An introduction to loricifera, cycliophora, and micrognathozoa.
Loriciferans, cycliophorans and micrognathozoans are amongst the latest groups of animals to be discovered. Other than all being microscopic, they have very different body plans and are not closely related. Loriciferans were originally assigned to the Aschelminthes. However, both new molecular and ultrastructural researches have shown that Aschelminthes consist of two unrelated groups, Cycloneuralia and Gnathifera. Cycloneuralia may be included in the Ecdysozoa, including all molting invertebrates, and Gnathifera are more closely related to Platyhelminthes. The phylum Loricifera shares many apomorphic characters (e.g., scalids on the introvert) with both Priapulida and Kinorhyncha, and can be included in the taxon Scalidophora, a subgroup of Cycloneuralia. Cycliophora was originally allied to the Entoprocta and Ectoprocta (Bryozoa) based on ultrastructual research. Subsequent molecular data show they may be related to Rotifera and Acanthocephala, within the taxon Gnathifera. The phylogenetic position of Cycliophora is therefore not settled, and more ultrastructural and molecular data are needed. Micrognathozoa is the most recent major group of animals to be described. They show strong affinities with both Rotifera and Gnathostomulida (within the taxon Gnathifera), especially in the fine structure of the pharyngeal apparatus, where the jaw elements have cuticular rods with osmiophilic cores. Furthermore the micrognathozoans have two rows of multiciliated cells that form a locomotory organ, similar to that seen in some gastrotrichs and interstitial annelids. This character is never seen in Rotifera or in the monociliated Gnathostomulida. Rotifera and Acanthocephala always have a syncytial epidermis (Syndermata). Micrognathozoa lack this characteristic feature. Therefore, they are postulated to be placed basally in the Gnathifera, either as a sister-group to Gnathostomulida or as a sister-group to Rotifera + Acanthocephala.


The vestibulo-ocular reflex assessment in patients with Ménière's disease: examining all semicircular canals.
Abstract Conclusion: The distribution of abnormal results is not uniform between different canals in each patient; the most frequent gain reduction is obtained for the posterior canal. Gain reduction reflects the disease duration and amount of hearing loss. To test the hypothesis that the vestibulo-ocular reflex (VOR) evoked after stimulation of each semicircular canal behaves in a different manner in patients with unilateral definite Ménière's disease. We studied the VOR evoked by rapid head-impulses in the plane of the 6 semicircular canals in 36 patients. It was evaluated with a video system that analyzes the head and eye velocity and the gain was the objective measure. In 12 (33.3%) patients the examination of both ears was normal for all the semicircular canals, in 12 patients the results from the affected ear were abnormal in at least 1 of the semicircular canals, in 11 (30.5%) patients the results were abnormal in at least 1 of the semicircular canals in both the affected and unaffected ears, and in 1 (2.9%) patient the results were abnormal only in the unaffected ear. The most frequent abnormal result was obtained from the posterior canal of the affected ear and from the coupled superior canal of the unaffected ear. The distribution of abnormal findings was dependent on the disease duration and hearing loss.


"My flying machine was out of order".
Why did the founders of this organization-which was established in 1884 as the American Climatological Association-want to study climatology and respiratory diseases? In particular, where did the idea of treating tuberculosis with pure air and sunlight come from? How effective was this treatment for a disease that in 1880 afflicted a third of the population of Colorado? Why did this Association not acknowledge technological advances such as weather forecasting or large 20(th) century population movements? This paper seeks to answer those questions in order to inform the Association's possible study of the effects of global climate change on human health, an issue that is arguably comparable to what the founders faced. Recent governmental reports suggest that the medical and health care communities have not yet become engaged. If the ACCA does not, then who will?


Designer Oncolytic Adenovirus: Coming of Age.
The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it's double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses' mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.


Efficient exciton concentrators built from colloidal core/crown CdSe/CdS semiconductor nanoplatelets.
We present the synthesis and the optical properties of a new type of two-dimensional heterostructure: core/crown CdSe/CdS nanoplatelets. They consist of CdSe nanoplatelets that are extended laterally with CdS. Both the CdSe core and the CdS crown dimensions can be controlled. Their thickness is controlled at the monolayer level. These novel nanoplatelet-based heterostructures have spectroscopic properties that can be similar to nanoplatelets or closer to quantum dots, depending on the CdSe core lateral size.


Improved glycerol utilization by a triacylglycerol-producing Rhodococcus opacus strain for renewable fuels.
Glycerol generated during renewable fuel production processes is potentially an attractive substrate for the production of value-added materials by fermentation. An engineered strain MITXM-61 of the oleaginous bacterium Rhodococcus opacus produces large amounts of intracellular triacylglycerols (TAGs) for lipid-based biofuels on high concentrations of glucose and xylose. However, on glycerol medium, MITXM-61 does not produce TAGs and grows poorly. The aim of the present work was to construct a TAG-producing R. opacus strain capable of high-cell-density cultivation at high glycerol concentrations. An adaptive evolution strategy was applied to improve the conversion of glycerol to TAGs in R. opacus MITXM-61. An evolved strain, MITGM-173, grown on a defined medium with 16 g L(-1) glycerol, produced 2.3 g L(-1) of TAGs, corresponding to 40.4% of the cell dry weight (CDW) and 0.144 g g(-1) of TAG yield per glycerol consumed. MITGM-173 was able to grow on high concentrations (greater than 150 g L(-1)) of glycerol. Cultivated in a medium containing an initial concentration of 20 g L(-1) glycerol, 40 g L(-1) glucose, and 40 g L(-1) xylose, MITGM-173 was capable of simultaneously consuming the mixed substrates and yielding 13.6 g L(-1) of TAGs, representing 51.2% of the CDM. In addition, when 20 g L(-1) glycerol was pulse-loaded into the culture with 40 g L(-1) glucose and 40 g L(-1) xylose at the stationary growth phase, MITGM-173 produced 14.3 g L(-1) of TAGs corresponding to 51.1% of the CDW although residual glycerol in the culture was observed. The addition of 20 g L(-1) glycerol in the glucose/xylose mix resulted in a TAG yield per glycerol consumed of 0.170 g g(-1) on the initial addition and 0.279 g g(-1) on the pulse addition of glycerol. We have generated a TAG-producing R. opacus MITGM-173 strain that shows significantly improved glycerol utilization in comparison to the parental strain. The present study demonstrates that the evolved R. opacus strain shows significant promise for developing a cost-effective bioprocess to generate advanced renewable fuels from mixed sugar feedstocks supplemented with glycerol.


The association of telomere length with family violence and disruption.
To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course. Children, age 5 to 15, were recruited from the greater New Orleans area, and exposure to family disruption and violence was assessed through caregiver report. Telomere length, from buccal cell DNA (buccal telomere length [bTL]), was determined by using monochrome multiplex quantitative real-time polymerase chain reaction. The association between bTL and adversity exposure was tested (n = 80). Cumulative exposure to interpersonal violence and family disruption was correlated with bTL. Controlling for other sociodemographic factors, bTL was significantly shorter in children with higher exposure to family violence and disruption. Witnessing family violence exerted a particularly potent impact. A significant gender interaction was found (β = -0.0086, SE = 0.0031, z test= -2.79, P = .0053) and analysis revealed the effect only in girls. bTL is a molecular biomarker of adversity and allostatic load that is detectable in childhood. The present results extend previous studies by demonstrating that telomeres are sensitive to adversity within the overarching family domain. These findings suggest that the family ecology may be an important target for interventions to reduce the biological impact of adversity in the lives of children.


Metoprolol in acute myocardial infarction. Mortality. The MIAMI Trial Research Group.
After 15 days there were 142 deaths in the placebo group (4.9%) and 123 deaths in the metoprolol group (4.3%), a difference of 13% (p = 0.29). The 95% confidence limits for the relative effect of metoprolol ranged from an 8% excess (-8%) to a 33% reduction (+33%) in mortality. There was generally a lower mortality rate for metoprolol-treated patients in most subgroups and a consistent tendency for a more pronounced difference between the treatment groups in those subgroups with a placebo mortality rate higher than the average for all placebo patients. Most deaths were cardiac and occurred among patients who developed a definite myocardial infarction (97%) and most of these had a Q-wave infarction (83%). Using a simple model, the placebo mortality was found to increase with increasing number of 8 risk predictors defined from prestudy experience, from 0% in patients with no risk predictors to 11.6% in patients with any 5 or more of these risk factors. Similarly, there was an increase in the difference between the treatment groups in favor of metoprolol with increasing number of placebo risk factors. Metoprolol had no apparent effect in a low-mortality risk group (less than or equal to 2 risk factors), but there was a difference in mortality of 29% in favor of metoprolol in a high-risk group (greater than or equal to 3 risk factors) comprising one-third of the trial population.(ABSTRACT TRUNCATED AT 250 WORDS)


Master equation simulation analysis of immunostained Bicoid morphogen gradient.
The concentration gradient of Bicoid protein which determines the developmental pathways in early Drosophila embryo is the best characterized morphogen gradient at the molecular level. Because different developmental fates can be elicited by different concentrations of Bicoid, it is important to probe the limits of this specification by analyzing intrinsic fluctuations of the Bicoid gradient arising from small molecular number. Stochastic simulations can be applied to further the understanding of the dynamics of Bicoid morphogen gradient formation at the molecular number level, and determine the source of the nucleus-to-nucleus expression variation (noise) observed in the Bicoid gradient. We compared quantitative observations of Bicoid levels in immunostained Drosophila embryos with a spatially extended Master Equation model which represents diffusion, decay, and anterior synthesis. We show that the intrinsic noise of an autonomous reaction-diffusion gradient is Poisson distributed. We demonstrate how experimental noise can be identified in the logarithm domain from single embryo analysis, and then separated from intrinsic noise in the normalized variance domain of an ensemble statistical analysis. We show how measurement sensitivity affects our observations, and how small amounts of rescaling noise can perturb the noise strength (Fano factor) observed. We demonstrate that the biological noise level in data can serve as a physical constraint for restricting the model's parameter space, and for predicting the Bicoid molecular number and variation range. An estimate based on a low variance ensemble of embryos suggests that the steady-state Bicoid molecular number in a nucleus should be larger than 300 in the middle of the embryo, and hence the gradient should extend to the posterior end of the embryo, beyond the previously assumed background limit. We exhibit the predicted molecular number gradient together with measurement effects, and make a comparison between conditions of higher and lower variance respectively. Quantitative comparison of Master Equation simulations with immunostained data enabled us to determine narrow ranges for key biophysical parameters, which for this system can be independently validated. Intrinsic noise is clearly detectable as well, although the staining process introduces certain limits in resolution.


Immobilization of biomolecules on polyurethane membrane surfaces.
Lipophilic polymer membranes incorporating binding sites are widely used in various potentiometric, amperometric, and optical sensors. Here, we report on the biofunctional modification of the surface of a Ca(2+)-selective membrane. A photoactivatable biotin derivative was synthesized and covalently immobilized on a soft polyurethane membrane. The modified polymer was characterized by X-ray photoelectron spectroscopy (XPS) as well as by potentiometric measurements. The selective binding of streptavidin by the photo-cross-linked biotin derivative was demonstrated. The surface coverage obtained with different experimental protocols was analyzed by autoradiography using [(35)S]-streptavidin. The new approach may significantly extend the scope of applicability of potentiometric sensors.


Perinatal care and cost effectiveness: changes in health expenditures and birth outcome following the establishment of a nurse-midwife program.
Estimates of infant health status and expenditures for perinatal care are presented for periods of time before and after implementation of a nurse-midwife program in rural Georgia. As the program developed, the infant mortality rate of the four counties served by the program showed a decrease. Similarly, the target population (pregnant women of low to moderate income who had no private physician) experienced decreases in the rate of neonatal mortality, low birthweight, and short gestational age. Estimated expenditures for perinatal care in the four counties decreased as well. These results are examined from the perspective of the National Health Planning and Resources Development Act of 1974 and the utility of using an epidemiologic approach for estimating the output of health services in terms of health status is emphasized.


Burden of Alzheimer's disease: population-based estimates and projections for New Zealand, 2006-2031.
To estimate the burden of Alzheimer's disease (AD, including 'mixed' dementia) in New Zealand in 2006, and project this burden out to 2031. An incidence to prevalence methodology was utilized, the foundation of which is a discrete time Markov model allowing for multiple stages of disease (early vs late). Population estimates and projections, and all-cause mortality rates, were obtained from Statistics New Zealand. In the absence of usable New Zealand data, data on disease incidence and progression were obtained from systematic reviews of the international (mainly European, Australian and North American) literature. Projection scenarios included a demographic scenario in which change resulted only from increases in population size and ageing; a prevention scenario in which incidence rates were reduced by 25% from 2011; a treatment scenario in which disease progression rates were likewise reduced by 25% from 2011; and a combined scenario capturing both interventions. The model estimated that approximately 28000 people are currently living with AD (whether formally diagnosed or not), approximately 55% in the early and 45% in the late stage of the disease; approximately 6600 people newly develop AD each year; and approximately 2300 people die from (as opposed to with) this condition. The model projected that the prevalence of AD will increase approximately 2.5-fold (to approx. 70,000 people) by 2031, if demographic drivers are unopposed. Plausible improvements in prevention and treatment, however, acting together, could reduce this growth by up to 50%, so that the prevalence of AD only doubles. Even this more optimistic projection has profound implications for the funding and provision of dementia care services, as well as for patients, their families, informal carers and the psychogeriatric workforce. New service configurations and models of care will be necessary. Access, quality and coordination standards for home care, day care, respite care, residential care and specialist services (including memory clinics) will need to respond accordingly.


Zap-70-independent Ca(2+) mobilization and Erk activation in Jurkat T cells in response to T-cell antigen receptor ligation.
The tyrosine kinase ZAP-70 has been implicated as a critical intermediary between T-cell antigen receptor (TCR) stimulation and Erk activation on the basis of the ability of dominant negative ZAP-70 to inhibit TCR-stimulated Erk activation, and the reported inability of anti-CD3 antibodies to activate Erk in ZAP-70-negative Jurkat cells. However, Erk is activated in T cells receiving a partial agonist signal, despite failing to activate ZAP-70. This discrepancy led us to reanalyze the ZAP-70-negative Jurkat T-cell line P116 for its ability to support Erk activation in response to TCR/CD3 stimulation. Erk was activated by CD3 cross-linking in P116 cells. However, this response required a higher concentration of anti-CD3 antibody and was delayed and transient compared to that in Jurkat T cells. Activation of Raf-1 and MEK-1 was coincident with Erk activation. Remarkably, the time course of Ras activation was comparable in the two cell lines, despite proceeding in the absence of LAT tyrosine phosphorylation in the P116 cells. CD3 stimulation of P116 cells also induced tyrosine phosphorylation of phospholipase C-gamma1 (PLCgamma1) and increased the intracellular Ca(2+) concentration. Protein kinase C (PKC) inhibitors blocked CD3-stimulated Erk activation in P116 cells, while parental Jurkat cells were refractory to PKC inhibition. The physiologic relevance of these signaling events is further supported by the finding of PLCgamma1 tyrosine phosphorylation, Erk activation, and CD69 upregulation in P116 cells on stimulation with superantigen and antigen-presenting cells. These results demonstrate the existence of two pathways leading to TCR-stimulated Erk activation in Jurkat T cells: a ZAP-70-independent pathway requiring PKC and a ZAP-70-dependent pathway that is PKC independent.


Nematic fluctuations in the cuprate superconductor Bi2Sr2CaCu2O8+δ.
Establishing the presence and the nature of a quantum critical point in their phase diagram is a central enigma of the high-temperature superconducting cuprates. It could explain their pseudogap and strange metal phases, and ultimately their high superconducting temperatures. Yet, while solid evidences exist in several unconventional superconductors of ubiquitous critical fluctuations associated to a quantum critical point, in the cuprates they remain undetected until now. Here using symmetry-resolved electronic Raman scattering in the cuprate [Formula: see text], we report the observation of enhanced electronic nematic fluctuations near the endpoint of the pseudogap phase. While our data hint at the possible presence of an incipient nematic quantum critical point, the doping dependence of the nematic fluctuations deviates significantly from a canonical quantum critical scenario. The observed nematic instability rather appears to be tied to the presence of a van Hove singularity in the band structure.


Perceptual organization without perception. The subliminal learning of global contour.
A critical step in visual perceptual processing is integrating local visual elements into contours so that shapes can be derived from them. It is often assumed that contour integration may reflect hardwired coding of low-level visual features. In this study, we present novel evidence indicating that integration of local elements into contours can be learned subliminally, despite being irrelevant to the training task and despite the local properties of the display varying randomly during training. Learning occurred only when contours were consistently paired with task-relevant targets--echoing the findings of previous studies on subliminal learning of low-level features. Our data indicate that task-irrelevant, exposure-based learning extends beyond local low-level visual features and may play a critical role at multiple levels of visual perceptual organization.


The Maternal Lifestyle Study: drug use by meconium toxicology and maternal self-report.
The objective of this study was to describe drug use by pregnant women participating in the 4-site Maternal Lifestyle Study of in utero cocaine and/or opiate exposure. Meconium specimens of 8527 newborns were analyzed by immunoassay with GC/MS confirmation for metabolites of cocaine, opiates, cannabinoids, amphetamines, and phencyclidine. Maternal self-report of drug use was determined by hospital interview. The prevalence of cocaine/opiate exposure in the 4 sites was 10.7% with the majority (9.5%) exposed to cocaine based on the combination of meconium analysis and maternal self-report. However, exposure status varied by site and was higher in low birth weight infants (18.6% for very low birth weight and 21.1% for low birth weight). Gas chromatography/mass spectrometry (GC/MS) confirmation of presumptive positive cocaine screens was 75.5%. In the cocaine/opiate-exposed group, 38% were cases in which the mother denied use but the meconium was positive. There was 66% agreement between positive meconium results and positive maternal report. Only 2% of mothers reported that they used only cocaine during pregnancy and mothers were 49 times more likely to use another drug if they used cocaine. Accurate identification of prenatal drug exposure is improved with GC/MS confirmation and when the meconium assay is coupled with a maternal hospital interview. However, the use of GC/MS may have different implications for research than for public policy. We caution against the use of quantitative analysis of drugs in meconium to estimate the degree of exposure. Our study also highlights the polydrug nature of what used to be thought of as a cocaine problem.


Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation.
Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure.


Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout.
Over the last two decades, there has been a constant increase in prescription rates of antidepressants. In parallel, neuroactive pharmaceuticals are making their way into aquatic environments at increasing concentrations. Among the antidepressants detected in the environment citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found. Given citalopram is specifically designed to alter mood and behaviour in humans, there is growing concern it can adversely affect the behaviour on non-target wildlife. In our study, brown trout were exposed to citalopram (nominal concentrations: 1, 10, 100, 1000 µg/L) in two different life stages. Larvae were exposed at 7 and 11 °C from the eyed ova stage until 8 weeks post yolk sac consumption, and juvenile brown trout were exposed for 4 weeks at 7 °C. At both stages we measured mortality, weight, length, tissue citalopram concentration, behaviour during exposure and behaviour in a stressfull environment. For brown trout larvae additionally hatching rate and heart rate, and for juvenile brown trout the tissue cortisol concentration were assessed. During the exposure, both larvae and juvenile fish exposed to the highest test concentration of citalopram (1 mg/L) had higher swimming activity and spent longer in the upper part of the aquaria compared to control fish, which is an indicator for decreased anxiety. Most probably due to the higher swimming activity during the exposure, the juveniles and larvae exposed to 1 mg/L citalopram showed decreased weight and length. Additionally, in a stressful artificial swimming measurement device, brown trout larvae displayed the anxiolytic effect of the antidepressant by reduced swimming activity during this stress situation, already at concentrations of 100 µg/L citalopram. Chemical analysis of the tissue revealed rising citalopram tissue concentrations with rising exposure concentrations. Tissue concentrations were 10 times higher in juvenile fish compared to brown trout larvae. Fish plasma concentrations were calculated, which exceeded human therapeutic levels for the highest exposure concentration, matching the behavioural results. Developmental parameters like hatching rate and heart rate, as well as mortality and tissue cortisol content were unaffected by the antidepressant. Overall, we could trace the pharmacological mode of action of the antidepressant citalopram in the non-target organism brown trout in two different life stages.


Change in the prevalence asthma, rhinitis and respiratory symptom over a 20 year period: associations to year of birth, life style and sleep related symptoms.
The aim of this investigation was to study change in adults over a 20 year period in the prevalence of respiratory symptoms and disorders and its association to year of birth, life style and sleep related variables. Adults 20-44 years of age, 6085 women and 5184 men, were randomly selected from seven centres in Northern Europe and followed for 20 years. The number of participants in the first survey was 21,595 and 11,269 participated in all three surveys. The participants were divided into three birth cohorts: 1944-1955, 1956-1965 and 1966-1975. During the 20 year period the prevalence of wheeze decreased (- 2%) and the prevalence of asthma (+ 4%) and allergic rhinitis (+ 5%) increased, whereas the prevalence of nocturnal respiratory symptoms was relatively unchanged. The increase in allergic rhinitis was largest in those born 1966 to 1975 except in Estonia. There was large decrease in smoking (- 20%), increase in obesity (+ 7%) and snoring (+ 6%) during the study period. Smoking, obesity, snoring and nocturnal gastroesophageal reflux (nGER) were related to a higher risk of all symptoms. Obesity, snoring and nGER were also independently related to asthma. We conclude that as our participants got older there was a decrease in wheeze, no change in nocturnal symptoms and an increase in reported asthma and allergic rhinitis. These changes in prevalence are probably related to a decrease in smoking being counteracted by an increase in allergy, obesity and sleep related disorders.


Hepatitis E vaccine: WHO position paper, May 2015--Recommendations.
This article presents the World Health Organization's (WHO) recommendations on the use of hepatitis E vaccine excerpted from the WHO position paper on hepatitis E vaccines - May 2015 recently published in the Weekly Epidemiological Record [1]. The current document is the first WHO position paper on hepatitis E vaccination and focuses primarily on the available evidence concerning the only hepatitis E vaccine that is currently licensed. The position paper gives consideration to the epidemiological features of the disease and assesses the use of the vaccine for public health benefits. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its October 2014 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html.


Precision diagnostics of Ewing's sarcoma by liquid biopsy: circulating EWS-FLI1 fusion transcripts.
Limited information is available on the applicative value of liquid biopsy (LB) in rare tumors, including Ewing's sarcoma (ES). The accepted precision diagnostics standards would greatly benefit from a non-invasive LB test monitoring pathognomonic gene rearrangements in the bloodstream. Tissue and blood samples were collected from six and four ES patients, respectively. Plasma was cleared by two successive rounds of centrifugation and stored frozen until RNA extraction by the QIAmp CNA kit. RNA was retro-transcribed and subjected to real-time quantitative polymerase chain reaction (RT-qPCR) and digital polymerase chain reaction (dPCR). Reactions were set up using two custom primer sets identifying types 1 and 2 EWS-FLI1 fusion transcripts. The two prevalent types of EWS-FLI1 rearrangements could be identified using only two sets of polymerase chain reaction primers, regardless of patient-specific EWS-FLI1 DNA breakpoints. RT-qPCR and dPCR discriminated the two variants in five tumor tissue RNAs and in four circulating tumor RNAs (ctRNAs). Of note, EWS-FLI1 molecular diagnosis was possible using blood samples even when tumor tissue was not available. ctRNA levels correlated (p < 0.05) with volume-based positron emission tomography (PET) parameters (metabolic tumor volume and total lesion glycolysis), and allowed the fine tracking of disease course after surgery, during adjuvant as well as neoadjuvant chemotherapy, and at follow up in one patient. To our knowledge, this is one of the few single-marker LB assays in solid tumors specifically designed to detect rearranged RNAs in blood, and the first study describing EWS circulating tumor RNAs in ES patients. Altogether, our results support the idea that LB may have a considerable impact on ES patient monitoring and management.


p53 tumor suppressor gene therapy for cancer.
Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non-small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date.


Use of videotaping to evaluate pediatric resident performance of health supervision examinations of infants.
To demonstrate reliability of a method for evaluating pediatric resident performance of health supervision examinations of infants using real patients and to evaluate pediatric resident performance of health supervision examinations of infants before and after an educational intervention consisting of a 6-month ambulatory rotation combined with video-assisted review of resident performance of the examination. Longitudinal cohort study in which all second-year residents were enrolled. Residents' preintervention (baseline) videotapes were compared with postintervention videotapes. Each resident served as his or her own control. University hospital pediatric resident continuity clinic. Sixteen second-year pediatric residents who were participating in a required 6-month ambulatory rotation. METHOD AND MAIN RESULTS: Reliability study: Using a 51-item instrument derived from the American Academy of Pediatrics Guidelines for Health Supervision, trained raters blind to the sequence and dates of the videotaped health supervision examinations independently rated 44 resident encounters (a minimum of two raters per tape) and achieved good interrater reliability (kappa = 0.80). Intervention study: After a 6-month ambulatory rotation which included resident-faculty reviews of preintervention videotapes, residents showed a 14% mean improvement in performance scores for the examination (P < .05). The results indicate that videotaped health supervision examinations using real patients can be reliably evaluated by observational techniques in a continuity practice. A 6-month ambulatory block rotation coupled with video-assisted interactive review of examinations is associated with measurable improvement in resident performance on the postintervention test.


Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC.
Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epidemiol Biomarkers Prev; 27(5); 531-40. ©2018 AACR.


Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.


Effects of chronic exercise on the coronary circulation in conscious rats with renovascular hypertension.
Since various studies suggest that chronic physical conditioning promotes myocardial vascularity, we investigated whether it could prevent the coronary reserve abnormalities of hypertensive cardiac hypertrophy. One week after operation, female Sprague-Dawley rats with two-kidney, one clip Goldblatt hypertension were either subjected to a moderate exercise program by swimming (n = 21) or kept sedentary (n = 16) for 9 weeks. Sedentary (n = 16) and exercised (n = 15) sham-operated rats served as controls. Maximal coronary blood flow and minimal coronary resistance, either per unit mass or for the entire left ventricle, an index of the functional cross-sectional area of the coronary resistance vessels, were determined in conscious, unrestrained rats by left atrial microsphere injection following maximal vasodilation with carbochrome (12 mg/kg). Following exercise, left ventricular mass was moderately (+5-10%) but significantly increased in normotensive rats, whereas left ventricular hypertrophy was significantly accentuated in the hypertensive rats. Minimal coronary resistance for the entire left ventricle was significantly decreased (-24%) in normotensive rats but did not change significantly in hypertensive rats. Minimal coronary resistance per unit mass (the coronary vasodilator reserve) tended to decrease in normotensive rats (-17%), whereas it tended to be further augmented in hypertensive rats (+13%). However, these differences were marginally significant and were not associated with any changes in maximal coronary blood flow per unit mass (the coronary flow reserve). Thus, in normal rats, exercise promoted myocardial arterial vascularity in parallel with the development of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)


Olfactory Pathology in Central Nervous System Demyelinating Diseases.
Olfactory dysfunction is common in multiple sclerosis (MS). Olfactory bulb and tract pathology in MS and other demyelinating diseases remain unexplored. A human autopsy cohort of pathologically confirmed cases encompassing the spectrum of demyelinating disease (MS; n = 17), neuromyelitis optica [(NMO); n = 3] and acute disseminated encephalomyelitis [(ADEM); n = 7] was compared to neuroinflammatory [herpes simplex virus encephalitis (HSE); n = 3], neurodegenerative [Alzheimer's disease (AD); n = 4] and non-neurologic (n = 8) controls. For each case, olfactory bulbs and/or tracts were stained for myelin, axons and inflammation. Inferior frontal cortex and hippocampus were stained for myelin in a subset of MS and ADEM cases. Olfactory bulb/tract demyelination was frequent in all demyelinating diseases [MS 12/17 (70.6%); ADEM 3/7 (42.9%); NMO 2/3 (66.7%)] but was absent in HSE, AD and non-neurologic controls. Inflammation was greater in the demyelinating diseases compared to non-neurologic controls. Olfactory bulb/tract axonal loss was most severe in MS where it correlated significantly with the extent of demyelination (r = 0.610, P = 0.009) and parenchymal inflammation (r = 0.681, P = 0.003). The extent of olfactory bulb/tract demyelination correlated with that found in the adjacent inferior frontal cortex but not hippocampus. We provide unequivocal evidence that olfactory bulb/tract demyelination is frequent, can occur early and is highly inflammatory, and is specific to demyelinating disease.


Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.
Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as evidenced by TRAF3 lysosomal and cytoplasmic accumulation. Eliglustat blocked autophagy by altering glycosphingolipid composition whilst restoration of missing glycosphingolipids rescued autophagy markers and TRAF3 degradation thus restoring osteoclastogenesis in bone marrow cells from myeloma patients. This work delineates both the mechanism by which glucosylceramide synthase inhibition prevents autophagic degradation of TRAF3 to reduce osteoclastogenesis as well as highlighting the clinical translational potential of eliglustat for the treatment of myeloma bone disease.


An arthropod cis-regulatory element functioning in sensory organ precursor development dates back to the Cambrian.
An increasing number of publications demonstrate conservation of function of cis-regulatory elements without sequence similarity. In invertebrates such functional conservation has only been shown for closely related species. Here we demonstrate the existence of an ancient arthropod regulatory element that functions during the selection of neural precursors. The activity of genes of the achaete-scute (ac-sc) family endows cells with neural potential. An essential, conserved characteristic of proneural genes is their ability to restrict their own activity to single or a small number of progenitor cells from their initially broad domains of expression. This is achieved through a process called lateral inhibition. A regulatory element, the sensory organ precursor enhancer (SOPE), is required for this process. First identified in Drosophila, the SOPE contains discrete binding sites for four regulatory factors. The SOPE of the Drosophila asense gene is situated in the 5' UTR. Through a manual comparison of consensus binding site sequences we have been able to identify a SOPE in UTR sequences of asense-like genes in species belonging to all four arthropod groups (Crustacea, Myriapoda, Chelicerata and Insecta). The SOPEs of the spider Cupiennius salei and the insect Tribolium castaneum are shown to be functional in transgenic Drosophila. This would place the origin of this regulatory sequence as far back as the last common ancestor of the Arthropoda, that is, in the Cambrian, 550 million years ago. The SOPE is not detectable by inter-specific sequence comparison, raising the possibility that other ancient regulatory modules in invertebrates might have escaped detection.


lambda 5, but not mu, is required for B cell maturation in a unique gamma 2b transgenic mouse line.
gamma 2b transgenic mice have a severe B cell defect, apparently caused by strong feedback inhibition of endogenous H-gene rearrangement coupled with an inability of gamma 2b to provide the survival/maturation functions of mu. A unique gamma 2b transgenic line, named the C line, was found to permit B cell development. When the C line is crossed with a mu-membrane knockout line, gamma 2b+ B cells develop in the homozygous knockout. In contrast, a transgenic line representative of all the other gamma 2b lines is completely B cell deficient when mu-mem is deleted. Strikingly, the C phenotype is dominant in C x other gamma 2b transgenic line crosses. There is no evidence for higher gamma 2b transgene expression or other position effects on the transgene in the C mouse. The sequences of the three gamma 2b transgene copies in the C line are identical to that of the original transgene. These results have led to the conclusion that in the C line the transgene integration constitutively induces a gene whose expression can replace mu. To more clearly delineate the stage at which the altered phenotype of the C line is expressed, C mice were crossed onto a lambda 5 knockout background. In the absence of lambda 5, the C line produces no B cells. Since it was also found that gamma 2b can associate with the surrogate light chain (sL; lambda 5/Vpre-B), the crosses between C line gamma 2b mice and lambda 5 knockout mice suggest that gamma 2b/sL is required for B cell maturation in this mouse line. Thus, gamma 2b alone is unable to replace mu for pre-B cell survival/maturation; however, in combination with an unknown factor and the sL, gamma 2b can provide these nurturing functions.


CACNA1D overexpression and voltage-gated calcium channels in prostate cancer during androgen deprivation.
Prostate cancer is often treated by perturbing androgen receptor signalling. CACNA1D, encoding CaV1.3 ion channels is upregulated in prostate cancer. Here we show how hormone therapy affects CACNA1D expression and CaV1.3 function. Human prostate cells (LNCaP, VCaP, C4-2B, normal RWPE-1) and a tissue microarray were used. Cells were treated with anti-androgen drug, Enzalutamide (ENZ) or androgen-removal from media, mimicking androgen-deprivation therapy (ADT). Proliferation assays, qPCR, Western blot, immunofluorescence, Ca2+-imaging and patch-clamp electrophysiology were performed. Nifedipine, Bay K 8644 (CaV1.3 inhibitor, activator), mibefradil, Ni2+ (CaV3.2 inhibitors) and high K+ depolarising solution were employed. CACNA1D and CaV1.3 protein are overexpressed in prostate tumours and CACNA1D was overexpressed in androgen-sensitive prostate cancer cells. In LNCaP, ADT or ENZ increased CACNA1D time-dependently whereas total protein showed little change. Untreated LNCaP were unresponsive to depolarising high K+/Bay K (to activate CaV1.3); moreover, currents were rarely detected. ADT or ENZ-treated LNCaP exhibited nifedipine-sensitive Ca2+-transients; ADT-treated LNCaP exhibited mibefradil-sensitive or, occasionally, nifedipine-sensitive inward currents. CACNA1D knockdown reduced the subpopulation of treated-LNCaP with CaV1.3 activity. VCaP displayed nifedipine-sensitive high K+/Bay K transients (responding subpopulation was increased by ENZ), and Ni2+-sensitive currents. Hormone therapy enables depolarization/Bay K-evoked Ca2+-transients and detection of CaV1.3 and CaV3.2 currents. Physiological and genomic CACNA1D/CaV1.3 mechanisms are likely active during hormone therapy-their modulation may offer therapeutic advantage.


Eco-Friendly Iron-Humic Nanofertilizers Synthesis for the Prevention of Iron Chlorosis in Soybean (Glycine max) Grown in Calcareous Soil.
Iron deficiency is a frequent problem for many crops, particularly in calcareous soils and iron humates are commonly applied in the Mediterranean basin in spite of their lesser efficiency than iron synthetic chelates. Development and application of new fertilizers using nanotechnology are one of the potentially effective options of enhancing the iron humates, according to the sustainable agriculture. Particle size, pH, and kinetics constrain the iron humate efficiency. Thus, it is relevant to understand the iron humate mechanism in the plant-soil system linking their particle size, characterization and iron distribution in plant and soil using 57Fe as a tracer tool. Three hybrid nanomaterials (F, S, and M) were synthesized as iron-humic nanofertilizers (57Fe-NFs) from leonardite potassium humate and 57Fe used in the form of 57Fe(NO3)3 or 57Fe2(SO4)3. They were characterized using Mössbauer spectroscopy, X-ray diffraction (XRD), extended X-ray absorption fine structure spectroscopy (EXAFS), transmission electron microscopy (TEM) and tested for iron availability in a calcareous soil pot experiment carried out under growth chamber conditions. Three doses (35, 75, and 150 μmol pot-1) of each iron-humic material were applied to soybean iron deficient plants and their iron nutrition contributions were compared to 57FeEDDHA and leonardite potassium humate as control treatments. Ferrihydrite was detected as the main structure of all three 57Fe-NFs and the plants tested with iron-humic compounds exhibited continuous long-term statistically reproducible iron uptake and showed high shoot fresh weight. Moreover, the 57Fe from the humic nanofertilizers remained available in soil and was detected in soybean pods. The Fe-NFs offers a natural, low cost and environmental option to the traditional iron fertilization in calcareous soils.


Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study).
Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM).Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. ©2017 AACR.


Magnetic deflection of neutral sodium-doped ammonia clusters.
We describe the setup and the performance of a new pulsed Stern-Gerlach deflector and present results for small sodium-doped ammonia clusters Na(NH3)n (n = 1-4) in a molecular beam. NaNH3 shows the expected deflection of a spin ½ system, while all lager clusters show much smaller deflections. Experimental deflection ratios are compared with the values calculated from molecular dynamics simulations. The comparison reveals that intracluster spin relaxation in NaNH3 takes place on a time scale significantly longer than 200 μs. Assuming that intracluster relaxation is the cause of the reduced deflection, relaxation times seem to be on the order of 200 μs for all larger clusters Na(NH3)n (n = 2-4). Our work is a first attempt to understand the magnetic properties of isolated, weakly-bound clusters with relevance to the variety of diamagnetic and paramagnetic species expected in solvated electron systems.


All thyroid ultrasound evaluations are not equal: sonographers specialized in thyroid cancer correctly label clinical N0 disease in well differentiated thyroid cancer.
Ultrasound (US) is a standard preoperative study in thyroid cancer. Accurate identification of lymph node (LN) disease in the central neck by US is debated, leading some surgeons to perform prophylactic central dissection. The purpose of this study was to evaluate if US performed by a surgeon with specialization in thyroid sonography correctly determined clinical N0 status. Retrospective identification of cN0 thyroid cancer patients from a prospectively maintained database was performed. Exclusion criteria included LN dissection with thyroidectomy or missing preoperative US. Demographics and outcomes were reviewed. Patients were categorized by who performed the thyroid US (surgeon vs. non-surgeon). Additional radioactive iodine (RAI) treatments or subsequent positive pathology defined recurrence. From 2005 to 2012, 177 patients met criteria. Forty-eight patients had surgeon US versus 129 patients with non-surgeon US. Groups were equivalent in age, gender, and tumor size. Forty-six percent had a preoperative diagnosis of cancer, whereas 19 % had benign and 35 % had indeterminate diagnoses. Surgeon US documented LN status more frequently (69 vs. 20 %, p < 0.01). RAI treatment and dose were equivalent. RAI uptake was lower with surgeon US (0.06 % ± 0.02 vs. 0.20 % ± 0.03, p < 0.01). Recurrence rates were higher in non-surgeon US (12 vs. 0 %, p = 0.01). Median time to recurrence was 11 months. Surgeons with thyroid US expertise correctly identify patients as N0, which may eliminate the need for prophylactic LN dissection without increasing risk of early recurrence. Because not all thyroid cancers are diagnosed preoperatively, US examination of the thyroid should include routine evaluation of the cervical LNs.


First Report of Blackleg Caused by Leptosphaeria maculans on Canola in Idaho.
Canola (Brassica napus L.) is produced in the dryland agriculture areas of eastern Washington State and northern Idaho, often in rotation with cereal cropping systems. Canola is also used as a rotation crop in irrigated circles in the Columbia Basin of Washington and southern Idaho, where potato is the main cash crop. In 2011, 7,700 ha of canola were harvested in Idaho and 4,200 ha in Washington. One of the major diseases of canola around the world is blackleg, caused by Leptosphaeria maculans (aggressive) and L. biglobosa (non-aggressive). Both Washington and Idaho have been considered blackleg-free, and production of canola in Idaho is subject to government regulations. Canola seed originating from outside of Washington and Idaho should have a phytosanitary certificate. This disease is widespread in Canada and the U.S. Northern Plains, Midwest, and South, and is the major disease of canola in these areas. In August 2011, a sample from a canola field in Bonners Ferry, Idaho, was brought for diagnosis to Washington State University. The canola stems showed the typical gray to dark grey lesions with black pycnidia. The pycnidia and conidia were examined microscopically, and found to be similar to descriptions of Phoma lingam, the anamorph of L. maculans (2). Samples were sent to the University of Manitoba for confirmation with PCR. The pathogen was cultured out of stems on V8 juice agar amended with streptomycin and 22 single pynidiospore isolates were made from the cultures. DNA was extracted from the cultures using methods described in Fernando et al. (1) and a multiplex PCR was performed with species-specific primers for L. maculans and L. biglobosa. The reaction should produce a 330-bp amplicon for L. maculans and a 440-bp amplicon for L. biglobosa. Based on this, all 22 isolates were identified as L. maculans. The susceptible cultivar Westar was inoculated with the isolates, by wound inoculating 7-day-old cotyledons with a concentration of 107 spores/ml. Plants were kept in a moist chamber at 23°C. After 14 days, plants were rated for disease with a 0 to 9 scale, where 0 = no infection and 9 = tissue collapse and appearance of pycnidiospores. Isolates with rating ≥5 are considered virulent. All isolates produced a rating of 7 to 9, indicating a high level of virulence. The source of the seed used in the infested fields is not known at this time. This disease is seedborne, and may pose a threat to the two major vegetable and oilseed brassica seed production areas of Washington: the Skagit River valley of western Washington and the Columbia Basin area of central Washington. In addition, the susceptibility of Pacific Northwest varieties of canola and other brassica oilseeds is largely unknown. References: (1) W. G. D. Fernando et al. Plant Dis. 90:1337, 2006. (2) S. Roger Rimmer et al. Compendium of Brassica Diseases, APS Press, 2007.


Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.
Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.


Reconstructing the evolutionary history of the Lorisidae using morphological, molecular, and geological data.
Major aspects of lorisid phylogeny and systematics remain unresolved, despite several studies (involving morphology, histology, karyology, immunology, and DNA sequencing) aimed at elucidating them. Our study is the first to investigate the evolution of this enigmatic group using molecular and morphological data for all four well-established genera: Arctocebus, Loris, Nycticebus, and Perodicticus. Data sets consisting of 386 bp of 12S rRNA, 535 bp of 16S rRNA, and 36 craniodental characters were analyzed separately and in combination, using maximum parsimony and maximum likelihood. Outgroups, consisting of two galagid taxa (Otolemur and Galagoides) and a lemuroid (Microcebus), were also varied. The morphological data set yielded a paraphyletic lorisid clade with the robust Nycticebus and Perodicticus grouped as sister taxa, and the galagids allied with Arctocebus. All molecular analyses maximum parsimony (MP) or maximum likelihood (ML) which included Microcebus as an outgroup rendered a paraphyletic lorisid clade, with one exception: the 12S + 16S data set analyzed with ML. The position of the galagids in these paraphyletic topologies was inconsistent, however, and bootstrap values were low. Exclusion of Microcebus generated a monophyletic Lorisidae with Asian and African subclades; bootstrap values for all three clades in the total evidence tree were over 90%. We estimated mean genetic distances for lemuroids vs. lorisoids, lorisids vs. galagids, and Asian vs. African lorisids as a guide to relative divergence times. We present information regarding a temporary land bridge that linked the two now widely separated regions inhabited by lorisids that may explain their distribution. Finally, we make taxonomic recommendations based on our results.


Evolution of an asymptomatic first stage of infection in a heterogeneous population.
Pathogens evolve different life-history strategies, which depend in part on differences in their host populations. A central feature of hosts is their population structure (e.g. spatial). Additionally, hosts themselves can exhibit different degrees of symptoms when newly infected; this latency is a key life-history property of pathogens. With an evolutionary-epidemiological model, we examine the role of population structure on the evolutionary dynamics of latency. We focus on specific power-law-like formulations for transmission and progression from the first infectious stage as a function of latency, assuming that the across-group to within-group transmission ratio increases if hosts are less symptomatic. We find that simple population heterogeneity can lead to local evolutionarily stable strategies (ESSs) at zero and infinite latency in situations where a unique ESS exists in the corresponding homogeneous case. Furthermore, there can exist more than one interior evolutionarily singular strategy. We find that this diversity of outcomes is due to the (possibly slight) advantage of across-group transmission for pathogens that produce fewer symptoms in a first infectious stage. Thus, our work reveals that allowing individuals without symptoms to travel can have important unintended evolutionary effects and is thus fundamentally problematic in view of the evolutionary dynamics of latency.


Compatibility effects between sound frequency and tactile elevation.
Participants made speeded discrimination responses to unimodal auditory (low-frequency vs. high-frequency sounds) or vibrotactile stimuli (presented to the index finger, upper location vs. to the thumb, lower location). In the compatible blocks of trials, the implicitly related stimuli (i.e. higher-frequency sounds and upper tactile stimuli; and the lower-frequency sounds and the lower tactile stimuli) were associated with the same response key; in the incompatible blocks, weakly related stimuli (i.e. high-frequency sounds and lower tactile stimuli; and the low-frequency sounds and the upper tactile stimuli) were associated with the same response key. Better performance was observed in the compatible (vs. incompatible) blocks, thus providing empirical support for the cross-modal association between the relative frequency of a sound and the relative elevation of a tactile stimulus.


Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer.
Pancreatic cancer has a poor prognosis. The benefit of chemotherapy, radiotherapy or both as a palliative treatment of advanced or relapsed disease is uncertain. To assess the effects of chemotherapy and/or radiotherapy in the management of pancreatic adenocarcinoma in people with inoperable advanced disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Trials Register (The Cochrane Library 2005, Issue 1); CANCERLIT (1975-2002); MEDLINE (1966 to January 2005); and EMBASE (1980 to January 2005). We handsearched reference lists from trials revealed by electronic searches to identify further relevant trials. We searched published abstracts from relevant conference proceedings. We contacted colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. Randomised controlled trials (single- or double-blind) in patients with advanced inoperable pancreatic cancer, in which one of the intervention types (chemotherapy or radiotherapy) was contrasted with either placebo or another type of intervention. Studies comparing non-chemotherapy agents such as biological agents, hormones, immunostimulants, vaccines and cytokines were excluded. Studies were assessed for eligibility and quality. Data were extracted by groups of two independent reviewers, with conflicts resolved by a third reviewer. Study authors were contacted for more information. Fifty trials (7043 participants) were included. Chemotherapy significantly reduced the one-year mortality (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.25 to 0.57, P value < 0.00001) when compared to best supportive care. Also, chemoradiation improved one year survival (0% versus 58%, P value 0.001) when compared to best supportive care. There was no significant difference in one-year mortality for 5FU alone versus 5FU combinations (OR 0.90, 95% CI 0.62 to 1.30); single-agent chemotherapy versus gemcitabine (OR 1.34, 95% CI 0.88 to 2.02, P value 0.17); or gemcitabine alone versus gemcitabine combinations (OR 0.88, 95% CI 0.74 to 1.05). However, subgroup analysis showed that platinum-gemcitabine combinations reduced six-month mortality compared to gemcitabine alone (OR 0.59, 95% CI 0.43 to 0.81, P value 0.001). A qualitative overview suggested that chemoradiation produced better survivals than either best supportive care or radiotherapy. Chemoradiation treatment was associated with more toxicity. Chemotherapy appears to prolong survival in people with advanced pancreatic cancer and can confer clinical benefits and improve quality of life. Combination chemotherapy did not improve overall survival compared to single-agent chemotherapy. Gemcitabine is an acceptable control arm for future trials investigating scheduling and combinations with novel agents. There is insufficient evidence to recommend chemoradiation in patients with locally advanced inoperable pancreatic cancer as a superior alternative to chemotherapy alone.


Viral transgene expression delivered by repeat intraocular adenoviral vector injection: in vivo live imaging study.
We delivered adenovirus vector (Ad) via intravitreous injection and monitored transgene (luciferase) expression in living mice (BALB/c) at multiple time points. In vivo live imaging technology was able to assess dynamically intraocular luciferase expression in a single animal population throughout the entire experiment period. Using this information, we were able to determine the optimal time point for readministration of Ad into the eyes and to dynamically study the time course of expression of a second Ad administration. Optical imaging demonstrated the limited period of transgene expression in eyes. Significant transgene signal was also detected in livers. The repeat intraocular delivery of the adenovirus resulted in significant blunting of transgene expression in both eyes and livers compared to the initial delivery. Periocular corticosteroid (triamcinolone acetonide) injection combined with initial Ad delivery was effective to rescue luciferase expression on repeat Ad vector delivery. However, this effect was not observed when corticosteroid was combined with repeat Ad delivery. Although corticosteroid enhanced ocular transgene expression, it also increased transgene expression in liver, which has potential safety implications. This dynamic transgene expression in eyes was successfully traced and monitored via a live imaging technique.


Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes.
Cholesterol homeostasis is critical for cellular proliferation. Liver X receptor (LXR) alpha and beta are the nuclear receptors responsible for regulation of cholesterol metabolism. In physiological conditions, high intracellular cholesterol levels cause increased synthesis of oxysterols, which activate LXR, thus triggering a transcriptional response for cholesterol secretion and catabolism. Here we employed a mouse model of partial hepatectomy (PH) to dissect the molecular pathways connecting cholesterol homeostasis, cellular proliferation, and LXR. First, we show that hepatic cholesterol content increases after PH, whereas the entire LXR transcriptome is down-regulated. Although LXR messenger RNA (mRNA) levels are unmodified, LXR target genes are significantly down-regulated on day 1 after PH and restored to control levels on day 7, when the liver reaches normal size. The inactivation of LXR following PH is related to the reduced oxysterol availability by way of decreased synthesis, and increased sulfation and secretion. On the contrary, cholesterol synthesis is up-regulated, and extracellular matrix remodeling is enhanced. Second, we show that reactivation of LXR by way of a synthetic ligand determines a negative modulation of hepatocyte proliferation. This effect is sustained by the reactivation of hepatic cholesterol catabolic and secretory pathways, coupled with a significant reduction of cholesterol biosynthesis. Our data unveil a previously unrecognized and apparently paradoxical scenario of LXR modulation. During liver regeneration LXR activity is abated in spite of increasing intracellular cholesterol levels. Turning off LXR-transcriptional pathways is crucial to guaranteeing the requisite intracellular cholesterol levels of regenerating hepatocytes. In line with this hypothesis, pharmacological LXR reactivation during PH significantly reduces liver regeneration capacity.


Requirement for vasoactive amines for production of delayed-type hypersensitvity skin reactions.
The skin sites of the mouse where delayed-type hypersensitivity (DTH) reactions are most easily elicited (foot pads and ears) are particularly rich in 5-hydroxytryptamine (5-HT)-containing mast cells. Since mice are deficient in circulating basophils, which play a role in at least some DTH reactions, we investigated the possibility that the mast cells were playing an important role in the evolution of the skin reactions of DTH in mice. We found that reserpine, a drug which depletes mast cells of 5-HT, abolished the ability of the mouse to make DTH reactions in the skin. The suppressive effect of reserpine could be partially blocked by monoamine oxidase inhibitors which prevent the degradation of 5-HT in the cytosol of the mast cell. Spleen cells of immune, reserpine-treated mice transferred DTH reactions to nonimmune mice normally, indicating that the reserpine treatment did not affect immune T cells. DTH reactions could not be transferred into reserpine-treated mice. We suggest that T cells are continually emigrating from the blood, through postcapillary venule endothelium, by a mechanism which does not depend on vasoactive amines. If they are appropriately immune and meet the homologous antigen in the tissue, they induce mast cells to release vasoactive amines which cause postcapillary venule endothelial cells to separate, allowing the egress from the blood of cells which ordinarily do not recirculate. The secondarily arriving vasoactive amine-dependent cells are responsible for the micro- and macroscopic lesions of DTH reactions. Chemotactic factors may also be involved in bringing cells to the DTH reaction sites but we propose that T-cell regulation of vasoactive amine-containing cells allows the effector cells to pass through the endothelial gates after they are called.


Phenethyl isothiocyanate in combination with dibenzoylmethane inhibits the androgen-independent growth of prostate cancer cells.
Phenethyl isothiocyanate (PEITC) is a naturally occurring compound found in some cruciferous vegetables. Dibenzoylmethane (DBM) is a minor constituent of licorice. Both compounds have been shown to exert anticancer activities. In the present study, we determined the effects of PEITC and DBM alone or in combination on androgen-independent growth of human prostate cancer cells cultured in vitro and prostate VCaP xenograft tumors in severe combined immunodeficient (SCID) mice. PEITC and DBM in combination had stronger effects on inhibiting the growth and inducing apoptosis than either compound alone in cultured prostate cancer cells. The combination also strongly inhibited cell migration and the formation of tumorspheres in VCaP cells. Mechanistic studies showed that the combined effects of PEITC and DBM on growth inhibition and apoptosis were associated with suppression of nuclear factor-κB (NF-κB), and a decrease in the levels of survivin and phospho-Akt (pAkt). In the in vivo study, SCID mice bearing VCaP tumors were surgically castrated and treated with PEITC and/or DBM. Treatment with PEITC and DBM in combination resulted in a strong inhibition of the progression of androgen-dependent VCaP prostate tumors to androgen independence. Our results indicate that administration of DBM and PEITC in combination may be an effective strategy for inhibiting/delaying the progression of prostate cancer to androgen independence.


Control of EGF receptor activation in Drosophila.
Diverse biological and developmental functions are mediated by signalling through the epidermal growth factor (EGF) receptor. In flies, many different mechanisms are used to control and restrict EGF-R signalling, including ligand processing, ligand variety (an inhibitor as well as activators), transcription and perhaps subcellular localization of the receptor. Since the components of EGF-R signalling have been well conserved, understanding these different modes of receptor regulation in flies should lead to general insights into the strategies of receptor activation.


HIV infection risk, behaviors, and attitudes about testing: are perceptions changing?
People at high risk for HIV infection could be increasing their risk behaviors, especially now that improved treatments for HIV infection are available. The goal was to investigate whether risk behaviors, perceptions of personal risk for HIV infection, and attitudes toward HIV testing among high-risk persons in Oregon differed in 1996 and 1998. Data from the HIV Testing Survey (HITS), a cross-sectional survey administered to HIV-negative men who have sex with men (MSM), heterosexual adults at high-risk for sexually transmitted diseases (STD), and intravenous drug users (IDUs) at high risk for HIV infection in 1996 (HITS-I), were compared with data from a similar group surveyed in 1998 (HITS-II). Proportions of participants reporting specific risk behaviors remained relatively constant in 1996 and 1998. Personal risk of HIV infection was perceived as low by 54% of HITS-II participants and 61.2% of HITS-I participants (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.9-1.7). IDUs in HITS-II were more likely than IDUs in HITS-I to perceive their risk as low (OR, 2.1; 95% CI, 1.2-3.7). Persons at high risk might underestimate their risk for HIV infection while practicing risky behaviors. The prevalence of risk behaviors in these populations could be considered the baseline against which to measure future prevention efforts.


Comparative Studies of Structures and Peroxidase-like Activities of Copper(II) and Iron(III) Complexes with an EDTA-Based Phenylene-Macrocycle and Its Acyclic Analogue.
With the objective of studying the conformational and macrocyclic effects of selected metal chelates on their peroxidase activities, Cu2+ and Fe3+ complexes were synthesized with a macrocyclic derivative of ethylenediaminetetraacetic acid and o-phenylenediamine (abbreviated as edtaodH2) and its new open-chain analogue (edtabzH2). The Fe3+ complex of edtaodH2 has a peroxidase-like activity, whereas the complex of edtabzH2 does not. The X-ray study of the former shows the formation of a dimeric molecule {[Fe(edtaod)]2O} in which each metal with an octahedral coordination is overposed over the macrocyclic cavity, as a result of rigid macrocyclic frame, to form an Fe-O-Fe bridge; the exposure of the central metal to the environment facilitates the capture of oxygen to drive the biomimetic activity. The peroxidase-inactive Fe3+ complex consists of a mononuclear complex ion [Fe(edtabz)(H2O)]+, the metal ion of which is suited in a distorted pentagonal bipyramid to be protected from environmental oxygen. The copper(II) complexes, which have mononuclear structures with high thermodynamic stability compared with the iron(III) complexes, show no peroxidase activity. The steric effects play a fundamental role in the biomimetic activity.


The epigenome of synovial fibroblasts: an underestimated therapeutic target in rheumatoid arthritis.
Perturbed epigenetic landscape and deregulated microRNA networks are central to the permanent activation and aggressiveness of synovial fibroblasts in rheumatoid arthritis. Current anti-cytokine therapies, although effectively halting synovitis, cannot reverse the stably activated destructive phenotype of rheumatoid arthritis synovial fibroblasts,offering rather limited protection against ongoing joint destruction in rheumatoid arthritis. Targeting the deregulated epigenome of rheumatoid arthritis synovial fibroblasts is key to developing joint-protective strategies in rheumatoid arthritis. To date, different pathogenic mechanisms have been identified that can profoundly impact the epigenetic derangements in rheumatoid arthritis synovial fibroblasts, including increased consumption of S-adenosylmethionine,a principal methyl donor in DNA methylation reactions, together with deregulation of crucial DNA- and histonemodifying enzymes. Re-establishing globally disturbed DNA methylation patterns in rheumatoid arthritis synovial fibroblasts by supplementing S-adenosylmethionine while preventing its leakage into polyamine cycles may bea promising therapeutic strategy in rheumatoid arthritis and the first epigenetic treatment to target rheumatoid arthritis synovial fibroblasts at the scene of the crime. Given the dynamic nature and reversibility of epigenetic modifications, their involvement in human diseases and recent perspectives on epigenetic therapies in cancer, epigenetic targeting of rheumatoid arthritis synovial fibroblasts should be within future reach.


Multiple instances of vocal sensorimotor adaptation to frequency-altered feedback within a single experimental session.
Vocal sensory-motor adaptation is typically studied by introducing a prolonged change in auditory feedback. While it may be preferable to perform multiple blocks of adaptation within a single experiment, it is possible that a carry-over effect from previous blocks of adaptation may affect the results of subsequent blocks. Speakers were asked to vocalize an /a/ sound and match a target note during ten adaptation blocks. Each block represented a unique combination of target note and shift direction. The adaptation response was found to be similar for all blocks, indicating that there were no carry-over effects from previous blocks of adaptation.


2,4-Dinitrotoluene dioxygenase from Burkholderia sp. strain DNT: similarity to naphthalene dioxygenase.
2,4-Dinitrotoluene (DNT) dioxygenase from Burkholderia sp. strain DNT catalyzes the initial oxidation of DNT to form 4-methyl-5-nitrocatechol (MNC) and nitrite. The displacement of the aromatic nitro group by dioxygenases has only recently been described, and nothing is known about the evolutionary origin of the enzyme systems that catalyze these reactions. We have shown previously that the gene encoding DNT dioxygenase is localized on a degradative plasmid within a 6.8-kb NsiI DNA fragment (W.-C. Suen and J. C. Spain, J. Bacteriol. 175:1831-1837, 1993). We describe here the sequence analysis and the substrate range of the enzyme system encoded by this fragment. Five open reading frames were identified, four of which have a high degree of similarity (59 to 78% identity) to the components of naphthalene dioxygenase (NDO) from Pseudomonas strains. The conserved amino acid residues within NDO that are involved in cofactor binding were also identified in the gene encoding DNT dioxygenase. An Escherichia coli clone that expressed DNT dioxygenase converted DNT to MNC and also converted naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. In contrast, the E. coli clone that expressed NDO did not oxidize DNT. Furthermore, the enzyme systems exhibit similar broad substrate specificities and can oxidize such compounds as indole, indan, indene, phenetole, and acenaphthene. These results suggest that DNT dioxygenase and the NDO enzyme system share a common ancestor.


Positive staircase effect in the rat heart.
The apparent lack of a positive staircase effect in ray myocardium may reflect inadequate metabolic support. Isolated rat hearts (n equals 10) were perfused at 37 degrees C with Krebs buffer containing 5 mM glucose. In 10 preparations increases in heart rate from 240 to 480/min resulted in twofold increases in left ventricular pressure and dP/dt. Pacing at a rate of 480/min resulted in mechanical deterioration of the preparation and in 50% decreases of myocardial ATP concentration within a 10-min period. Hearts of open-chest rats driven at the same rate for the same period maintained normal ATP stores. In isolated papillary muscles contracting isometrically at a rate of 30/min, peak stress 15g/mm2 (mean plus or minus SE, n equals 8) and was not changed by increasing the concentration of glucose from 5 to 30 mM. When frequency was raised from 30 to 300/min, stress declined to 5.0 plus or minus .15 g/mm2 in the presence of 5mM glucose (P smaller than .001) but increased to 8.8 plus or minus .21 g/mm2 (P smaller than 0.001) in the presence of 30 mM glucose. Thus, rat ventricular myocardium exhibits a positive staircase effect at physiological heart rates when metabolic support is adequate.


The Shape Bias in Children With Autism Spectrum Disorder: Potential Sources of Individual Differences.
Children with autism spectrum disorder (ASD) demonstrate many mechanisms of lexical acquisition that support language in typical development; however, 1 notable exception is the shape bias. The bases of these children's difficulties with the shape bias are not well understood, and the current study explored potential sources of individual differences from the perspectives of both attentional and conceptual accounts of the shape bias. Shape bias performance from the dataset of Potrzeba, Fein, and Naigles (2015) was analyzed, including 33 children with typical development (M = 20 months; SD = 1.6), 15 children with ASD with high verbal abilities (M = 33 months; SD = 4.6), and 14 children with ASD with low verbal abilities (M = 33 months; SD = 6.6). Lexical predictors (shape-side noun percentage from the MacArthur-Bates Communicative Development Inventory; Fenson et al., 2007) and social-pragmatic predictors (joint attention duration during play sessions) were considered as predictors of subsequent shape bias performance. For children in the low verbal ASD group, initiation of joint attention (positively) and passive attention (negatively) predicted subsequent shape bias performance, controlling for initial language and developmental level. Proportion of child's known nouns with shape-defined properties correlated negatively with shape bias performance in the high verbal ASD group but did not reach significance in regression models. These findings suggest that no single account sufficiently explains the observed individual differences in shape bias performance in children with ASD. Nonetheless, these findings break new ground in highlighting the role of social communicative interactions as integral to understanding specific language outcomes (i.e., the shape bias) in children with ASD, especially those with low verbal abilities, and point to new hypotheses concerning the linguistic content of these interactions. https://doi.org/10.23641/asha.7299581.


Rapid Removal of Atmospheric CO2 by Urban Soils.
The measured calcium carbonate content of soils to a depth of 100 mm at a large urban development site has increased over 18 months at a rate that corresponds to the sequestration of 85 t of CO2/ha (8.5 kg of CO2 m(-2)) annually. This is a consequence of rapid weathering of calcium silicate and hydroxide minerals derived from the demolition of concrete structures, which releases Ca that combines with CO2 ultimately derived from the atmosphere, precipitating as calcite. Stable isotope data confirm an atmospheric origin for carbonate carbon, and 14C dating indicates the predominance of modern carbon in the pedogenic calcite. Trial pits show that carbonation extends to depths of ≥1 m. Work at other sites shows that the occurrence of pedogenic carbonates is widespread in artificially created urban soils containing Ca and Mg silicate minerals. Appropriate management of fewer than 12000 ha of urban land to maximize calcite precipitation has the potential to remove 1 million t of CO2 from the atmosphere annually. The maximal global potential is estimated to be approximately 700-1200 Mt of CO2 per year (representing 2.0-3.7% of total emissions from fossil fuel combustion) based on current rates of production of industry-derived Ca- and Mg-bearing materials.


Parent Involvement Intervention in Developing Weight Management Skills for both Parents and Overweight/Obese Children.
The purpose of the study was to evaluate a parent involvement intervention for childhood obesity intended to increase parents' skills in managing children's weight-related behavior and to improve child-parent relationships. Many studies reported on parental influence on childhood obesity, emphasizing parent involvement in prevention and management of childhood obesity. A randomized controlled trial was conducted. Forty-two parents of overweight/obese children were recruited from four cities and randomized to the experimental group or control group. The parental intervention was provided only to parents in the experimental group and consisted of weekly newsletters and text messages for a period of 5 weeks. Exercise classes and nutrition education were provided to all children. Lifestyle Behaviour Checklist and the Child-Parent Relationship Scale (CPRS) were used for measurement of parent outcome. For the child outcome, dietary self-efficacy, exercise frequency, and body mass index were measured. A mixed-design analysis of variance was performed with city location entered as a random effect. After the intervention, CPRS of parents and dietary self-efficacy of children showed an increase in the experimental group (p < .05). Intervention effects differed significantly according to the city location regarding the control efficacy of parents and dietary self-efficacy of children (p < .05). The results support the effectiveness of the parent involvement intervention in promoting child-parent relationship and dietary self-efficacy of children. However, a 5-week parent involvement intervention was not sufficient to produce significant changes in children's body mass index. Further research is needed to investigate effects of parent involvement intervention with long-term evaluation.


Prepare dispersed CIS nano-scale particles and spray coating CIS absorber layers using nano-scale precursors.
In this study, the Mo-electrode thin films were deposited by a two-stepped process, and the high-purity copper indium selenide-based powder (CuInSe2, CIS) was fabricated by hydrothermal process by Nanowin Technology Co. Ltd. From the X-ray pattern of the CIS precursor, the mainly crystalline phase was CIS, and the almost undetectable CuSe phase was observed. Because the CIS powder was aggregated into micro-scale particles and the average particle sizes were approximately 3 to 8 μm, the CIS power was ground into nano-scale particles, then the 6 wt.% CIS particles were dispersed into isopropyl alcohol to get the solution for spray coating method. Then, 0.1 ml CIS solution was sprayed on the 20 mm × 10 mm Mo/glass substrates, and the heat treatment for the nano-scale CIS solution under various parameters was carried out in a selenization furnace. The annealing temperature was set at 550°C, and the annealing time was changed from 5 to 30 min, without extra Se content was added in the furnace. The influences of annealing time on the densification, crystallization, resistivity (ρ), hall mobility (μ), and carrier concentration of the CIS absorber layers were well investigated in this study.


Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium.
To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. 148,731 current, former and never-smokers of European ancestry aged ≥ 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Waist and hip circumferences, and waist-hip ratio. The data included up to 66,809 never-smokers, 43,009 former smokers and 38,913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.


Glucose modulates event-related potential components of recollection and familiarity in healthy adolescents.
Behavioural evidence supports the notion that oral glucose ingestion enhances recognition memory judgements based on recollection, but not familiarity. The present study sought to clarify and extend upon these behavioural findings by investigating the influence of glucose administration on event-related potential (ERP) components that are thought to be differentially mediated by recollection and familiarity processes in healthy adolescents. In a within-subjects design, participants performed a recognition memory task, during which time electroencephalogram (EEG) was recorded, subsequent to ingestion of either (a) glucose or (b) placebo in a counterbalanced order. Response times during the recognition memory task were observed to be faster for the glucose condition, relative to a placebo control. Further, glucose ingestion was associated with an enhanced left parietal old/new ERP effect (a marker of recollection) and an enhanced mid-frontal old/new ERP effect (known to be mediated by familiarity). These findings (a) support the results of previous research that the 'glucose memory facilitation effect' can be extended to healthy adolescents, but (b) suggest that glucose enhances both the recollection and familiarity components of recognition memory. The observed ERP profile has important implications for the proposal that glucose specifically targets the hippocampus in modulating cognitive performance.


Tensile strength and ultrastructure of a compomer and a composite in aqueous and non-aqueous storage media.
To compare the ultimate tensile strength (UTS) of a compomer (Dyract AP) and a composite (Spectrum TPH) that were stored in an aqueous or a non-aqueous medium for up to 180 days. 156 hourglass-shaped specimens of each material with cylindrical cross-sectional areas along the test regions were prepared. For each material, 12 beams were stressed to failure using a microtensile testing method to obtain the baseline UTS data. The rest were divided into two groups. One group was stored in de-ionized water (W), and the other (control) in silicone fluid (O) at 37 degrees C. 12 beams were removed from the respective storage medium after 1, 7, 14, 30, 90, 180 days for evaluation of the NTS. Materials retrieved from the intact central cylindrical portion of the fractured 180-day specimens were prepared for transmission electron microscopy (TEM). Baseline UTS for Dyract AP (D) and Spectrum TPH (S) were 76 +/- 16 MPa and 92 +/- 13 MPa, respectively. One-way ANOVA on ranks and Dunn's multiple comparison tests showed that UTS of Groups D-O, S-O and S-W remained stable during 180 days and were not significantly different from the baseline results. There was a significant drop in UTS in Group D-W after 90 and 180 days when compared with the 1-day result (P < 0.05). A highly significant nonlinear correlation was also observed in Group D-W between the mean UTS after the first day and the storage time (P < 0.01). No difference could be seen between the filler-matrix interface in S-O and S-W. A very thin glass-ionomer phase (ca. 200 nm thick siliceous hydrogel layer) could be observed in D-W, but not in D-O.