Blur and the perception of depth at occlusions.
The depth ordering of two surfaces, one occluding the other, can in principle be determined from the correlation between the occlusion border's blur and the blur of the two surfaces. If the border is blurred, the blurrier surface is nearer; if the border is sharp, the sharper surface is nearer. Previous research has found that observers do not use this informative cue. We reexamined this finding. Using a multiplane display, we confirmed the previous finding: Our observers did not accurately judge depth order when the blur was rendered and the stimulus presented on one plane. We then presented the same simulated scenes on multiple planes, each at a different focal distance, so the blur was created by the optics of the eye. Performance was now much better, which shows that depth order can be reliably determined from blur information but only when the optical effects are similar to those in natural viewing. We asked what the critical differences were in the single- and multiplane cases. We found that chromatic aberration provides useful information but accommodative microfluctuations do not. In addition, we examined how image formation is affected by occlusions and observed some interesting phenomena that allow the eye to see around and through occluding objects and may allow observers to estimate depth in da Vinci stereopsis, where one eye's view is blocked. Finally, we evaluated how accurately different rendering and displaying techniques reproduce the retinal images that occur in real occlusions. We discuss implications for computer graphics.


Sample, data use and protection in biobanking in Europe: legal issues.
The sharing of samples and data stored in biobanks for research has implications for donor privacy, but also raises questions on the regulation of research within Europe. Many legal documents and principles within Europe, with a direct impact on biobanking, have not been developed specifically to support this activity. Moreover, while some new regulations have been set up at national level, there are many variations in the definitions, scope and purpose of these legal instruments. This has resulted in unnecessary hurdles for genome-based research, particularly if samples are shared across national borders. The question is also raised on whether new, specific legislative and governance frameworks designed for biobanking are needed, or whether it is sufficient to modify current general law and to develop specific guidelines, or to accommodate issues raised by biobanking in the current regulation. A workshop with experts from academia and industry, lawyers, national data protection authorities, representatives from the European Commission and the European Data Protection Supervisor was held to review the existing legal bottlenecks and future needs of biobanking, with special regard to the collection, exchange and linkage of samples and data. This report presents highlights of the presentations and discussions from the workshop held in Sevilla, Spain, in March 2007 and the conclusions that followed. The workshop focused on the internal linkage of data and samples stored in a biobank, and the external linkage of biobanks with secondary information resources, such as cancer registries.


Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines.
In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.


Differential antigen processing by dendritic cell subsets in vivo.
Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.


NeuroNames 2002.
NeuroNames is a nomenclature designed as a tool for indexing digital databases of neuroscientific information. It can be used, for example, as the entry point to a digital dictionary of neuroanatomy, to a brain atlas, or to a database of information referenced to specific brain structures. The user can query with terms from many different nomenclatures. One can create a neuroanatomic ontology from NeuroNames by relating an appropriate subset of terms to a conceptual model represented by structures illustrated in a brain atlas. At the conceptual core of NeuroNames are primary structures, the elementary units of the brain in the spatial domain. Each primary structure is associated with a set of synonyms that represent the structure in the symbolic domain. One of the synonyms is designated the default name for use in verbal definitions of other structures. A unique abbreviation based on the default name is provided for labeling images. Neuroscientists classify structures in different contexts reflecting different attributes of interest. Thus, the name of a given structure can appear in any number of hierarchical contexts. In NeuroNames all primary structures are now represented in at least two hierarchies. The first is a nine-level "Brain Hierarchy," in which volumetric structures are grouped by proximity to form successively larger units that represent the brain at different levels of dissection. Secondly, primary structures are categorized in a three-level "spatial attribute hierarchy" used to color- code them for visual display. Grouped structures in the nine-level volumetric hierarchy are designated superstructures, each of which has synonyms, a default term, and an abbreviation. All names of structures not in the hierarchy are designated ancillary terms and are defined in words using the default names of hierarchy structures. With NeuroNames as entry point, we have developed BrainInfo (http://braininfo.rprc.washington.edu), a website that allows searchers to proceed intuitively in a few steps to descriptions and images of specific structures. Currently NeuroNames resides in a Microsoft ACCESS database and includes some 12,200 terms in seven languages.


Synthesis, characterization and histomorphometric analysis of cellular response to a new elastic DegraPol® polymer for rabbit Achilles tendon rupture repair.
Tendon rupture repair is a surgical field where improvements are still required due to problems such as repeat ruptures, adhesion formation and joint stiffness. In the current study, a reversibly expandable and contractible electrospun tube based on a biocompatible and biodegradable polymer was implanted around a transected and conventionally sutured rabbit Achilles tendon. The material used was DegraPol® (DP), a polyester urethane. To make DP softer, more elastic and surgeon-friendly, the synthesis protocol was slightly modified. Material properties of conventional and new DP film electrospun meshes are presented. At 12 weeks post-surgery, tenocyte and tenoblast density, nuclei and width, collagen fibre structure and inflammation levels were analyzed histomorphometrically. Additionally, a comprehensive histological scoring system by Stoll et al. (2011) was used to compare healing outcomes. Results showed that there were no adverse reactions of the tendon tissue following the implant. No differences were found whether the DP tube was applied or not for both traditional and new DP materials. As a result, the new DP material was shown to be an excellent carrier for delivery of growth factors, stem cells and other agents responsible for tendon healing.


Subspace Regularized Sparse Multitask Learning for Multiclass Neurodegenerative Disease Identification.
The high feature-dimension and low sample-size problem is one of the major challenges in the study of computer-aided Alzheimer's disease (AD) diagnosis. To circumvent this problem, feature selection and subspace learning have been playing core roles in the literature. Generally, feature selection methods are preferable in clinical applications due to their ease for interpretation, but subspace learning methods can usually achieve more promising results. In this paper, we combine two different methodological approaches to discriminative feature selection in a unified framework. Specifically, we utilize two subspace learning methods, namely, linear discriminant analysis and locality preserving projection, which have proven their effectiveness in a variety of fields, to select class-discriminative and noise-resistant features. Unlike previous methods in neuroimaging studies that mostly focused on a binary classification, the proposed feature selection method is further applicable for multiclass classification in AD diagnosis. Extensive experiments on the Alzheimer's disease neuroimaging initiative dataset showed the effectiveness of the proposed method over other state-of-the-art methods.


Selenite-reducing capacity of the copper-containing nitrite reductase of Rhizobium sullae.
Rhizobium sullae strain HCNT1 contains a nitric oxide-producing nitrite reductase of unknown function due to the absence of a complementary nitric oxide reductase. HCNT1 had the ability to grow on selenite concentrations as high as 50 mM, and during growth, selenite was reduced to the less toxic elemental selenium. An HCNT1 mutant lacking nitrite reductase grew poorly in the presence of 5 mM selenite, was unable to grow in the presence of 25 or 50 mM selenite and also showed no evidence of selenite reduction. A naturally occurring nitrite reductase-deficient R. sullae strain, CC1335, also showed little growth on the higher concentrations of selenite. Mobilization of a plasmid containing the HCNT1 gene encoding nitrite reductase into CC1335 increased its resistance to selenite. To confirm that this ability to grow in the presence of high concentrations of selenite correlated with nitrite reductase activity, a new nitrite reductase-containing strain was isolated from the same location where HCNT1 was isolated. This strain was also resistant to high concentrations of selenite. Inactivation of the gene encoding nitrite reductase in this strain increased selenite sensitivity. These data suggest that the nitrite reductase of R. sullae provides resistance to selenite and offers an explanation for the radically truncated denitrification found uniquely in this bacterium.


ψ-Phosphorene: a new allotrope of phosphorene.
Based on the crystal structure prediction, we propose a new allotrope of phosphorene, ψ-phosphorene (ψ-P), with a porous structure, which is both thermally and dynamically stable in comparison with the previously reported allotropes. Due to its unique atom configuration, ψ-P has highly orientation-dependent mechanical properties and excellent flexibility. Calculations using the HSE functional predict that ψ-P is semiconducting with an indirect band gap of 1.57 eV and possesses anisotropic transport properties. Particularly, the electron mobility along the x-direction is up to 1.3 × 104 cm2 V-1 s-1, which is comparable with that of black phosphorene. Considering its intrinsic porous structure, the performance of monolayer ψ-P as a gas purification membrane was investigated. The calculation demonstrates that ψ-P could be used for hydrogen purification from the mixture of CH4, CO2, N2, CO, and H2 with high selectivity. Furthermore, combining a suitable band gap with high carrier mobility, a MoSe2/ψ-P van der Waals heterojunction is predicted to be a good solar cell material, whose power conversion efficiency is estimated up to 20.26%. Finally, we demonstrated that the Au(110) surface could be a suitable substrate for the synthesis of ψ-P.


Patrilocal Residence and Female Labor Supply: Evidence From Kyrgyzstan.
Many people live in patrilocal societies, which prescribe that women move in with their husbands' parents, relieve their in-laws from housework, and care for them in old age. This arrangement is likely to have labor market consequences, in particular for women. We study the effect of coresidence on female labor supply in Kyrgyzstan, a strongly patrilocal setting. We account for the endogeneity of coresidence by exploiting the tradition that youngest sons usually live with their parents. In both OLS and IV estimations, the effect of coresidence on female labor supply is negative and insignificant. This finding is in contrast to previous studies, which found positive effects in less patrilocal settings. We go beyond earlier work by investigating effect channels. In Kyrgyzstan, coresiding women invest more time in elder care than women who do not coreside, and they do not receive parental support in housework.


Fine-tuning the nucleophilic reactivities of boron ate complexes derived from aryl and heteroaryl boronic esters.
Boron ate complexes derived from thienyl and furyl boronic esters and aryllithium compounds have been isolated and characterized by X-ray crystallography. Products and mechanisms of their reactions with carbenium and iminium ions have been analyzed. Kinetics of these reactions were monitored by UV/Vis spectroscopy, and the influence of the aryl substituents, the diol ligands (pinacol, ethylene glycol, neopentyl glycol, catechol), and the counterions on the nucleophilic reactivity of the boron ate complexes were examined. A Hammett correlation confirmed the polar nature of their reactions with benzhydrylium ions, and the correlation lg k(20 °C)=sN (E+N) was employed to determine the nucleophilicities of the boron ate complexes and to compare them with those of other borates and boronates. The neopentyl and ethylene glycol derivatives were found to be 10(4) times more reactive than the pinacol and catechol derivatives.


Effects of moderate beer consumption on health and disease: A consensus document.
A large evidence-based review on the effects of a moderate consumption of beer on human health has been conducted by an international panel of experts who reached a full consensus on the present document. Low-moderate (up to 1 drink per day in women, up to 2 in men), non-bingeing beer consumption, reduces the risk of cardiovascular disease. This effect is similar to that of wine, at comparable alcohol amounts. Epidemiological studies suggest that moderate consumption of either beer or wine may confer greater cardiovascular protection than spirits. Although specific data on beer are not conclusive, observational studies seem to indicate that low-moderate alcohol consumption is associated with a reduced risk of developing neurodegenerative disease. There is no evidence that beer drinking is different from other types of alcoholic beverages in respect to risk for some cancers. Evidence consistently suggests a J-shaped relationship between alcohol consumption (including beer) and all-cause mortality, with lower risk for moderate alcohol consumers than for abstainers or heavy drinkers. Unless they are at high risk for alcohol-related cancers or alcohol dependency, there is no reason to discourage healthy adults who are already regular light-moderate beer consumers from continuing. Consumption of beer, at any dosage, is not recommended for children, adolescents, pregnant women, individuals at risk to develop alcoholism, those with cardiomyopathy, cardiac arrhythmias, depression, liver and pancreatic diseases, or anyone engaged in actions that require concentration, skill or coordination. In conclusion, although heavy and excessive beer consumption exerts deleterious effects on the human body, with increased disease risks on many organs and is associated to significant social problems such as addiction, accidents, violence and crime, data reported in this document show evidence for no harm of moderate beer consumption for major chronic conditions and some benefit against cardiovascular disease.


miR-TV: an interactive microRNA Target Viewer for microRNA and target gene expression interrogation for human cancer studies.
MicroRNAs (miRNAs) have been identified in many organisms, and they are essential for gene expression regulation in many critical cellular processes. The expression levels of these genes and miRNAs are closely associated with the progression of diseases such as cancers. Furthermore, survival analysis is a significant indicator for evaluating the criticality of these cellular processes in cancer progression. We established a web tool, miRNA Target Viewer (miR-TV), which integrates 5p-arm and 3p-arm miRNA expression profiles, mRNA target gene expression levels in healthy and cancer populations, and clinical data of cancer patients and their survival information. The developed miR-TV obtained miRNA-seq, mRNA-seq and clinical data from the Cancer Genome Atlas and potential miRNA target gene predictions from miRDB, targetScan and miRanda. The data presentation was implemented using the D3 javascript toolkit. The D3 toolkit is frequently used to provide an easy-to-use interactive interface. Our miR-TV provides a user-friendly and interactive interface, which can be beneficial for biomedical researchers to freely interrogate miRNA expression information and their potential target genes. We believe that such a data visualization bioinformatics tool is excellent for obtaining information from massive biological data. Database URL: http://mirtv.ibms.sinica.edu.tw.


The Pudendal Nerve and Its Branches in Relation to Richter's Procedure.
Variations in the branching pattern of the pudendal nerve (PN) have been described in the literature. This study investigated these variations in order to comment on a safe area for the placement of a Richter's stitch. Richter's procedure was performed on nine unembalmed female cadavers and followed by dissection. PN dissections were done on another 20 embalmed female cadavers. Variations in the branching pattern of the PN were noted and the distance between the Richter's stitch placed and the PN/or the inferior rectal nerve (IRN) measured. The IRN entered the gluteal region as a separate structure in 6/29 cases. The separate IRN was found to pass between 4.1 and 14.45 mm medial to the ischial spine in 18/29 cases. In one case, the Richter's stitch was found to pierce the IRN. The distance between the stitch and the PN and/or the IRN ranged from 0 to 17.8 mm. To minimize the risk of nerve damage or entrapment, the Richter's stitch should be placed >20 mm from the ischial spine. This recommended area should be revised for different population groups, as variations might exist between groups.


Palmitoylation of the synaptic vesicle fusion machinery.
The fusion of synaptic vesicles with the pre-synaptic plasma membrane mediates the secretion of neurotransmitters at nerve terminals. This pathway is regulated by an array of protein-protein interactions. Of central importance are the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins syntaxin 1 and SNAP25, which are associated with the pre-synaptic plasma membrane and vesicle-associated membrane protein (VAMP2), a synaptic vesicle SNARE. Syntaxin 1, SNAP25 and VAMP2 interact to form a tight complex bridging the vesicle and plasma membranes, which has been suggested to represent the minimal membrane fusion machinery. Synaptic vesicle fusion is stimulated by a rise in intraterminal Ca2+ levels, and a major Ca2+ sensor for vesicle fusion is synaptotagmin I. Synaptotagmin is likely to couple Ca2+ entry to vesicle fusion via Ca2+-dependent and independent interactions with membrane phospholipids and the SNARE proteins. Intriguingly, syntaxin 1, SNAP25, VAMP2 and synaptotagmin I have all been reported to be modified by palmitoylation in neurons. In this review, we discuss the mechanisms and dynamics of palmitoylation of these proteins and speculate on how palmitoylation might contribute to the regulation of synaptic vesicle fusion.


Considerations on the electromagnetic flow in Airy beams based on the Gouy phase.
We reexamine the Gouy phase in ballistic Airy beams (AiBs). A physical interpretation of our analysis is derived in terms of the local phase velocity and the Poynting vector streamlines. Recent experiments employing AiBs are consistent with our results. We provide an approach which potentially applies to any finite-energy paraxial wave field that lacks a beam axis.


Hypothalamic-Pituitary--Adrenal Axis-Feedback Control.
The hypothalamo-pituitary-adrenal axis (HPA) is responsible for stimulation of adrenal corticosteroids in response to stress. Negative feedback control by corticosteroids limits pituitary secretion of corticotropin, ACTH, and hypothalamic secretion of corticotropin-releasing hormone, CRH, and vasopressin, AVP, resulting in regulation of both basal and stress-induced ACTH secretion. The negative feedback effect of corticosteroids occurs by action of corticosteroids at mineralocorticoid receptors (MR) and/or glucocorticoid receptors (GRs) located in multiple sites in the brain and in the pituitary. The mechanisms of negative feedback vary according to the receptor type and location within the brain-hypothalmo-pituitary axis. A very rapid nongenomic action has been demonstrated for GR action on CRH neurons in the hypothalamus, and somewhat slower nongenomic effects are observed in the pituitary or other brain sites mediated by GR and/or MR. Corticosteroids also have genomic actions, including repression of the pro-opiomelanocortin (POMC) gene in the pituitary and CRH and AVP genes in the hypothalamus. The rapid effect inhibits stimulated secretion, but requires a rapidly rising corticosteroid concentration. The more delayed inhibitory effect on stimulated secretion is dependent on the intensity of the stimulus and the magnitude of the corticosteroid feedback signal, but also the neuroanatomical pathways responsible for activating the HPA. The pathways for activation of some stressors may partially bypass hypothalamic feedback sites at the CRH neuron, whereas others may not involve forebrain sites; therefore, some physiological stressors may override or bypass negative feedback, and other psychological stressors may facilitate responses to subsequent stress.


Interventions for primary vesicoureteric reflux.
Vesicoureteric reflux (VUR) results in urine passing retrograde up the ureter. Urinary tract infections (UTI) associated with VUR have been considered a cause of permanent renal parenchymal damage in children with VUR. Management of these children has been directed at preventing UTI by antibiotic prophylaxis and/or surgical correction of VUR. The optimum strategy is not clear. To evaluate the benefits and harms of different treatment options for primary VUR. In August 2010 we searched CENTRAL, MEDLINE and EMBASE and screened reference lists of papers and abstracts from conference proceedings. RCTs in any language comparing any treatment of VUR including surgical or endoscopic correction, antibiotic prophylaxis, non-invasive non-pharmacological techniques and any combination of therapies. Two authors independently searched the literature, determined study eligibility, assessed quality, extracted and entered data. We expressed dichotomous outcomes as risk ratios (RR) and their 95% confidence intervals (CI) and continuous data as mean differences (MD) and their 95% CI's Data were pooled using the random effects model. Twenty RCTs (2324 children) were included. Long-term low-dose antibiotic prophylaxis compared to no treatment/placebo did not significantly reduce repeat symptomatic UTI (846 children: RR 0.68, 95% CI 0.39 to 1.17) or febrile UTI (946 children: RR 0.77, 95% CI 0.47 to 1.24) at two years. There was considerable heterogeneity in the analyses and only one study was adequately blinded. At one to three years, antibiotic prophylaxis reduced the risk of new or progressive renal damage on DMSA scan (446 children: RR 0.35, 95% CI 0.15 to 0.80). Side effects were infrequent when reported, but antibiotics increased the likelihood of bacterial drug resistance threefold (132 UTIs: RR 2.94, 95% CI 1.39 to 6.25).When long-term antibiotic prophylaxis was compared with surgical or endoscopic correction of VUR plus antibiotics for one to 24 months (10 studies, 1141 children), the risk of symptomatic UTI was not significantly different at any time point. Combined surgical and antibiotic treatment caused a 57% reduction in febrile UTI by five years (2 studies, 449 children: RR 0.43, 95% CI 0.27 to 0.70) but did not decrease the risk of new or progressive renal damage at any time point. Postoperative obstruction was seen in 0% and 7% of children in two surgical studies and 0% in one endoscopic study. Compared with no treatment, use of long-term, low-dose antibiotics did not significantly reduce the number of repeat symptomatic and febrile UTIs in children with VUR. Considerable heterogeneity in the analyses and inclusion of only one adequately blinded study, made drawing firm conclusions challenging. Antibiotic prophylaxis significantly reduced the risk of developing new or progressive renal damage, but assuming an 8% baseline risk, 33 children would need long-term antibiotic prophylaxis to prevent one more child developing kidney damage over the course of two to three years.The added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone remains unclear. Eight children would require combined surgical and antibiotic treatment to prevent one additional child developing febrile UTI by five years, but it would not cause fewer children developing renal damage.


Recombination Rate Heterogeneity within Arabidopsis Disease Resistance Genes.
Meiotic crossover frequency varies extensively along chromosomes and is typically concentrated in hotspots. As recombination increases genetic diversity, hotspots are predicted to occur at immunity genes, where variation may be beneficial. A major component of plant immunity is recognition of pathogen Avirulence (Avr) effectors by resistance (R) genes that encode NBS-LRR domain proteins. Therefore, we sought to test whether NBS-LRR genes would overlap with meiotic crossover hotspots using experimental genetics in Arabidopsis thaliana. NBS-LRR genes tend to physically cluster in plant genomes; for example, in Arabidopsis most are located in large clusters on the south arms of chromosomes 1 and 5. We experimentally mapped 1,439 crossovers within these clusters and observed NBS-LRR gene associated hotspots, which were also detected as historical hotspots via analysis of linkage disequilibrium. However, we also observed NBS-LRR gene coldspots, which in some cases correlate with structural heterozygosity. To study recombination at the fine-scale we used high-throughput sequencing to analyze ~1,000 crossovers within the RESISTANCE TO ALBUGO CANDIDA1 (RAC1) R gene hotspot. This revealed elevated intragenic crossovers, overlapping nucleosome-occupied exons that encode the TIR, NBS and LRR domains. The highest RAC1 recombination frequency was promoter-proximal and overlapped CTT-repeat DNA sequence motifs, which have previously been associated with plant crossover hotspots. Additionally, we show a significant influence of natural genetic variation on NBS-LRR cluster recombination rates, using crosses between Arabidopsis ecotypes. In conclusion, we show that a subset of NBS-LRR genes are strong hotspots, whereas others are coldspots. This reveals a complex recombination landscape in Arabidopsis NBS-LRR genes, which we propose results from varying coevolutionary pressures exerted by host-pathogen relationships, and is influenced by structural heterozygosity.


Impact of social deprivation on length of stay for common infectious diseases in two French university-affiliated general pediatric departments.
Adult deprived patients consume more healthcare resources than others, particularly in terms of increased length of stay (LOS) and costs. Very few pediatric studies have focused on LOS, although the effect of deprivation could be greater in children due to the vulnerability of this population. Our objective was to compare LOS between deprived and nondeprived children hospitalized for acute infectious diseases in two university-affiliated pediatric departments located in a low-income area of northern Paris. We performed a prospective observational multicenter study in two university-affiliated hospitals, Hôpital Robert-Debré and Hôpital Jean-Verdier. All the patients under 15 years of age admitted to the general pediatric department for pneumonia, bronchiolitis, gastroenteritis, or pyelonephritis between 20 October 2016 and 20 March 2017 were included. Deprivation was assessed with an individual questionnaire and score (EPICES). Endpoints included length of stay, costs, and readmission rates at 15 days in each quintile of deprivation. Multivariate regression assessed the association between deprivation and each endpoint. A total of 556 patients were included in the study and 540 were analyzed. Sixty percent were boys and the mean age was 9 months±18. Bronchiolitis was the most frequent diagnosis (67.8%). Fifty-six percent of patients were considered to be deprived based on the EPICES questionnaire. Mean LOS was 4.6±3.5 days and we found no significant difference in LOS between the different deprivation quintiles (P=0.83). Multivariate regression did not show an association between LOS and deprivation. There was no difference between deprived and nondeprived patients in terms of LOS. Deprivation may therefore impact hospitals in other ways such as admission rates. The impact of deprivation during hospitalization for chronic diseases should also be investigated.


An assessment of genomic connectedness measures in Nellore cattle.
An important criterion to consider in genetic evaluations is the extent of genetic connectedness across management units (MU), especially if they differ in their genetic mean. Reliable comparisons of genetic values across MU depend on the degree of connectedness: the higher the connectedness, the more reliable the comparison. Traditionally, genetic connectedness was calculated through pedigree-based methods; however, in the era of genomic selection, this can be better estimated utilizing new approaches based on genomics. Most procedures consider only additive genetic effects, which may not accurately reflect the underlying gene action of the evaluated trait, and little is known about the impact of non-additive gene action on connectedness measures. The objective of this study was to investigate the extent of genomic connectedness measures, for the first time, in Brazilian field data by applying additive and non-additive relationship matrices using a fatty acid profile data set from seven farms located in the three regions of Brazil, which are part of the three breeding programs. Myristic acid (C14:0) was used due to its importance for human health and reported presence of non-additive gene action. The pedigree included 427,740 animals and 925 of them were genotyped using the Bovine high-density genotyping chip. Six relationship matrices were constructed, parametrically and non-parametrically capturing additive and non-additive genetic effects from both pedigree and genomic data. We assessed genome-based connectedness across MU using the prediction error variance of difference (PEVD) and the coefficient of determination (CD). PEVD values ranged from 0.540 to 1.707, and CD from 0.146 to 0.456. Genomic information consistently enhanced the measures of connectedness compared to the numerator relationship matrix by at least 63%. Combining additive and non-additive genomic kernel relationship matrices or a non-parametric relationship matrix increased the capture of connectedness. Overall, the Gaussian kernel yielded the largest measure of connectedness. Our findings showed that connectedness metrics can be extended to incorporate genomic information and non-additive genetic variation using field data. We propose that different genomic relationship matrices can be designed to capture additive and non-additive genetic effects, increase the measures of connectedness, and to more accurately estimate the true state of connectedness in herds.


The pH Response and Sensing Mechanism of n-Type ZnO/Electrolyte Interfaces.
Ever since the discovery of the pH-sensing properties of ZnO crystals, researchers have been exploring their potential in electrochemical applications. The recent expansion and availability of chemical modification methods has made it possible to generate a new class of electrochemically active ZnO nanorods. This reduction in size of ZnO (to a nanocrystalline form) using new growth techniques is essentially an example of the nanotechnology fabrication principle. The availability of these ZnO nanorods opens up an entire new and exciting research direction in the field of electrochemical sensing. This review covers the latest advances and mechanism of pH-sensing using ZnO nanorods, with an emphasis on the nano-interface mechanism. We discuss methods for calculating the effect of surface states on pH-sensing at a ZnO/electrolyte interface. All of these current research topics aim to explain the mechanism of pH-sensing using a ZnO bulk- or nano-scale single crystal. An important goal of these investigations is the translation of these nanotechnology-modified nanorods into potential novel applications.


Planning and initiation of the ONDCP National Youth Anti-Drug Media Campaign.
An alarming upsurge in substance use among American youth in the past decade prompted the Office of National Drug Control Policy (ONDCP) to organize the multifaceted, primary prevention National Youth Anti-Drug Media Campaign. The campaign focuses on adolescents (especially ages 11-13 years), but also targets adolescents' parents and other influential adults. The campaign's main goal is to educate and enable American youth to reject illegal drugs. The purpose of this article is to describe the origin of campaign objectives, processes for the development of specific advertising messages to fulfill these objectives, and how the ONDCP experience could provide a model for other health-oriented media campaigns.


Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis.
Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology. In the liver, ACLP is specifically expressed in hepatic stellate cells (HSCs). As fatty liver disease progresses, ACLP expression is enhanced via activation of STAT3 signaling by obesity-related factors in serum. ACLP specifically binds to frizzled-8 and low-density lipoprotein-related receptor 6 to form a ternary complex that activates canonical WNT signaling. Consequently, ACLP activates HSCs by inhibiting PPARγ signals. HSC-specific ACLP deficiency inhibits fibrosis progression in NASH by inhibiting canonical WNT signaling in HSCs. The present study elucidates the role of canonical WNT pathway activation by ACLP in NASH pathology, indicating that NASH can be treated by targeting ACLP-induced canonical WNT pathway activation in HSCs.


Sustained attention-deficit confirmed in euthymic bipolar disorder but not in first-degree relatives of bipolar patients or euthymic unipolar depression.
Cognitive dysfunction persists in the euthymic phase of bipolar disorder and may provide a marker of underlying neuropathology and disease vulnerability. This study aimed to replicate a deficit in sustained attention in euthymic bipolar patients and investigate sustained attention in first-degree relatives of bipolar probands and in remitted patients with major depressive disorder. The rapid visual information processing (RVIP) task was used to measure sustained attention in 15 euthymic patients with bipolar disorder and 15 control subjects in experiment 1 and in 27 first-degree relatives of bipolar probands, 15 remitted patients with major depressive disorder, and 46 control subjects in experiment 2. Sustained attention deficit was confirmed in the euthymic bipolar patients in experiment 1, but the deficit was not statistically significant in remitted major depressed patients or in the relatives of bipolar probands. A deficit of sustained attention is not present in patients with recurrent major depression tested during remission nor is it discriminable in the first-degree relatives of bipolar probands. Thus, the confirmed abnormality in euthymic bipolar patients may be acquired as a consequence of bipolar illness. However, future studies of relatives will require larger sample sizes to exclude or utilize small genetic effects.


Exogenous collagen cross-linking reduces scleral permeability: modeling the effects of age-related cross-link accumulation.
To investigate the relationship between scleral permeability and nonenzymatic cross-link density. Scleral discs 18 mm in diameter were dissected from the medial and lateral equatorial regions of 60 cadaveric porcine eyes. Samples were incubated for 24 hours with control solution or methylglyoxal at concentrations of 0.001%, 0.01%, 0.10%, and 1.00%. Nonenzymatic cross-link density in treated and control groups was quantified with the use of papain digest and fluorescence spectrophotometry. Treated scleral discs were mounted in a customized Ussing-type chamber connected to vertical tubing, and specific hydraulic conductivity was determined according to the descent of a column of degassed saline at room temperature. Permeability to diffusion of fluorescein in a static chamber was determined for another set of treated scleral samples. Methylglyoxal treatment effectively increased nonenzymatic cross-link content, as indicated by the average fluorescence for each group. Specific hydraulic conductivity (m(2)) was reduced with increasing cross-link density. Similarly, the permeability coefficient for the fluorescein solute consistently decreased with increasing methylglyoxal concentration, indicating diffusion impedance from the treatment. Nonenzymatic cross-link density can be significantly increased by treatment with methylglyoxal. Porcine sclera showed a nonlinear reduction in solute permeability and specific hydraulic conductivity with increasing cross-link density. This model indicates that age-related nonenzymatic cross-link accumulation can have a substantial impact on scleral permeability.


Improving Theory of Mind in Schizophrenia by Targeting Cognition and Metacognition with Computerized Cognitive Remediation: A Multiple Case Study.
Schizophrenia is associated with deficits in theory of mind (ToM) (i.e., the ability to infer the mental states of others) and cognition. Associations have often been reported between cognition and ToM, and ToM mediates the relationship between impaired cognition and impaired functioning in schizophrenia. Given that cognitive deficits could act as a limiting factor for ToM, this study investigated whether a cognitive remediation therapy (CRT) that targets nonsocial cognition and metacognition could improve ToM in schizophrenia. Four men with schizophrenia received CRT. Assessments of ToM, cognition, and metacognition were conducted at baseline and posttreatment as well as three months and 1 year later. Two patients reached a significant improvement in ToM immediately after treatment whereas at three months after treatment all four cases reached a significant improvement, which was maintained through 1 year after treatment for all three cases that remained in the study. Improvements in ToM were accompanied by significant improvements in the most severely impaired cognitive functions at baseline or by improvements in metacognition. This study establishes that a CRT program that does not explicitly target social abilities can improve ToM.


How calorie-focused thinking about obesity and related diseases may mislead and harm public health. An alternative.
Prevailing thinking about obesity and related diseases holds that quantifying calories should be a principal concern and target for intervention. Part of this thinking is that consumed calories - regardless of their sources - are equivalent; i.e. 'a calorie is a calorie'. The present commentary discusses various problems with the idea that 'a calorie is a calorie' and with a primarily quantitative focus on food calories. Instead, the authors argue for a greater qualitative focus on the sources of calories consumed (i.e. a greater focus on types of foods) and on the metabolic changes that result from consuming foods of different types. In particular, the authors consider how calorie-focused thinking is inherently biased against high-fat foods, many of which may be protective against obesity and related diseases, and supportive of starchy and sugary replacements, which are likely detrimental. Shifting the focus to qualitative food distinctions, a central argument of the paper is that obesity and related diseases are problems due largely to food-induced physiology (e.g. neurohormonal pathways) not addressable through arithmetic dieting (i.e. calorie counting). The paper considers potential harms of public health initiatives framed around calorie balance sheets - targeting 'calories in' and/or 'calories out' - that reinforce messages of overeating and inactivity as underlying causes, rather than intermediate effects, of obesity. Finally, the paper concludes that public health should work primarily to support the consumption of whole foods that help protect against obesity-promoting energy imbalance and metabolic dysfunction and not continue to promote calorie-directed messages that may create and blame victims and possibly exacerbate epidemics of obesity and related diseases.


Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria.
Twenty percent of the familial form of amyotrophic lateral sclerosis (ALS) is caused by mutations in the Cu, Zn-superoxide dismutase gene (SOD1) through the gain of a toxic function. The nature of this toxic function of mutant SOD1 has remained largely unknown. Here we show that WT SOD1 not only hastens onset of the ALS phenotype but can also convert an unaffected phenotype to an ALS phenotype in mutant SOD1 transgenic mouse models. Further analyses of the single- and double-transgenic mice revealed that conversion of mutant SOD1 from a soluble form to an aggregated and detergent-insoluble form was associated with development of the ALS phenotype in transgenic mice. Conversion of WT SOD1 from a soluble form to an aggregated and insoluble form also correlates with exacerbation of the disease or conversion to a disease phenotype in double-transgenic mice. This conversion, observed in the mitochondrial fraction of the spinal cord, involved formation of insoluble SOD1 dimers and multimers that are crosslinked through intermolecular disulfide bonds via oxidation of cysteine residues in SOD1. Our data thus show a molecular mechanism by which SOD1, an important protein in cellular defense against free radicals, is converted to aggregated and apparently ALS-associated toxic dimers and multimers by redox processes. These findings provide evidence of direct links among oxidation, protein aggregation, mitochondrial damage, and SOD1-mediated ALS, with possible applications to the aging process and other late-onset neurodegenerative disorders. Importantly, rational therapy based on these observations can now be developed and tested.


Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM.
Abdominal obesity, particularly excess intraperitoneal fat, is considered to play a major role in causing insulin resistance and NIDDM. To determine if NIDDM patients accumulate excess intraperitoneal fat, and whether this contributes significantly to their insulin resistance, 31 men with mild NIDDM with a wide range of adiposity were compared with 39 nondiabetic, control subjects for insulin sensitivity (measured using euglycemic-hyperinsulinemic clamp technique with [3-3H]glucose turnover) and total and regional adiposity (assessed by hydrodensitometry and by measuring subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses using magnetic resonance imaging [MRI], and truncal and peripheral skinfold thicknesses using calipers). MRI analysis revealed that intraperitoneal fat was not increased in NIDDM patients compared with control subjects; in both groups it averaged 11% of total body fat. NIDDM patients, however, had increased truncal-to-peripheral skinfolds thickness ratios. In NIDDM patients, as in control subjects, amounts of truncal subcutaneous fat showed a stronger correlation with glucose disposal rate than intraperitoneal or retroperitoneal fat; however, NIDDM patients were more insulin resistant at every level of total or regional adiposity. Further, no particular influence of excess intraperitoneal fat on hepatic insulin sensitivity was noted. We conclude that NIDDM patients do not have excess intraperitoneal fat, but that their fat distribution favors more truncal and less peripheral subcutaneous fat. Moreover, for each level of total and regional adiposity, NIDDM patients have a heightened state of insulin resistance.


A Scoping Review of Mixed Methods Research About Physical Activity for Children With Disabilities.
The purpose of this scoping review was to examine how mixed methods research (MMR) has been applied in adapted physical activity (APA) research about children and adolescents age 5-18 years with a disability. Six electronic databases were searched to retrieve relevant studies published between 2003 and 2020. Sixty-four studies were identified and analyzed. The findings were organized into five categories of interest: publication information, study objectives, mixed methods research design, participants' information, and data integration. Challenges related to the design and publication of MMR in APA were uncovered, and suggestions for improvement are provided. This study adds to the knowledge of MMR design, and it provides an understanding of the underlying processes and methodological strategies that have guided this approach in APA research. This article will encourage APA researchers to engage in MMR while also aligning future studies with contemporary MMR literature and publication standards.


Obesity prevention: a proposed framework for translating evidence into action.
Obesity as a major public health and economic problem has risen to the top of policy and programme agendas in many countries, with prevention of childhood obesity providing a particularly compelling mandate for action. There is widespread agreement that action is needed urgently, that it should be comprehensive and sustained, and that it should be evidence-based. While policy and programme funding decisions are inevitably subject to a variety of historical, social, and political influences, a framework for defining their evidence base is needed. This paper describes the development of an evidence-based, decision-making framework that is particularly relevant to obesity prevention. Building upon existing work within the fields of public health and health promotion, the Prevention Group of the International Obesity Task Force (IOTF) developed a set of key issues and evidence requirements for obesity prevention. These were presented and discussed at an IOTF workshop in April 2004 and were then further developed into a practical framework. The framework is defined by five key policy and programme issues that form the basis of the framework. These are: (i) building a case for action on obesity; (ii) identifying contributing factors and points of intervention; (iii) defining the opportunities for action; (iv)evaluating potential interventions; and (v) selecting a portfolio of specific policies, programmes, and actions. Each issue has a different set of evidence requirements and analytical outputs to support policy and programme decision-making. Issue 4 was identified as currently the most problematic because of the relative lack of efficacy and effectiveness studies. Compared with clinical decision-making where the evidence base is dominated by randomized controlled trials with high internal validity, the evidence base for obesity prevention needs many different types of evidence and often needs the informed opinions of stakeholders to ensure external validity and contextual relevance.


CD4+ but not CD8+ cells are essential for allorejection.
The generation of knockout mice with targeted gene disruption has provided a valuable tool for studying the immune response. Here we describe the use of CD4 and CD8 knockout mice to examine the role of CD4+ and CD8+ cells in initiating allotransplantation rejection. Pretreatment with a brief course of depletive anti-CD4 monoclonal antibody therapy allowed permanent survival of heart, but not skin, allografts transplanted across a major histocompatibility barrier. However, skin as well as heart grafts were permanently accepted in the CD4 knockout mice. Transfer of CD4+ cells into CD4 knockout recipient mice 1 d before skin engraftment reconstituted rejection, demonstrating that CD4+ cells are necessary for initiating rejection of allogeneic transplants. Major histocompatibility complex disparate heart and skin allografts transplanted into CD8 knockout recipients were rejected within 10 d. This study demonstrates that CD4+ but not CD8+ T cells are absolutely required to initiate allograft rejection.


Geometry-affinity relationships of the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
With the exception of its two aromatic rings and basic nitrogen atom, 9-(aminomethyl)-9,10-dihydroanthracene (AMDA; 1) is remarkably devoid of the pharmacophore features usually associated with high-affinity receptor ligands such as the heteroatom hydrogen bonding features of the endogenous ligand serotonin. AMDA does contain a phenylethylamine skeleton within a tricyclic ring system, and the presence of the second aromatic group is necessary for optimal receptor affinity. The structural requirements for the binding of AMDA at 5-HT(2A) receptors were investigated with respect to the geometric relationship between the two aromatic rings. It appears that the geometry of the AMDA parent is in the optimal range for fold angle between aromatic moieties. Evaluation of conformationally constrained derivatives of AMDA suggests that a chain extended trans, gauche form is most likely responsible for high affinity.


Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials.
Although erectile dysfunction (ED) is associated with cardiovascular risk factors and atherosclerosis, it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease. We evaluated whether ED is predictive of mortality and cardiovascular outcomes, and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events, we also tested the effects on ED of randomized treatments with telmisartan, ramipril, and the combination of the 2 drugs (ONTARGET), as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors (TRANSCEND). In a prespecified substudy, 1549 patients underwent double-blind randomization, with 400 participants assigned to receive ramipril, 395 telmisartan, and 381 the combination thereof (ONTARGET), as well as 171 participants assigned to receive telmisartan and 202 placebo (TRANSCEND). ED was evaluated at baseline, at 2-year follow-up, and at the penultimate visit before closeout. ED was predictive of all-cause death (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.21 to 2.81, P=0.005) and the composite primary outcome (HR 1.42, 95% CI 1.04 to 1.94, P=0.029), which consisted of cardiovascular death (HR 1.93, 95% CI 1.13 to 3.29, P=0.016), myocardial infarction (HR 2.02, 95% CI 1.13 to 3.58, P=0.017), hospitalization for heart failure (HR 1.2, 95% CI 0.64 to 2.26, P=0.563), and stroke (HR 1.1, 95% CI 0.64 to 1.9, P=0.742). The study medications did not influence the course or development of ED. ED is a potent predictor of all-cause death and the composite of cardiovascular death, myocardial infarction, stroke, and heart failure in men with cardiovascular disease. Trial treatment did not significantly improve or worsen ED. URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00153101.


A Comparison of the Reactions of Caregivers of Patients With Cancer Versus Patients With Other Chronic Medical Conditions.
To explore positive and negative aspects of the experiences of informal caregivers of patients with cancer and patients with other chronic medical conditions, to compare the reactions of caregivers of patients with cancer and patients with other chronic medical conditions, and to study the association of caregiver reactions with demographic factors. . Descriptive, correlational. . A comprehensive cancer center and a community hospital, both in Philadelphia, PA. . 111 informal caregivers. . A survey that could be completed either in paper format or electronically was administered. . Self-esteem, impact on schedule, impact on finances, impact on health, lack of family support, positive aspects of caregiving. . For caregivers, offering emotional and psychological support was most challenging, whereas providing transportation was least challenging. Caregivers reported high self-esteem and moderately positive aspects of caregiving. Caregivers of patients with cancer identified more positive aspects of caregiving. Differences in the caregiving experience based on demographic factors (e.g., gender, race, ethnicity) were found. . Caregivers reported positive and negative aspects of caregiving. Reactions of informal caregivers to the caregiving experience vary more based on individual demographic factors than on the diagnosis of the patient. Differences exist in the caregiving experience based on race and ethnicity. . Nurses need to be aware that positive and negative reactions to the caregiving experience exist. Assessment and care planning should include consideration for individual factors, such as gender, race, and ethnicity.


Societal causes of, and responses to, ocean acidification.
Major climate and ecological changes affect the world's oceans leading to a number of responses including increasing water temperatures, changing weather patterns, shrinking ice-sheets, temperature-driven shifts in marine species ranges, biodiversity loss and bleaching of coral reefs. In addition, ocean pH is falling, a process known as ocean acidification (OA). The root cause of OA lies in human policies and behaviours driving society's dependence on fossil fuels, resulting in elevated CO2 concentrations in the atmosphere. In this review, we detail the state of knowledge of the causes of, and potential responses to, OA with particular focus on Swedish coastal seas. We also discuss present knowledge gaps and implementation needs.


Monitoring of shallow sea environment by using snapping shrimps.
We examine the validity of pulse count of snapping shrimps for sea environmental monitoring. Snapping shrimps, which make a peculiar pulse sound, are found everywhere in the world. Pulse count can be achieved merely by recording their sounds for a few minutes by using a hydrophone without special biological knowledge. From field surveys and laboratory experiments, we found that the pulse count depends on water temperature when sea environment is normal, and it falls due to the occurrence of oxygen-deficient water. The results show that this method can be a useful index of the effect of water pollution on benthic animals in fixed-point observation.


Phylogenomics and the dynamic genome evolution of the genus Streptococcus.
The genus Streptococcus comprises important pathogens that have a severe impact on human health and are responsible for substantial economic losses to agriculture. Here, we utilize 46 Streptococcus genome sequences (44 species), including eight species sequenced here, to provide the first genomic level insight into the evolutionary history and genetic basis underlying the functional diversity of all major groups of this genus. Gene gain/loss analysis revealed a dynamic pattern of genome evolution characterized by an initial period of gene gain followed by a period of loss, as the major groups within the genus diversified. This was followed by a period of genome expansion associated with the origins of the present extant species. The pattern is concordant with an emerging view that genomes evolve through a dynamic process of expansion and streamlining. A large proportion of the pan-genome has experienced lateral gene transfer (LGT) with causative factors, such as relatedness and shared environment, operating over different evolutionary scales. Multiple gene ontology terms were significantly enriched for each group, and mapping terms onto the phylogeny showed that those corresponding to genes born on branches leading to the major groups represented approximately one-fifth of those enriched. Furthermore, despite the extensive LGT, several biochemical characteristics have been retained since group formation, suggesting genomic cohesiveness through time, and that these characteristics may be fundamental to each group. For example, proteolysis: mitis group; urea metabolism: salivarius group; carbohydrate metabolism: pyogenic group; and transcription regulation: bovis group.


Batf promotes growth arrest and terminal differentiation of mouse myeloid leukemia cells.
Batf is a basic leucine zipper transcription factor belonging to the activator protein-1 superfamily. Batf expression is regulated following stimulation of both lymphoid and myeloid cells. When treated with leukemia inhibitory factor, mouse M1 myeloid leukemia cells commit to a macrophage differentiation program that is dependent on Stat3 and involves the induction of Batf gene transcription via the binding of Stat3 to the Batf promoter. RNA interference was employed to block Batf induction in this system and the cells failed to growth arrest or to terminally differentiate. Restoring Batf expression not only reversed the differentiation-defective phenotype but also caused the cells to display signs of spontaneous differentiation in the absence of stimulation. Efforts to define genetic targets of the Batf transcription factor in M1 cells led to the identification of c-myb, a proto-oncogene known to promote blood cell proliferation and to inhibit the differentiation of M1 cells. These results provide strong evidence that Batf mediates the differentiation-inducing effects of Stat3 signaling in M1 cells and suggest that Batf may play a similar role in other blood cell lineages where alterations to the Jak-Stat pathway are hallmarks of disrupted development and disease.


Laser Treatment of Nongenital Verrucae: A Systematic Review.
Although cutaneous warts are common lesions, full remission is not always achieved with conventional therapies. Laser modalities including carbon dioxide (CO2), erbium:yttrium-aluminum-garnet (Er:YAG), pulsed dye (PDL), and Nd:YAG have been investigated as alternative treatments for warts. To review the use and efficacy of lasers for treating nongenital cutaneous warts. Published randomized clinical trials (RCTs), cohort studies, case series, and case reports involving laser treatment of nongenital warts were retrieved by searching PubMed with no date limits. Quality ratings of studies were based on a modified version of the Oxford Centre for Evidence-Based Medicine scheme for rating individual studies. A higher emphasis was placed on RCTs and prospective cohort studies with large sample sizes and detailed methodology. There were 35 studies published between 1989 and 2015 that comprised an aggregate of 2149 patients. Simple and recalcitrant nongenital warts treated with lasers show variable response rates (CO2 laser, 50%-100%; Er:YAG laser, 72%-100%; PDL, 47%-100%; and Nd:YAG laser, 46%-100%). Current RCTs suggest that PDL is equivalent to conventional therapies such as cryotherapy and cantharidin. Combination therapies with lasers and other agents including bleomycin, salicylic acid, and light-emitting diode have shown some success. Lasers can be an effective treatment option for both simple and recalcitrant warts. The lasers most studied for this purpose are CO2, PDL, and Nd:YAG, and of these, PDL has the fewest adverse effects. Currently, use of lasers for wart treatment is limited by lack of established treatment guidelines. Future studies are needed to compare laser modalities with each other and with nonlaser treatment options, and to establish optimal treatment protocols.


Ciliary defects associated with the development of bronchopulmonary dysplasia. Ciliary motility and ultrastructure.
We have on several occasions studied the nasal respiratory epithelium of an infant with hyaline membrane disease that evolved into bronchopulmonary dysplasia and observed an association between the clinical status and naso-ciliary motion and ultrastructure. At 4 months of age, when the patient had significant respiratory disease, few cilia were present and they beat with a slow dyskinetic motion. The specimens contained primarily necrotic and squamous epithelial membranes; the occasional cilia present had swollen or ruptured membranes. Partial recovery of the epithelium was noted at 4.5 months, with 45% of the cilia having normal ultrastructure. The beat frequency was 15.2 +/- 1.5 Hz (mean +/- SD), and although some degree of dyskinesia was evident, primarily normal ciliary motion was observed. By 10 months of age, significant clinical improvement had occurred and the nasal epithelium had regenerated; 96% of the cilia had normal ultrastructure, and the ciliary beat frequency (12.4 +/- 1.2 Hz) and motion were normal.


Effects of three fentanyl plasma concentrations on the minimum alveolar concentration of isoflurane in Hispaniolan Amazon parrots (Amazona ventralis).
OBJECTIVE To determine effects of 3 plasma concentrations of fentanyl on the minimum alveolar concentration of isoflurane (MACiso) and cardiovascular variables in Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS 6 adult parrots. PROCEDURES In phase 1, anesthesia was induced and maintained with isoflurane; intermittent positive-pressure ventilation was provided. The MACiso was determined for each bird by use of a bracketing method and supramaximal electrical stimulus. Fentanyl (20 μg/kg) was administered IV, and blood samples were collected over time to measure plasma fentanyl concentrations for pharmacokinetic calculations. In phase 2, pharmacokinetic values for individual birds were used for administration of fentanyl to achieve target plasma concentrations of 8, 16, and 32 ng/mL. At each concentration, MACiso and cardiovascular variables were determined. Data were analyzed with mixed-effects multilevel linear regression analysis. RESULTS Mean ± SD fentanyl plasma concentrations were 0 ng/mL, 5.01 ± 1.53 ng/mL, 12.12 ± 3.58 ng/mL, and 24.93 ± 4.13 ng/mL, and MACiso values were 2.09 ± 0.17%, 1.45 ± 0.32%, 1.34 ± 0.31%, and 0.95 ± 0.14% for fentanyl target concentrations of 0, 8, 16, and 32 ng/mL, respectively. Fentanyl significantly decreased MACiso in a dose-dependent manner. Heart rate and blood pressure significantly decreased at all fentanyl doses, compared with values for MACiso at 0 ng of fentanyl/mL. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl significantly decreased the MACiso in healthy Hispaniolan Amazon parrots, but this was accompanied by a depressive effect on heart rate and blood pressure that would need to be considered for application of this technique in clinical settings.