Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro.
The objectives of this study were to determine the structural characteristics of perfluoroalkyl acids (PFAAs) that confer estrogen-like activity in vivo using juvenile rainbow trout (Oncorhynchus mykiss) as an animal model and to determine whether these chemicals interact directly with the estrogen receptor (ER) using in vitro and in silico species comparison approaches. Perfluorooctanoic (PFOA), perfluorononanoic (PFNA), perfluorodecanoic (PFDA), and perfluoroundecanoic (PFUnDA) acids were all potent inducers of the estrogen-responsive biomarker protein vitellogenin (Vtg) in vivo, although at fairly high dietary exposures. A structure-activity relationship for PFAAs was observed, where eight to ten fluorinated carbons and a carboxylic acid end group were optimal for maximal Vtg induction. These in vivo findings were corroborated by in vitro mechanistic assays for trout and human ER. All PFAAs tested weakly bound to trout liver ER with half maximal inhibitory concentration (IC(50)) values of 15.2-289 μM. Additionally, PFOA, PFNA, PFDA, PFUnDA, and perlfuorooctane sulfonate (PFOS) significantly enhanced human ERα-dependent transcriptional activation at concentrations ranging from 10-1000 nM. Finally, we employed an in silico computational model based upon the crystal structure for the human ERα ligand-binding domain complexed with E2 to structurally investigate binding of these putative ligands to human, mouse, and trout ERα. PFOA, PFNA, PFDA, and PFOS all efficiently docked with ERα from different species and formed a hydrogen bond at residue Arg394/398/407 (human/mouse/trout) in a manner similar to the environmental estrogens bisphenol A and nonylphenol. Overall, these data support the contention that several PFAAs are weak environmental xenoestrogens of potential concern.


Growth of Holstein dairy heifers in the United States.
Data were collected on the heart girth (n = 8,565; a measure of body weight) and height at withers (n = 8,568) of Holstein dairy heifers from 659 dairy farms as part of the National Dairy Heifer Evaluation Project during 1991 and 1992. Means and standard deviations for weight and height were determined for ages .5 to 23.5 mo. Third-order polynomial regression equations were derived to study the relationship of weight and height to age. Stepwise mixed-model regression, using REML estimation, was used to identify factors associated with Holstein heifer growth and to build a multivariate model describing Holstein heifer growth across the United States. Holstein heifers on the sample of dairy farms in this study were heavier and taller at the withers than standards published 30 to 50 yr ago. Increased rolling herd average milk production was associated with a greater rate of growth in Holstein heifers. Holstein heifers in the West and Midwest were larger at a given age than those in the Northeast and Southeast.


Effects of oestradiol-17-beta and progesterone on total and nuclear-protein synthesis in epithelial and stromal tissues of the mouse uterus, and of progesterone on the ability of these tissues to bind oestradiol-17-beta.
1. A method is described for separating uterine epithelium that is 80% pure and connective-tissue stroma that is 60% pure. This was used to study the effects of steroid hormones on total and nuclear-protein synthesis in these tissues. 2. Oestradiol-17beta given alone produces mitoses in the epithelium but not in the stroma. It stimulated incorporation in vitro of [(14)C]lysine into total protein, histones and acidic nuclear proteins to a greater extent in epithelium than stroma. Incorporation into acidic nuclear proteins was most markedly stimulated, reaching four to six times the normal value 4h after treatment, and then declining rapidly. This peak was only seen in epithelial preparations. 3. After pretreatment with progesterone, oestradiol-17beta has the reverse effect, producing mitoses only in stroma. Progesterone alone had no effect on the amounts or rates of incorporation of [(14)C]lysine into stromal nuclear proteins, but changes after oestradiol-17beta treatment were similar to those seen in epithelium with oestradiol-17beta alone. In the epithelium, progesterone alone depressed incorporation into histones and acidic nuclear proteins, but did not abolish the subsequent response to oestradiol-17beta. With this treatment there was a rapid, large and transient increase in incorporation into epithelial total protein not seen with oestradiol-17beta alone. 4. Progesterone had no qualitative effect on the distribution of specific oestrogen-binding proteins, as judged by sucrose-density-gradient centrifugation. However, progesterone treatment increased the uptake in vivo of [6,7-(3)H]oestradiol-17beta by stroma, and it is possible that this is important although the differences were not apparent after labelling in vitro.


Combined Primary Cleft Lip and Palate Repair: Is It Safe?
Single-stage primary cleft lip and palate (PCLP) repair is controversial in the United States, and most patients are treated with a staged approach. In this study, early postoperative complications of the single-stage approach as compared to primary cleft lip (PCL) or primary cleft palate (PCP) alone were evaluated. This study represents the largest cohort of patients undergoing combined cleft lip and palate repair. The American College of Surgeons National Surgical Quality Improvement Program-Pediatric database was used to identify patients undergoing single-stage PCLP, PCL, or PCP repairs. Preoperative factors and postoperative outcomes were compared between the 3 groups, as well as within the PCLP group between patients with and without complications. Univariate and multivariate analyses were performed. A TOTAL OF:: 181 patients were included in the single-stage PCLP group, 1007 in the PCP group and 783 in the PCL group. There was no difference in the rates of early complications between the 3 groups. Within the PCLP group, cardiac risk factors (β = 35.19; 95% confidence interval [CI] 7.88-75.21; P = 0.04) and complications (β = 77.31; 95% CI 35.82-118.79; P < 0.001) were significant risk factors for longer operative time. Analysis of a national database showed that single-stage PCLP repair is not associated with increased risk of early postoperative complications as compared to primary lip or palate repair alone. In-depth long-term analyses of craniofacial morphology, fistulae rate, speech, and dental outcomes are essential for a comprehensive assessment of the effects of combined cleft lip and palate repair.


Preparation of stoichiometric molecularly imprinted polymer coatings on magnetic particles for the selective extraction of auramine O from water.
A novel magnetic molecularly imprinted polymer for the selective recognition of auramine O was rationally designed via screening from a library of nonimprinted polymers. A stoichiometric ratio of functional monomer (itaconic acid) and template molecule (auramine O) was found to be 1.5. Meanwhile, the synthesized SiO2 @Fe3 O4 was modified by 0.5 mol/L hydrochloric acid to facilitate the preparation of magnetic molecularly imprinted polymer particles. Adsorption experiments showed that the magnetic polymer particles exhibited good selectivity, recoveries, and enrichment performance. The stoichiometric imprinted polymers have been employed for the selective preconcentration of auramine O from lake water sample. The high specificity of the stoichiometric imprinted polymers was proven in the extraction of mixture solution of auramine O, auramine O hydrochloride, and chrysoidine, and the recoveries ranged between 99.66 and 108.75% (RSD 2.6-3.7%, n = 3) for lake water. These results suggest that this method is effective and can be successfully applied to the analysis of auramine O in environmental water samples.


The combined effect of behavioural risk factors on disability in aging adults from the Canadian Longitudinal Study on Aging (CLSA).
The objective of this study was to explore how behavioural risk factors (smoking, physical activity, and nutrition) cluster together and assess how clusters of behavioural risk factors are associated with functional disability by age and sex at the individual and population level. We used currently available baseline cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The CLSA is a national, population-based longitudinal study established to understand and examine health of an aging population. This study included 51,338 Canadian men and women aged 45 to 85 years residing in the community in 10 Canadian provinces. Behavioural risk factors included smoking, physical activity, and nutrition. The main outcome used in the study was functional disability, which was assessed using a questionnaire adapted from the Older Americans Resources and Services Multidimensional Assessment Questionnaire. In this analyses of unique combinations of the risk factors of smoking, physical activity, and nutritional risk, the magnitude of the association of the behavioural risk factors with functional disability was dependent on which risk factors were included and differed by age and sex strata. Of the risk factors, physical activity accounted for between 70% to 90% of the total population level risk in individuals with all three risk factors, suggesting it is a key driver of the population burden of disability. Together, these results show that considering unique clusters of risk factors, as well as age and sex, is essential for tailoring public health strategies to reduce the burden of disability among aging populations.


Stimulatory effect of counterflow centrifugal elutriation in large-scale separation of peripheral blood monocytes can be reversed by storing the cells at 37 degrees C.
Transfusion of peripheral blood monocytes may be of benefit as adjuvant treatment of leukopenic patients with serious infections. To study the feasibility of this approach, a large-scale monocyte separation procedure employing leukapheresis, density gradient centrifugation, and counterflow centrifugal elutriation was established. By processing 5 to 6 liters of normal donor blood, it was possible to obtain a mean of 1.1 x 10(9) (range: 0.5-1.7 x 10(9) cells) of mononuclear cells, of which 89% (range: 82-94%) were monocytes by Wright's stain morphology. When the elutriation was performed in XVIVO-10, a commercially available, serum-free medium developed for adoptive immunotherapy, spontaneous secretion of superoxide by the monocytes was significantly higher than for monocytes elutriated in Hanks' balanced salt solution without calcium and magnesium or non-elutriated peripheral blood mononuclear cells. This stimulated state of the monocytes was observed both immediately after elutriation and after overnight storage at 4 degrees C, and it was not affected by the type of storage vessel used. Overnight storage of the monocytes at 37 degrees C resulted in a reversal of the stimulated state of the cells. Monocytes elutriated in XVIVO-10 and kept overnight at 4 degrees C released high amounts of arachidonic acid. A subsequent decrease in this release was seen after additional storage at 37 degrees C for 18 hours. These observations demonstrate that separation and storage variables have important effects on the state of stimulation of monocytes. Further investigations of such variables may suggest improved procedures for preparation and storage of these cells, as well as possible ways to stimulate monocytes prior to transfusion.


Seeing the Unseen: Evaluating Testicular Vascularity in Neonates by Using the Superb Microvascular Imaging Ultrasound Technique.
To evaluate testicular vascularity in neonates by using the novel Superb Microvascular Imaging (SMI; Toshiba Medical Systems Corporation, Tokyo, Japan) ultrasound (US) technique and to compare this technique to conventional Doppler US techniques. A total of 140 healthy neonates between 2 and 60 days old who were admitted for routine screening were included in the study. However, in 9 cases, the Doppler study could not be completed. In the remaining 131 cases, color Doppler imaging (CDI), power Doppler imaging (PDI), Advanced Dynamic Flow (ADF; Toshiba Medical Systems), and monochrome SMI (mSMI) techniques were performed on a single representative testicle. Real-time cine images were captured for 5 to 10 seconds for each technique by using a high-frequency (7.2-14-MHz) linear transducer. The images were evaluated by 3 observers using a grading system to quantify the degree of vascularity and artifact interference. A total of 131 testicles (74 right and 57 left) were evaluated, and vascularity was shown in 110 (84%) testicles with CDI, 109 (83%) with PDI, 94 (72%) with ADF, and 128 (98%) with mSMI by the consensus of all observers. The Doppler techniques were ranked from highest to lowest in the following order based on the degree of vascularity detected: mSMI > PDI > CDI > ADF (P < .001). Based on the presence of artifacts, the Doppler techniques were ranked as follows from high to low: ADF > CDI > PDI > mSMI (P < .001). Superb Microvascular Imaging is a promising US technique that appears to detect testis vascularity better than conventional Doppler US techniques; however, further research is needed to support the results of this study.


Effect of donor age in patients with acute myeloid leukemia undergoing haploidentical hematopoietic cell transplantation vary by conditioning intensity and recipient age.
We investigated the impact of donor age (younger [≤35 years] vs. older [>35 years]) after accounting for other non-HLA and HLA factors on outcomes of patients with acute myeloid leukemia undergoing HLA-haploidentical hematopoietic cell transplantation (n = 790). The effect differed by conditioning-partly related to the differences in the recipient age in myeloablative (MAC; median 46 years) versus reduced-intensity/non-myeloablative conditioning (RIC/NMA; median 61 years) groups. With MAC (n = 320), donor age had no impact on acute graft-versus-host disease (GVHD), but older donors were associated with a significantly higher risk of chronic GVHD (hazard ratio [HR]: 1.6, 95% confidence interval [CI]: 1.10-2.30, p = .02) independent of recipient age and other factors. Donor age had no impact on either relapse or non-relapse mortality (NRM). The impact of donor/recipient age on overall survival changed over time. Older donors were associated with significantly higher late overall mortality (>6 months) in younger recipients (≤ 50 years; HR: 2.2, 95% CI: 1.03-4.6, p = .04) but not older recipients. With RIC/NMA (n = 470), neither recipient's nor donor's age influenced the risk of GVHD. Donor age had no significant impact on the risk of relapse, but older donors were associated with a significantly higher risk of NRM (HR: 1.6, 95% CI: 1.02-2.6, p = .04) independent of recipient age. Older donor age was associated with significantly higher late overall mortality (>9 months) in older recipients (>50 years; HR: 1.66, 95% CI: 1.0-2.67; p = .049) but not in younger recipients. Donor selection based on donor age may require a tailored approach for a particular recipient.


Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal and malignant cell origin.
Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis. VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy. VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy. Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium.


Formation and Evolution of Solvent-Extracted and Nonextractable Environmentally Persistent Free Radicals in Fly Ash of Municipal Solid Waste Incinerators.
Environmentally persistent free radicals (EPFRs) are emerging contaminants occurring in combustion-borne particulates and atmospheric particulate matter, but information on their formation and behavior on fly ash from municipal solid waste (MSW) incinerators is scarce. Here, we have found that MSW-associated fly ash samples contain an EPFR concentration of 3-10 × 1015 spins g-1, a line width (ΔHp-p) of ∼8.6 G, and a g-factor of 2.0032-2.0038. These EPFRs are proposed to be mixtures of carbon-centered and oxygen-centered free radicals. Fractionation of the fly ash-associated EPFRs into solvent-extracted and nonextractable radicals suggests that the solvent-extracted part accounts for ∼45-73% of the total amount of EPFRs. Spin densities of solvent-extracted EPFRs correlate positively with the concentrations of Fe, Cu, Mn, Ti, and Zn, whereas similar correlations are comparatively insignificant for nonextractable EPFRs. Under natural conditions, these two types of EPFRs exhibit different stabilization that solvent-extracted EPFRs are relatively unstable, whereas the nonextractable fraction possesses a long life span. Significant correlations between concentrations of solvent-extracted EPFRs and generation of hydroxyl and superoxide radicals are found. Overall, our results suggest that the fractionated solvent-extracted and nonextractable EPFRs may experience different formation and stabilization processes and health effects.


Inflorescence photosynthetic contribution to fitness releases Arabidopsis thaliana plants from trade-off constraints on early flowering.
Leaves are thought to be the primary carbon source for reproduction in plants, so a positive relationship between vegetative size and reproductive output is expected, establishing a trade-off between time to reproduction and reproductive output. A common response to higher temperatures due to climate changes is the induction of earlier transition into reproduction. Thus, in annual plants, earlier transition into flowering can potentially constrain plant size and reduce seed production. However, trade-offs between early reproduction and fitness are not always observed, suggesting mechanisms to escape the constraints of early flowering do exist. Here, we test whether inflorescence photosynthesis contribution to the reproductive output of Arabidopsis thaliana can offset the cost of early reproduction. We followed the development, growth rate and fitness of 15 accessions, and removed all rosette leaves at flowering (prior to the completion of inflorescence development or any fruit production) in half of the plants to determine the ability of inflorescences to maintain fitness in the absence of leaves. Although leaf removal significantly reduced fruit number, seed weight and plant height, even the most severely impacted accessions maintained 35% of their fitness with the inflorescence as the sole photosynthetic organ; and some accessions experienced no reduction in fitness. Differences between accessions in their ability to maintain fitness after leaf removal is best explained by earlier flowering time and the ability to maintain as many or more branches after leaf removal as in the control treatment. Although earlier flowering does constrain plant vegetative size, we found that inflorescence photosynthesis can significantly contribute to seed production, explaining why early flowering plants can maintain high fitness despite a reduction in vegetative size. Thus, plants can be released from the usually assumed trade-offs associated with earlier reproduction, and selection on inflorescence traits can mediate the impact of climate change on phenology.


Review of backscatter measurement in kilovoltage radiotherapy using novel detectors and reduction from lack of underlying scattering material.
Lack of underlying material can lead to dose reduction in kilovoltage radiotherapy treatments because of backscatter reduction. Conversely, the use of lead shielding can lead to large dose enhancement close to the lead interface. GAFCHROMIC film has been shown to be of use in verification of local backscatter factors compared to reference data in codes of practice, but careful handling and multiple readings are required to reduce systematic uncertainties to between 3% and 4%. Monte Carlo modeling of the specific treatment unit should be performed in cases which are found to differ from reference values before alternative values are adopted clinically, but these cases are expected to be few. GAFCHROMIC film may also be used to estimate backscatter reduction more readily than customized ionization chambers, for a range of beam qualities, applicator sizes and depth, with and without lead shielding. Differences were found between different studies, and it is not clear to what extent these are due to variation in equipment and/or technique. However, a layer of wax around lead shielding of 1 mm thickness should be sufficient to eliminate lead enhancement effects for all kilovoltage energies from 40 kV to 300 kV.


Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death.
The risk and the predictors of liver disease progression in carriers of inactive hepatitis B virus (HBV) are unclear. Participants in the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study who were seronegative for hepatitis B e antigen; had serum levels of HBV DNA <10,000 copies/mL; and did not have cirrhosis, hepatocellular carcinoma, or increased serum levels of alanine aminotransferase were classified as carriers of inactive HBV (n = 1932). Study participants who were seronegative for HB surface antigen and antibodies against hepatitis C virus, yet had similar clinical liver features, were the controls (n = 18,137). Liver-related death and new cases of hepatocellular carcinoma were ascertained through computerized data linkage with National Cancer Registry and Death Certification profiles. The disease progression rates were estimated. The multivariate-adjusted hazard ratios for risk predictors were derived from Cox regression models. There were 20,069 participants, contributing a total of 262,122 person-years, with a mean follow-up of 13.1 years. Annual incidence rates of hepatocellular carcinoma and liver-related death were 0.06% and 0.04%, respectively, for inactive HBV carriers; rates were 0.02%, and 0.02% for controls, respectively. The multivariate-adjusted hazard ratios for carriers of inactive HBV, compared to controls, were 4.6 (95% confidence interval: 2.5-8.3) for hepatocellular carcinoma and 2.1 (95% confidence interval: 1.1-4.1) for liver-related death. Older age and alcohol drinking habits were independent predictors of risk for carriers of inactive HBV to develop hepatocellular carcinoma. Carriers of inactive HBV have a substantial risk of hepatocellular carcinoma and liver-related death compared with individuals not infected with HBV.


Use of global symmetries in automated signal class recognition by a bayesian method
Automated or semiautomated pattern recognition in multidimensional NMR spectroscopy is strongly hampered by the large number of noise and artifact peaks occurring under practical conditions. A general Bayesian method which is able to assign probabilities that observed peaks are members of given signal classes (e.g., the class of true resonance peaks or the class of noise and artifact peaks) was proposed previously. The discriminative power of this approach is dependent on the choice of the properties characterizing the peaks. The automated class recognition is improved by the addition of a nonlocal feature, the similarities of peak shapes in symmetry-related positions. It turns out that this additional property strongly decreases the overlap of the multivariate probability distributions for true signals and noise and hence largely increases the discrimination of true resonance peaks from noise and artifacts. Copyright 1997 Academic Press. Copyright 1997Academic Press


Physical Links: defining and detecting inter-chain entanglement.
Fluctuating filaments, from densely-packed biopolymers to defect lines in structured fluids, are prone to become interlaced and form intricate architectures. Understanding the ensuing mechanical and relaxation properties depends critically on being able to capture such entanglement in quantitative terms. So far, this has been an elusive challenge. Here we introduce the first general characterization of non-ephemeral forms of entanglement in linear curves by introducing novel descriptors that extend topological measures of linking from close to open curves. We thus establish the concept of physical links. This general method is applied to diverse contexts: equilibrated ring polymers, mechanically-stretched links and concentrated solutions of linear chains. The abundance, complexity and space distribution of their physical links gives access to a whole new layer of understanding of such systems and open new perspectives for others, such as reconnection events and topological simplification in dissipative fields and defect lines.


Long-term results after restoring nasal tip support using auricular cartilage as an intercrural columellar strut graft: the "I-Beam" technique.
The lack of nasal tip support resulting in poor protection and projection of the nose is a common cause of nasal obstruction and cosmetic impairment. Although septal cartilage is preferred for restoration of nasal tip support, there is often not enough septal cartilage available. We describe an intercrural columellar strut graft in a circumferential soft tissue pocket: the I-Beam technique. In this cohort study over an 8-year period the clinical and biometrical long-term results after restoration of nasal tip support with an autologous auricular cartilage graft, the I-Beam technique, is evaluated. Out of the 72 consecutive septorhinoplasties with the I-Beam technique, we studied 66 patients in the median long-term follow-up of 89 months. In all patients a significant improvement in nasal tip projection was found. A functional improvement in nasal breathing was achieved in 86%. The overall satisfaction with the I-Beam graft was of 83%. No deterioration in smell perception was found after surgery. The I-Beam technique using back-to-back sutured autologous auricular cartilage is a safe and effective technique and gives long-term structural support and enhances tip projection.


Chimpanzee Coordination and Potential Communication in a Two-touchscreen Turn-taking Game.
Recent years have seen a growing interest in the question of whether and how groups of nonhuman primates coordinate their behaviors for mutual benefit. On the one hand, it has been shown that chimpanzees in the wild and in captivity can solve various coordination problems. On the other hand, evidence of communication in the context of coordination problems is scarce. Here, we investigated how pairs of chimpanzees (Pan troglodytes) solved a problem of dynamically coordinating their actions for achieving a joint goal. We presented five pairs of chimpanzees with a turn-taking coordination game, where the task was to send a virtual target from one computer display to another using two touch-screens. During the joint practice of the game some subjects exhibited spontaneous gesturing. To address the question whether these gestures were produced to sustain coordination, we introduced a joint test condition in which we simulated a coordination break-down scenario: subjects appeared either unwilling or unable to return the target to their partner. The frequency of gesturing was significantly higher in these test trials than in the regular trials. Our results suggest that at least in some contexts chimpanzees can exhibit communicative behaviors to sustain coordination in joint action.


SEROUS MACULAR DETACHMENT IN BEST DISEASE: A Masquerade Syndrome.
To describe the clinical and multimodal imaging findings of a series of cases of serous macular detachment (SMD) caused by Best disease (BD) masquerading as neovascular age-related macular degeneration or central serous chorioretinopathy that were inappropriately treated with intravitreal anti-vascular endothelial growth factor or laser therapy. This study will also present data to support age-related progressive choroidal thickening in BD patients, which may play a role in the development of SMD in this population. Clinical examination and multimodal imaging findings, including color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography-angiography, were reviewed and analyzed. Subfoveal choroidal thickness was also formally measured, and an age-related choroidal thickness analysis was performed and compared with a normal population. Twenty-six eyes of 13 patients (5 women) were included. Median age was 44 years. Nine patients presented with a history of SMD and subretinal fluid recalcitrant to various therapies, including intravitreal anti-vascular endothelial growth factor injections and photodynamic therapy. Best disease was subsequently diagnosed genetically in six patients and by detailed family history in seven. Mean logarithm of the minimum angle of resolution best-corrected visual acuity for all 26 eyes at last follow-up was +0.36 (Snellen equivalent of 20/46). Subfoveal choroidal thickness positively correlated with age for our cohort, increasing linearly at a rate of 25.6 µm per decade (R = 0.64; P < 0.001). Choroidal neovascularization was identified in four eyes on optical coherence tomography angiography, but these eyes did not respond to anti-vascular endothelial growth factor treatment. The diagnosis of BD should be considered in patients presenting with SMD and recalcitrant subretinal fluid masquerading as neovascular age-related macular degeneration or chronic central serous chorioretinopathy to avoid unnecessary treatment procedures. The positive correlation of subfoveal choroidal thickness with age in BD patients may be a factor in the pathogenesis and development of SMD in this population. Recognizing the multimodal imaging features of SMD associated with BD, described in detail in this study, will guide practitioners to the accurate diagnosis of BD and reduce the risk of unnecessary intraocular procedures with potential complications.


Preselectable Optical Fingerprints of Heterogeneous Upconversion Nanoparticles.
The control in optical uniformity of single nanoparticles and tuning their diversity in multiple dimensions, dot to dot, holds the key to unlocking nanoscale applications. Here we report that the entire lifetime profile of the single upconversion nanoparticle (τ2 profile) can be resolved by confocal, wide-field, and super-resolution microscopy techniques. The advances in both spatial and temporal resolutions push the limit of optical multiplexing from microscale to nanoscale. We further demonstrate that the time-domain optical fingerprints can be created by utilizing nanophotonic upconversion schemes, including interfacial energy migration, concentration dependency, energy transfer, and isolation of surface quenchers. We exemplify that three multiple dimensions, including the excitation wavelength, emission color, and τ2 profile, can be built into the nanoscale derivative τ2-dots. Creating a vast library of individually preselectable nanotags opens up a new horizon for diverse applications, spanning from sub-diffraction-limit data storage to high-throughput single-molecule digital assays and super-resolution imaging.


Magnetic resonance imaging in the evaluation of tibial eminence fractures in adults.
Proton density and T2-weighted sagittal, axial, coronal, and inversion recovery fat suppression magnetic resonance imaging (MRI) sequences were reviewed in 21 adults (10 men and 11 women) with 22 tibial eminence fractures. Average patient age was 43 years (range: 19-62 years). There were 3 type I, 3 type II, 12 type III, and 4 type IV fractures. The average fracture fragment size was 21 x 23 mm, and the average displacement was 5.5 mm (range: 0-12 mm). The MRI disclosed anterior cruciate ligament (ACL) insertional avulsions in 20 (91%), distal posterior cruciate ligament (PCL) avulsions in 4 (18%), intrasubstance ACL damage in 9 (41%), intrasubstance PCL injury in 3 (14%), medial collateral ligament (MCL) tears in 9 (41%) knees, retinacular injury in 8 (36%), posterolateral corner damage in 8 (36%), medial meniscal tears in 5 (23%), and 4 (18%) had lateral meniscal tears. Occult subchondral osseous injuries were seen in the posterolateral tibial plateau in 13 (59%) knees, anterolateral femoral condyle in 4 (18%), and posteromedial tibial plateau in 5 (23%) knees. Discrete osteochondral fractures were present in 7 (32%) knees. Significant osseous, cartilaginous, meniscal, and ligamentous damage was discovered in all patients. Based on these findings, we recommend MRI evaluation of all tibial eminence fractures to accurately detect all knee damage.


Novel therapeutic targets for allergic airway disease in children.
The aim of precision medicine is setting up targeted therapies for selected patients that would ideally have high effectiveness and few side effects. This is made possible by targeted therapy drugs that selectively act on a specific pathway. Precision medicine is spreading to many medical specialties, and there is increasing interest in the context of allergic airway diseases, such as allergic rhinitis, chronic rhinosinusitis, and asthma. This review is an update of new targets in the treatment of childhood allergic upper airway diseases and asthma, including the most recent biologic drugs that have already been licensed or are in the pipeline to be tested with children.


Pre-verbal Children's Participation in a New Key. How Intersubjectivity Can Contribute to Understanding and Implementation of Child Rights in Early Childhood.
Children's participation and involvement has increasingly been on the agenda for the last few decades. The right for children to participate was established in the United Nations Convention on the Rights of the Child (UNCRC). However, even though the UNCRC gives the right to participate to all children, national policy and practice seems to draw a line on verbal language and exclude pre-verbal infants from participation. The spur of this paper is to challenge the exclusion of infants, to describe how pre-linguistic children communicate their intentions, and to show how an understanding of children's participation grounded in intersubjectivity, can inform and reframe the participation of all children as being fundamentally about close relationships with sensitive and containing adults who look within themselves for the voice of the child. The infant's proto-conversational narrative communicates interests and feelings through sympathetic rhythms of what infant researchers have named "communicative musicality," and it can surface in the mother's narrative about the child and their relationship. Intersubjectivity oppose the monadic view of man as separate and left only to imitate others and claims that humans from the very start are intertwined in a fundamental thirdness of co-created reality. Infants are powerful communicators who actively engage in intersubjective relationships with their caretakers only days after birth, and newborns actively influence and even control the mental process of those who communicate with them. Early childhood participation then, would be to find within ourselves the voice of the child. A research project building on the theories and ideas described in the first part of the article, is presented.


Establishing linear-free-energy relationships for the quadricyclane-to-norbornadiene reaction.
The kinetics of the thermal quadricyclane-to-norbornadiene (QC-to-NBD) isomerization reaction was studied for a large selection of derivatives where the one NBD double bond contains a cyano and aryl substituent of either electron-withdrawing or -donating character. While the kinetics data did not satisfy a linear-free-energy-relationship for all the derivatives based on Hammett σ values, we found individual linear relationships for derivatives containing either electron-withdrawing or electron-donating para substituents on the aryl group; with the most electron-witdrawing substituent in the one series and with the most electron-donating substituent in the other providing the fastest reaction (corresponding to opposite slopes of the Hammett plots). All data were well described, however, by a linear relationship when using Creary radical values; the correlation could be slightly improved by using a combination of σ and values (used in ratio of 0.104 : 1). The results imply a combination of polar and free radical effects for the isomerization reaction of this specific class of derivatives, with the latter playing the most significant role. The NBD derivatives were prepared by Diels-Alder cycloaddition reactions between cyclopentadiene and 3-arylpropiolonitriles, and in the case of bromophenyl derivatives further cyanation and Sonogashira coupling reactions were performed.


Evaluating Origin-Destination Matrices Obtained from CDR Data.
Understanding and correctly modeling urban mobility is a crucial issue for the development of smart cities. The estimation of individual trips from mobile phone positioning data (i.e., call detail records (CDR)) can naturally support urban and transport studies as well as marketing applications. Individual trips are often aggregated in an origin-destination (OD) matrix counting the number of trips from a given origin to a given destination. In the literature dealing with CDR data there are two main approaches to extract OD matrices from such data: (a) in time-based matrices, the analysis focuses on estimating mobility directly from a sequence of CDRs; (b) in routine-based matrices (OD by purpose) the analysis focuses on routine kind of movements, like home-work commute, derived from a trip generation model. In both cases, the OD matrix measured by CDR counts is scaled to match the actual number of people moving in the area, and projected to the road network to estimate actual flows on the streets. In this paper, we describe prototypical approaches to estimate OD matrices, describe an actual implementation, and present a number of experiments to evaluate the results from multiple perspectives.


Detection of novel viruses in porcine fecal samples from China.
Pigs are well known source of human infectious disease. To better understand the spectrum of viruses present in pigs, we utilized the 454 Life Sciences GS-FLX high-throughput sequencing platform to sequence stool samples from healthy pigs. Total nucleic acid was extracted from stool samples of healthy piglets and randomly amplified. The amplified materials were pooled and processed using a high-throughput pyrosequencing technique. The raw sequences were deconvoluted on the basis of the barcode and then processed through a standardized bioinformatics pipeline. The unique reads (348, 70 and 13) had limited similarity to known astroviruses, bocaviruses and parechoviruses. Specific primers were synthesized to assess the prevalence of the viruses in healthy piglets. Our results indicate extremely high rates of positivity. Several novel astroviruses, bocaviruses and Ljungan-like viruses were identified in stool samples from healthy pigs. The rates of isolation for the new viruses were high. The high detection rate, diverse sequences and categories indicate that pigs are well-established reservoirs for and likely sources of different enteric viruses.


The US Agency for Healthcare Research and Quality's activities in patient safety research.
To update the international community on the US Agency for Healthcare Research and Quality's (AHRQ) recent and current activities in improving patient safety. Review of the literature concerning the importance of patient safety as a health care quality issue, international perspectives on patient safety, a review of research solicitations, and early results of funded studies. A representative sample of patient safety studies from those currently being funded by AHRQ. In response to a growing interest in patient safety in general and a recent US Institute of Medicine report on patient safety in particular, the US Agency for Healthcare Research and Quality has refocused its quality research mission. In the fiscal year 2002, AHRQ spent US$55 million on patient safety research. This investment was spread across six complementary research areas: (1) health systems error reporting, analysis, and safety improvement research demonstrations; (2) Clinical Informatics to Promote Patient Safety (CLIPS); (3) Centers of Excellence for patient safety research and practice (COE); (4) Developmental Centers for Evaluation and Research in Patient Safety (DCERPS); (5) The Effect of Health Care Working Conditions on Quality of Care; and (6) Partnerships for Quality: Patient Safety Research Dissemination and Education. Internal teams of researchers at AHRQ have published studies on patient safety, such as documenting the impact of medication errors. In addition to funding research on patient safety, AHRQ is an integral partner in several national and international collaborations to form strategic synergies that build upon each member organization's strengths, reduce redundant efforts, and benefit from each other's successes. As evidence on patient safety is generated, AHRQ also serves the important mission of disseminating information to the public. The patient safety research field has undergone a period of rapid evolution. It is now incumbent upon the international health care quality improvement community to translate the future results of this research investment into improved safety for patients.


Corrigendum to: Australians' understanding of the decline in fertility with increasing age and attitudes towards ovarian reserve screening.
The aim of this study is to determine Australians' understanding of the decline in fertility with age, social determinants that influence their decision to start a family and attitudes towards ovarian reserve screening as a tool allowing personalised reproductive life planning. An online survey of 383 childless Australian men and women, aged 18-45 years, was conducted. Both sexes overestimated natural and in vitro fertilization (IVF)-assisted fertility potential with increasing age, with the magnitude of overestimation being more pronounced for men and IVF treatment compared with natural conception. The primary determinants for starting a family were a stable relationship, followed by establishment of career; availability of accessible child care and paid parental leave were considered less important. Finally, the majority of women (74%) would alter their reproductive life planning if they were identified as having low ovarian reserve on screening. Despite increased education, Australians continue to have a poor understanding of age-related decline in natural and IVF-assisted conception, potentially explaining why many delay starting a family. Ovarian reserve screening may help identify individuals at increased risk of premature diminished fertility, giving these women the ability to bring forward their plans for natural conception or undertake fertility preservation (oocyte freezing).


AHRA survey. Job content and salary survey. Part III: Chief technologist.
In October, 1993, the AHRA surveyed its members on the scope of their jobs, as well as their salaries, benefits and raises. Data was collected on facility demographics, member characteristics, areas of responsibility, volume of procedures performed, number of full-time equivalent (FTE) personnel supervised, and operating budget. The relationship of these factors to salary was investigated. Part I (Radiology Management 16.2, spring, 1994) presented general demographic information and average salary for administrative directors of radiology in hospitals and nonhospitals. Part II (Radiology Management 16.3, summer, 1994) presented information about job content for administrative directors of radiology and compared the results to previous AHRA job content and salary surveys. Part III presents information about demographics, job content and average salary for chief technologists in hospitals and nonhospitals. One hundred and fourteen chief technologists working in hospitals and 16 working in nonhospital facilities responded to the survey. It is important to remember the small number of nonhospital respondents when reviewing the results. Fifty-eight percent of hospital and 56% of nonhospital chief technologists report no change in their benefits package in the past 12 months. Eighty-three percent of respondents from hospitals and 81% from nonhospitals received a salary increase in the past 12 months. The average salary increase was 5% in hospitals and 4% in nonhospitals. Average salary is reported as a function of several variables, which may be interdependent. In hospitals, the average chief technologist's salary is $45,838. In nonhospitals, the average salary is $42,562, 7% lower than for hospitals.


Effect of reducing ultraprocessed food consumption on obesity among US children and adolescents aged 7-18 years: evidence from a simulation model.
Children and adolescents in the USA consume large amounts of daily calories from ultraprocessed foods (UPFs). Recent evidence links UPF consumption to increased body fat in youth. We aimed to estimate the potential impact of reducing UPF consumption on childhood obesity rate in the USA. We developed a microsimulation model to project the effect of reducing UPF consumption in children's diet on reducing the prevalence of overweight or obesity among US youth. The model incorporated nationally representative data on body mass index (BMI) percentile and dietary intake of 5804 children and adolescents aged 7-18 years from the National Health and Nutrition Examination Survey 2011-2016, and the effect of reducing UPF consumption on calorie intake from a recent randomised controlled trial. Uncertainties of model inputs were incorporated using probabilistic sensitivity analysis with 1000 simulations. Reducing UPFs in children's diet was estimated to result in a median of -2.09 kg/m2 (95% uncertainty interval -3.21 to -0.80) reduction in BMI among children and adolescents aged 7-18 years. The median prevalence of overweight (BMI percentile ≥85th) and obesity (BMI percentile ≥95th percentile) was reduced from 37.0% (35.9%, 38.1%) to 20.9% (15.1%, 29.9%) and from 20.1% (19.2%, 21.0%) to 11.0% (7.86%, 15.8%), respectively. Larger BMI and weight reductions were seen among boys than girls, adolescents than children, non-Hispanic black and Hispanic youth than non-Hispanic white youth, and those with lower levels of parental education and family income. Reducing UPF consumption in children's diet has the potential to substantially reduce childhood obesity rate among children and adolescents in the USA.


On-line detection of heavy metals and brominated flame retardants in technical polymers with laser-induced breakdown spectrometry.
The use of laser-induced breakdown spectrometry (LIBS) for the analysis of heavy metals and brominated flame retardants in end-of-life waste electric and electronic equipment (EOL-WEEE) pieces is investigated. Single- and double-pulse plasma excitation as well as the influence of detection parameters is studied to yield a parameter field with improved sensitivity and limits of detection. A LIBS analyzer was set up as an on-line measuring unit to detect heavy metals and brominated flame retardants in moving EOL-WEEE pieces in an automatic sorting line. An autofocusing unit with an adjustment range of 50 mm was incorporated to permit measurements of objects that pass by a LIBS analyzer with their surfaces at various distances from it. Tests with EOL-WEEE monitor housings on the conveyor belt of a pilot sorting system successfully demonstrated the capability of the LIBS analyzer to quantify the concentration of hazardous elements in real waste EOL-WEEE pieces.


Associations between School-Behavior-Health Difficulties and Subsequent Injuries among Younger Adolescents: A Population-based Study.
ObjectiveSchool-behavior-health difficulties (SBHDs) may alter physical/mental capabilities and consequently increase injury risk during daily activities. This study assessed the associations of potential SBHDs and their cumulative number (SBHDcn) with various injury types among younger adolescents. Methods: The study population included 1,559 middle-school adolescents in France (10-18 years, 98% under 16,778 boys and 781 girls). They completed a questionnaire at school-year end collecting socioeconomic features (nationality, family structure, parents' education/occupation/income), school/out-of-school injuries during the school-year (dependent variables), and SBHDs starting before the school-year (low academic performance, alcohol/tobacco/cannabis/other-illicit-drugs use, physical/verbal violence, sexual abuse, perpetrated violence, poor social support, poor general health status, sleep difficulty, depressive symptoms, and suicide attempt). Data were analyzed using logistic regression models and Kaplan-Meier estimates. Results: Injuries were frequent during school-physical/sports-training (10.9%), other-school-training (4.7%), school-free-time (7.4%), out-of-school-sports-activity (16.5%), and traffic (2.2%). Single injury (one injury all injury types combined) and ≥2 injury types affected 23.3 and 7.9% of subjects, respectively. The proportion of adolescents without SBHDs decreased with age more quickly among those with each injury type than among those without injury. Various SBHDs were associated with most injury types, single injury, and ≥2 injury types (sex-age-adjusted odds/relative-risk ratios reaching 11, p < .001). A dose-effect association was found between SBHDcn 1-2/3-5/≥6 and both single injury and ≥2 injury types (sex-age adjusted relative risk ratios reaching 12.66, p < .001, vs. SBHDcn = 0). Socioeconomic features had a moderate confounding role in these associations. Conclusions: SBHDs strongly predict injuries among adolescents. Our findings may inform healthcare providers about their prominent role in detecting/reducing SBHDs and injuries.


Correction of technical bias in clinical microarray data improves concordance with known biological information.
The performance of gene expression microarrays has been well characterized using controlled reference samples, but the performance on clinical samples remains less clear. We identified sources of technical bias affecting many genes in concert, thus causing spurious correlations in clinical data sets and false associations between genes and clinical variables. We developed a method to correct for technical bias in clinical microarray data, which increased concordance with known biological relationships in multiple data sets.


Association of Two Polymorphisms, rs1061170 and rs1410996, in Complement Factor H with Age-Related Macular Degeneration in an Asian Population: A Meta-Analysis.
With the increasing number of studies indicating that two single-nucleotide polymorphisms (SNPs), rs1061170 and rs1410996, in complement factor H (CFH) might be associated with the susceptibility to age-related macular degeneration (AMD), the exact association still remains uncertain. Thus, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and the AMD risk particularly in an Asian population. A systematic search of studies on the association of two SNPs with the susceptibility to AMD was conducted in PubMed, Embase and Web of Science. Summary odds ratios (ORs) and 95% confidence intervals (CIs) of allele contrast and genotype contrast were estimated using the random or fixed effects model. The Q statistic test was used to identify heterogeneity, and the funnel plot was adopted to evaluate publication bias. A total of 19 case-control studies on rs1061170 and 8 studies on rs1410996 were included. Clearly a significantly increased trend of AMD was observed with the rs1061170 (T vs. C: OR = 1.91, 95% CI = 1.71-2.13, pH = 0.029; TC vs. CC: OR = 2.11, 95% CI = 1.30-3.42, pH = 0.792; TT vs. CC: OR = 3.90, 95% CI = 2.45-6.22, pH = 0.774). Similarly, the rs1410996 polymorphism also showed a rising AMD tendency (T vs. C: OR = 1.48, 95% CI = 1.17-1.87, pH < 0.001; TC vs. CC: OR = 1.52, 95% CI = 1.13-2.04, pH = 0.002; TT vs. CC: OR = 2.10, 95% CI = 1.27-3.49, pH < 0.001). What is more, subgroup analysis revealed that both polymorphisms indicated a high risk of nAMD (neovascular AMD) in Asian populations. This meta-analysis suggested that CFH rs1061170 and rs1410996 polymorphisms were associated with AMD risk, both of which demonstrated a higher susceptibility to AMD, especially to nAMD. However, the results of rs1410996 should be interpreted with caution due to the limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.


Telomerase immortalization of human neural progenitor cells.
It is necessary to expand human neural progenitor cells in vitro to obtain large numbers for research purposes and cell transplantation. A potential obstacle to in vitro expansion, however, is that neural progenitor cells have a limited replication life-span and gradually lose their differentiation potential. We report here that ectopic expression of the catalytic subunit of human telomerase (hTERT) gene in neural progenitor cells could induce telomerase activity, stabilize telomeres and extend their replicative life-spans. The telomerase-immortalized cells (hNPC-TERT) maintained the normal diploid karyotype, expressed the markers of human neural progenitor cells and meanwhile held the differentiation potential in vitro for up to 120 population doublings. This study provides a new approach for obtaining unlimited quantities of normal phenotypic and homogeneous human neural progenitor cells in vitro.


Real-time glucose sensors in children and adolescents with type-1 diabetes.
The increased availability of continuous glucose sensors is likely to have a significant impact on pediatric diabetes therapy and education in the future. While a recent meta-analysis of retrospective first-generation Holter-type sensors was not able to show advantages compared to self-monitoring of blood glucose levels, this review focuses on current real-time sensors. Our own experience with 23 children aged 10 (3-15) years with sensor-augmented pump therapy showed high ratings for overall satisfaction and ease of use of the system (5.8 on a 7 point Likert scale). The results of our ongoing international pediatric ONSET trial will show the impact of this technology on learning to live with diabetes by having the biofeedback of glucose excursions from the onset of diabetes. Families previously relying on self-monitoring of blood glucose need to understand the difference between estimating the absolute blood glucose value (point accuracy) and the change in blood glucose (rate accuracy), and how to take into consideration the inherent interstitial time lag. Selection of patients capable and motivated to use continuous sensors accompanied with proper age-appropriate education remain key factors for the long-term success of these new technological advances in diabetes therapy as long as closed loop systems are not available.


Three-dimensional magnetic resonance imaging of physeal injury: reliability and clinical utility.
Injuries to the physis are common in children with a subset resulting in an osseous bar and potential growth disturbance. Magnetic resonance imaging allows for detailed assessment of the physis with the ability to generate 3-dimensional physeal models from volumetric data. The purpose of this study was to assess the interrater reliability of physeal bar area measurements generated using a validated semiautomated segmentation technique and to highlight the clinical utility of quantitative 3-dimensional (3D) physeal mapping in pediatric orthopaedic practice. The Radiology Information System/Picture Archiving Communication System (PACS) at our institution was searched to find consecutive patients who were imaged for the purpose of assessing a physeal bar or growth disturbance between December 2006 and October 2011. Physeal segmentation was retrospectively performed by 2 independent operators using semiautomated software to generate physeal maps and bar area measurements from 3-dimensional spoiled gradient recalled echo sequences. Inter-reliability was statistically analyzed. Subsequent surgical management for each patient was recorded from the patient notes and surgical records. We analyzed 24 patients (12M/12F) with a mean age of 11.4 years (range, 5-year to 15-year olds) and 25 physeal bars. Of the physeal bars: 9 (36%) were located in the distal tibia; 8 (32%) in the proximal tibia; 5 (20%) in the distal femur; 1 (4%) in the proximal femur; 1 (4%) in the proximal humerus; and 1 (4%) in the distal radius. The independent operator measurements of physeal bar area were highly correlated with a Pearson correlation coefficient (r) of 0.96 and an intraclass correlation coefficient for average measures of 0.99 (95% confidence interval, 0.97-0.99). Four patients underwent resection of the identified physeal bars, 9 patients were treated with epiphysiodesis, and 1 patient underwent bilateral tibial osteotomies. Semiautomated segmentation of the physis is a reproducible technique for generating physeal maps and accurately measuring physeal bars, providing quantitative and anatomic information that may inform surgical management and prognosis in patients with physeal injury. Level IV.


Stress fracture of the eighth rib in a female collegiate rower: a case report.
To present the case of a stress fracture of the eighth rib in a female collegiate rower. A female collegiate rower experienced severe pain in her chest, increasing with movement, deep breathing, and erect posture. No acute mechanism of injury was apparent. The team physician diagnosed a rib stress reaction based on clinical examination. The athlete rested for 2 days and then was able to resume rowing workouts. Five months later, she experienced the same sharp pain, with the diagnosis and treatment being the same. The athlete was able to compete in the championships 3 weeks later. At the end of the season, a bone scan revealed a stress fracture of the eighth rib. The athlete rested for 3 weeks and then returned to activity. Intercostal muscle strain, serratus anterior muscle strain. Active rest, involving pain-free cardiovascular workouts and weight training, cessation of rowing until the athlete was asymptomatic, strengthening of dynamic support structures, and analgesic modalities. Most stress fractures occur in the lower extremity. Those that do occur in the rib cage most often involve the first rib. A limited number of published works have addressed stress fractures to the remaining ribs; of these, posterior and posterolateral fracture sites are most often reported. This case is unique in that the fracture site was on the anterolateral aspect of the eighth rib. Stress fractures are thought to result from a variety of causes, including muscular fatigue, sudden changes in training intensity or duration, and microtrauma to bone at the muscular origin and insertion sites ("wear-and- tear" theory). In addition, hormonal factors in women can predispose an athlete with amenorrhea to a decrease in bone mineral content. Athletic trainers should be aware of these potential causes and focus on the prevention of stress fractures.


A novel route to cyclic dominance in voluntary social dilemmas.
Cooperation is the backbone of modern human societies, making it a priority to understand how successful cooperation-sustaining mechanisms operate. Cyclic dominance, a non-transitive set-up comprising at least three strategies wherein the first strategy overrules the second, which overrules the third, which, in turn, overrules the first strategy, is known to maintain biodiversity, drive competition between bacterial strains, and preserve cooperation in social dilemmas. Here, we present a novel route to cyclic dominance in voluntary social dilemmas by adding to the traditional mix of cooperators, defectors and loners, a fourth player type, risk-averse hedgers, who enact tit-for-tat upon paying a hedging cost to avoid being exploited. When this cost is sufficiently small, cooperators, defectors and hedgers enter a loop of cyclic dominance that preserves cooperation even under the most adverse conditions. By contrast, when the hedging cost is large, hedgers disappear, consequently reverting to the traditional interplay of cooperators, defectors, and loners. In the interim region of hedging costs, complex evolutionary dynamics ensues, prompting transitions between states with two, three or four competing strategies. Our results thus reveal that voluntary participation is but one pathway to sustained cooperation via cyclic dominance.


Mealtime Environment and Feeding Practices in Urban Family Child Care Homes in the United States.
Background: Family Child Care Homes (FCCHs) are the second-largest childcare option in the US. Given that young children are increasingly becoming overweight and obese, it is vital to understand the FCCH mealtime environment. There is much interest in examining the impact of the Child and Adult Care Food Program (CACFP), a federal initiative to support healthy nutrition, by providing cash reimbursements to eligible childcare providers to purchase nutritious foods. This study examines the association among the FCCH provider characteristics, the mealtime environment, and the quality of foods offered to 2-5-year-old children in urban FCCHs and examines the quality of the mealtime environment and foods offered by CACFP participation. Methods: A cross-sectional design with a proportionate stratified random sample of urban FCCHs by the CACFP participation status was used. Data were collected by telephone using the Nutrition and Physical Activity Self-Assessment for Child Care survey. Results: A total of 91 licensed FCCHs (69 CACFP, 22 non-CACFP) participated. FCCH providers with formal nutrition training met significantly more of the quality standards for foods offered than providers without nutrition training (β = 0.22, p = 0.034). The mealtime environment was not related to any FCCH provider characteristics. CACFP-participating FCCH providers had a healthier mealtime environment (β = 0.326, p = 0.002) than non-CACFP FCCHs. Conclusions: Findings suggest that nutrition training and CACFP participation contribute to the quality of nutrition-related practices in the FCCH. We recommend more research on strengthening the quality of foods provided in FCCHs and the possible impact on childhood obesity.


Quantification of Hand Motor Symptoms in Parkinson's Disease: A Proof-of-Principle Study Using Inertial and Force Sensors.
This proof-of-principle study describes the methodology and explores and demonstrates the applicability of a system, existing of miniature inertial sensors on the hand and a separate force sensor, to objectively quantify hand motor symptoms in patients with Parkinson's disease (PD) in a clinical setting (off- and on-medication condition). Four PD patients were measured in off- and on- dopaminergic medication condition. Finger tapping, rapid hand opening/closing, hand pro/supination, tremor during rest, mental task and kinetic task, and wrist rigidity movements were measured with the system (called the PowerGlove). To demonstrate applicability, various outcome parameters of measured hand motor symptoms of the patients in off- vs. on-medication condition are presented. The methodology described and results presented show applicability of the PowerGlove in a clinical research setting, to objectively quantify hand bradykinesia, tremor and rigidity in PD patients, using a single system. The PowerGlove measured a difference in off- vs. on-medication condition in all tasks in the presented patients with most of its outcome parameters. Further study into the validity and reliability of the outcome parameters is required in a larger cohort of patients, to arrive at an optimal set of parameters that can assist in clinical evaluation and decision-making.


Altered placental structure induced by maternal food restriction in guinea pigs: a role for circulating IGF-II and IGFBP-2 in the mother?
Maternal feed restriction may restrict fetal growth in part indirectly by impairing placental functional development. Such actions could be mediated by the insulin-like growth factors (IGF), which are important modulators of placental growth and differentiation and more generally, are influenced by nutrient availability. While a role for the fetal IGF axis has been demonstrated, less is known of the influence, if any, of that in the mother. This study aimed to determine whether alterations in the maternal IGF axis and placental functional and structural development due to maternal food restriction are related. We therefore examined the associations between placental structural parameters, the ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea concentration, and maternal circulating IGF-I, IGF-II and IGFBP-2 in ad libitum fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea pigs. In mid-gestation, fetal weight (r = 0.65, P = 0.008, n = 17), volume of the maternal blood space (r = 0.58, P = 0.048, n = 17), and surface density of syncytiotrophoblast (r = 0.65, P = 0.023, n = 17), were positively correlated, and syncytiotrophoblast thickness was negatively correlated, with maternal plasma IGF-II concentration (r = -0.69, P = 0.014, n = 17). Late in gestation, fetal weight, placental weight and total exchange surface area in the placenta were each negatively correlated with maternal plasma IGFBP-2 concentration (all P < 0.01), while the arithmetic mean thickness of syncytiotrophoblast was positively correlated with maternal plasma IGFBP-2 concentration. Late in gestation, the ratio of maternal to fetal plasma glucose was positively correlated with fetal weight (r = 0.54, P = 0.038, n = 15) and the ratio of fetal to maternal plasma urea concentration was positively correlated with placental weight (r = 0.52, P=0.046, n=15). Maternal feed restriction reduced the ratio of maternal plasma IGF-II to IGFBP-2 in late gestation by 75 per cent (P = 0.001) and this ratio was positively correlated with fetal weight (r = 0.56, P = 0.01, n = 20), placental weight (r = 0.59, P = 0.006), placental diameter (r = 0.621, P = 0.003), placental volume (r = 0.57, P=0.009), weight of trophoblast (r = 0.51, P=0.037), weight of fetal capillaries (r = 0.49, P = 0.046), syncytiotrophoblast surface density (r = 0.611, P = 0.009) and negatively correlated with syncytiotrophoblast thickness (r = -0.55, P = 0.021). Our results suggest that in mid-pregnancy, maternal circulating IGF-II promotes placental structural development, while later in pregnancy, IGFBP-2 inhibits it, and their relative abundance and interaction strongly influences placental structure and function near term.


Neuroprotective Properties of the Standardized Extract from Camellia sinensis (Green Tea) and Its Main Bioactive Components, Epicatechin and Epigallocatechin Gallate, in the 6-OHDA Model of Parkinson's Disease.
Camellia sinensis (green tea) is largely consumed, mainly in Asia. It possesses several biological effects such as antioxidant and anti-inflammatory properties. The objectives were to investigate the neuroprotective actions of the standardized extract (CS), epicatechin (EC) and epigallocatechin gallate (EGCG), on a model of Parkinson's disease. Male Wistar rats were divided into SO (sham-operated controls), untreated 6-OHDA-lesioned and 6-OHDA-lesioned treated for 2 weeks with CS (25, 50, or 100 mg/kg), EC (10 mg/kg), or EGCG (10 mg/kg) groups. One hour after the last administration, animals were submitted to behavioral tests and euthanized and their striata and hippocampi were dissected for neurochemical (DA, DOPAC, and HVA) and antioxidant activity determinations, as well as immunohistochemistry evaluations (TH, COX-2, and iNOS). The results showed that CS and catechins reverted behavioral changes, indicating neuroprotection manifested as decreased rotational behavior, increased locomotor activity, antidepressive effects, and improvement of cognitive dysfunction, as compared to the untreated 6-OHDA-lesioned group. Besides, CS, EP, and EGCG reversed the striatal oxidative stress and immunohistochemistry alterations. These results show that the neuroprotective effects of CS and its catechins are probably and in great part due to its powerful antioxidant and anti-inflammatory properties, pointing out their potential for the prevention and treatment of PD.


The roles of conserved amino acids on substrate binding and conformational integrity of ClpB N-terminal domain.
Escherichia coli heat shock protein ClpB disaggregates denatured protein in cooperation with the DnaK chaperone system. Several studies showed that the N-terminal domain is essential for the chaperone activity, but its role is still largely unknown. The N-terminal domain contains two structurally similar subdomains, and conserved amino acids Thr7 and Ser84 share the same position in two apparent sequence repeats. T7A and S84A substitutions affected chaperone activity of ClpB without significantly changing the native conformation [Liu, Z. et al. (2002) J. Mol. Biol. 321, 111-120]. In this study, we aimed to better understand the roles of several conserved amino acid residues, including Thr7 and Ser84, in the N-terminal domain. We investigated the effects of mutagenesis on substrate binding and conformational states of ClpB N-terminal domain fragment (ClpBN). Fluorescence polarization analysis showed that the T7A and S84A substitutions enhanced the interaction between ClpBN and protein aggregates. Interestingly, further analyses suggested that the mechanisms by which they do so are quite different. For T7A substitution, the increased substrate affinity could be due to a conformational change in the hydrophobic core as revealed by NMR spectroscopy. In contrast, for S84A, increased substrate binding would be explained by a unique conformational state of this mutant as revealed by pressure perturbation analysis. The thermal transition temperature of the S84A mutant, monitored by DSC, was 6.1 degrees C lower than that of wild-type. Our results revealed that conserved amino acids Thr7 and Ser84 both participated in maintaining the conformational integrity of the ClpB N-terminal domain.


Water availability as an agent of selection in introduced populations of Arabidopsis thaliana: impacts on flowering time evolution.
Flowering is one of the most influential events in the life history of a plant and one of the main determinants of reproductive investment and lifetime fitness. It is also a highly complex trait controlled by dozens of genes. Understanding the selective pressures influencing time to flowering, and being able to reliably predict how it will evolve in novel environments, are unsolved challenges for plant evolutionary geneticists. Using the model plant species, Arabidopsis thaliana, we examined the impact of simulated high and low winter precipitation levels on the flowering time of naturalized lines from across the eastern portion of the introduced North American range, and the fitness consequences of early versus late flowering. Flowering time order was significantly correlated across two environments-in a previous common garden experiment and in environmental chambers set to mimic mid-range photoperiod and temperature conditions. Plants in low water flowered earlier, had fewer basal branches and produced fewer fruits. Selection in both treatments favored earlier flowering and more basal branches. Our analyses revealed an interaction between flowering time and water treatment for fitness, where flowering later was more deleterious for fitness in the low water treatment. Our results are consistent with the hypothesis that differences in winter precipitation levels are one of the selective agents underlying a flowering time cline in introduced A. thaliana populations.


Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex.
The rational design of a well-defined protein-like tertiary structure formed by small peptide building blocks is still a formidable challenge. By using peptide-oligonucleotide conjugates (POC) as building blocks, we present the self-assembly of miniature coiled-coil α-helical peptides guided by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex under physiological pH, and to be capable of templating the three peptide sequences to constitute a small coiled-coil motif displaying remarkable α-helicity. The formed trimeric complex was characterized by ultraviolet thermal denaturation, gel electrophoresis, circular dichroism (CD) spectroscopy, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12 nm) in solution was revealed to be independent of concentration. The topological folding of the peptide moiety differed strongly from those of the individual POC strands and the unconjugated peptide, exclusively adopting the designed triple helical structure.


Physiological effects of unequal alternating monocular exposure.
1. In order to investigate the effects of an imbalance in stimulation to the eyes without the confounding influence of continuous deprivation of one eye, we reared cats with unequal alternating monocular exposure (AME) and, for comparison, cats with equal AME. We recorded extracellularly from single cells in area 17 of visual cortex. 2. For unequal AME cats, a majority of the cells that were visually responsive were dominated by the eye that had received more patterned visual experience. The percentage of cells dominated by the more experienced eye was greater with a large imbalance in stimulation to the two eyes (AME 8/1, 77%) than with a small imbalance (AME 8/4, 62%). 3. For both equal AME cats and unequal AME cats, we obtained evidence for differences in cells activated by the contralateral and by the ipsilateral afferents. a) In equal AME cats receiving only 1 h of exposure per day, we obtained a greater dominance by the contralateral eye (60%) than in equal AME cats receiving 8 h of exposure per day (42%). b) Although a large imbalance in stimulation (AME 8/1) resulted in a shift in ocular dominance in both cortical hemispheres, a moderate imbalance (AME 8/4) resulted in a smaller shift, which was apparent only in the hemisphere ipsilateral to the less-experienced eye. 4. The percentage of cortical cells responsive to each eye was uniform throughout the depth of cortex. Thus, for the unequal AME cats, cells activated by the less-experienced eye were no more frequent in layer IV of visual cortex than in the infragranular and supragranular layers. 5. Although almost all cells recorded from AME cats had relatively normal receptive-field properties, three receptive-field properties of cells in unequal AME cats showed an effect of the rearing. In each case cells dominated by the less-experienced eye and recorded in the cortical hemisphere ipsilateral to it showed the largest changes. These cells a) were more poorly tuned, b) had lower cutoff velocities, and c) had smaller receptive fields. 6. It is suggested that cortical cells that putatively receive Y-cell afferents from the dorsal lateral geniculate nucleus (LGNd) are more affected by an imbalance in stimulation than are cortical cells that putatively receive X-cell afferents. Thus, the decrease in mean receptive-field area and cutoff velocity for the cells dominated by the less-experienced eye is suggested to be due to a greater shift in ocular dominance by the cortical cells receiving Y-cell afferents from the LGNd. 7. The interaction between binocular competition and deprivation of pattern vision may contribute to differences between monocularly deprived cats and unequal AME cats.


Spontaneous regression of follicular, mantle cell, and diffuse large B-cell non-Hodgkin's lymphomas detected by FDG-PET imaging.
Spontaneous regression of non-Hodgkin lymphoma (NHL) has been reported in low-grade tumors but is an extremely rare event in intermediate- and high-grade disease. Documentation of spontaneous regression by serial fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging has not been reported in the literature. We present 3 cases of spontaneous regression, 1 each of follicular lymphoma (FL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL), which showed spontaneous regression on serial FDG-PET imaging. All patients underwent serial whole-body FDG-PET scans 60 minutes after intravenous injection of 9-11 mCi of this radiotracer. None of them had any chemotherapy, radiotherapy, or surgery after the baseline PET scan. Spontaneous regression of disease in all 3 cases was correlated with conventional imaging and clinical course. All 3 patients had positive FDG-PET results on their baseline scan. There was complete disappearance of FDG uptake on a follow-up PET scan for the patient with follicular lymphoma. These results suggest complete regression. The patients with MCL and DLBCL both showed a significant reduction in FDG uptake on serial whole-body PET scans, suggesting partial regression in both cases. Although spontaneous regression of lymphoma is uncommon, this phenomenon can be successfully demonstrated by FDG-PET imaging. Therefore, serial PET imaging may play an important role in detecting this unusual event and may further enhance our understanding of the biologic behavior of this malignancy.


A cell-based screen for inhibitors of flagella-driven motility in Chlamydomonas reveals a novel modulator of ciliary length and retrograde actin flow.
Cilia are motile and sensory organelles with critical roles in physiology. Ciliary defects can cause numerous human disease symptoms including polycystic kidneys, hydrocephalus, and retinal degeneration. Despite the importance of these organelles, their assembly and function is not fully understood. The unicellular green alga Chlamydomonas reinhardtii has many advantages as a model system for studies of ciliary assembly and function. Here we describe our initial efforts to build a chemical-biology toolkit to augment the genetic tools available for studying cilia in this organism, with the goal of being able to reversibly perturb ciliary function on a rapid time-scale compared to that available with traditional genetic methods. We screened a set of 5520 compounds from which we identified four candidate compounds with reproducible effects on flagella at nontoxic doses. Three of these compounds resulted in flagellar paralysis and one induced flagellar shortening in a reversible and dose-dependent fashion, accompanied by a reduction in the speed of intraflagellar transport. This latter compound also reduced the length of cilia in mammalian cells, hence we named the compound "ciliabrevin" due to its ability to shorten cilia. This compound also robustly and reversibly inhibited microtubule movement and retrograde actin flow in Drosophila S2 cells. Ciliabrevin may prove especially useful for the study of retrograde actin flow at the leading edge of cells, as it slows the retrograde flow in a tunable dose-dependent fashion until flow completely stops at high concentrations, and these effects are quickly reversed upon washout of the drug.


Prioritization of Candidate Genes in QTL Regions for Physiological and Biochemical Traits Underlying Drought Response in Barley (Hordeum vulgare L.).
Drought is one of the most adverse abiotic factors limiting growth and productivity of crops. Among them is barley, ranked fourth cereal worldwide in terms of harvested acreage and production. Plants have evolved various mechanisms to cope with water deficit at different biological levels, but there is an enormous challenge to decipher genes responsible for particular complex phenotypic traits, in order to develop drought tolerant crops. This work presents a comprehensive approach for elucidation of molecular mechanisms of drought tolerance in barley at the seedling stage of development. The study includes mapping of QTLs for physiological and biochemical traits associated with drought tolerance on a high-density function map, projection of QTL confidence intervals on barley physical map, and the retrievement of positional candidate genes (CGs), followed by their prioritization based on Gene Ontology (GO) enrichment analysis. A total of 64 QTLs for 25 physiological and biochemical traits that describe plant water status, photosynthetic efficiency, osmoprotectant and hormone content, as well as antioxidant activity, were positioned on a consensus map, constructed using RIL populations developed from the crosses between European and Syrian genotypes. The map contained a total of 875 SNP, SSR and CGs, spanning 941.86 cM with resolution of 1.1 cM. For the first time, QTLs for ethylene, glucose, sucrose, maltose, raffinose, α-tocopherol, γ-tocotrienol content, and catalase activity, have been mapped in barley. Based on overlapping confidence intervals of QTLs, 11 hotspots were identified that enclosed more than 60% of mapped QTLs. Genetic and physical map integration allowed the identification of 1,101 positional CGs within the confidence intervals of drought response-specific QTLs. Prioritization resulted in the designation of 143 CGs, among them were genes encoding antioxidants, carboxylic acid biosynthesis enzymes, heat shock proteins, small auxin up-regulated RNAs, nitric oxide synthase, ATP sulfurylases, and proteins involved in regulation of flowering time. This global approach may be proposed for identification of new CGs that underlies QTLs responsible for complex traits.


Prevalence trends and individual patterns of antiepileptic drug use in pregnancy 2006-2016: A study in the five Nordic countries, United States, and Australia.
To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching. We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester. Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%). Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED.


Electron Donor-Acceptor Complex Enabled Radical Cyclization of α-Diazodifluoroethyl Sulfonium Salt with Unactivated Alkynes.
An α-diazodifluoroethane sulfonium reagent was developed in this study to undergo [3 + 2] radical cyclization with unactivated alkynes to give the corresponding 3-difluoromethyl pyrazoles under blue light irradiation conditions. The key to the success of this transformation lies in the formation of an electron donor-acceptor (EDA) complex between an electron-deficient α-diazo sulfonium salt and an electron-rich triaryl amine. This study circumvents a major substrate scope limitation in polar cycloaddition reactions of existent diazodifluoroethane reagents.


Lekking behavior in kafue lechwe.
The Kafue lechwe (Kobus leche kafuensis) exhibits lekking behavior in which a number of males occupy small territories clustered together in discrete areas where females go for mating. Similar behavior in antelope is known only in the Uganda kob (Kobus kob thomasi). Lechwe lekking occurs only during a main rutting season although some breeding occurs throughout the year.


Exploration of tetra-branched multiple-site SO2 capture materials.
We designed a series of tetra-branched anionic structures centered with Al for more efficient SO2 capture. By using the home-made configuration search program coupled with electronic structure calculations, we have systematically explored the large reaction space consisting of these anions, cations, and SO2 molecules. Unique insertion structures of the reaction complexes featuring a SO2 molecule inserted into a branch were found to be prevalent and sometimes to be the ground states. Cations can either enhance or compress the anion-SO2 interactions, highly depending on the anion, as they have multiple ways to interact with anions and SO2 molecules. According to the calculated sequential SO2 binding energies (with the cation effect included), [Al(Im)4]- is expected to be the best among the designed structures for reversible SO2 capture. This approach can be easily extended to design and screen sorbents for other acidic gases.


Mycobacterium cookii sp. nov.
Strains of a new type of slowly growing scotochromogenic mycobacterium were isolated repeatedly from sphagnum vegetation and surface water of moors in New Zealand. These strains grew at 31 and 22 degrees C but not at 37 degrees C and possessed catalase, acid phosphatase, and arylsulfatase activities. They did not split amides, and most of them were susceptible to antituberculotic drugs. Furthermore, they did not tolerate 0.1% NaOH2 and 0.2% picric acid and did not grow on compounds used as single carbon sources and single nitrogen and carbon sources. The internal similarity of the strains as determined by numerical taxonomy methods was 96.6% +/- 3.09%. The whole-mycolate pattern is unique in that it has not been found previously in 23 species of slowly growing mycobacteria. Evaluation of long-reverse-transcriptase-generated stretches of the primary structure of the 16S rRNA confirmed that these organisms belong to the genus Mycobacterium. The phylogenetic position of these bacteria is unique; they are situated between slowly growing pathogenic and rapidly growing saprophytic species. The strains are not pathogenic for mice, guinea pigs, and rabbits, but they provoke a nonspecific hypersensitivity reaction to bovine tuberculin. Hence, they are considered members of a new species of nonpathogenic, slowly growing mycobacteria, for which the name Mycobacterium cookii is proposed. Strain NZ2 is the type strain; a culture of this strain has been deposited in the American Type Culture Collection as strain ATCC 49103.


Muscle glycogenolysis during exercise: dual control by epinephrine and contractions.
The interaction of epinephrine and contractions on muscle metabolism was studied in the isolated perfused rat hindquarter. Subtetanic contractions (180/min) through 20 min elicited glycogenolysis and increased phosphorylase a activity. In the soleus, a slow-twitch red muscle, these effects were transient, but when epinephrine at a physiological concentration (2.4 X 10(-8) M) was added to the perfusate, glycogenolysis and phosphorylase activity were sustained throughout contractions. At this high frequency of contractions, the effect of epinephrine was much smaller in the fast-twitch red fibers and not significant in the fast-twitch white fibers of the gastrocnemius muscle. However, during less frequent contractions (30/min) epinephrine increased glycogenolysis and phosphorylase a activity in fast-twitch muscle. The data suggest that epinephrine and muscle contractions exert a dual control of muscle glycogenolysis during exercise: contractions principally stimulate glycogenolysis early in exercise, and a direct effect of epinephrine on muscle is needed for continued glycogenolysis. In addition, epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated hindquarters and, under some conditions, it had a positive inotropic effect on contracting muscle.


Providing web-based mental health services to at-risk women.
We examined the feasibility of providing web-based mental health services, including synchronous internet video conferencing of an evidence-based support/education group, to at-risk women, specifically poor lone mothers. The objectives of this study were to: (i) adapt a face-to-face support/education group intervention to a web-based format for lone mothers, and (ii) evaluate lone mothers' response to web-based services, including an online video conferencing group intervention program. Participating mothers were recruited through advertisements. To adapt the face-to-face intervention to a web-based format, we evaluated participant motivation through focus group/key informant interviews (n = 7), adapted the intervention training manual for a web-based environment and provided a computer training manual. To evaluate response to web-based services, we provided the intervention to two groups of lone mothers (n = 15). Pre-post quantitative evaluation of mood, self-esteem, social support and parenting was done. Post intervention follow up interviews explored responses to the group and to using technology to access a health service. Participants received $20 per occasion of data collection. Interviews were taped, transcribed and content analysis was used to code and interpret the data. Adherence to the intervention protocol was evaluated. Mothers participating in this project experienced multiple difficulties, including financial and mood problems. We adapted the intervention training manual for use in a web-based group environment and ensured adherence to the intervention protocol based on viewing videoconferencing group sessions and discussion with the leaders. Participant responses to the group intervention included decreased isolation, and increased knowledge and confidence in themselves and their parenting; the responses closely matched those of mothers who obtained same service in face-to-face groups. Pre-and post-group quantitative evaluations did not show significant improvements on measures, although the study was not powered to detect these. We demonstrated that an evidence-based group intervention program for lone mothers developed and evaluated in face-to-face context transferred well to an online video conferencing format both in terms of group process and outcomes.


Beta4 integrin and laminin 5 are aberrantly expressed in polycystic kidney disease: role in increased cell adhesion and migration.
Extracellular matrix alterations have been suggested to be part of the early events occurring in Autosomal Dominant Polycystic Kidney Disease (ADPKD), a disease characterized by formation of renal cysts and progressive renal failure. Here we report that cDNA array analysis identified beta(4) integrin aberrant expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main alpha(6)beta(4) integrin ligand, was also found to be abnormally expressed in ADPKD. Studies performed with ADPKD cyst-lining epithelial cells (CC) by comparison with normal tubular cells indicate that integrin alpha(6)beta(4)-Ln-5 interactions are involved in cellular events of potential importance for cystogenesis: 1) laminin 5 is a preferential adhesion substrate for CC, mainly through alpha(6)beta(4) interaction, 2) CC increased haptotactic and chemotactic motility depends on the presence of Ln-5 and requires integrin alpha(3)beta(1) cooperation, and 3) CC haptotactic or chemotactic migration is specifically increased by mAb-mediated beta(4) integrin ligation, through an alpha(3)beta(1) integrin-dependent and independent pathway, respectively. These results highlight the role of Ln-5 and alpha(6)beta(4) integrin in adhesive and motility properties of cyst-lining epithelial cells, and further suggest that integrins and extracellular matrix modifications may be of general relevance to kidney epithelial cell cyst formation.


Dyadobacter fermentans gen. nov., sp. nov., a novel gram-negative bacterium isolated from surface-sterilized Zea mays stems.
A Gram-negative bacterium, designated NS114T, was isolated from duplicate treatments of surface-sterilized Zea mays stems. The plants were grown in synthetic soil under greenhouse conditions and watered with fertilizer containing no nitrogen. Strain NS114T could not be isolated from plants watered with the standard level or 20% (w/v) of the standard level of nitrogen. Cells occurred as pairs in young cultures that attached to form angled arrangements in R2A broth and occasionally formed rounded, horseshoe arrangements in YM broth. Cell variation resulted in flocculent chains of coccoid cells in old cultures. Strain NS114T fermented glucose and sucrose. The G + C content was 48 mol%. Phylogenetic analysis of the 16S rRNA gene showed that the strain was a member of the domain Bacteria and branched from a point equidistant from an aquatic organism, Runella slithyformis and a marine isolate, 'Microscilla furvescens'. Phenotypic and genotypic analyses indicated that strain NS114T could not be assigned to any recognized genus; therefore a new genus and species, Dyadobacter fermentans gen. nov., sp. nov., is proposed, for which NS114T is the type strain.


Interobserver reliability to interpret intrapartum electronic fetal heart rate monitoring: Does a standardized algorithm improve agreement among clinicians?
Our aim was to investigate the accuracy in predicting intrapartum fetal acidaemia and the interobserver reproducibility of a mathematical algorithm for the interpretation of electronic fetal heart rate (FHR) monitoring throughout labour. Eight physicians (blinded to the clinical outcomes of the deliveries) evaluated four randomly selected intrapartum FHR tracings by common visual interpretation, trying to predict umbilical artery base excess at birth. They subsequently were asked to re-evaluate the tracings using a mathematical algorithm for FHR tracing interpretation. Common visual interpretation allowed a correct estimation of the umbilical artery base excess in 34.4% of cases, with a poor interobserver reproducibility (Kappa correlation coefficient = 0.24). After implementation of the algorithm, the proportion of correct estimates significantly increased to 90.6% (p < 0.001), with excellent inter-clinician agreement (κ: 0.85). To conclude, incorporation of a standardised algorithm reduces the interobserver variability and allows a better estimation of fetal acidaemia at birth.


Dynamic translation of surface coarseness into whisker vibrations.
Rodents in their natural environment use their whiskers to distinguish between surfaces having subtly different textures and shapes. They do so by actively sweeping their whiskers across surfaces in a rhythmic motion. To determine how textures are transformed into vibration signals in whiskers and how these vibrations are expressed in neuronal discharges, we induced active whisking in anesthetized rats, monitored the movement of whiskers across surfaces, and concurrently recorded from trigeminal ganglion (TG) neurons. We show that tactile information is transmitted through high-frequency micromotions superimposed on whisking macro motions. Consistent with this, we find that in most TG neurons, spike activity, and high-frequency micromotions are closely correlated. To determine whether these vibration signals can support texture discrimination, we examined their dependence on surface roughness and found that both vibration signals carry information about surface coarseness. Despite a large variability in this translation process, different textures are translated into distinct vibrations profiles. These profiles depend on whiskers properties, on radial distance to the surface, and on whisking frequency. Using the characteristics of these signals, we employ linear discriminant analysis and found that all whiskers were able to discriminate between different textures. While deteriorating with radial distance, this classification did not depend on whisking frequency. Finally, increasing the number of whisks and integrating tactile information from multiple whiskers improved texture discrimination. These results indicate that surface roughness is translated into distinct whisker vibration signals that result in neuronal discharges. However, due to the dynamic nature of this translation process, we propose that texture discrimination may require the integration of signals from multiple spatial and temporal sensory channels to disambiguate surface roughness.