resulting reduction in output of emissions (and their relative value based on a national emissions value) under an assumption of constant methane yield, where methane yield is defined as kg methane/kg dry matter intake (DMI). Overall, increasing the FP estimated breeding value by one unit (i.e. 1 kg of more efficiently converted DMI during the cow’s first lactation) translates to a total lifetime saving of 3.23 kg in DMI and 0.055 kg in methane with the economic values of CAD $0.82 and CAD $0.07, respectively. Therefore, the estimated total economic value for FP is CAD $0.89/unit. The proposed model is robust and could also be applied to determine the economic value for feed efficiency traits within a selection index in other production systems and countries.
The current study examined whether self-reported memory problems among cognitively intact older adults changed concurrently with, preceded, or followed depressive symptoms over time.
Data were collected annually via in-person comprehensive medical and neuropsychological examinations as part of the Einstein Aging Study.
Community-dwelling older adults in an urban, multi-ethnic area of New York City were interviewed.
The current study included a total of 1,162 older adults (Mage = 77.65, SD = 5.03, 63.39% female; 74.12% White). Data were utilized from up to 11 annual waves per participant.
Multilevel modeling tested concurrent and lagged associations between three types of memory self-report (frequency of memory problems, perceived one-year decline, and perceived ten-year decline) and depressive symptoms.
Results showed that self-reported frequency of memory problems covaried with depressive symptoms only in participants who were older at baseline. Changes in perceived one-year and ten-year memory decline were related to changes in depressive symptoms across all ages. Depressive symptoms increased the likelihood of perceived ten-year memory decline the next year; however, perceived ten-year memory decline did not predict future depressive symptoms. Additionally, no significant temporal relationship was observed between depressive symptoms and self-reported frequency of memory problems or perceived one-year memory decline.
Our findings highlight the importance of testing the unique associations of different types of self-reported memory problems with depressive symptoms.
High-starch diets (HSDs) fed to high-producing ruminants are often responsible for rumen dysfunction and could impair animal health and production. Feeding HSDs are often characterized by transient rumen pH depression, accurate monitoring of which requires costly or invasive methods. Numerous clinical signs can be followed to monitor such diet changes but no specific indicator is able to make a statement at animal level on-farm. The aim of this pilot study was to assess a combination of non-invasive indicators in dairy cows able to monitor a HSD in experimental conditions. A longitudinal study was conducted in 11 primiparous dairy cows fed with two different diets during three successive periods: a 4-week control period (P1) with a low-starch diet (LSD; 13% starch), a 4-week period with an HSD (P2, 35% starch) and a 3-week recovery period (P3) again with the LSD. Animal behaviour was monitored throughout the experiment, and faeces, urine, saliva, milk and blood were sampled simultaneously in each animal at least once a week for analysis. A total of 136 variables were screened by successive statistical approaches including: partial least squares-discriminant analysis, multivariate analysis and mixed-effect models. Finally, 16 indicators were selected as the most representative of a HSD challenge. A generalized linear mixed model analysis was applied to highlight parsimonious combinations of indicators able to identify animals under our experimental conditions. Eighteen models were established and the combination of milk urea nitrogen, blood bicarbonate and feed intake was the best to detect the different periods of the challenge with both 100% of specificity and sensitivity. Other indicators such as the number of drinking acts, fat:protein ratio in milk, urine, and faecal pH, were the most frequently used in the proposed models. Finally, the established models highlight the necessity for animals to have more than 1 week of recovery diet to return to their initial control state after a HSD challenge. This pilot study demonstrates the interest of using combinations of non-invasive indicators to monitor feed changes from a LSD to a HSD to dairy cows in order to improve prevention of rumen dysfunction on-farm. However, the adjustment and robustness of the proposed combinations of indicators need to be challenged using a greater number of animals as well as different acidogenic conditions before being applied on-farm.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Interactions at magnetic interfaces are central to the operation of virtually all magnetic heterostructures. When the interface is between two magnetic materials, the exchange interaction between spins at the interface is often a dominant force, and can dramatically change the magnetic response of the overall heterostructure. In ferromagnet (FM)/antiferromagnet (AFM) heterostructures, this interaction is often referred to as exchange anisotropy or bias and it has been widely used over the past decade in a wide array of applications such as magnetic recording heads, MRAMs, etc. The powerful implications of interactions between an AFM and a FM have been realized in a wide range of thin film heterostructure with both metallic and oxide constituents. There is, however, much less work on oxide-oxide FM/AFM systems. On the other hand, the development and understanding of functional oxide materials, especially multifunctional materials like BiFeO3 (BFO), have piqued the interest of researchers worldwide with the promise of coupling between order parameters such as ferroelectricity and antiferromagnetism. Recent research suggests that there is exchange coupling and anisotropy between the metallic ferromagnet Co0.9Fe0.1 (CoFe) and the multiferroic, antiferromagnet BFO, showing the possibility to create highly desirable multifunctional systems with new possibilities for device design. Such a result provides the driving force to create multifunctional oxide-oxide systems where exchange interactions could be much stronger then in metal/oxide structures due the added epitaxial nature of the interface. In this study, we use La0.7Sr0.3MnO3(LSMO)/BFO thin film heterostructures as a model system to explore the exchange interaction at an oxide interface. The heterostructures are grown on various vicinal cuts of SrTiO3 single crystal substrates using laser MBE. Structural analysis using x-ray diffraction, transmission electron microscopy and Rutherford backscattering spectrometry reveals high quality films with the pristine interfaces required for exchange coupling. First results from photoemission electron microscope (PEEM) studies reveal that the magnetic LSMO domain structure mimics underneath ferroelectric BFO domain structure, i..e, it is strongly pinned by the underlying AFM structure. The coupling behavior is being characterized by magnetic measurements (SQUID, VSM), which shows a strong enhancement in the coercivity of the LSMO layer, suggesting the existence of exchange bias coupling. We are probing the strength of this coupling using a combination of careful laser MBE growth experiments and physical property measurements. In this paper, we will report results of experiments in which the LSMO layer has been grown by laser MBE in the thickness range of 2-50nm on a  BFO layer.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Characterization of nanobioparticles is a demanding task. This problem is particularly evident in the case of biomedical applications of nanoparticles where toxicological indices and ADME parameters are the result of complex interactions of the nanoparticle at the molecular, cellular and tissue levels. Furthermore, particles of this size frequently behave in ways that are intrinsically different than those at meso and sub-nano scale. The success of the biological application of nanoparticles depends, however, to a large extent, on our ability to characterize, and eventually predict and control, the properties and behavior of nanoscale particles in realistic biological environments. To help this process, the development of computer-aided nanoparticle characterization approaches is highly desirable. Nanobioparticles include a large array of dissimilar materials under a common name, making the definition of common microscopic criteria matching the modeled molecular properties with the macroscopically observed ones, a daunting task. In this presentation we will review our efforts at devising strategies that, from in-silico simulations of nanoparticles, will help us infer their behavior in complex environments. The approaches presented rely on the application of sensitivity analysis techniques that probe the intrinsic stability of the particle. Particles will be suitable candidates for biological use only if they show low sensitivity to those challenges. The nature of the parameters explored and the possible generalization of this approach will be discussed by presenting our results using metal-loaded fullerenes, gold particles and dendrimers. This work has been funded in part with funds from the NCI-NIH (Contract No. NO1-CO-12400). The contents of this publication do not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
In the past four decades lipid vesicles (liposomes) have evolved from widely used biomembrane models into important drug and gene carriers. The phosphatidylcholine phospholipids PC used in the drug carriers are biocompatible and biodegradable but they function as a relatively inert shell and require the incorporation of cholesterol to maintain the drug encapsulated in the liposome; The PC are also incapable of associating with ligands and have very weak interactions with nucleic acids. Moreover, they are not particularly good for cytoplasmic delivery of the encapsulated cargo. Recently, we have devised three classes of new lipids and have improved the synthesis of a fourth class that enable the preparation of a bioresponsive targeted carrier with improved nucleic acid delivery. Class 1 are low pH sensitive and include a diortho ester PEG lipid or a di-orthoester PC. Class two are redox sensitive lipids and include thiocholesterol based and thio diacyl chain based lipids that can be used in a sequential assembly process to encapsulate nucleic acid drugs in a charge neutral or negatively charged nanolipid particle. Class 3 is a new family of lipids that provide increased in vivo bilayer stability without the need for crosslinking of the bilayer. Class 4 is an improved synthesis of a triNTA diacyl lipid. This lipid can be used to attach His-6 containing molecules to the bilayer vesicle after the liposomes have been prepared and loaded with drugs. These lipids form a tool kit that can be used to prepare a variety of targeted drug, protein and nucleic acid delivery vesicles with attached targeting ligands. The synthesis, characterization and use of these lipids in a variety of drug delivery applications will be described. Suported by NIH EB003008 & NIH GM061851.
Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.
The Upper Cretaceous Kanguk Formation of the Sverdrup Basin, Canadian Arctic Islands, contains numerous diagenetically altered volcanic ash layers (bentonites). Eleven bentonites were sampled from an outcrop section on Ellesmere Island for U–Pb zircon secondary ion mass spectrometry dating and whole-rock geochemical analysis. Two distinct types of bentonite are identified from the geochemical data. Relatively thick (0.1 to 5 m) peralkaline rhyolitic to trachytic bentonites erupted in an intraplate tectonic setting. These occur throughout the upper Turonian to lower Campanian (c. 92–83 Ma) outcrop section and are likely associated with the alkaline phase of the High Arctic Large Igneous Province. Two thinner (<5 cm) subalkaline dacitic to rhyolitic bentonites of late Turonian to early Coniacian age (c. 90–88 Ma) are also identified. The geochemistry of these bentonites is consistent with derivation from volcanoes within an active continental margin tectonic setting. The lack of nearby potential sources of subalkaline magmatism, together with the thinner bed thickness of the subalkaline bentonites and the small size of zircon phenocrysts therein (typically 50–80 μm in length) are consistent with a more distal source area. The zircon U–Pb age and whole-rock geochemistry of these two subalkaline bentonites correlate with an interval of intense volcanism in the Okhotsk–Chukotka Volcanic Belt, Russia. It is proposed that during late Turonian to early Coniacian times intense volcanism within the Okhotsk–Chukotka Volcanic Belt resulted in widespread volcanic ash dispersal across Arctic Alaska and Canada, reaching as far east as the Sverdrup Basin, more than 3000 km away.