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Several life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.
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.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Reflection high-energy electron diffraction (RHEED) is one of the most robust and widespread techniques used for in-situ monitoring during molecular beam epitaxy (MBE) growth. Thus, all MBE systems have an electron gun allowing additional electron-beam stimulated in-situ characterizations. At WVU we are developing two such techniques, spectral analysis of cathodoluminescence (CL) in wide bandgap semiconductors and reflection high-energy electron diffraction-total reflection angle x-ray spectroscopy (RHEED-TRAXS) for in-situ composition monitoring and control.A pressing issue remaining for epitaxial growth is real-time compositional control to a high level of accuracy. For many materials, such as multi-element nitrides and oxides with unity sticking coefficients, it would be extremely beneficial to monitor the composition to a fraction of a monolayer. This technique needs to be both element-specific and surface-sensitive. RHEED-TRAXS is a leading contender as such a technique. The electron beam from a RHEED gun impinges on the sample at a small angle of incidence approximately equal to the critical angle for x-ray reflection. This geometry ensures that the measurement is extremely surface sensitive. This technique can be used to obtain both structural information, via RHEED, and chemical information, via x-ray detection. We are currently developing a compact RHEED-TRAXS using a state-of-the-art Si P-intrinsic-N (PIN) photodiode technology. We have used this system to investigate Ga and In coverage during the growth of GaN, and have observed Ga bi-layer evolution during growth, Mg destabilization of the Ga wetting layer, and significant In surface segregation. We are also investigating the in-situ, real-time composition measurements in complex oxide systems such as YMnO3 with promising initial results.In-situ cathodoluminescence (CL) occurring during RHEED is a strong candidate to determine the growth temperature and alloy composition for wide bandgap semiconductors. CL is easily detected up to and beyond typical growth temperatures for GaN and InGaN, accurately and reproducibly determining sample temperature during growth. Room CL measurement at room temperature can also be used as a means to check the quality of the substrate by comparing intensities of the GaN band edge energy peak and defect peaks. We have performed a detailed study of the factors influencing high temperature CL, and find the reproducibility of CL data and ability for fast CL scanning provide strong advantages for use in the growth of GaN films. CL could also be observed during growth using a ccd camera. This could be used to see temperature inhomogenaities, and potentially to map alloy composition fluctuations. Using tunable narrow bandpass optical filters, we can obtain a spatial/spectral map of sample CL. We will present CL images of samples at differing temperatures.This work was supported by the AFOSR MURI F49620-03-1-0330 and by ONR Grant N00014-02-1-0974.
The second order nonlinear optical (NLO) properties of two different ionic selfassembled multilayer (ISAM) films combined with Ag nanoparticles have been investigated. The plasmon resonances in the Ag particles concentrate the incident light, markedly increasing in the NLO efficiencies of the films. We find that the efficiency enhancement is significantly larger in conventional ISAM films compared to films made using a hybrid covalent ISAM technique (HCISAM), even though the intrinsic bulk second order non-linear susceptibility (χ(2)) is much larger for HCISAM films. We attribute this to the interfaces in HCISAM films being much easier to disrupt by external perturbations such as the metal deposition by which the nanoparticles are fabricated. We conclude that because the plasmon decay length is very short, the plasmonic enhancement of NLO effects primarily occurs at and near the film-particle interface. To discern the importance of the interfaces, we surrounded thin ISAM and HCISAM films with NLOinactive buffer layers, which confirmed this hypothesis, particularly in the case of HCISAM films.
A new ESCA (electron spectroscopy for chemical analysis) instrument has been developed to provide high sensitivity and efficient operation for laboratory analysis of composition and chemical bonding in very thin surface layers of solid samples. High sensitivity is achieved by means of the high-intensity, efficient X-ray source described by Davies and Herglotz at the 1968 Denver X-Ray Conference, in combination with the new electron energy analyzer described by Lee at the 1972 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. A sample chamber designed to provide for rapid introduction and replacement of samples has adequate facilities for various sample treatments and conditioning followed immediafely by ESCA analysis of the sample.
Examples of application are presented, demonstrating the sensitivity and resolution achievable with this instrument. Its usefulness in trace surface analysis is shown and some “chemical shifts” measured by the instrument are compared with those obtained by X-ray spectroscopy.
X-ray diffraction techniques have been used for the structure characterization of Y-Ba-Cu-O and Tl-Ca-Ba-Cu-O thin films. A powder diffraction analysis of Y-Ba-Cu-O films showed that the films deposited at 650°C on Si are polycrystalline and have an orthorhambic structure similar to that of the YBa2Cu3O7 bulk superconductors. In addition to the conventional powder diffraction technique, both the rocking curve and the grazing incidence diffraction methods were used to characterize a YBa2Cu3O7 film on (110) SrTiO3 substrate. Results showed that the film was epitaxially grown and aligned with its substrate in a true epitaxy. Phase identification and line broadening analyses of Tl-Ca-Ba-Cu-O films showed that the films are comprised of one or more superconducting phases and probably contain stacking faults.
Findings as to whether individuals’ experiences of physical maltreatment from their parents in childhood predict their own perpetration of physical maltreatment toward their children in adulthood are mixed. Whether the maltreatment experienced is severe versus moderate or mild may relate to the strength of intergenerational associations. Furthermore, understanding of the roles of possible mediators (intervening mechanisms linking these behaviors) and moderators of the intervening mechanisms (factors associated with stronger or weaker mediated associations) is still relatively limited. These issues were examined in the present study. Mediating mechanisms based on a social learning model included antisocial behavior as assessed by criminal behaviors and substance use (alcohol and drug use), and the extent to which parental angry temperament moderated any indirect effects of antisocial behavior was also examined. To address these issues, data were used from Generations 2 and 3 of a prospective three-generational study, which is an extension of the Oregon Youth Study. Findings indicated modest intergenerational associations for severe physical maltreatment. There was a significant association of maltreatment history, particularly severe maltreatment with mothers’ and fathers’ delinquency. However, neither delinquency nor substance use showed significant mediational effects, and parental anger as a moderator of mediation did not reach significance.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.
Rapid, non-destructive methods for measuring seed germination and vigour are valuable. Standard germination and seed vigour were determined using 81 soybean seed lots. From these data, seed lots were separated into high and low germinating seed lots as well as high, medium and low vigour seed lots. Near-infrared spectra (950–1650 nm) were collected for training and validation samples for each seed category and used to create partial least squares (PLS) prediction models. For both germination and vigour, qualitative models provided better discrimination of high and low performing seed lots compared with quantitative models. The qualitative germination prediction models correctly identified low and high germination seed lots with an accuracy between 85.7 and 89.7%. For seed vigour, qualitative predictions for the 3-category (low, medium and high vigour) models could not adequately separate high and medium vigour seeds. However, the 2-category (low, medium plus high vigour) prediction models could correctly identify low vigour seed lots between 80 and 100% and the medium plus high vigour seed lots between 96.3 and 96.6%. To our knowledge, the current study is the first to provide near-infrared spectroscopy (NIRS)-based predictive models using agronomically meaningful cut-offs for standard germination and vigour on a commercial scale using over 80 seed lots.
Postglacial emergence curves are used to infer mantle rheology, delimit ice extent, and test models of the solid Earth response to changing ice and water loads. Such curves are rarely produced by direct dating of land emergence; rather, most rely on the presence of radiocarbon-datable organic material and inferences made between the age of sedimentary deposits and landforms indicative of former sea level. Here, we demonstrate a new approach, 10Be dating, to determine rates of postglacial land emergence in two different settings. In southern Greenland (Narsarsuaq/Igaliku), we date directly the exposure, as relative sea level fell, of gravel beaches and rocky outcrops allowing determination of rapid, post–Younger Dryas emergence. In western Greenland (Kangerlussuaq), we constrain Holocene isostatic response by dating the sequential stripping of terrace sediment driven by land-surface uplift, relative sea-level fall, and resulting fluvial incision. The technique we employ provides high temporal and elevation resolution important for quantifying rapid emergence immediately after deglaciation and less rapid uplift during the middle Holocene. 10Be-constrained emergence curves can improve knowledge of relative sea-level change by dating land emergence along rocky coasts, at elevations and locations where radiocarbon-datable sediments are not present, and without the lag time needed for organic material to accumulate.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.
In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.
An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.
CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.
The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data.
Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI).
Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes).
The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.
Dietary conjugated linoleic acids (CLA) offer significant health benefits for man, and ruminant products are the major dietary sources (Bauman et al., 2001). The synthesis of CLA in the ruminant animal occurs either directly in the rumen or in the tissue from trans -vaccenic acid (TVA), formed primarily as intermediate products of ruminal biohydrogenation of linoleic acid (C18:2) to stearic acid (C18:0). Within the rumen, the pattern of biohydrogenation and the products formed appear to differ between the particle rich and the liquid fractions of the rumen (Singh and Hawke, 1979), with biohydrogenation occurring primarily on small particles. The aim of this study was to investigate whether the pattern of CLA and TVA formation differs in these fractions.
Rapid breakdown of herbage proteins in the rumen and inefficient capture of nitrogen (N) by the rumen microbial populations are a major source of N loss and pollution in pasture-based ruminant agriculture. Degree of cell damage during mastication and ingestion varies between grass species with consequences for release of cell contents (protein, sugars and lipids) into the rumen (Kim et al., 2008). Consequently, grazing cattle on different grass species may provide an opportunity to manipulate N efficiency. The purpose of this study was to compare N utilisation efficiency by dairy cattle grazing grass species differing in chemical and morphological characteristics.
As grazing ruminants rely almost entirely on mastication to disrupt plant tissues, a series of processes (mastication, bolus formation and ingestion) will impact on the viability and number of cells that remain intact, and consequently alive, after ingestion (Kingston-Smith and Theodorou, 2000). Preliminary work in our group has shown substantial variation in the degree of cell damage during mastication and ingestion between grass species, resulting in differences in the rate of release of cell contents (protein, sugars and lipids) into the rumen (E.J. Kim, unpublished). These differences may affect nutrient utilisation by ruminal micro-organisms. The aim of this study was to compare the extent of nutrient release from three contrasting grass species following ingestion of the fresh forage by dairy cows.
Forages are a rich source of beneficial n-3 PUFAs (?-linolenic acid; C18:3n- 3) and may be a useful means of modifying the fatty acid composition of ruminant products. Altering the fatty acid composition of ruminant products is difficult due to the biohydrogenation action of rumen micro-organisms, which hydrogenate the PUFAs into monounsaturated and saturated fatty acids. Little information is available on biohydrogenation of PUFAs in forages hence this study investigated this in steers fed on perennial ryegrass, red or white clover silages or combinations thereof.