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Stratigraphic, geochronologic, and geochemical patterns of Neoproterozoic to Cambrian sedimentary and volcanic rocks in Utah, Nevada, and SE Idaho record a dynamically evolving landscape along the North American Cordillera margin, which included: (1) initial development of intracratonic basins with deposition of siliciclastic strata of the Uinta Mountain Group from ~ 770 to 740 Ma; (2) early rifting and volcanism along a N–S (present day geographic coordinates) basin system with deposition of diamictite-bearing strata of the Perry Canyon and related formations from ~ 720 to 660 Ma; (3) early, broad subsidence with deposition of mature siliciclastic strata of the lower Brigham and McCoy Creek groups from ~ 660 to 580 Ma; (4) final rifting, volcanism, and transition to drift with deposition of variably immature siliciclastic strata of the Prospect Mountain and correlative formations from ~ 570 to 520 Ma; and (5) regional subsidence along a passive margin with deposition of Middle Cambrian to Devonian carbonate-rich strata. The Uinta Mountain Group comprises fluvial to marine, feldspathic to quartzose sandstone, conglomerate, and mudstone, with detrital zircon (DZ) patterns recording a mix of local basement sources to the N and distal Laurentian sources to the SE. The lower Perry Canyon and related formations contain variably feldspathic sandstone, quartz-pebble diamictite deposited during an older glacial episode, and mudstone, with DZ patterns recording a mix of distal sources, local basement sources, and sediment recycling during early rifting. The upper Perry Canyon and related formations contain mafic volcanic rocks, polymict diamictite deposited during a younger glacial episode, volcaniclastic wacke, and mudstone, with DZ patterns recording local basement sources along an evolving rift margin and felsic volcanism from ~ 700 to 670 Ma. Mafic volcanic rocks and trachyte to rhyolite clasts in diamictite have geochemical signatures typical of continental rifting. The lower Brigham and McCoy Creek groups contain mostly mature quartz arenite deposited in shallow marine environments, with DZ patterns recording distal Laurentian sources. The base of the Prospect Mountain and correlative formations is marked by an influx of feldspathic, coarse-grained sediment derived from local basement sources and ~ 570–540 Ma basalt volcanism, which was followed by deposition of subfeldspathic strata with dominant 1.7–1.8 Ga DZ grains, recording sources from the SE rift margin and a marked decrease in distal sources during uplift of the Transcontinental Arch. Overlying carbonate-rich strata were deposited in shallow marine settings, with episodic influx of siliciclastic sediment derived from basement exposed during regressions. Stratigraphic thickness-age relations of Neoproterozoic to early Paleozoic strata are consistent with two episodes of rifting concentrated at ca. 700–670 Ma and 570–540 Ma along western Laurentia, leading to final development of a passive margin. Early rifting was incomplete with an estimated 25–40% extension of initially thick lithosphere that was weakened by igneous activity. Final rifting of previously thinned lithosphere involved an estimated 20–35% additional extension, renewed igneous activity, and thermal thinning of mantle lithosphere, with localized extension culminating in final separation along the continental margin. Stratigraphic, geochronologic, and available paleomagnetic data are consistent with linkage of western Laurentia to Australia–East Antarctica within Rodinia, followed by protracted rifting and drift during Cambrian time.

Large-magnitude retroarc shortening of Cretaceous age is well documented in the Sevier orogenic belt of the western United States, and has been associated with eastward Franciscan subduction that began in the Middle–Late Jurassic, but evidence for major Late Jurassic retroarc shortening has been lacking. Here we report new Lu-Hf garnet geochronology, pressure-temperature ( P - T ) paths, and 40 Ar/ 39 Ar thermochronology data that document tectonic burial of Late Jurassic age in a Barrovian metamorphic terrain, the Funeral Mountains metamorphic core complex, California, located in the hinterland of the Sevier orogenic belt. The P - T paths determined from growth-zoned garnets in upper greenschist facies pelitic schist show steep P - T trajectories consistent with metamorphism during thrust loading. The age of thrust loading is constrained by a five-point Lu-Hf garnet isochron to be 158.2 ± 2.6 Ma (2σ). Partial exhumation, recorded in 146–153 Ma 40 Ar/ 39 Ar muscovite cooling ages, closely followed garnet growth. Late Jurassic Barrovian metamorphism has not been previously recognized in Cordilleran metamorphic core complexes, possibly due to being obscured by Late Cretaceous to Tertiary deformation, magmatism, and metamorphism. This study finds that the period of large-magnitude crustal shortening in the retroarc extended into the Late Jurassic, and may have closely followed the formation of the coherent orogenic system associated with east-dipping Franciscan subduction.

Objectives: To assess the validity of an educational method of vertical integration as a transitional stage from discipline-based to fully integrated medical curriculum in a community oriented medical school. Methods: involved a quarterly “Integrative Medical Education Symposium (IMES)” series targeting third- and fourth-year medical students. This series handled one or more clinical topics per symposium, which were carefully selected by the IMES Committee. The topics were presented in a Problem/ Case-Based Learning (PBL) format with interactive discussion of differential diagnosis of the case. Occasionally, actors portrayed patients. Upon conclusive diagnosis, integrated basic sciences and clinical reviews of the topic were presented in different ways. At the end of each symposium, students were invited to complete a 5-point Likert scale survey, which involved 6 questions to evaluate clinical and basic science education, integration, student interaction, effect on diagnostic skills, and overall program efficacy. Each question’s data collected from eighteen IMES series were analyzed and classified into two groups; accept and reject. The “accept” group represented the sum of students who “strongly agree” (score “5” on Likert scale) and simply “agree” (score “4” on Likert scale) of a survey question. The “reject” group represented the sum of students who “strongly disagree” (score “1” on Likert scale) and simply “disagree” (score “2” on Likert scale) of the same survey question. The two groups of each question were then statistically compared to each other using students’-test, where p

Fetal alcohol spectrum disorders (FASD) are a highly variable set of phenotypes caused by fetal alcohol exposure. Numerous factors influence FASD phenotypes, including genetics. The zebrafish is a powerful vertebrate model system with which to identify these genetic factors. Many zebrafish mutants are housed at the Zebrafish International Resource Center (ZIRC). These mutants are readily accessible and an excellent source to screen for ethanol (EtOH)-sensitive developmental structural mutants.We screened mutants obtained from ZIRC for sensitivity to EtOH teratogenesis. Embryos were treated with 1% EtOH (41 mM tissue levels) from 6 hours postfertilization onward. Levels of apoptosis were evaluated at 24 hours postfertilization. At 4 days postfertilization, the craniofacial skeleton, peripheral axon projections, and sensory neurons of neuromasts were examined. Fish were genotyped to determine whether there were phenotype/genotype correlations.Five of 20 loci interacted with EtOH. Notable among these was that vangl2, involved in convergent extension movements of the embryonic axis, interacted strongly with EtOH. Untreated vangl2 mutants had normal craniofacial morphology, while severe midfacial defects including synophthalmia and narrowing of the palatal skeleton were found in all EtOH-treated mutants and a low percentage of heterozygotes. The cell cycle gene, plk1, also interacted strongly with EtOH. Untreated mutants have slightly elevated levels of apoptosis and loss of ventral craniofacial elements. Exposure to EtOH results in extensive apoptosis along with loss of neural tissue and the entire craniofacial skeleton. Phenotypes of hinfp, mars, and foxi1 mutants were also exacerbated by EtOH.Our results provide insight into the gene-EtOH interactions that may underlie EtOH teratogenesis. They support previous findings that EtOH disrupts elongation of the embryonic axis. Importantly, these results show that the zebrafish is an efficient model with which to test for gene-EtOH interactions. Understanding these interactions will be crucial to understanding of the FASD variation.

Lipophorin (Lp) is a major insect lipoprotein and is responsible for lipid transport between organs. In this study, the effect of starvation on Lp properties was analyzed in larval Manduca sexta during the fifth instar. Lp hemolymph concentrations in larvae at days 1 and 2 were around 2-3 mg/ml and at day 3 it increased to 8 mg/ml. When larvae were starved for 24 h, they did not grow, but their body mass and hemolymph volume did not decrease significantly. Differences in Lp densities were observed. In fed larvae, from days 1 to 4, two major Lp populations were found with densities of 1.124 ± 0.002 (high density Lp-larval1 , HDLp-L1 ) and 1.141 ± 0.002 g/ml (HDLp-L2 ). When larvae were starved for 24 h, only one Lp population was present, with density 1.114 ± 0.001 g/ml (HDLp-Ls ). When larvae were abdominally ligated at day 1 or 2 of fifth instar, only HDLp-Ls was found after 24 h, indicating that the formation of this HDLp population was not dependent on any factor released by head. On the other hand, larvae that were ligated at day 3 showed the same Lp populations as the fed ones. In 24-h starved larvae, lipid load in Lp was higher as compared to the fed controls. In 24-h ligated larvae Lp lipid content increased when ligation was performed on day 1 or 2, but not on day 3. So, different responses to starvation can be observed depending on the developmental phase of the same larval instar.

Schools alone do not have the capacity to plan and implement the wide range of interventions needed to ensure a safe school environment for students. A collaborative approach among education and other community systems can best address the intersecting factors that contribute to antisocial behaviors. The Safe Schools/Healthy Students Initiative, launched in 1999, is a comprehensive approach to help ensure children feel safe in their schools. This article elaborates on efforts by grantees and their partners to improve coordination and service integration with an emphasis on the successful reintegration of students into schools. Keypoints Coordination and integration of programs and activities provided by community stakeholders are critical to improve youth outcomes. This article highlights efforts by communities to provide a more supportive school environment to address issues of safety and student well-being. Comprehensive efforts contribute to minimizing duplication of services, preserving scarce resources and better identifying and serving students at risk for or already affected by violence, substance use, and mental health issues.

To explore Swedish child health nurses' views on their role of involving fathers at the Child Health Centres (CHCs).Interviews with 17 experienced Swedish Child Health nurses were recorded, transcribed and analysed using systematic text condensation. Following the first analysis, the transtheoretical model of behavioural change was used to interpret the results.Four themes emerged during the analysis: (1) the nurses' own agenda; (2) nurses' opinion about the father's role; (3) nurses' gatekeeping; and (4) wanting more father involvement. Most nurses were in the precontemplation stage according to the transtheoretical model when they expressed their roles as nurses (Theme 1), how they perceived the father's role within the family (Theme 2) and how they actively encouraged mothers, but not fathers, to visit the CHCs (Theme 3/Mothers are our priority). Nurses in the contemplation stage started to consider involving fathers in the CHCs (Theme 3/The gate is closed...). Still others were in the preparation (Theme 4/Fathers are worthy of change) and action stages (Theme 4/Active in involving fathers), respectively.Child Health nurses place more emphasis on engaging mothers than fathers in the services. To increase father involvement, nurses need support to become aware, initiate and maintain action.

Triple P is a parenting program that aims to prevent behavioral, emotional, and developmental problems in children. Because Triple P is a new parenting program in Sweden, it is important to see how parents felt about the intervention. The aim of this study was to find out why parents of preschool children chose to participate in Triple P in Sweden, what they thought of the Triple P curriculum, and how the program related to their parenting philosophy in general. This is a qualitative study using semi-structured interviews with seven mothers and three fathers who participated in Triple P. The interviews were transcribed verbatim and were analysed using Malterud’s method of Systematic Text Condensation. Parents chose to participate in Triple P for several reasons: they wanted to learn more about the intervention; they had specific problems that they sought help for; or they felt encouraged to participate due to advertisements and recommendations from friends. Of the Triple P curriculum, the participants especially enjoyed the “directed discussion” technique, the positive reinforcement sections, and the instructions on how to communicate effectively with their child by staying calm, close, and maintaining eye contact. It was important for many of the parents to feel validated and respected, and they liked having discussions with the preschool teacher rather than being told what to do. Parents in this Swedish sample generally liked and selectively used the strategies they learned from participating in Triple P, depending on how well these fit with their own parenting experiences and philosophy.

A major challenge in foundational science courses in dental curricula is the application of information from the classroom to a clinical setting. To bridge this gap, the aim of this study was to increase students' learning in a foundational pharmacology course through increasing clinical relevance and using formative assessment. Second-year dental students in an introductory pharmacology course were presented material in a traditional basic science lecture format and in brief examples of pharmacy-generated clinical content (Medication Minutes). Short-term retention was assessed with a series of five post-class session, non-graded quizzes, each containing four questions: two knowledge-based (one from basic science material and one Medication Minute) and two application-based (one from basic science material and one Medication Minute). Ten knowledge-based (basic science material) questions and ten application-based (Medication Minutes) questions were included on exams throughout the semester. The primary outcome was to measure long-term retention using performance on these questions on an assessment the following semester. Additionally, the impact of student engagement on examination performance was evaluated based on the number of quizzes each student completed. Students who completed three or more quizzes (n=43, 53%) were designated as "highly engaged," while students who completed less than three quizzes (n=36, 44%) were defined as "less engaged." Two students (3%) were excluded for not completing the long-term assessment or not consenting to the study. On short-term retention measures, the students performed better on the Medication Minute (M=0.76) than basic science (M=0.58) (p

Chronic liver disease has multiple causes, many of which are increasing in prevalence. The final common pathway of chronic liver disease is tissue destruction and attempted regeneration, a pathway that triggers fibrosis and eventual cirrhosis. Assessment of fibrosis is important not only for diagnosis but also for management, prognostic evaluation, and follow-up of patients with chronic liver disease. Although liver biopsy has traditionally been considered the reference standard for assessment of liver fibrosis, noninvasive techniques are the emerging focus in this field. Ultrasound-based elastography and magnetic resonance (MR) elastography are gaining popularity as the modalities of choice for quantifying hepatic fibrosis. These techniques have been proven superior to conventional cross-sectional imaging for evaluation of fibrosis, especially in the precirrhotic stages. Moreover, elastography has added utility in the follow-up of previously diagnosed fibrosis, the assessment of treatment response, evaluation for the presence of portal hypertension (spleen elastography), and evaluation of patients with unexplained portal hypertension. In this article, a brief overview is provided of chronic liver disease and the tools used for its diagnosis. Ultrasound-based elastography and MR elastography are explored in depth, including a brief glimpse into the evolution of elastography. Elastography is based on the principle of measuring tissue response to a known mechanical stimulus. Specific elastographic techniques used to exploit this principle include MR elastography and ultrasonography-based static or quasistatic strain imaging, one-dimensional transient elastography, point shear-wave elastography, and supersonic shear-wave elastography. The advantages, limitations, and pitfalls of each modality are emphasized.

Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs. However, here we show that genetic ablation of AXL has no effect on ZIKV entry or ZIKV-mediated cell death in human induced pluripotent stem cell (iPSC)-derived NPCs or cerebral organoids. These findings call into question the utility of AXL inhibitors for preventing birth defects after infection and suggest that further studies of viral attachment factors in NPCs are needed.

Non-alcoholic steatohepatitis (NASH) is an emerging public health problem without effective therapies. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into bioactive epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory and protective effects. However, the functional relevance of the CYP epoxyeicosanoid metabolism pathway in the pathogenesis of NASH remains poorly understood. Our studies demonstrate that both mice with methionine-choline deficient (MCD) diet-induced NASH and humans with biopsy-confirmed NASH exhibited significantly higher free EET concentrations compared to healthy controls. Targeted disruption of Ephx2 (the gene encoding for soluble epoxide hydrolase) in mice further increased EET levels and significantly attenuated MCD diet-induced hepatic steatosis, inflammation and injury, as well as high fat diet-induced adipose tissue inflammation, systemic glucose intolerance and hepatic steatosis. Collectively, these findings suggest that dysregulation of the CYP epoxyeicosanoid pathway is a key pathological consequence of NASH in vivo, and promoting the anti-inflammatory and protective effects of EETs warrants further investigation as a novel therapeutic strategy for NASH.

Congestive hepatopathy (CH) refers to hepatic abnormalities that result from passive hepatic venous congestion. Prolonged exposure to elevated hepatic venous pressure may lead to liver fibrosis and cirrhosis. Liver dysfunction and corresponding clinical signs and symptoms typically manifest late in the disease process. Recognition of CH at imaging is critical because advanced liver fibrosis may develop before the condition is suspected clinically. Characteristic findings of CH on conventional images include dilatation of the inferior vena cava and hepatic veins; retrograde hepatic venous opacification during the early bolus phase of intravenous contrast material injection; and a predominantly peripheral heterogeneous pattern of hepatic enhancement due to stagnant blood flow. Extensive fibrosis can be seen in chronic or severe cases. Hyperenhancing regenerative nodules that may retain hepatobiliary contrast agents are often present. Magnetic resonance (MR) elastography can show elevated liver stiffness and may be useful in evaluation of fibrosis in CH because it can be incorporated easily into routine cardiac MR imaging. Preliminary experience with MR elastography suggests its future use in initial evaluation of patients suspected of having CH, for monitoring of disease, and for assessment after therapy. To facilitate appropriate workup and treatment, radiologists should be familiar with findings suggestive of CH at radiography, ultrasonography, computed tomography, MR imaging, and MR elastography. In addition, knowledge of underlying pathophysiology, comparative histologic abnormalities, and extrahepatic manifestations is useful to avoid diagnostic pitfalls and suggest appropriate additional diagnostic testing. (©)RSNA, 2016.

To explore the needs of and support given to lesbian, gay, bisexual, transgendered and inter-sex parents within the Nordic child health field.The number of lesbian, gay, bisexual, transgendered and inter-sex parents is growing around the world. However, they face fear, discrimination and heteronormativity within the child health field. The Nordic countries (Sweden, Norway, Denmark, Finland and Iceland) rank as the most gender equal countries in the world; therefore, they may support lesbian, gay, bisexual, transgendered and inter-sex parents to a greater extent.Systematic literature review and meta-synthesis.A systematic search was conducted for lesbian, gay, bisexual, transgendered and inter-sex parents' experiences in the child health field, which consists of prenatal, labour and birth, postnatal and child health clinics, using PubMed, PsychInfo, Sociological Abstracts and CINAHL, as well as searching the grey literature, from 2000-2015. Ten articles were included. A quality assessment and a meta-synthesis of the articles were performed.Nearly all studies were qualitative, and most articles had at least one area of insufficient reporting. Only two countries, Sweden and Norway, had lesbian, gay, bisexual, transgendered and inter-sex parents reporting on the child health field. However, gay, bisexual, transgender and inter-sex parents' perspectives were nonexistent in the literature; therefore, the results all relate to same-sex mothers. Five themes were found: Acceptance of Same-sex Mothers, Disclosing Sexual Orientation, Heteronormative Obstacles, Co-mothers are Not Fathers, and Being the Other Parent.Same-sex mothers are generally accepted within the Nordic child health field, but they still face overt and covert heteronormative obstacles, resulting in forms of discrimination and fear. Co-mothers feel invisible and secondary if they are not treated like an equal parent, but feel noticed and important when they are given equal support.Changes at the organisational and personnel levels can be made to better support same-sex mothers and co-mothers. Recognising both parents benefits the whole family.

UNLABELLED Sweden has a reputation for gender equality, and its child health services seek to support both parents. However, this meta-ethnographic analysis of 62 studies from 2000 to 2015 covering prenatal clinics, labour and birth wards, postnatal wards and child health centres found programmes had not been designed around paternal needs. Therefore, despite the policy change nearly 50 years ago to include both parents, fathers were still not fully accepted and supported. CONCLUSION To provide fathers in Sweden with greater support throughout the child health field, organisational changes should be considered, as this could provide further beneficial outcomes for children, families and society.

Dosage compensation balances gene expression levels between the sex chromosomes and autosomes and sex-chromosome-linked gene expression levels between the sexes. Different dosage compensation strategies evolved in different lineages, but all involve changes in chromatin. This paper discusses our current understanding of how modifications of the histone H4 tail, particularly changes in levels of H4 lysine 16 acetylation and H4 lysine 20 methylation, can be used in different contexts to either modulate gene expression levels twofold or to completely inhibit transcription.

The Safe Schools/Healthy Students (SS/HS) Initiative offers a unique opportunity to conduct large-scale, multisite, multilevel program evaluation in the context of a federal environment that places many requirements and constraints on how the grants are conducted and managed. Federal programs stress performance-based outcomes, valid and reliable data, addressing important problems, ensuring efficiency and fiscal responsibility, reducing burden on federal staff and grantees, and developing and disseminating useful solutions and recommendations. MANILA Consulting Group, Inc., (MANILA), in partnership with Battelle Centers for Public Health Research and Evaluation (Battelle) and RMC Research Corporation (RMC), has been conducting the SS/HS national cross-site evaluation, which involves the coordinated efforts of federal Project Officers, local education agencies, technical assistance providers, communication specialists, and national and local evaluators across a diverse set of socioeconomic and cultural contexts. To date, the national cross-site evaluation has provided data indicating that the SS/HS Initiative is, in fact, meeting these goals. Findings revealed that fewer students reported they had experienced violence and fewer students reported they had witnessed violence. Fully 96 percent of school staff said SS/HS had improved school safety. There was a 263 percent increase in the number of students who received school-based mental health services and a 519 percent increase in those receiving community-based mental health services. In addition, more than 80 percent of school staff reported that they saw reductions in alcohol and other drug use among their students. These encouraging results stress the need for ongoing coordination at all levels of the Initiative to continue to ensure safer schools and healthier students. This article provides an overview of the initiative and introduces four articles in this special issue.

The Safe Schools/Healthy Students (SS/HS) national evaluation seeks to assess both the implementation process and the results of the SS/HS initiative, exploring factors that have contributed to or detracted from grantee success. Each site is required to forge partnerships with representatives from education, mental health, juvenile justice, and law enforcement, coordinating and integrating their efforts and working together to contribute to comparable outcomes (e.g., reduced violence and alcohol and drug use, improved mental health services). The evaluation uses multiple data collection techniques (archival data, surveys, site visits, interviews, and focus groups) from a variety of sources (project directors, community partners, schools, and students) over several years. Certain characteristics of the SS/HS initiative represent unique challenges for the evaluation, including the absence of common metrics for baseline, outcome data, and lack of comparison group. A unifying program theory was required to address these challenges and synthesize the large amounts of qualitative and quantitative information collected. This article stresses the role of program theory in guiding the evaluation.

A three-level growth-curve model was applied to estimate perceived impact growth trajectories, using multi-year data from project and school surveys on outcome and program implementation collected from 59 sites and approximately 1165 participating schools in the Safe Schools and Healthy Students Initiative. Primary interest is to determine whether and how project-level and school-level correlates affect schools' perceptions of the Initiative's effectiveness over time when the effects of the pre-grant environmental conditions, grant operations, and near-term outcomes are considered. Coordination and service integration, comprehensive programs and activities for early childhood development, and change in school involvement were found to be significant predictors of school-perceived overall impact when the effect of poverty was considered. Partnership functioning, perceived importance of school resources, and school involvement were found to be significant predictors of school-perceived impact on substance use prevention when the effect of poverty was considered. Language: en

Male chimpanzees, Pan troglodytes, defend group territories, and sometimes injure or kill members of other groups. To test which factors best predict the occurrence and outcomes of intergroup encounters, we analysed 15 years of data on intergroup encounters, party composition, ranging and feeding behaviour in the Kanyawara community of chimpanzees, Kibale National Park, Uganda. During this time, researchers observed 120 intergroup encounters, most of which (85%) involved only acoustic contact. The majority of encounters (63%) occurred in the southeast quadrant of the range. Multiple logistic regression found that intergroup encounters occurred more often when chimpanzees were far from the centre of their range, especially in the south, and when eating foods that were most abundant in the south. Multiple linear regression found that chimpanzees travelled further from the centre of their range, and further south, when eating a few key foods, especially fruits of Uvariopsis congensis, and when in parties with more males. Upon hearing calls from foreign chimpanzees, Kanyawara chimpanzees were more likely to vocalize in response, and to travel towards the foreign chimpanzees, when they had more males in their party. Measures of two resource values, food and mates, were negatively correlated with the probability of vocalizing and approaching intruders, respectively. These findings indicate that, in this population, resources affect the timing of intergroup encounters, but the decision to escalate a contest depends mainly on numerical strength, rather than the value of resources being contested.

Background Anopheles mosquitoes are vectors for malaria, a disease with continued grave outcomes for human health. Transmission of malaria from mosquitoes to humans occurs by parasite passage through the salivary glands (SGs). Previous studies of mosquito SG architecture have been limited in scope and detail. Methods We developed a simple, optimized protocol for fluorescence staining using dyes and/or antibodies to interrogate cellular architecture in Anopheles stephensi adult SGs. We used common biological dyes, antibodies to well-conserved structural and organellar markers, and antibodies against Anopheles salivary proteins to visualize many individual SGs at high resolution by confocal microscopy. Results These analyses confirmed morphological features previously described using electron microscopy and uncovered a high degree of individual variation in SG structure. Our studies provide evidence for two alternative models for the origin of the salivary duct, the structure facilitating parasite transport out of SGs. We compare SG cellular architecture in An. stephensi and Drosophila melanogaster, a fellow Dipteran whose adult SGs are nearly completely unstudied, and find many conserved features despite divergence in overall form and function. Anopheles salivary proteins previously observed at the basement membrane were localized either in SG cells, secretory cavities, or the SG lumen. Our studies also revealed a population of cells with characteristics consistent with regenerative cells, similar to muscle satellite cells or midgut regenerative cells. Conclusions This work serves as a foundation for linking Anopheles stephensi SG cellular architecture to function and as a basis for generating and evaluating tools aimed at preventing malaria transmission at the level of mosquito SGs. Electronic supplementary material The online version of this article (doi:10.1186/s13071-015-1229-z) contains supplementary material, which is available to authorized users.

Aim: To explore parents' perspectives on providing their preschool child with a healthy lifestyle, including obstacles and resources.Methods: Five semi-structured focus group interviews were cond ...

The authors present a case illustrating the importance of obtaining a biopsy of any facial skin lesions in a patient presenting with an intracranial tumor involving the facial or trigeminal nerve. Conventional malignant melanoma metastasizes to the brain frequently and does not usually pose diagnostic difficulties. Direct intracranial spread of cutaneous melanoma is rare. In our patient, desmoplastic melanoma with perineural spread to the Meckel cave mimicked a malignant peripheral nerve sheath tumor clinically, radiographically, and histologically.

Extensional detachment systems separate hot footwalls from cool hanging walls, but the degree to which this thermal gradient is the product of ductile or brittle deformation or a preserved original transient geotherm is unclear. Oxygen isotope thermometry using recrystallized quartz-muscovite pairs indicates a smooth thermal gradient (140 °C/100 m) across the gently dipping, quartzite-dominated detachment zone that bounds the Raft River core complex in northwest Utah (United States). Hydrogen isotope values of muscovite (δD Ms ~ –100‰) and fl uid inclusions in quartz (δD Fluid ~ –85‰) indicate the presence of meteoric fl uids during detachment dynamics. Recrystallized grain-shape fabrics and quartz c-axis fabric patterns reveal a large component of coaxial strain (pure shear), consistent with thinning of the detachment section. Therefore, the high thermal gradient preserved in the Raft River detachment refl ects the transient geotherm that developed owing to shearing, thinning, and the potentially prominent role of convective fl ow of surface fl uids.

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan–McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice., National Institute of Mental Health (U.S.) (NIMH/NIH (R01MH081201)), Hartwell Foundation (Hartwell Individual Biomedical Research Award), Simons Foundation (Autism Research Initiative (SFARI) grant Award), Brain and Behavior Research Foundation (NARSAD Young Investigator Award), National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award (F32MH084460)), National Institutes of Health (U.S.) (NIH grant (R03MH085224)), Fundação para a Ciência e a Tecnologia (SFRH/BD/15231/2004), Fundação para a Ciência e a Tecnologia (SFRH/BD/15855/2005), Instituto Gulbenkian de Ciência (“Programa Gulbenkian de Doutoramento em Biomedicina” (PGDB, Oeiras, Portugal)), University of Coimbra. Center for Neuroscience and Cell Biology (“Programa Doutoral em Biologia Experimental e Biomedicina” (CNC, Coimbra, Portugal))

Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence.

The Late Cretaceous to Paleogene Sevier hinterland of east-central Nevada is widely regarded as an orogenic plateau that has since undergone topographic collapse. New U-Pb detrital zircon age data consisting of 1296 analyses from the Lower Cretaceous Newark Canyon Formation and the Upper Cretaceous to Eocene Sheep Pass Formation indicate that Precambrian detrital zircon populations recycled from local Paleozoic strata are dominant. Subordinate Mesozoic zircon populations are derived mainly from local backarc volcanic centers of Late Jurassic and Early Cretaceous age, while ca. 38–36 Ma detrital zircon age peaks record the local onset of Eocene volcanism. Sevier hinterland deposits of east-central Nevada lack significant Triassic, Early Jurassic, and Late Cretaceous populations common in terranes of western Nevada and the Sierra Nevada magmatic arc. These data suggest that long-term evolution of the Sevier Plateau involved geographic isolation through a combination of high relief and rugged topography related to Early Cretaceous shortening, and continued isolation through development of latest Cretaceous to Eocene internally drained, extensional basins. The (U-Th)/He zircon ages obtained from the Sheep Pass Formation record late Paleo zoic, Early Cretaceous, and Late Cretaceous cooling through 180 °C. Preservation of late Paleozoic (ca. 265 Ma) cooling ages indicates that much of the Upper Paleozoic section within east-central Nevada that contributed detritus to the Sheep Pass basin was unaffected by deep thrust burial, or by burial beneath thick Mesozoic sedimentary cover. Early Cretaceous (ca. 135 Ma) cooling ages are potentially coeval with shortening along the central Nevada fold-and-thrust belt, although ca. 80 Ma cooling ages within the Sheep Pass Formation are coeval with hinterland midcrustal extension. Together, these new data provide support for previous interpretations that the Sevier hinterland represents an ancient high-elevation orogenic plateau, and that the latest Cretaceous locally marks a transition from contraction to extension.

Two groups of coyotes in which genealogical relationships were known were studied in the Grand Teton National Park, outside of Jackson, Wyoming, U.S.A., from 1977–1982. One group, a pack consisting of parents and some non-dispersing and non-breeding offspring, defended a territory and the food (mainly elk carrion) contained within it, especially during winter, and also had helpers at den sites (5 of 6 were males). The other group, a mated resident pair, all of whose young dispersed during the first year of life, did not defend a territory and never had helpers at dens. Delayed dispersal and retention of some offspring as helpers was related to the presence of an abundant, clumped, and defendable winter food resource. Dispersing yearlings suffered higher mortality than did non-dispersing individuals. Litter size was the same for the pack and resident pair; litter size was not significantly correlated with number of adults in the group or with the number or percentage of pups that survived to 5–6 months of age. The presence of pack helpers was not significantly correlated with pup survival, although there was a positive correlation (rs = +0.37) between the number of adults attending a den(s) and pup survival. Helpers rarely fed pups and their presence had no appreciable effect on juvenile weight. Helpers partook in den-sitting (pup-guarding), but they did not reduce the amount of time that parents spent at den sites. Helpers also actively initiated and took part in territorial and food defense. The proportion of times that pack members initiated defense was inversely related to intruder density (r = –0.94).

Cuticular hydrocarbons (CHCs) are information-rich signals in social insects that coordinate behaviors within nests. However, in some taxa, the precise information conveyed by CHCs is poorly understood. In particular, there is a debate over whether CHCs convey information about their bearer's dominance or fertility. Distinguishing between dominance and fertility signaling is difficult because fertility and rank are frequently correlated within social insect colonies. This study disentangles those relationships by examining CHCs of Polistes dominulus paper wasps during the early nest-founding stage before dominance and fertility become correlated. First, we confirm that dominance and fertility are not associated in early spring foundresses. Then we show that CHCs are more strongly associated with fertility than dominance. There was no relationship between cuticular hydrocarbon profiles and a wasp’s ability to dominate rivals through aggression, suggesting that CHCs are unlikely to provide information about dominance. However, there was a significant correlation between ovarian development and the CHC profile, suggesting that CHCs could convey valuable information about their bearer's fertility. Furthermore, our data provide a potential mechanism for chemical signaling of fecundity, as there is a relationship between endogenous juvenile hormone titer (a gonadotropin), degree of ovarian development, and the CHC profile. Hormonal regulation of CHC profile expression offers a physiological mechanism to coordinate behavior, physical state, and signal expression.

Alluvial and lacustrine deposits of the >1 km thick, uppermost Cretaceous to middle Eocene Sheep Pass Formation of east-central Nevada provide a unique opportunity to test models of the tectonic and palaeogeographic evolution of the Sevier hinterland. Within the south Egan Range, new 1:12,000 geologic mapping and stratigraphic observations reveal that latest Cretaceous initiation of the Sheep Pass basin was marked by megabreccia deposition, growth faults, and fanning dips that formed in response to down-to-the-northwest motion along the Ninemile fault, a presently low-angle normal fault displaying 4 km of stratigraphic throw. Continued Maastrichtian to Late Palaeocene motion along the Ninemile fault is suggested by widespread soft-sediment deformation within the Sheep Pass Formation, interpreted as seismites. Located 20 km to the south of the Sheep Pass Formation type section, the Shingle Pass fault similarly shows evidence for late Palaeocene motion. A subsequent episode of Eocene extension is recorded w...

The hinterland of the Sevier orogenic belt of western North America is widely interpreted as a Cretaceous to Paleogene orogenic plateau. Although evidence for mid-crustal extension of Late Cretaceous age within the Sevier hinterland is widespread, coeval surface-breaking normal fault systems have not been documented. New 1:12,000-scale mapping within the type section of the latest Cretaceous to Eocene Sheep Pass Formation of east-central Nevada suggests that deposition occurred in response to normal fault movement recording up to 4 km of Late Cretaceous and Paleogene stratigraphic throw. Intrabasinal normal faulting caused lateral thickness variations within the basal Sheep Pass Formation, although upper members are largely unaffected. An extensional basin setting best explains the fanning of bedding dips, the deposition of megabreccia, and the presence of syndepositional normal faults within the Sheep Pass Formation. Deposition of the basal member of the Sheep Pass Formation is bracketed between ca. 81.3 ± 3.7 Ma and 66.1 ± 5.4 Ma, based on the (U-Th)/He cooling ages of detrital zircons, and on a U-Pb carbonate age derived from the overlying lacustrine limestone member. These new data provide the strongest evidence to date for the existence of Late Cretaceous, surface-breaking normal faults in the Sevier hinterland. Normal faulting was coeval with mid-crustal hinterland extension and with continued contraction within the Sevier foreland to the east.

We performed in situ Th–Pb dating of monazite in upper amphibolite facies pelitic schist from the Grouse Creek Mountains in northwest Utah. Sixty-six ages from inclusions in four garnet grains range from 37 to 72 Ma and decrease with radial distance from garnet cores. The age range of 30 matrix monazite grains overlaps and extends to younger ages than inclusions (25– 58 Ma). The monazite grains are not intersected by cracks in the garnets, through which dissolution, reprecipitation or Pb loss might occur, and are generally too small (

Rolipram, an inhibitor of phosphodiesterase 4 (PDE4) proteins that hydrolyze cAMP, increases axonal regeneration following spinal cord injury (SCI). Recent evidence indicates that rolipram also protects against a multitude of apoptotic signals, many of which are implicated in secondary cell death post-SCI. In the present study, we used immunohistochemistry and morphometry to determine potential spinal cord targets of rolipram and to test its protective potential in rats undergoing a cervical spinal cord contusive injury. We found that 3 PDE4 subtypes (PDE4A, B, D) were expressed by spinal cord oligodendrocytes. OX-42 immunopositive microglia only expressed the PDE4B subtype. Oligodendrocyte somata were quantified within the cervical ventrolateral funiculus, a white matter region critical for locomotion, at varying time points after SCI in rats receiving rolipram or vehicle treatments. We show that rolipram significantly attenuated oligodendrocyte death at 24 hours post-SCI continuing through 72 hours, the longest time point examined. These results demonstrate for the first time that spinal cord glial cells express PDE4 subtypes and that the PDE4 inhibitor rolipram protects oligodendrocytes from secondary cell death following a contusive SCI. They also indicate that further investigations into neuroprotection and axonal regeneration with rolipram are warranted for treating SCI.

Extension during plate convergence and mountain building is widely recognized, yet the causes of synconvergent extension remain controversial. Here we propose that delamination of lithospheric mantle, aided by decoupling of the crust from the mantle via a reduction in the viscosity of the lower crust through heating, incursion of fl uids, and partial melting, explains many enigmatic yet prevalent aspects of the metamorphic, magmatic, and kinematic history of the Sevier-Laramide orogen of the western United States during the Late Cretaceous. Extension, heating, anatexis, magmatism, and perhaps rock uplift were widespread during a restricted time interval in the Late Cretaceous (75‐67 Ma) along the axis of maximum crustal thickening within the Mojave sector of the Sevier orogen, and to a lesser extent within the interior of the Idaho-Utah-Wyoming sector to the north; similar processes may have been active in the Peninsular Range, Sierran, western Mojave, and Salinian segments of the Mesozoic Cordilleran arc. These processes are viewed as predictable consequences of the thermal, rheological, and dynamic state of the overlying crust following delamination of mantle lithosphere beneath isostatically compensated mountain belts. The proposed delamination would have occurred immediately prior to eastward propagation of lowangle subduction of the Farallon plate during the inception of the Laramide orogeny. Following delamination, extension and anatexis of the North American crust were aided locally by egress of slab-derived fl uids from the low-angle Farallon slab. We suggest that lithospheric delamination may have aided in the shallowing of the slab to achieve lowangle subduction geometry. Delamination has been proposed to be common in areas of thickened continental lithosphere in the terminal phase or late in orogenesis. The Late Cretaceous delamination event proposed here for the Sevier-Laramide orogen occurred during protracted plate convergence and was synchronous with, and followed by, continued shortening in the external part of the orogen.

Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPS) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-C6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPS) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI.

Metamorphic pressure–temperature (P–T) paths derived from 16 growth-zoned garnets, nine from this study and seven from a previous study, have been combined to construct a detailed composite path for an area in the hinterland of the Cretaceous to early Tertiary Sevier orogenic belt in southern Idaho and north-west Utah. Samples are from two Proterozoic units in the footwall of the Basin-Elba thrust: the schist of Mahogany Peaks in the central Albion Mountains, Idaho, and the schist of Stevens Spring in the Basin Creek area of the Grouse Creek Mountains, Utah, ∼40 km to the south. The simulated portions of the garnets analysed in this study grew from reactions involving the breakdown of chlorite in the upper greenschist to lower amphibolite facies. Multiple garnets were analysed from three samples. Overlapping segments of P–T paths from different garnets in the same sample correlate with respect to slope and garnet Mn concentration. The composite P–T path documents three episodes of sharply increasing pressures separated by two episodes of pressure decrease, all during progressively increasing temperatures. The path is interpreted to represent alternating episodes of synconvergent thrusting and extensional exhumation in the hinterland of the Sevier orogen. Burial was probably caused by the Basin-Elba fault, the only major thrust exposed in the region. Extensional exhumation may have occurred along the Mahogany Peaks or Emigrant Spring faults, or by extensional reactivation of the Basin-Elba fault. This method of correlating partial P–T paths to reveal a more complete composite path provides a powerful tool in unveiling orogenic histories in metamorphic terranes, where evidence of major structures responsible for burial and exhumation is commonly obscured by later events.

We describe a 2-year-old African-American boy with a 4-month history of gradually worsening unilateral edema that was initially noted on his left hand and then approximately 2 weeks later on his left lower extremity. In addition, linear hypopigmented patches were noted along the left forearm and leg, with no appreciable scarring or induration. The edema on the left-hand side of his body progressed so that he developed tense bullae on his left hand. Two months later, the hypopigmented patches were indurated and bound-down, especially over the left groin and thigh. A biopsy specimen from this area showed features characteristic of morphea. In this patient, dilated lymphatic channels secondary to the sclerosis of the morphea caused the bullae. Bullous morphea is a rare condition. We were unable to find any reports its occurrence in children under 18 with associated lymphedema. This entity should be included in the differential for acquired unilateral edema in children.

We have developed a novel molecular genetic approach to investigating gene regulation in adult mosquitoes called whole body transfection (WBT). This DNA microinjection method allows for both constitutive and regulated expression of plasmid vectors in the fat body and midgut of adult mosquitoes within 24 h of injection. Using a luciferase reporter gene containing the Aedes aegypti heat shock protein 70 (Hsp70) promoter, we optimized the WBT protocol at various times post-injection and used these parameters to measure the expression of a vitellogenin-luciferase reporter gene in response to blood meal feeding. These studies showed that a 843 bp fragment of the Ae. aegypti vitellogenin-C (VgC) promoter caused a greater than 200-fold induction of luciferase activity in a strict tissue-specific manner, and only in response to feeding. Functional mapping of the VgC promoter by WBT identified essential upstream regulatory elements in the region spanning -780 to -182 bp from the transcriptional start site. We also constructed a lipopolysaccharide-regulated expression vector using a 1096 bp genomic fragment of the Ae. aegypti cecropin B (CecB) promoter. Our data show that four days after WBT injection, the CecB-luciferase reporter gene could be induced more than 100-fold in the fat body following lipopolysaccharide injection. Moreover, we found that lipopolysaccharide-induction of the CecB reporter gene occurred up to 28 days post-WBT injection. These data suggest that WBT could provide a novel strategy to express recombinant proteins and RNAi constructs in adult mosquitoes using conventional microinjection methods.

Aim: Using a public health perspective, this study examined the characteristics of mothers and fathers who attended, compared to those who did not attend, a community-based practitioner-led universally offered parenting program. Method: Mothers (141) and fathers (96) of 4- to 5-year-olds completed a set of questionnaires, including their demographic characteristics, their child’s behavioral and emotional problems, and their own parenting behavior. They were all then given the opportunity to attend level 2 of the Triple P – Positive Parenting Program. During the first six months of the study, 33 mothers and 11 fathers opted to attend the program. Results: The relation between program attendance and parental characteristics was similar for mothers and fathers. In general, fathers, non-native and lower educated parents were less likely to attend the program. Mothers, but not fathers, were more likely to attend if they reported more child behavior problems, while fathers, but not mothers, were observed at a trend level to attend if they perceived their child as having more emotional problems. In addition, parents in general were more likely to attend if they used more harsh parenting strategies. Conclusions: Although the universal offer did not reach parents universally, generally those parents who needed it were more likely to attend. Furthermore, this study shows that different factors may impact mothers’ and fathers’ attendance; therefore, parental data should be analyzed separately and different recruitment strategies should be used for mothers and fathers.

Developmental disabilities, including attention-deficit hyperactivity disorder (ADHD), intellectual disability (ID), and autism spectrum disorders (ASD), affect one in six children in the USA. Recently, gene mutations in patched domain containing 1 (PTCHD1) have been found in ∼1% of patients with ID and ASD. Individuals with PTCHD1 deletion show symptoms of ADHD, sleep disruption, hypotonia, aggression, ASD, and ID. Although PTCHD1 is probably critical for normal development, the connection between its deletion and the ensuing behavioural defects is poorly understood. Here we report that during early post-natal development, mouse Ptchd1 is selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1 deletion attenuates TRN activity through mechanisms involving small conductance calcium-dependent potassium currents (SK). TRN-restricted deletion of Ptchd1 leads to attention deficits and hyperactivity, both of which are rescued by pharmacological augmentation of SK channel activity. Global Ptchd1 deletion recapitulates learning impairment, hyper-aggression, and motor defects, all of which are insensitive to SK pharmacological targeting and not found in the TRN-restricted deletion mouse. This study maps clinically relevant behavioural phenotypes onto TRN dysfunction in a human disease model, while also identifying molecular and circuit targets for intervention., Simons Foundation Autism Research Initiative (Grant 307913), National Institutes of Health (U.S.) (Grant R01MH097104), National Institute of Mental Health (U.S.) (Grant R01MH097104), National Institutes of Health (U.S.) (Grant R01MH107680)

Hand injury risk is a concern in many organizations across the upstream oil and gas industry. Despite strong focus on hand safety, hand injuries continue to occur in high numbers due to the very hands-on nature of the industry both on the rig floor as well as throughout the many processes supporting exploration and production activities. A total approach to manage hand injury risk is required to look at hand injury risk from a lifecycle approach with the aim of making hands-on job hands-free. In this paper, the authors explore a fit-for-purpose program that addresses the challenges of reducing hand injuries by communicating and implementing a simplified and easy-to-understand set of rules to govern risks to hand injuries in a total approach. This holistic approach focuses on the hearts and mind effort to change mindsets that hands on practices can be done safer through alternative work methods and also developing and implementing new ways of performing high risk hands on jobs. Ideas to improve hand hazards recognition through innovative risk assessment methodologies like video risk assessments and hand hazard picture books will further help to reinforce the hearts and mind effort. Eliminating hand injuries is possible and putting the right focus and strategy will go a long way in making the industry safer for the hands that work in it.

Rocks may undergo complex pressure–temperature (P–T) histories during orogenesis in response to alternating episodes of synconvergent burial and exhumation. In this study, chemical zoning in garnets combined with textural and chemical evidence from the schist of Willow Creek in the Albion Mountains of south-central Idaho (USA), reveals a complex P–T path during the early stages of Sevier orogenesis. The distribution of quartz inclusions combined with internal resorption features establishes a hiatus in garnet growth. Chemical zoning was simulated using a G-minimization approach to yield a P–T path consisting of three distinct pressure changes during increasing temperature, defining an “N” shape. Lu–Hf isochron ages from multiple garnet fractions and whole-rock analyses in two samples are 132.1 ± 2.4 and 138.7 ± 3.5 Ma. The samples were collected from the hanging wall of the Basin-Elba thrust fault and yielded results similar to those previously obtained from the footwall. This leads to several conclusions: (1) Both the hanging wall and footwall experienced the same metamorphic event, (2) the paths document a previously unrecognized crustal thickening and synorogenic extension cycle that fills an important time gap in the shortening history of the Sevier retroarc, suggesting progressive eastward growth of the orogen rather than a two-stage history, and (3) episodes of extensional exhumation during protracted convergent orogenesis are increasingly well recognized and highlight the dynamic behavior of orogenic belts.