Quality of life in dyspepsia and its subgroups using EQ-5D (EuroQol) questionnaire.
Dyspepsia has a significant impact on the quality of life. Health-related quality of life (HRQoL) can be assessed by disease-specific and generic HRQoL instruments. The present study evaluated HRQoL and compared it among dyspepsia subgroups by using EQ (Euro QoL)-5D questionnaire. Patients with abnormal findings on upper gastrointestinal endoscopy were classified to have organic dyspepsia, whereas those with normal endoscopy were classified as functional dyspepsia if they met the ROME III criteria or as endoscopy negative recent dyspepsia if symptom duration was <6 months. HRQoL was assessed using the EQ-5D questionnaire, and the overall health status on a visual analogue scale (VAS); and the frequency of impairment in each dimension were compared between the dyspepsia subgroups. The overall health status was affected equally in all three dyspepsia subgroups. Impairment in HRQoL was commonly seen in the dimensions of pain (98.4%), usual activities (66.20%), and anxiety/depression (70.60%), however, much less so in mobility (22.70%) and self-care (10.9%). Any impairment in HRQoL was not significantly different between the three subgroups in the dimensions of mobility and usual activities. Self-care was more commonly affected in organic dyspepsia, anxiety/depression was more common with functional dyspepsia, while pain, though significantly different among various subgroups, was very common in all three subgroups. HRQoL was equally affected in all three subgroups of dyspepsia but variably so in the different domains of EQ-5D. These differences need to be studied further to improve the management of different etiological subgroups of dyspepsia.


The National Health Service (NHS) response to the COVID-19 pandemic: a colorectal surgeons experience in the UK.
The UK government was arguably slow to take action against the COVID-19 pandemic. However, since switching their policy from "mitigation" to "suppression", swift changes have been implemented to all aspects of life. In this unprecedented crisis healthcare has been on the battlefront across the globe. Every effort has been made in the UK to stop the National Health Service (NHS) from being overwhelmed, leading to the national slogan: "Stay at home. Protect the NHS. Save lives". In this article, a consultant general and colorectal surgeon in Southampton reports on the NHS response to the COVID-19 pandemic.


Results From Venezuela's 2016 Report Card on Physical Activity for Children and Youth.
The Venezuelan Report Card on Physical Activity for Children and Youth is the first assessment of information related to physical activity in Venezuela. It provides a compilation of existing information throughout the country and assesses how well it is doing at promoting opportunities for children and youth. The aim of this article is to summarize the information available. Thirteen physical activity indicators were graded by a committee of experts using letters A to F (A, the highest, to F, the lowest) based on national surveys, peer review studies, and policy documents. Some indicators report incomplete information or a lack of data. Overweight and Obesity were classified as A; Body Composition and Nongovernmental Organization Policies as B; Municipal Level Policies as C; and Overall Physical Activity Levels and National Level Policies as D. 63% of children and youth have low physical activity levels. Venezuela needs to undergo a process of articulation between the several existing initiatives, and for said purposes, political will and a methodological effort is required. Investments, infrastructure, and opportunities will be more equal for all children and youth if more cooperation between institutions is developed and communication strategies are applied.


Differences in patient-reported experiences of care by race and acculturation status.
Patient-reported experiences of care are an important focus in health disparities research. This study explored the association of patient-reported experiences of care with race and acculturation status in a primary care setting. 881 adult patients (African-American 34%; Hispanic--classified as unacculturated or biculturated--31%; Caucasian 33%; missing race 2%), in outpatient Family Medicine clinics, completed a written survey in Spanish or English. Consumer Assessment of Healthcare Providers and Systems (CAHPS) Clinician & Group (CAG) Survey Adult Primary Care instrument was used for experiences of care and Short Form-12 survey for health status. Controlling for other variables, race and acculturation were significantly associated with several CAG subscales. Hispanic patients gave significantly higher ratings for care experiences and expressed greater interest in shared decision making. Selected patient-reported measures of care are associated with patients' race and acculturation status (for Hispanic patients). We discuss implications for both provision and measurement of quality care.


Two major medicinal honeys have different mechanisms of bactericidal activity.
Honey is increasingly valued for its antibacterial activity, but knowledge regarding the mechanism of action is still incomplete. We assessed the bactericidal activity and mechanism of action of Revamil® source (RS) honey and manuka honey, the sources of two major medical-grade honeys. RS honey killed Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa within 2 hours, whereas manuka honey had such rapid activity only against B. subtilis. After 24 hours of incubation, both honeys killed all tested bacteria, including methicillin-resistant Staphylococcus aureus, but manuka honey retained activity up to higher dilutions than RS honey. Bee defensin-1 and H₂O₂ were the major factors involved in rapid bactericidal activity of RS honey. These factors were absent in manuka honey, but this honey contained 44-fold higher concentrations of methylglyoxal than RS honey. Methylglyoxal was a major bactericidal factor in manuka honey, but after neutralization of this compound manuka honey retained bactericidal activity due to several unknown factors. RS and manuka honey have highly distinct compositions of bactericidal factors, resulting in large differences in bactericidal activity.


BREX is a novel phage resistance system widespread in microbial genomes.
The perpetual arms race between bacteria and phage has resulted in the evolution of efficient resistance systems that protect bacteria from phage infection. Such systems, which include the CRISPR-Cas and restriction-modification systems, have proven to be invaluable in the biotechnology and dairy industries. Here, we report on a six-gene cassette in Bacillus cereus which, when integrated into the Bacillus subtilis genome, confers resistance to a broad range of phages, including both virulent and temperate ones. This cassette includes a putative Lon-like protease, an alkaline phosphatase domain protein, a putative RNA-binding protein, a DNA methylase, an ATPase-domain protein, and a protein of unknown function. We denote this novel defense system BREX (Bacteriophage Exclusion) and show that it allows phage adsorption but blocks phage DNA replication. Furthermore, our results suggest that methylation on non-palindromic TAGGAG motifs in the bacterial genome guides self/non-self discrimination and is essential for the defensive function of the BREX system. However, unlike restriction-modification systems, phage DNA does not appear to be cleaved or degraded by BREX, suggesting a novel mechanism of defense. Pan genomic analysis revealed that BREX and BREX-like systems, including the distantly related Pgl system described in Streptomyces coelicolor, are widely distributed in ~10% of all sequenced microbial genomes and can be divided into six coherent subtypes in which the gene composition and order is conserved. Finally, we detected a phage family that evades the BREX defense, implying that anti-BREX mechanisms may have evolved in some phages as part of their arms race with bacteria.


Deciphering the molecular mechanisms of mother-to-egg immune protection in the mealworm beetle Tenebrio molitor.
In a number of species, individuals exposed to pathogens can mount an immune response and transmit this immunological experience to their offspring, thereby protecting them against persistent threats. Such vertical transfer of immunity, named trans-generational immune priming (TGIP), has been described in both vertebrates and invertebrates. Although increasingly studied during the last decade, the mechanisms underlying TGIP in invertebrates are still elusive, especially those protecting the earliest offspring life stage, i.e. the embryo developing in the egg. In the present study, we combined different proteomic and transcriptomic approaches to determine whether mothers transfer a "signal" (such as fragments of infecting bacteria), mRNA and/or protein/peptide effectors to protect their eggs against two natural bacterial pathogens, namely the Gram-positive Bacillus thuringiensis and the Gram-negative Serratia entomophila. By taking the mealworm beetle Tenebrio molitor as a biological model, our results suggest that eggs are mainly protected by an active direct transfer of a restricted number of immune proteins and of antimicrobial peptides. In contrast, the present data do not support the involvement of mRNA transfer while the transmission of a "signal", if it happens, is marginal and only occurs within 24h after maternal exposure to bacteria. This work exemplifies how combining global approaches helps to disentangle the different scenarios of a complex trait, providing a comprehensive characterization of TGIP mechanisms in T. molitor. It also paves the way for future alike studies focusing on TGIP in a wide range of invertebrates and vertebrates to identify additional candidates that could be specific to TGIP and to investigate whether the TGIP mechanisms found herein are specific or common to all insect species.


Gross Motor Milestones and Subsequent Development.
We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins. In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at ∼4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins. Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, -11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI-2 score after adjustment for gestational age and birth weight. This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy.


Neural mechanisms of rapid natural scene categorization in human visual cortex.
The visual system has an extraordinary capability to extract categorical information from complex natural scenes. For example, subjects are able to rapidly detect the presence of object categories such as animals or vehicles in new scenes that are presented very briefly. This is even true when subjects do not pay attention to the scenes and simultaneously perform an unrelated attentionally demanding task, a stark contrast to the capacity limitations predicted by most theories of visual attention. Here we show a neural basis for rapid natural scene categorization in the visual cortex, using functional magnetic resonance imaging and an object categorization task in which subjects detected the presence of people or cars in briefly presented natural scenes. The multi-voxel pattern of neural activity in the object-selective cortex evoked by the natural scenes contained information about the presence of the target category, even when the scenes were task-irrelevant and presented outside the focus of spatial attention. These findings indicate that the rapid detection of categorical information in natural scenes is mediated by a category-specific biasing mechanism in object-selective cortex that operates in parallel across the visual field, and biases information processing in favour of objects belonging to the target object category.


Comparative characterization of endo-polygalacturonase (Pgu1) from Saccharomyces cerevisiae and Saccharomyces paradoxus under winemaking conditions.
Wine strains of Saccharomyces cerevisiae have no to weak natural pectinase activity, despite their genetic ability to secrete an endo-polygalacturonase. The addition of external pectinase of fungal origin has therefore become a common step of winemaking in order to enhance the extraction of compounds located in the grape berry skins during maceration and to ease wine clarification after maturation. Recently, the strong pectinase activity of a wine strain of Saccharomyces paradoxus has been reported. In this study, the endo-polygalacturonase-encoding gene of S. paradoxus was sequenced and its activity was characterised, compared with that of S. cerevisiae and tested under winemaking conditions through overexpression of both genes individually in S. cerevisiae. A few differences in the amino acids sequences between the two proteins were revealed and the activity of the Pgu1 enzyme of S. paradoxus was shown to be weaker under winemaking conditions. Clear indicators of extracellular activity were observed in the wines made with both recombinant strains (i.e. enzyme activity in cell-free wine, higher methanol concentration and higher free-run wine), but the actual composition of the wines fermented with the mutants was only sparingly altered. Although unexpectedly found in lower concentrations in the latter wines, phenolic compounds were shown to be the most discriminatory components. Overexpressing the PGU1 gene of S. paradoxus or that of S. cerevisiae did not make much difference, showing that the higher activity of S. paradoxus strains under laboratory conditions could be due to a different regulation mechanism rather than to a different sequence of PGU1.


Role of microRNAs in plant and animal development.
Small RNAs, including microRNAs (miRNAs) and short interfering RNAs (siRNAs), are key components of an evolutionarily conserved system of RNA-based gene regulation in eukaryotes. They are involved in many molecular interactions, including defense against viruses and regulation of gene expression during development. miRNAs interfere with expression of messenger RNAs encoding factors that control developmental timing, stem cell maintenance, and other developmental and physiological processes in plants and animals. miRNAs are negative regulators that function as specificity determinants, or guides, within complexes that inhibit protein synthesis (animals) or promote degradation (plants) of mRNA targets.


Sorption efficiency of chitosan nanofibers toward metal ions at low concentrations.
Chitosan fibers showing narrow diameter distribution with a mean of 42 nm were produced by electrospinning and utilized for the sorption of Fe(III), Cu(II), Ag(I), and Cd(II) ions from aqueous solutions. The ion concentrations in the supernatant solutions were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The filtration efficiency of the fibers toward these ions was studied by both batch and microcolumn methods. High efficiency in sorption of the metal ions was obtained in the both methods. The effects of sorbent amount (0.10-0.50 mg), shaking time (15-120 min), initial metal ion concentration (10.0-1000.0 μg·L(-1)), and temperature (25 and 50 °C) on the extent of sorption were examined. The sorbent amount did not significantly alter the efficiency of sorption; however, shaking time, temperature, and metal ion concentration were found to have a strong influence on sorption. By virtue of its mechanical integrity, the applicability of the chitosan mat in solid phase extraction under continuous flow looks promising.


Prognostic value of long non-coding RNA signatures in bladder cancer.
Bladder cancer (BLCA) is a devastating cancer whose early diagnosis can ensure better prognosis. Aim of this study was to evaluate the potential utility of lncRNAs in constructing lncRNA-based classifiers of BLCA prognosis and recurrence. Based on the data concerning BLCA retrieved from TCGA, lncRNA-based classifiers for OS and RFS were built using the least absolute shrinkage and selection operation (LASSO) Cox regression model in the training cohorts. More specifically, a 14-lncRNA-based classifier for OS and a 12-lncRNA-based classifier for RFS were constructed using the LASSO Cox regression. According to the prediction value, patients were divided into high/low-risk groups based on the cut-off of the median risk-score. The log-rank test showed significant differences in OS and RFS between low- and high-risk groups in the training, validation and whole cohorts. In the time-dependent ROC curve analysis, the AUCs for OS in the first, third, and fifth year were 0.734, 0.78, and 0.78 respectively, whereas the prediction capability of the 14-lncRNA classifier was superior to a previously published lncRNA classifier. As for the RFS, the AUCs in the first, third, and fifth year were 0.755, 0.715, and 0.740 respectively. In summary, the two-lncRNA-based classifiers could serve as novel and independent prognostic factors for OS and RFS individually.


An outbreak of group B meningococcal disease: tracing the causative strain of Neisseria meningitidis by DNA fingerprinting.
Following an outbreak of meningococcal disease in three schoolchildren in a small community in northern Norway, DNA fingerprinting, serotyping with monoclonal antibodies, serogrouping, and sulfonamide sensitivity testing were applied for characterization and tracing of the causative agent. The three case isolates were genomically indistinguishable, sulfonamide-resistant, serogroup B, serotype 15 meningococci. Throat specimens were collected from 552 healthy contacts, including all children below age 17 and their parents. Among the 36 carrier isolates (carrier rate, 6.5%) 13 showed DNA fingerprints identical, or almost identical, to the index pattern. All of these 13 isolates were sulfonamide resistant, 12 were of serotype 15, and 8 were of polysaccharide serogroup B (5 were nongroupable). These closely related isolates were almost exclusively recovered from schoolchildren of 2 of 15 small villages, one of which included the homes of two of the patients. The remaining 23 carrier isolates were nonresistant, non-type 15 meningococci of widely differing DNA restriction patterns. Our results confirm that DNA fingerprinting has potential as an efficient tool in practical meningococcal epidemiology.


Mutational analysis of Ca(2+)-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II.
Previous studies with synthetic peptides indicate that residues 290-309, corresponding to the calmodulin (CaM)-binding domain of Ca2+/CaM-dependent protein kinase II interact with the catalytic core of the enzyme as a pseudosubstrate (Colbran, R. J., Smith, M. K., Schworer, C. M., Fong, Y. L., and Soderling, T. R. (1989) J. Biol. Chem. 264, 4800-4804). In the present study, we attempted to locate the pseudosubstrate motif by generation or removal of potential substrate recognition sequences (RXXS/T) at selected positions using site-directed mutagenesis. Based on previous results, Arg297, Thr305/306, and Ser314 were selected as key residues. Single mutations such as N294S, K300S, A302R, A309R, and R311A were expressed, purified, and characterized. Several of the mutants exhibited decreased binding of and activation by CaM, not surprising since the mutations were within the CaM-binding domain. None of the mutants exhibited enhanced Ca(2+)-independent kinase activity toward exogenous substrate, but the K300S and N294S mutants showed a significant enhancement in the rate and stoichiometry of 32P incorporation during Ca(2+)-independent autophosphorylation. Using two-dimensional peptide mapping and phosphoamino acid analyses, enhanced phosphorylation of the introduced Ser residue was demonstrated in the K300S mutant but not in the N294S mutant. This specific Ca(2+)-independent autophosphorylation of Ser300 is consistent with the hypothesis that Arg297 may occupy the P (-3) position in a pseudosubstrate autoinhibitory interaction with the catalytic core in the nonactivated state of the kinase.


A reassessment of sensory evoked potential parameters in multiple sclerosis: a discriminant analysis approach.
The sensitivity of the different parameters (absolute latency, interwave latency, latency asymmetry, amplitude) of both cervical and cerebral responses evoked by stimulation of the median nerve at the wrist was assessed in patients with multiple sclerosis by discriminant analysis. The peak latency of N13 or N20 SEP components or both was found to be more sensitive than their amplitude, provided that a preliminary covariation with the height of the subjects was performed. The measurement of latency asymmetry between the two sides increased the test's sensitivity, while amplitude asymmetry turned out to be of little diagnostic value. A linear discriminant function with four variates (that is mean amplitude, mean latency, latency asymmetry and height of the subject) was computed to summarise the information provided by the different parameters to give a rapid and exact method for the assessment of SEP abnormalities in multiple sclerosis patients.


How lysenkoism became pseudoscience: dobzhansky to velikovsky.
At some point in America in the 1940s, T. D. Lysenko's neo-Lamarckian hereditary theories transformed from a set of disputed doctrines into a prime exemplar of "pseudoscience." This paper explores the context in which this theory acquired this pejorative status by examining American efforts to refute Lysenkoism both before and after the famous August 1948 endorsement of Lysenko's doctrines by the Stalinist state, with particular attention to the translation efforts of Theodosius Dobzhansky. After enumerating numerous tactics for combating perceived pseudoscience, the Lysenko case is then juxtaposed with another American case of alleged pseudoscience: the notorious 1950 scandal surrounding Immanuel Velikovsky's Worlds in Collision (1950, Worlds in Collision. New York: Macmillan). On several levels, the characterization of Lysenkoism as pseudoscientific served as a template for casting other rejected theories, including Velikovsky's, in the same light.


Migraine history, nonsteroidal anti-inflammatory drug use, and risk of postmenopausal endometrial cancer.
Endometrial cancer is primarily a hormonally mediated disease. As such, factors that mediate or reflect exposure to estrogens, or that mediate response to such exposure, may plausibly be associated with endometrial cancer risk. History of migraines, another hormonally mediated condition, has recently been associated with a reduced risk of hormone receptor-positive breast cancer; however, the relationship between migraines and endometrial cancer has not previously been explored. We evaluated the relationship between migraine history and endometrial cancer risk in postmenopausal women, considering also the potential impact of nonsteroidal anti-inflammatory drug (NSAID) use, given the relationship of NSAIDs to hormones and to migraine history. We identified 93,384 women participating in the Women's Health Initiative prospective cohort who had an intact uterus at the time of study entry. Using Cox proportional hazards regression, we assessed risk of endometrial cancer during study follow-up according to history of migraines and according to current NSAID use at the time of study entry, adjusting for age, study arm, race, and hormone therapy use. We also evaluated interaction in these associations by body mass index. Having a history of migraines was not associated with endometrial cancer risk [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.75-1.11], regardless of body mass index (BMI) or NSAID use status. Similarly, current NSAID use was not associated with endometrial cancer risk (HR = 1.01, 95% CI = 0.88-1.16), regardless of BMI. Migraine history and NSAID use do not appear to be associated with risk of endometrial cancer.


Chromatic aberration correction of the human eye for retinal imaging in the near infrared.
An achromatizing lens has been designed for the human eye in the near infrared range, from 700 to 900 nm, for retinal imaging purposes. Analysis of the performance of the lens, including tolerance to misalignments, has been mathematically accomplished by using an existing eye model. The calculations have shown a virtually perfect correction of the ocular longitudinal chromatic aberration, while still keeping a high optical quality. Ocular aberrations in five subjects have been measured with and without the achromatizing lens by using a Hartmann-Shack wavefront sensor and a broad bandwidth femtosecond Ti:sapphire laser in the spectral range of interest with a set of interference filters, studying the benefits and limits in the use of the achromatizing lens. Ocular longitudinal chromatic aberration has been experimentally demonstrated to be fully corrected by the proposed lens, with no induction of any other parasitic aberration. The practical implementation of the achromatizing lens for Ophthalmoscopy, specifically for optical coherence tomography where the use of polychromatic light sources in the near infrared portion of the spectrum is mandatory, has been considered. The potential benefits of using this lens in combination with adaptive optics to achieve a full aberration correction of the human eye for retinal imaging have also been discussed.


An aggrecan fragment drives osteoarthritis pain through Toll-like receptor 2.
Pain is the predominant symptom of osteoarthritis, but the connection between joint damage and the genesis of pain is not well understood. Loss of articular cartilage is a hallmark of osteoarthritis, and it occurs through enzymatic degradation of aggrecan by cleavage mediated by a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS-4) or ADAMTS-5 in the interglobular domain (E373-374A). Further cleavage by MMPs (N341-342F) releases a 32-amino-acid aggrecan fragment (32-mer). We investigated the role of this 32-mer in driving joint pain. We found that the 32-mer excites dorsal root ganglion nociceptive neurons, both in culture and in intact explants. Treatment of cultured sensory neurons with the 32-mer induced expression of the proalgesic chemokine CCL2. These effects were mediated through TLR2, which we demonstrated was expressed by nociceptive neurons. In addition, intra-articular injection of the 32-mer fragment provoked knee hyperalgesia in WT but not Tlr2-null mice. Blocking the production or action of the 32-mer in transgenic mice prevented the development of knee hyperalgesia in a murine model of osteoarthritis. These findings suggest that the aggrecan 32-mer fragment directly activates TLR2 on joint nociceptors and is an important mediator of the development of osteoarthritis-associated joint pain.


Proteomic patterns of preinvasive bronchial lesions.
A proteomics approach is warranted to further elucidate the molecular steps involved in lung tumor development. We asked whether we could classify preinvasive lesions of airway epithelium according to their proteomic profile. We obtained matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiles from 10-microm sections of fresh-frozen tissue samples: 25 normal lung, 29 normal bronchial epithelium, and 20 preinvasive and 36 invasive lung tumor tissue samples from 53 patients. Proteomic profiles were calibrated, binned, and normalized before analysis. We performed class comparison, class prediction, and supervised hierarchic cluster analysis. We tested a set of discriminatory features obtained in a previously published dataset to classify this independent set of normal, preinvasive, and invasive lung tissues. We found a specific proteomic profile that allows an overall predictive accuracy of over 90% of normal, preinvasive, and invasive lung tissues. The proteomic profiles of these tissues were distinct from each other within a disease continuum. We trained our prediction model in a previously published dataset and tested it in a new blinded test set to reach an overall 74% accuracy in classifying tumors from normal tissues. We found specific patterns of protein expression of the airway epithelium that accurately classify bronchial and alveolar tissue with normal histology from preinvasive bronchial lesions and from invasive lung cancer. Although further study is needed to validate this approach and to identify biomarkers of tumor development, this is a first step toward a new proteomic characterization of the human model of lung cancer tumorigenesis.


Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.
Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38-0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31-0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans.


Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study).
Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2).


Residential Air Pollution, Road Traffic, Greenness and Maternal Hypertension: Results from GINIplus and LISAplus.
The public health burden of hypertension is high, but its relationship with long-term residential air pollution, road traffic, and greenness remains unclear. To investigate associations between residential air pollution, traffic, greenness, and hypertension among mothers. Information on doctor-diagnosed maternal hypertension was collected at the 15-year follow-up of two large population-based multicenter German birth cohorts-GINIplus and LISAplus (n=3063). Residential air pollution was modelled by land use regression models within the ESCAPE and universal kriging within the APMoSPHERE projects. Road traffic was defined as traffic load on major roads within a 100-m buffer around residences. Vegetation level (ie, greenness) was defined as the mean Normalized Difference Vegetation Index in a 500-m buffer around residences and was assessed from Landsat 5 TM satellite images. All the exposure variables were averaged over three residential addresses during the last 10 years and categorized into tertiles or dichotomized. The individual associations between each of the exposure variables and hypertension were assessed using logistic regression analysis. No significant and consistent associations across different levels of adjustment were observed between the exposures of interest and hypertension. The only significant estimate was found with coarse particulate matter concentrations (OR 1.66, 95% CI 1.01 to 2.74; 3rdvs 1st tertile) among mothers residing in the Wesel area. No significant associations were observed with traffic load or greenness. This study does not provide evidence on detrimental effects of air pollution and road traffic or beneficial effects of greenness on hypertension among German adults.


Comparing the adaptive landscape across trait types: larger QTL effect size in traits under biotic selection.
In a spatially and temporally variable adaptive landscape, mutations operating in opposite directions and mutations of large effect should be commonly fixed due to the shifting locations of phenotypic optima. Similarly, an adaptive landscape with multiple phenotypic optima and deep valleys of low fitness between peaks will favor mutations of large effect. Traits under biotic selection should experience a more spatially and temporally variable adaptive landscape with more phenotypic optima than that experienced by traits under abiotic selection. To test this hypothesis, we assemble information from QTL mapping studies conducted in plants, comparing effect directions and effect sizes of detected QTL controlling traits putatively under abiotic selection to those controlling traits putatively under biotic selection. We find no differences in the fraction of antagonistic QTL in traits under abiotic and biotic selection, suggesting similar consistency in selection pressure on these two types of traits. However, we find that QTL controlling traits under biotic selection have a larger effect size than those under abiotic selection, supporting our hypothesis that QTL of large effect are more commonly detected in traits under biotic selection than in traits under abiotic selection. For traits under both abiotic and biotic selection, we find a large number of QTL of large effect, with 10.7% of all QTLs detected controlling more than 20% of the variance in phenotype. These results suggest that mutations of large effect are more common in adaptive landscapes strongly determined by biotic forces, but that these types of adaptive landscapes do not result in a higher fraction of mutations acting in opposite directions. The high number of QTL of large effect detected shows that QTL of large effect are more common than predicted by the infinitesimal model of genetic adaptation.


pCO2 effects on species composition and growth of an estuarine phytoplankton community.
The effects of ongoing changes in ocean carbonate chemistry on plankton ecology have important implications for food webs and biogeochemical cycling. However, conflicting results have emerged regarding species-specific responses to pCO2 enrichment and thus community responses have been difficult to predict. To assess community level effects (e.g., production) of altered carbonate chemistry, studies are needed that capitalize on the benefits of controlled experiments but also retain features of intact ecosystems that may exacerbate or ameliorate the effects observed in single-species or single cohort experiments. We performed incubations of natural plankton communities from Narragansett Bay, RI, USA in winter at ambient bay temperatures (5-13 °C), light and nutrient concentrations under three levels of controlled and constant CO2 concentrations, simulating past, present and future conditions at mean pCO2 levels of 224, 361, and 724 μatm respectively. Samples for carbonate analysis, chlorophyll a, plankton size-abundance, and plankton species composition were collected daily and phytoplankton growth rates in three different size fractions (<5, 5-20, and >20 μm) were measured at the end of the 7-day incubation period. Community composition changed during the incubation period with major increases in relative diatom abundance, which were similar across pCO2 treatments. At the end of the experiment, 24-hr growth responses to pCO2 levels varied as a function of cell size. The smallest size fraction (<5 μm) grew faster at the elevated pCO2 level. In contrast, the 5-20 μm size fraction grew fastest in the Present treatment and there were no significant differences in growth rate among treatments in the > 20 μm size fraction. Cell size distribution shifted toward smaller cells in both the Past and Future treatments but remained unchanged in the Present treatment. Similarity in Past and Future treatments for cell size distribution and growth rate (5-20 μm size fraction) illustrate non-monotonic effects of increasing pCO2 on ecological indicators and may be related to opposing physiological effects of high CO2 and low pH both within and among species. Interaction of these effects with other factors (e.g., nutrients, light, temperature, grazing, initial species composition) may explain variability among published studies. The absence of clear treatment-specific effects at the community level suggest that extrapolation of species-specific responses or experiments with only present day and future pCO2 treatments levels would produce misleading predictions of ocean acidification impacts on plankton production.


Deep reefs are not universal refuges: Reseeding potential varies among coral species.
Deep coral reefs (that is, mesophotic coral ecosystems) can act as refuges against major disturbances affecting shallow reefs. It has been proposed that, through the provision of coral propagules, such deep refuges may aid in shallow reef recovery; however, this "reseeding" hypothesis remains largely untested. We conducted a genome-wide assessment of two scleractinian coral species with contrasting reproductive modes, to assess the potential for connectivity between mesophotic (40 m) and shallow (12 m) depths on an isolated reef system in the Western Atlantic (Bermuda). To overcome the pervasive issue of endosymbiont contamination associated with de novo sequencing of corals, we used a novel subtraction reference approach. We have demonstrated that strong depth-associated selection has led to genome-wide divergence in the brooding species Agaricia fragilis (with divergence by depth exceeding divergence by location). Despite introgression from shallow into deep populations, a lack of first-generation migrants indicates that effective connectivity over ecological time scales is extremely limited for this species and thus precludes reseeding of shallow reefs from deep refuges. In contrast, no genetic structuring between depths (or locations) was observed for the broadcasting species Stephanocoenia intersepta, indicating substantial potential for vertical connectivity. Our findings demonstrate that vertical connectivity within the same reef system can differ greatly between species and that the reseeding potential of deep reefs in Bermuda may apply to only a small number of scleractinian species. Overall, we argue that the "deep reef refuge hypothesis" holds for individual coral species during episodic disturbances but should not be assumed as a broader ecosystem-wide phenomenon.


Dispersion polymerizations in supercritical carbon dioxide.
Conventional heterogeneous dispersion polymerizations of unsaturated monomers are performed in either aqueous or organic dispersing media with the addition of interfacially active agents to stabilize the colloidal dispersion that forms. Successful stabilization of the polymer colloid during polymerization results in the formation of high molar mass polymers with high rates of polymerization. An environmentally responsible alternative to aqueous and organic dispersing media for heterogeneous dispersion polymerizations is described in which supercritical carbon dioxide (CO(2)) is used in conjunction with molecularly engineered free radical initiators and amphipathic molecules that are specifically designed to be interfacially active in CO(2). Conventional lipophilic monomers, exemplified by methyl methacrylate, can be quantitatively (>90 percent) polymerized heterogeneously to very high degrees of polymerization (>3000) in supercritical CO(2) in the presence of an added stabilizer to form kinetically stable dispersions that result in micrometer-sized particles with a narrow size distribution.


Association Between Neighborhood Walkability and Predicted 10-Year Cardiovascular Disease Risk: The CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Cohort.
Background Individuals living in unwalkable neighborhoods appear to be less physically active and more likely to develop obesity, diabetes mellitus, and hypertension. It is unclear whether neighborhood walkability is a risk factor for future cardiovascular disease. Methods and Results We studied residents living in major urban centers in Ontario, Canada on January 1, 2008, using linked electronic medical record and administrative health data from the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) cohort. Walkability was assessed using a validated index based on population and residential density, street connectivity, and the number of walkable destinations in each neighborhood, divided into quintiles (Q). The primary outcome was a predicted 10-year cardiovascular disease risk of ≥7.5% (recommended threshold for statin use) assessed by the American College of Cardiology/American Heart Association Pooled Cohort Equation. Adjusted associations were estimated using logistic regression models. Secondary outcomes included measured systolic blood pressure, total and high-density lipoprotein cholesterol levels, prior diabetes mellitus diagnosis, and current smoking status. In total, 44 448 individuals were included in our analyses. Fully adjusted analyses found a nonlinear relationship between walkability and predicted 10-year cardiovascular disease risk (least [Q1] versus most [Q5] walkable neighborhood: odds ratio =1.09, 95% CI: 0.98, 1.22), with the greatest difference between Q3 and Q5 (odds ratio=1.33, 95% CI: 1.23, 1.45). Dose-response associations were observed for systolic blood pressure, high-density lipoprotein cholesterol, and diabetes mellitus risk, while an inverse association was observed with smoking status. Conclusions In our setting, adults living in less walkable neighborhoods had a higher predicted 10-year cardiovascular disease risk than those living in highly walkable areas.


Morphological Feature Extraction From a Continuous Intracranial Pressure Pulse via a Peak Clustering Algorithm.
An increase in intracranial pressure (ICP) is frequently observed in patients with severe traumatic brain injury (TBI). The information derived from the observation of temporal changes in the mean ICP is insufficient for assessment of the compensatory reserve of the injured brain. This assessment can be achieved via continuous morphological analysis of the pulse waveform of the ICP. Continuous arterial blood pressure (ABP) and ICP recordings from 292 TBI patients were analyzed. The algorithm extracted morphological landmarks (peaks, troughs, and flats) from the ICP. Among the extracted peaks, P1, P2, and P3 were assigned through peak clustering. The performance of the proposed method was validated through a comparison of the algorithm-defined peaks and those manually identified by experienced observers. The proposed algorithm successfully identified the three distinguishing peaks of the ICP with satisfactory accuracy (95.3%, 87.8%, and 87.5% for P1, P2, and P3, respectively), even from minimally filtered raw signals. The algorithm extracted the morphological features from both ABP and ICP recordings with high accuracy. The ABP and ICP pulse waveforms can be simultaneously analyzed in real time using the proposed algorithm. The morphological features from these signals may aid the continuous care of patients with TBI.


A National Plan for Physical Activity: The Enabling Role of the Built Environment.
Evidence shows significant relationships between aspects of the built environment and physical activity. Land use and transportation investments are needed to create environments that support and promote physical activity. The policy relevance of recent evidence on the built environment and physical activity is discussed, along with an assessment of near, medium, and longer term pricing and regulatory actions that could be considered to promote physical activity. These actions are evaluated based on their consistency with the current evidence on what would support and promote physical activity. A wide range of pricing and regulatory strategies are presented that would promote physical activity. There is an unmet demand for activity friendly, walkable environments. Creating more walkable places is an essential component of a national plan to increase physical activity levels of Americans. The built environment is an enabler or disabler of physical activity. Creating more walkable environments is an essential step in averting what is currently a market failure where the supply and demand for walkable environments is misaligned. The desire to be more physically active would be supported through investments in walking, biking, and transit. Concentration of development within existing urban areas supported by transit and implementing pricing strategies can support physical activity.


A correlative study of clinical and histological findings of revision hip arthroplasty for rheumatoid arthritis and inflammatory joint disease.
Primary hip arthroplasty in rheumatoid arthritis (RA) and other forms of inflammatory joint disease (IJD) is generally thought to be associated with a less favourable outcome in terms of implant survival and other complications. Whether the duration of implant survival correlates with the degree of rheumatoid-like inflammatory changes in periprosthetic tissues is uncertain. Histopathological changes in periprosthetic tissues obtained following revision surgery of 34 total hip replacements on 27 patients with IJD (RA 18 cases: ankylosing spondylitis three cases; juvenile chronic arthritis six cases) were examined. A heavy diffuse lymphocyte and plasma cell infiltrate +/- lymphoid aggregates was noted in 29% of cases in whom the mean implant survival was 5.6 years (range: 2-8 years). Where little or no lymphocytic infiltrate was noted in periprosthetic tissues, the mean implant survival was 8.6 years (range: 1-17 years). Revision arthroplasty was not undertaken for early or late infection of a primary hip replacement. Our findings indicate that implant survival is less in those cases where there is a heavy lymphocyte and plasma-cell infiltrate in periprosthetic tissues. These findings suggest that the presence of a heavy chronic inflammatory-cell infiltrate in periprosthetic tissues is likely to be a contributory factor in causing early implant failure in RA.


Left-side hepatectomy in living donors: through a reduced upper-midline incision for liver transplantation.
We present our attempts at reducing the length of incision in living donor left-side hepatectomy without laparoscopic approach. The chief surgeon initially made a 10-cm upper midline incision and performed all procedures through a minilaparotomy without abdominal wall lifting or pneumoperitoneum. For the procedures in the lateral and deep areas, we effectively applied traction to the wound in multiple directions using a wound retraction system so that the chief surgeon could obtain a good direct view. We also placed a fiberscope on the minilaparotomy so that the assistant surgeons could obtain an additional video view via a monitor. Surgeons lengthened the incision at their own discretion if the initial length was thought to be too short for the donor's safety. Since February 2009, we have employed this operation for 19 living donors (12 lateral segmentectomies and 7 left hepatectomies) and compared parameters between the 19 donors and 34 previous donors who underwent the procedure with standard incision (11 lateral segmentectomies and 23 left hepatectomies). The resultant length of incision was significantly reduced in operations with reduced incision length as compared with standard incision. Clinical outcomes such as operation time and length of hospital stay were comparable or significantly reduced with the reduced incision. The resultant incision length remained within 10 and 12 cm in lateral segmentectomy and left hepatectomy cases, respectively, whose body mass index was less than 22. It appears to be feasible to reduce the incision length for living donor left-side hepatectomy, especially in nonobese cases.


Validation of a Metallomics Analysis of Placenta Tissue by Inductively-Coupled Plasma Mass Spectrometry.
Trace elements can play an important role in maternal health and fetal development, and deficiencies in some essential minerals including zinc and copper have been correlated in some individuals to the development of birth defects and adverse health outcomes later in life. The exact etiology of conditions like preeclampsia and the effects of fetal exposure to toxic metals has not been determined, making the assessment of trace element levels crucial to the elucidation of the causes of conditions like preeclampsia. Previous studies analyzing serum and placenta tissue have produced conflicting findings, suggesting the need for a robust, validated sample preparation and analysis method for the determination of trace elements in placenta. In this report, an acid digestion method and analysis by ICP-MS for a broad metallomics/mineralomics panel of trace elements is developed and validated over three experimental days for inter- and intraday precision and accuracy, linear range, matrix impact, and dilution verification. Spike recovery experiments were performed for the essential elements chromium (Cr), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), and zinc (Zn), and the toxic elements arsenic (As), cadmium (Cd), and lead (Pb) at levels equal to and in excess of native concentrations in control placenta tissue. The validated method will be essential for the development of scientific studies of maternal health and toxic metal exposure effects in childhood.


Asymmetric prefrontal cortex functions predict asymmetries in number space.
Little is known about the neuropsychological factors that contribute to individual differences in the asymmetric orientation along the mental number line. The present study documents healthy subjects' preference for small numbers over large numbers in a random number generation task. This preference, referred to as "small-number bias" (SNB), varied with prefrontal functional lateralization: it was larger in participants with over-proportionately better performance in design fluency compared to letter fluency than in participants with over-proportionately better performance in letter fluency when compared to design fluency. Asymmetries in learning and memory tasks (verbal vs. non-verbal) were not related to direction or size of the SNB. We conclude that hemispheric asymmetries of specifically prefrontal executive functions are predictive of an individual's lateral orientation bias along the mental number line. Therefore, the focus on parietal contributions to spatial-numerical associations may not be justified. Random number generation may be a helpful method to further explore these associations uncontaminated by the asymmetric involvement of response effectors.


Secondary Surgery Versus Chemotherapy for Recurrent Ovarian Cancer.
The best course of treatment for recurrent ovarian cancer is uncertain. We sought to determine whether secondary cytoreductive surgery for first recurrence of ovarian cancer improves overall survival compared with other treatments. We assessed survival using Surveillance, Epidemiology and End Results-Medicare data for advanced stage ovarian cancer cases diagnosed from January 1, 1997 to December 31, 2007 with survival data through 2010 using multinomial propensity weighted finite mixture survival regression models to distinguish true from misclassified recurrences. Of 35,995 women ages 66 years and older with ovarian cancer, 3439 underwent optimal primary debulking surgery with 6 cycles of chemotherapy; 2038 experienced a remission. One thousand six hundred thirty-five of 2038 (80%) women received treatment for recurrence of whom 72% were treated with chemotherapy only, 16% with surgery and chemotherapy and 12% received hospice care. Median survival of women treated with chemotherapy alone, surgery and chemotherapy, or hospice care was 4.1, 5.4, and 2.2 years, respectively (P<0.001). Of those receiving no secondary treatments, 75% were likely true nonrecurrences with median survival of 15.9 years and 25% misclassified with 2.4 years survival. Survival among women with recurrence was greater for those treated with surgery and chemotherapy compared with chemotherapy alone (hazard ratio=1.67; 95% confidence interval, 1.13-2.47). Women who were older with more comorbidities and high-grade cancer had worse survival. Secondary surgery with chemotherapy to treat recurrent ovarian cancer increases survival by 1.3 years compared with chemotherapy alone and pending ongoing randomized trial results, may be considered a standard of care.


Evaluations of sexual assault: perceptions of guilt and legal elements for male and female aggressors using various coercive strategies.
This study examines the extent to which verdict, guilt, and legal components associated with jury instructions of sexual assault differ as a function of aggressor gender, participant gender, and sexual strategy used (consensual, verbal coercion, alcohol, or physical aggression) to obtain sex. Participants (N = 423; 276 women and 147 men) read a vignette depicting either a couple having consensual sex (control), or a male or female aggressor who initiates sexual intercourse via verbal coercion, use of alcohol, or physical abuse. College students were provided with legal instructions of sexual assault then asked to provide a verdict, degree of guilt, and legal components. Female participants rated guilt and coercion higher than did male participants. Ratings of guilt were highest in the physical assault condition followed by the alcohol, verbal, and control conditions. Female aggressors were rated less guilty than male aggressors. Results are explained in relation to sexual scripts and legal decision making. Lack of significance in verdict decisions and interaction effects suggests male and female aggressors are evaluated similarly using coercive strategies; yet, consent for sex was assumed and attributions of guilt was lower when the aggressor was female. Implications for jury instructions and future research are discussed.


The control of Malpighian tubule secretion in a predacious hemipteran insect, the spined soldier bug Podisus maculiventris (Heteroptera, Pentatomidae).
Spined soldier bugs, Podisus maculiventris, are heteropteran insects that feed voraciously on other insects, particular the soft bodied larval forms of Lepidoptera and Coleoptera. The response of P. maculiventris Malpighian tubules (MTs) to serotonin and known diuretic and antidiuretic peptides has been investigated, and is compared with that of MT from the hematophagous and phytophagous heteropteran bugs Rhodnius prolixus and Acrosternum hilare, respectively. A CRF-related peptide diuretic hormone (DH) from the termite Zootermopsis nevadensis (Zoone-DH) stimulated MT secretion, which was reversed by a member of the CAP(2b) family of peptides from A. hilare (Acrhi-CAP(2b)-2), an antidiuretic effect. Serotonin had no effect on secretion, neither did a representative calcitonin-like DH, kinin, tachykinin-related peptide, and an antidiuretic factor from the mealworm Tenebrio molitor (Tenmo-ADFb) in both P. maculiventris or A. hilare. Serotonin is a DH in R. prolixus, and its lack of effect on MT from P. maculiventris and A. hilare suggests this is an adaptation to hematophagy. On the other hand, the antidiuretic activity of members of the CAP(2b) family in all three bugs is consistent with this being a heteropteran feature rather than a specialism for hematophagy.


Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus.
A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0.5-3.9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 mumol/l (244 mug/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs.Only 2 (5.4%) of the tolbutamide-treated patients and 10 (16.7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5.5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8.0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient.There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug.We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.


Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening.
Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.


Association of potassium channel Kv3.4 subunits with pre- and post-synaptic structures in brainstem and spinal cord.
Voltage-gated K+ channels (Kv) are divided into eight subfamilies (Kv1-8) and play a major role in determining the excitability of neurones. Members of the Kv3 subfamily are highly abundant in the CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique pattern of expression, although single neurones can express more than one subtype. Of the Kv3 subunits relatively little is known of the Kv3.4 subunit distribution in the nervous system, particularly in the brainstem and spinal cord of the rat. We performed immunohistochemistry to determine both the cellular and sub-cellular distribution of the Kv3.4 subunit in these areas. Kv3.4 subunit immunoreactivity (Kv3.4-IR) was widespread, with dense, punctate staining in many regions including the intermediolateral cell column (IML) and the dorsal vagal nucleus (DVN), nucleus ambiguus (NA) and nucleus tractus solitarius (NTS). In the ventral horn a presynaptic location was confirmed by co-localization of Kv3.4-IR with the synaptic vesicle protein, SV2 and also with the glutamate vesicle markers vesicular glutamate transporter (VGluT) 1, VGluT2 or the glycine transporter GlyT2, suggesting a role for the channel in both excitatory and inhibitory neurotransmission. Electron microscopy confirmed a presynaptic terminal location of Kv3.4-IR in the VH, IML, DVN, NA and NTS. Interestingly however, patches of Kv3.4-IR were also revealed postsynaptically in dendritic and somatic structures throughout these areas. This staining was striking due to its localization at synaptic junctions at terminals with morphological features consistent with excitatory functions, suggesting an association with the postsynaptic density. Therefore the pre and postsynaptic localization of Kv3.4-IR suggests a role both in the control of transmitter release and in regulating neuronal excitability.


The Use of Social Robots for Supporting Language Training of Children.
A number of studies have found that robots can contribute to engagement and motivation in educational settings. We wanted to explore the possibilities and challenges of using a social robot as an assistive tool for learning and training of basic concepts and words. Robots are considered promising tools in language training because they can contribute to systematic interaction and repetition. A prototype was developed using an Aldebaran NAO robot combined with pictures that could be presented on a tablet, PC or on the wall using a projector. The prototype was piloted in two pre-projects with different groups of children learning Norwegian. One project targeted second language learners in a kindergarten and the other targeted young primary school pupils with autism spectrum disorder. Both of these groups need more systematic training than they usually get during the normal kindergarten and school schedule. We wanted to study whether and how the use of a social robot could contribute to more systematic training, increased learning intensity, more repetitions and ultimately more effective language learning. In this paper we present experiences from developing, implementing and using the prototype in the two different settings. The prototype is described, as well as the pedagogical settings of the two pilots. We present results from observations of the children and interviews with teachers and supporting personnel. We discuss differences between the two cases and methodological limitations. Finally, we discuss possibilities and challenges of using robots in language learning and training of children.


Serum levels of N-terminal-pro B-type natriuretic peptide as a diagnostic marker for left ventricular dysfunction in children with end-stage renal disease on hemodialysis.
The objective of this study was to determine the diagnostic cutoff value of N-terminal-pro B-type natriuretic peptide (NT-pro BNP) as a marker of left ventricular (LV) dysfunction in children with end-stage renal disease (ESRD) on regular hemodialysis (HD). The study was carried out on thirty children with ESRD on regular HD and thirty healthy controls. Echocardiographic studies were done, including a conventional mode for ejection fraction, fractional shortening, tissue Doppler imaging, and longitudinal global strain by speckle tracking. Serum levels of NT-pro BNP were measured in venous blood samples before and about 30 min after HD by ELISA. Volume status was assessed by calculating interdialytic weight gain %. There were significant higher serum NT-pro BNP levels before HD (mean: 702.3 ± 274.3 ng/L) compared to controls (mean: 365.55 ± 76.5 ng/L) (P <0.001) and these levels decreased significantly after the HD session (mean: 625.1 ± 117.69 ng/L) (P = 0.031). Echocardiographic studies showed a significant impairment of LV function of the patients compared to controls. Patients with LV dysfunction had significant higher serum concentrations of NT-pro BNP compared to patients without dysfunction both before (P = 0.003) and after dialysis (P <0.001). Receiver operating curve demonstrated better prediction of LV dysfunction by NT-pro BNP levels after HD compared to its levels before HD (area under the curve was 0.9 and 0.73, respectively). Using a cutoff value of 630 ng/L, serum NT-pro BNP levels after dialysis were a diagnostic predictor of LV dysfunction with a sensitivity of 86.6%, specificity of 93.3%, positive predictive value of 92.8%, and negative predictive value of 87.5%. Serum NT-pro BNP levels were strongly correlated with the parameters of LV dysfunction in children with ESRD on regular HD. A postdialysis cutoff value of 630 ng/L could serve as a biochemical marker of LV dysfunction in those children regardless of chronic fluid overload.


Synthesis, properties and structures of NbOF3 complexes and comparisons with NbOCl3 analogues.
The first series of complexes of niobium(v) oxide trifluoride, [NbOF3(OPR3)2] (R = Me or Ph), [NbOF3(dppmO2)] (dppmO2 = Ph2P(O)CH2P(O)Ph2), [NbOF3(dmso)2], [NbOF3(tmeda)] (tmeda = Me2N(CH2)2NMe2) and [NbOF3(diimine)] (diimine = 2,2'-bipy, 1,10-phen) have been prepared, either by reaction of the corresponding complexes of NbF5 and hexamethyldisiloxane (HMDSO) in CH2Cl2-MeCN solution, or directly from NbF5, ligand and HMDSO. They were characterised by IR, (1)H, (31)P{(1)H} and (19)F{(1)H} NMR spectroscopy, and X-ray crystal structures are reported for [NbOF3(OPR3)2] (R = Me or Ph) and [NbOF3(dppmO2)]. Complexes of NbOCl3, [NbOCl3(OPPh3)2], [NbOCl3(dppmO2)], [NbOCl3(dppeO2)] (dppeO2 = Ph2P(O)(CH2)2P(O)Ph2), [NbOCl3(tmeda)] and [NbOCl3(diimine)] were made from NbCl5 and HMDSO in MeCN (which forms [NbOCl3(MeCN)2] in situ), followed by addition of the neutral ligand. Their properties are compared with the oxide fluoride analogues. X-ray structures are reported for [NbOCl3(dppmO2)], [NbOCl3(dppeO2)], [NbOCl3(tmeda)] and [NbOCl3(2,2'-bipy)]. The synthesis and spectroscopic characterisation of [MF5L] (M = Nb or Ta; L = OPR3, OAsPh3) and [MF4(diimine)2][MF6] are also described, and the key properties of the four series of complexes compared.


Signal transduction involved in MCP-1-mediated monocytic transendothelial migration.
Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and T lymphocytes. The MonoMac6 cell line was used to examine MCP-1 receptor-mediated signal transduction events in relation to MCP-1-mediated monocytic transendothelial migration. MCP-1 stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). SAPK1/JNK1 activation was blocked by piceatannol, indicating that it is regulated by Syk kinase, whereas SAPK2/p38 activation was inhibited by PP2, revealing an upstream regulation by Src-like kinases. In contrast, ERK activation was insensitive to PP2 and piceatannol. Pertussis toxin, a blocker of Go/Gi proteins, abrogated MCP-1-induced ERK activation, but was without any effect on SAPK1/JNK1 and SAPK2/p38 activation. These results underscore the major implication of Go/Gi proteins and nonreceptor tyrosine kinases in the early MCP-1 signaling. Furthermore, MCP-1-mediated chemotaxis and transendothelial migration were significantly diminished by a high concentration of SB202190, a broad SAPK inhibitor, or by SB203580, a specific inhibitor of SAPK2/p38, and abolished by pertussis toxin treatment. Altogether, these data suggest that coordinated action of distinct signal pathways is required to produce a full response to MCP-1 in terms of monocytic locomotion.


Drink to prevent: review on the cardioprotective mechanisms of alcohol and red wine polyphenols.
Moderate alcohol consumption has convincingly been associated with decreased cardiovascular mortality in epidemiological studies and metaanalyses. This decreased mortality has been attributed to changes in lipid profiles, decreased coagulation, increased fibrinolysis, inhibition of platelets, increased nitric oxide, and antioxidant capacities of alcoholic beverages. Most of these laboratory and animal studies, as well as small intervention trials in human volunteers, have revealed many interesting mechanisms that contribute to the cardioprotective effects of alcohol, red wine, or red wine polyphenolic compounds. An update on putative mechanisms is presented in this review.


Target engagement approaches for pharmacological evaluation in animal models.
The field of chemical biology has introduced several approaches, typically using chemical probes, to measure the direct binding interaction of a small molecule with its biological target in cells. The use of these direct target engagement assays in pharmaceutical development can support mechanism of action hypothesis testing, rank ordering of compounds, and iterative improvements of chemical matter. This Feature Article highlights a newer application of these approaches: the quantification of target engagement in animal models to support late stage preclinical development and the nomination of a drug candidate to clinical trials. Broadly speaking, these efforts can be divided between compounds that covalently and reversibly interact with protein targets; recent examples for both categories are discussed for a range of targets, along with their limitations. New, promising technologies are also highlighted, in addition to the application of target engagement determination to new therapeutic modalities.


Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling.
Biomaterials for bone tissue engineering must be able to instruct cell behavior in the presence of the complex biophysical and biomolecular environments encountered in vivo. While soluble supplementation strategies have been identified to enhance osteogenesis, they are subject to significant diffusive loss in vivo or the need for frequent re-addition in vitro. This investigation therefore explored whether biophysical and biochemical properties of a mineralized collagen-GAG scaffold were sufficient to enhance human mesenchymal stem cell (hMSC) osteogenic differentiation and matrix remodeling in the absence of supplementation. We examined hMSC metabolic health, osteogenic and matrix gene expression profiles, as well as matrix remodeling and mineral formation as a function of scaffold mineral content. We found that scaffold mineral content enhanced long term hMSC metabolic activity relative to non-mineralized scaffolds. While osteogenic supplementation or exogenous BMP-2 could enhance some markers of hMSC osteogenesis in the mineralized scaffold, we found the mineralized scaffold was itself sufficient to induce osteogenic gene expression, matrix remodeling, and mineral formation. Given significant potential for unintended consequences with the use of mixed media formulations and potential for diffusive loss in vivo, these findings will inform the design of instructive biomaterials for regenerative repair of critical-sized bone defects, as well as for applications where non-uniform responses are required, such as in biomaterials to address spatially-graded interfaces between orthopedic tissues.


Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus.
Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes. To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years. A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California. Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease. At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55). Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.


Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury.
Umbilical cord blood is a rich source of hematopoietic stem cells. It is routinely used for transplantation to repopulate cells of the immune system. Recent studies, however, have demonstrated that intravenous infusions of umbilical cord blood can ameliorate neurologic deficits associated with ischemic brain injury in rodents. Moreover, the infused cells penetrate into the parenchyma of the brain and adopt phenotypic characteristics typical of neural cells. In the present study we tested the hypothesis that the administration of umbilical cord blood can also diminish neurologic deficits caused by intracerebral hemorrhage (ICH). Intracerebral hemorrhage is a major cause of morbidity and mortality, and at the present time there are no adequate therapies that can minimize the consequences of this cerebrovascular event. ICH was induced in rats by intrastriatal injections of collagenase to cause bleeding in the striatum. Twenty-four hours after the induction of ICH rats received intravenous saphenous vein infusions of human umbilical cord blood (2.4 x 10(6) to 3.2 to 10(6) cells). Animals were evaluated using a battery of tests at day 1 after ICH, but before the administration of umbilical cord blood, and at days 7, and 14 after ICH (days 6 and 13, respectively, after cord blood administration). These tests included a neurological severity test, a stepping test, and an elevated body-swing test. Animals with umbilical cord blood infusions exhibited significant improvements in (1) the neurologic severity test at 6 and 13 days after cord blood infusion in comparison to saline-treated animals (P < 0.05); (2) the stepping test at day 6 (P < 0.05); and (3) the elevated body-swing test at day 13 (P< 0.05). These results demonstrate that the administration of human umbilical cord blood cells can ameliorate neurologic deficits associated with intracerebral hemorrhage.


Anti-interleukin 8 autoantibody:interleukin 8 immune complexes visualized by laser confocal microscopy in injured lung.
Anti-interleukin 8 autoantibody:interleukin 8 (anti-IL-8 autoantibody:IL-8) complexes are present in lung fluids of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and levels of these complexes correlate with progression to and the outcome of ARDS. Fc gammaRIIa, an immunoglobulin G (IgG) receptor, mediates proinflammatory activity of the complexes. To evaluate lung tissues from patients with ARDS for presence of anti-IL-8 autoantibody:IL-8 complexes and to establish whether the complexes associate with Fc gammaRIIa. Lung tissue sections from 3 patients with ARDS and sections of normal lung tissues from 3 patients were stained with antibodies against IL-8 and IgG to detect immune complexes and with antibody against Fc gammaRIIa. In some experiments, sections were blocked with anti-Fc gamma RIIa antibody before staining. Samples were analyzed using confocal microscopy. Interleukin 8 costained with IgG and Fc gammaRIIa in lung tissues from patients with ARDS but not in control tissues, suggesting that anti-IL-8 autoantibody:IL-8 complexes are deposited in lungs of patients with ARDS via Fc gammaRIIa. Further, colocalization between IL-8 and Fc gammaRIIa could be blocked by anti-Fc gammaRIIa. Our data demonstrate that anti-IL-8 autoantibody:IL-8 complexes are present in lung tissues of patients with ARDS, and are attached to Fc gammaRIIa.


Cerium chloride reduces enamel lesion initiation and progression in vitro.
Determination of the potential of cerium chloride to reduce artificial carious mineral loss and lesion depth progression. A total of 160 enamel samples were prepared from 40 bovine lower central incisors. Crowns were sectioned into four pieces, embedded in acrylic resin, ground flat and allocated to eight groups (S1-S4 and D1-D4; n = 20). Specimens of groups D1-D4 were stored (for 7 days) in a demineralizing buffer solution to induce caries-like lesions. Afterwards, samples were treated for 30 s with one of the following solutions: placebo (S1 and D1), amine fluoride (S2 and D2), cerium chloride (S3 and D3) and a combination of fluoride and cerium chloride (S4 and D4). After another 7 (D1-D4) or 14 (S1-S4) days in demineralizing buffer solution, integrated mineral loss and lesion depth were determined by transversal microradiography and compared by Scheffé's post hoc tests. In groups S1-S4, the highest values for integrated mineral loss and lesion depth were observed for group S1 (placebo), the lowest values for group S4. The results in groups S2-S4 were not significantly different. In groups D1-D4, the highest values for integrated mineral loss and lesion depth were observed for group D1 (placebo), the lowest values in groups D3 and D4. In group D2, integrated mineral loss and lesion depth were significantly lower as compared to D1, but significantly higher compared to groups D3 and D4. Cerium chloride and its combination with fluoride are able to significantly reduce carious mineral loss and the progression of lesion depth.


Comparison of the 18-item and 6-item Lubben Social Network Scales with community-dwelling older adults in Mongolia.
This study compares the psychometric properties of two versions of the Lubben Social Network Scale (LSNS-18 and LSNS-6) with community dwelling older adults in Mongolia. We recruited 650 older adult in the capital city of Ulaanbaatar and the country's four rural regions. We used the Geriatric Depression Scale (GDS-15), the Short Form 12 (SF-12) physical and mental health functioning measures, and a multi-dimensional scale of social isolation for confirmatory factor analyses of the LSNS-18 and the LSNS-6. Both versions demonstrated excellent internal consistency and intraclass correlation and both correlated in expected directions with other study measures. Only the LSNS-6 provided a good fit to the data. The LSNS-6 is a viable instrument for assessing the social networks of older adults in Mongolia. The study adds to the sparse literature on measuring social and behavioral determinants of health in resource-constrained settings characterized by aging populations and high internal migration rates.


Impedance matching in photonic crystal microcavities for second-harmonic generation.
By numerically integrating the three-dimensional Maxwell equations in the time domain with reference to a dispersive quadratically nonlinear material, we study second-harmonic generation in planar photonic crystal microresonators. The proposed scheme allows efficient coupling of the pump radiation to the defect resonant mode. The outcoupled generated second harmonic is maximized by impedance matching the photonic crystal cavity to the output waveguide.


HD 181068: a red giant in a triply eclipsing compact hierarchical triple system.
Hierarchical triple systems comprise a close binary and a more distant component. They are important for testing theories of star formation and of stellar evolution in the presence of nearby companions. We obtained 218 days of Kepler photometry of HD 181068 (magnitude of 7.1), supplemented by ground-based spectroscopy and interferometry, which show it to be a hierarchical triple with two types of mutual eclipses. The primary is a red giant that is in a 45-day orbit with a pair of red dwarfs in a close 0.9-day orbit. The red giant shows evidence for tidally induced oscillations that are driven by the orbital motion of the close pair. HD 181068 is an ideal target for studies of dynamical evolution and testing tidal friction theories in hierarchical triple systems.


Stability and Biological Activity of E. coli Derived Soluble and Precipitated Bone Morphogenetic Protein-2.
There is a plethora of studies on recombinant human bone morphogenetic protein-2 (rhBMP-2) application and delivery systems, but surprisingly few reports address the biophysical properties of the protein which are of crucial importance to develop effective delivery systems or to solve general problems related to rhBMP-2 production, purification, analysis and application. The solubility, stability and bioactivity of rhBMP-2 obtained by renaturation of E. coli derived inclusion bodies was assessed at different pH and in different buffer systems using (dynamic) light scattering and thermal shift assays as well as intrinsic fluorescence measurements and luciferase based bioassays. rhBMP-2 is poorly soluble at physiological pH and higher. The presence of divalent anions further decreases the solubility even under acidic conditions. Thermal stability analyses revealed that rhBMP-2 precipitates are more stable compared to the soluble protein. Moreover, correctly folded rhBMP-2 is also bioactive as precipitated protein and precipitates readily dissolve under appropriate buffer conditions. Once properly formed rhBMP-2 also retains biological activity after temporary exposure to high concentrations of chaotropic denaturants. However, care should be taken to discriminate bioactive rhBMP-2 precipitates from misfolded rhBMP-2 aggregates, e.g. resolvability in MES buffer (pH 5) and a discrete peak in thermoshift experiments are mandatory for correctly folded rhBMP-2. Our analysis revealed that E. coli derived rhBMP-2 precipitates are not only bioactive but are also more stable compared to the soluble dimeric molecules. Knowledge about these unusual properties will be helpful to design improved delivery systems requiring lower amounts of rhBMP-2 in clinical applications.


Flight speed and body mass of nectar-feeding bats (Glossophaginae) during foraging.
Aerodynamic theory predicts that minimum power (Vmp) and maximum range (Vmr) flight speeds increase when the body mass of an individual animal increases. To evaluate whether foraging bats regulate their flight speed within a fixed speed category relative to Vmp or Vmr, I investigated how the natural daily changes in body mass caused by feeding affected the flight speed of neotropical nectar-feeding bats (Phyllostomidae: Glossophaginae) within a strictly defined, stereotyped behavioural context. Individual bats were maintained in a flight tunnel (lengths of five different types 14-50 m) with a fully automated feeding, weighing (using an electronic balance at the roost) and flight speed measuring system. Flight speeds were measured during normal nocturnal foraging activity by an undisturbed bat while it flew between the two ends of the flight tunnel to obtain food from two computer-controlled nectar-feeders. For a comparison of flight enclosure measurements with field data, flight speeds were also obtained from unrestrained bats foraging in their natural environment (Costa Rica). Foraging flight speeds spanned a range of at least a factor 3 within a single species, which demonstrates the wide range of speeds possible to these animals. Significant, positive correlations between flight speed and the natural individual variability in body mass were found in nearly all cases, with body mass exponents ranging between 0.44 and 2.1. Bats flying at normal speeds were therefore not near their upper limit of muscle power. The most reliable measurements of speed increase with mass (with individual mass changes of up to 30%) were close to the increase theoretically predicted for Vmp and Vmr for an individual bat (with constant wing span and area), which should vary as M0.42, where M is mass. This provides evidence that the glossophagine bats attemped to maintain their flight speed within a fixed speed category relative to Vmp or Vmr during foraging. Among differently sized species of glossophagine bat (N=4), flight speeds V varied with V=20M0.23, in agreement with the mass exponent of 0.21 expected from aerodynamic models for interspecific variation. In addition to the mass effect, at least five other variables significantly influenced flight speed. (1) Both mean and maximum flight speeds increased with the length and the cross-sectional area of the flight tunnel. Mean (maximum) flight speeds of 11-12 g Glossophaga soricina bats (in m s-1) were 4.6 (5.3) over a 7 m and 7. 3 (10.5) over a 50 m flight path. (2) The flight speed range adopted by a bat during one night could vary significantly between nights, independently of body mass and the effect of the size of the flight enclosure. (3) Bats flew significantly faster under illumination than in darkness. This effect was shown (i) by bats kept under natural ambient illumination that initiated foraging during the twilight phase of the evening, (ii) when bats continued to feed into the light phase directly after the dark-light transition in the laboratory and (iii) during foraging under constant, artificial illumination. (4) After a period of rest, the initial flight speed during a foraging bout was significantly increased by 25%, but declined to the mean level within 20 s of activity. (5) Flight speed could differ significantly between foraging (flight from feeder to feeder) versus non-foraging (flight from end to end of the enclosure without visiting the feeders) flights. The results of this study demonstrate a clear ability of bats to regulate their flight speed in response to small natural changes in body mass as predicted by aerodynamic theory for Vmp and Vmr. The set point in flight speed regulation, however, was influenced by multiple additional variables.


Stress hormone levels of children of depressed mothers.
Research suggests that disruptions in early caretaking can have long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response. Children of depressed mothers are at increased risk for developing internalizing problems in part because of disruptions in their caretaking environment. The present study investigated whether children of depressed mothers exhibit elevated salivary cortisol levels. Salivary cortisol samples were collected from 45 7- to 8-year-old children of mothers with a history of depression and 29 children of nondepressed mothers. Samples were collected soon after arrival to the laboratory and after a mild laboratory stressor and at home after wakeup and before bedtime. Children who had elevated levels of intemalizing symptoms and whose mothers had a history of depression showed elevated laboratory baseline cortisol levels. Children who were reported to have clinically significant internalizing symptoms were also more likely to show an elevated stress response to a mild laboratory stressor. When the longitudinal history of maternal depression was examined, matemal depression during the child's first 2 years of life was the best predictor of elevations in baseline cortisol at age 7 years. This study provides evidence that internalizing symptoms exist in conjunction with a more reactive hormonal stress system in children of depressed mothers. The results also provide preliminary evidence that exposure to maternal depression in the first 2 years of life may be related to children's cortisol levels later in life.


Ophthalmic examination findings of Thoroughbred racehorses in Australia.
To record the prevalence and document the types of eye disease in population of Thoroughbred racehorses in Victoria, Australia. Prospective study. Two hundred four Thoroughbred racehorses. All horses and both eyes were examined at four metropolitan and two country racing stable complexes. Ophthalmic exam was performed following dark adaptation with a transilluminator, biomicroscope, and direct ophthalmoscope. Intraocular pressures were measured when indicated. Both pupils were dilated with tropicamide when indicated. One hundred eighty-two (89.2%) flat-racing and 22 (10.8%) jump-racing (hurdle or steeple) horses were examined. Age range: 2-9 years (mean 3.7 years, median 3); 97 (47.5%) male-neuter, 74 (36. 3%) female, 33 (16.2%) male. Potential vision-threatening eye disease was present in 15 (7.4%) different horses: complete lenticular cataracts 3, posterior lens luxation and cataract 1, large peripapillary 'butterfly' inactive lesions 3, large peripapillary 'butterfly' active lesions 2, peripapillary focal inactive 'bullet hole' chorioretinal lesions (> 20) 5, optic nerve atrophy 1. Non-vision threatening eye disease was present in 117 (57.4%) different horses, involving one or more ocular structures: lower eyelid scars 3; periocular fibropapillomatous disease 1; third eyelid squamous cell carcinoma 1; corneal scars 6; corneal band opacity 2; anterior iris synechia 1; developmental cataracts 36 (17.2%); peripapillary focal inactive 'bullet hole' chorioretinal lesions (< 20) 103 (50.0%); linear peripapillary hyperpigmentation bands 16 (7.9%). Unusual variations of normal ocular anatomy and colobomata was recorded in 11 (5.4%) different horses: granular iridica hypoplasia 3, granular iridica hyperplasia 2, multilobular granular iridica cyst 1, microcornea 1, hyaloid remnant 1, rotated optic nerve head 1, coloboma of the lens 1, atypical coloboma of the retina 1. This survey demonstrates that the prevalence of vision-threatening eye disease in racing horses may be greater than previously perceived, and highlights the importance of ocular examination within any routine physical examination of horses.


Heterogeneous functional expression of calcium channels at sensory and synaptic regions in nodose neurons.
1. In the present study we have taken advantage of the unique anatomy of visceral sensory neurons that enabled us to isolate and examine the role of calcium channel subtypes at the soma, central synaptic terminals, and peripheral sensory endings. 2. N-type calcium channels dominated somatic currents (60%), with lesser (16% and 12%) contributions from P- and L-type channels, respectively, in patch-clamped dispersed nodose neurons using toxins selective for each calcium channel subtype. 3. These toxins also blocked the release of neurotransmitters from these visceral synaptic terminals in a brain stem slice. Similar to the profile at the soma, N-type calcium channels were most responsible for neurotransmission at this central glutamatergic synapse (57%), with P- and L-type channels making small contributions (12% and 11%, respectively). 4. In contrast to the soma and central synapses, these calcium channel toxins failed to affect the sensory transduction at aortic baroreceptor endings. 5. Therefore calcium channel subtypes have dramatically heterogenous distributions in sensory neurons that presumably subserve the specialized functions that occur at different cellular regions.


Partial maze procedure is effective treatment for chronic atrial fibrillation associated with valve disease.
The maze procedure may be performed in combination with valve operations to treat chronic atrial fibrillation associated with valve dysfunction. Although we initially used the modified Cox maze III procedure, a more limited partial maze procedure is now preferred because the left atrium might be considered as the electrical impetues for atrial fibrillation. In this study we compared the results of 30 patients (group I) who underwent the full biatrial modified Cox maze III and 20 (group II) patients the partial maze procedure. While the rates of restored sinus rhythm were the same in both groups at 6-month follow-up (I: 83.3%, vs II: 80%), the following advantages were noted in the patients undergoing the partial maze procedure: shorter operative times, lesser elevations of creatine phosphokinase, lower rate of blood transfusion, lower rate of junctional rhythm soon after the operation, and a higher P wave in those patients with restored sinus rhythm. The effectiveness of the partial maze procedure seems equal to that of the biatrial modified Cox maze III procedure for atrial fibrillation associated with valve disease. The partial maze procedure is simple and less invasive, and thus might be applied more frequently as an additional procedure to valve operations without additional risk.


Analysis of the Campylobacter jejuni genome by SMRT DNA sequencing identifies restriction-modification motifs.
Campylobacter jejuni is a leading bacterial cause of human gastroenteritis. The goal of this study was to analyze the C. jejuni F38011 strain, recovered from an individual with severe enteritis, at a genomic and proteomic level to gain insight into microbial processes. The C. jejuni F38011 genome is comprised of 1,691,939 bp, with a mol.% (G+C) content of 30.5%. PacBio sequencing coupled with REBASE analysis was used to predict C. jejuni F38011 genomic sites and enzymes that may be involved in DNA restriction-modification. A total of five putative methylation motifs were identified as well as the C. jejuni enzymes that could be responsible for the modifications. Peptides corresponding to the deduced amino acid sequence of the C. jejuni enzymes were identified using proteomics. This work sets the stage for studies to dissect the precise functions of the C. jejuni putative restriction-modification enzymes. Taken together, the data generated in this study contributes to our knowledge of the genomic content, methylation profile, and encoding capacity of C. jejuni.