Systematic review: do we need a new gastro-oesophageal reflux disease questionnaire?
Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. To evaluate the validity of available GERD measurement tools. An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use. A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria. There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.


Diffusion in a granular fluid. I. Theory.
Many important properties of granular fluids can be represented by a system of hard spheres with inelastic collisions. Traditional methods of nonequilibrium statistical mechanics are effective for analysis and description of the inelastic case as well. This is illustrated here for diffusion of an impurity particle in a fluid undergoing homogeneous cooling. An appropriate scaling of the Liouville equation is described such that the homogeneous cooling ensemble and associated time correlation functions map to those of a stationary state. In this form the familiar methods of linear response can be applied, leading to Green-Kubo and Einstein representations of diffusion in terms of the velocity and mean-square displacement correlation functions. These correlation functions are evaluated approximately using a cumulant expansion and from kinetic theory, providing the diffusion coefficient as a function of the density and the restitution coefficients. Comparisons with results from molecular-dynamics simulation are given in the following companion paper.


A causal role for hyperinsulinemia in obesity.
Insulin modulates the biochemical pathways controlling lipid uptake, lipolysis and lipogenesis at multiple levels. Elevated insulin levels are associated with obesity, and conversely, dietary and pharmacological manipulations that reduce insulin have occasionally been reported to cause weight loss. However, the causal role of insulin hypersecretion in the development of mammalian obesity remained controversial in the absence of direct loss-of-function experiments. Here, we discuss theoretical considerations around the causal role of excess insulin for obesity, as well as recent studies employing mice that are genetically incapable of the rapid and sustained hyperinsulinemia that normally accompanies a high-fat diet. We also discuss new evidence demonstrating that modest reductions in circulating insulin prevent weight gain, with sustained effects that can persist after insulin levels normalize. Importantly, evidence from long-term studies reveals that a modest reduction in circulating insulin is not associated with impaired glucose homeostasis, meaning that body weight and lipid homeostasis are actually more sensitive to small changes in circulating insulin than glucose homeostasis in these models. Collectively, the evidence from new studies on genetic loss-of-function models forces a re-evaluation of current paradigms related to obesity, insulin resistance and diabetes. The potential for translation of these findings to humans is briefly discussed.


Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model.
Propionibacterium acnes is well-known as a human skin commensal but can also act as an invasive pathogen causing implant-associated infections. In order to resolve these types of P. acnes infections, the implants must be removed, due to the presence of an established biofilm that is recalcitrant to antibiotic therapy. In order to identify those P. acnes proteins produced in vivo during a biofilm infection, we established a rabbit model of implant-associated infection with this pathogen. P. acnes biofilms were anaerobically grown on dextran beads that were then inoculated into the left tibias of rabbits. At 4 weeks postinoculation, P. acnes infection was confirmed by radiograph, histology, culture, and PCR. In vivo-produced and immunogenic P. acnes proteins were detected on Western blot using serum samples from rabbits infected with P. acnes after these bacterial proteins were separated by two-dimensional gel electrophoresis. Those proteins that bound host antibodies were then isolated and identified by tandem mass spectrometry. Radiographs and histology demonstrated a disruption in the normal bone architecture and adherent biofilm communities in those animals with confirmed infections. A total of 24 immunogenic proteins were identified; 13 of these proteins were upregulated in both planktonic and biofilm modes, including an ABC transporter protein. We successfully adapted a rabbit model of implant-associated infection for P. acnes to identify P. acnes proteins produced during a chronic biofilm-mediated infection. Further studies are needed to evaluate the potential of these proteins for either a diagnostic test or a vaccine to prevent biofilm infections caused by P. acnes.


The evolutionary history and mechanistic basis of female ornamentation in a tropical songbird.
Ornamentation, such as the showy plumage of birds, is widespread among female vertebrates, yet the evolutionary pressures shaping female ornamentation remain uncertain. In part this is due to a poor understanding of the mechanistic route to ornamentation in females. To address this issue, we evaluated the evolutionary history of ornament expression in a tropical passerine bird, the White-shouldered Fairywren, whose females, but not males, strongly vary between populations in occurrence of ornamented black-and-white plumage. We first use phylogenomic analysis to demonstrate that female ornamentation is derived and that female ornamentation evolves independently of changes in male plumage. We then use exogenous testosterone in a field experiment to induce partial ornamentation in naturally unornamented females. By sequencing the transcriptome of experimentally induced ornamented and natural feathers, we identify genes expressed during ornament production and evaluate the degree to which female ornamentation in this system is associated with elevated testosterone, as is common in males. We reveal that some ornamentation in females is linked to testosterone and that sexes differ in ornament-linked gene expression. Lastly, using genomic outlier analysis we identify a candidate melanogenesis gene that lies in a region of high genomic divergence among populations that is also differentially expressed in feather follicles of different female plumages. Taken together, these findings are consistent with sex-specific selection favoring the evolution of female ornaments and demonstrate a key role for testosterone in generating population divergence in female ornamentation through gene regulation. More broadly, our work highlights similarities and differences in how ornamentation evolves in the sexes.


Moderate toxic effects following acute zonisamide overdose.
Zonisamide is an antiepileptic drug that acts on voltage-sensitive sodium and calcium channels, with a modulatory effect on GABA-mediated neuronal inhibition and an inhibitory effect on carbonic anhydrase. It is used mainly for the treatment of partial seizures, and is generally well tolerated at therapeutic doses. The most common reported adverse effects are somnolence, anorexia, dizziness, and headache. There are limited data on zonisamide overdose in the literature, and no case of zonisamide mono-intoxication has been published to date. We describe the first case of zonisamide mono-intoxication in a 25-year-old woman who ingested 12.6 g of this substance with suicidal intent. Despite a plasma zonisamide concentration of 182 mg/L on admission, the patient exhibited a benign clinical course with vomiting and central nervous system depression, requiring brief intubation. Somnolence persisted for 50 hours, and normal-anion-gap metabolic acidosis and polyuria for several days. Complete recovery may be expected with supportive care, even after ingestion of large zonisamide overdoses.


Carbon nanotubes as an efficient hole collector for high voltage methylammonium lead bromide perovskite solar cells.
A high open circuit voltage (V(OC)) close to 1.4 V under AM 1.5, 100 mW cm(-2) conditions is achieved when carbon nanotubes (CNTs) are used as a hole conductor in methyl ammonium lead bromide (MAPbBr3) perovskite solar cells. Time-resolved photoluminescence and impedance spectroscopy investigations suggest that the observed high V(OC) is a result of the better charge extraction and lower recombination of the CNT hole conductor. Tandem solar cells with all perovskite absorbers are demonstrated with a MAPbBr3/CNT top cell and a MAPbI3 bottom cell, achieving a V(OC) of 2.24 V in series connection. The semitransparent and high voltage MAPbBr3/CNT solar cells show great potential for applications in solar cell windows, tandem solar cells and solar driven water splitting.


Nasal douching as a valuable adjunct in the management of chronic rhinosinusitis.
The effect of nasal douching in 40 patients with chronic rhinosinusitis was tested, and two different preparations compared: 19 receiving traditional alkaline nasal douche and 21 receiving a sterile sea water spray, in addition to their regular treatment. Douching per se improved endoscopic appearances (p = .009), and quality of life scores (p = .008). These measures did not change in a control group (n = 22) who received standard treatment for chronic rhinosinusitis, but no douche. There were significant differences between the two douching preparations in that the alkaline nasal douche improved endoscopic appearances but not quality of life, whereas the opposite was true for the spray.


Using Raman spectroscopy to assess hemoglobin oxygenation in red blood cell concentrate: an objective proxy for morphological index to gauge the quality of stored blood?
Blood banking is an essential aspect of modern medical care. When red blood cells (RBCs) are stored, they become damaged by various chemical processes, such as accumulation of their own waste products and oxidative injury, among others. These processes lead to the development of the RBC storage lesion, a complex condition where the severity is reflected through the morphology of the stored cells. It was hypothesized that Raman spectroscopy could be used to monitor certain structural and compositional changes associated with such ageing effects and that a relationship between these features and traditional morphology (as measured using a morphology index) could be observed. The hypothesis was tested by measuring spectral features associated with hemoglobin oxygenation from dry-fixed smears and liquid RBCs for twenty-nine different donors (combined), and comparing the trends with morphological scoring from seven of these donors. After appropriately fitting the two data sets to either power or linear curves, the oxygenation state was shown to change in a manner that was donor-dependent and that closely tracked morphological changes. This study suggests Raman analysis has promise for providing a rapid and objective measure of the cell quality of stored RBCs through measurements of hemoglobin oxygenation that is comparable to traditional morphological assessment.


Experiences of forced sex among female patrons of alcohol-serving venues in a South African township.
South Africa has among the highest rates of forced sex worldwide, and alcohol use has consistently been associated with risk of forced sex in South Africa. However, methodological challenges affect the accuracy of forced sex measurements. This study explored the assessment of forced sex among South African women attending alcohol-serving venues and identified factors associated with reporting recent forced sex. Women (n = 785) were recruited from 12 alcohol-serving venues in a peri-urban township in Cape Town. Brief self-administered surveys included questions about lifetime and recent experiences of forced sex. Surveys included a single question about forced sex and detailed questions about sex by physical force, threats, verbal persuasion, trickery, and spiked drinks. We first compared the single question about forced sex to a composite variable of forced sex as unwanted sex by physical force, threats, or spiked drinks. We then examined potential predictors of recent forced sex (demographics, drinking behavior, relationship to the venue, abuse experiences). The single question about forced sex had low sensitivity (0.38); more than half of the respondents who reported on the detailed questions that they had experienced forced sex by physical force, threats, or spiked drinks reported on the single question item that they had not experienced forced sex. Using our composite variable, 18.6% of women reported lifetime and 10.8% reported recent experiences of forced sex. In our adjusted logistic regression model, recent forced sex using the composite variable was significantly associated with hazardous drinking (OR = 1.92), living farther from the venue (OR = 1.81), recent intimate partner violence (OR = 2.53), and a history of childhood sexual abuse (OR = 4.35). The findings support the need for additional work to refine the assessment of forced sex. Efforts to prevent forced sex should target alcohol-serving venues, where norms and behaviors may present particular risks for women who frequent these settings.


Quantitative surface analysis of a binary drug mixture--suppression effects in the detection of sputtered ions and post-ionized neutrals.
A systematic mass spectrometric study of two of the most common analgesic drugs, paracetamol and ibuprofen, is reported. The drugs were studied by means of secondary ion mass spectrometry (SIMS) and secondary neutral mass spectrometry (SNMS) using laser post-ionization (LPI) both in pure samples and in a two-component mixture. Ion suppression within the two-component system observed in SIMS mode is ameliorated using LPI under room temperature analysis. However, suppression effects are apparent in LPI mode on performing the analysis at cryogenic temperatures, which we attribute to changes in the desorption characteristics of sputtered molecules, which influences the subsequent post-ionization efficiency. This suggests different mechanisms of ion suppression in SIMS and LPI modes.


Feasibility of using terahertz spectroscopy to detect seven different pesticides in wheat flour.
This study investigated the feasibility of detecting pesticides using terahertz (THz) spectroscopy in high-density polyethylene and/or wheat flour mixtures. The absorption spectra of seven pesticides (dicofol, chlorpyrifos, chlorpyrifos-methyl, daminozide, imidacloprid, diethyldithiocarbamate, and dimethyldithiocarbamate) were measured in the frequency range 0.1 to 3 THz at room temperature. Five of the seven pesticides exhibited specific absorption peaks in the low-energy THz range. The two remaining pesticides had no specific absorption peaks in this frequency range, but they exhibited different frequency-dependent refractive indices. The absorption coefficients of imidacloprid increased with its increasing weight ratio in high-density polyethylene, and the fitted power absorptions and refractive indices using a Maxwell-Garnett effective medium model were comparable to the measured data. Imidacloprid was also identified from its characteristic absorption peaks in wheat flour mixtures, and a linear relationship between the absorption coefficient and the weight ratio was observed. Our results show the potential of detection of selected pesticides in foods, such as wheat flour, using THz spectroscopy.


Bilirubin/Albumin Ratio for Predicting Acute Bilirubin-induced Neurologic Dysfunction.
The aim of this study was to evaluate the bilirubin albumin (B/A) ratio in comparison with total serum bilirubin (TSB) for predicting acute bilirubin-induced neurologic dysfunction (BIND). Fifty two term and near term neonates requiring phototherapy and exchange transfusion for severe hyperbilirubinemia in Children's Medical Center, Tehran, Iran, during September 2007 to September 2008, were evaluated. Serum albumin and bilirubin were measured at admission. All neonates were evaluated for acute BIND based on clinical findings. Acute BIND developed in 5 (3.8%) neonates. B/A ratio in patients with BIND was significantly higher than in patients without BIND (P<0.001). Receiver operation characteristics (ROC) analysis identified a TSB cut off value of 25 mg/dL [area under the curve (AUC) 0.945] with a sensitivity of 100% and specificity of 85%. Also, according to the ROC curve, B/A ratio cut off value for predicting acute BIND was 8 (bil mg/al g) (AUC 0.957) with sensitivity of 100% and specificity of 94%. Based on our results, we suggest using B/A ratio in conjunction with TSB. This can improve the specificity and prevent unnecessary invasive therapy such as exchange transfusion in icteric neonates.


The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers: Implications for counseling.
The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC). From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n = 351) or mutation carriers who had a previous unilateral BC (n = 294), respectively. The risks of PBC and CBC were calculated using the Kaplan-Meier survival method with death considered as a competing risk event. Women with BRCA-associated OC had lower 2-year, 5-year, and 10-year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P = .03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC, the 2-year, 5-year, and 10-year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P = .06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P < .001). Patients with BRCA-associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted.


Carbamylation of immunoglobulin abrogates activation of the classical complement pathway.
Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG1 carbamylation under inflammatory conditions and the effects that this modification has on the ability of antibodies to trigger complement activation via the classical pathway. We found that the lysine residues of IgG1 are rapidly modified after brief exposure to CNO- . Interestingly, modifications were not random, but instead limited to only few lysines within the hinge area and the N-terminal fragment of the CH2 domain. A complement activation assay combined with mass spectrometry analysis revealed a highly significant inverse correlation between carbamylation of several key lysine residues within the hinge region and N-terminus of the CH2 domain and the proper binding of C1q to human IgG1 followed by subsequent complement activation. This severely hindered complement-dependent cytotoxicity of therapeutic IgG1 . The reaction can apparently occur in vivo, as we found carbamylated antibodies in synovial fluid from rheumatoid arthritis patients. Taken together, our data suggest that carbamylation has a profound impact on the complement-activating ability of IgG1 and reveals a pivotal role for previously uncharacterized lysine residues in this process.


A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume.
Atlas normalization, as commonly used by functional data analysis, provides an automated solution to the widely encountered problem of correcting for head size variation in regional and whole-brain morphometric analyses, so long as an age- and population-appropriate target atlas is used. In the present article, we develop and validate an atlas normalization procedure for head size correction using manual total intracranial volume (TIV) measurement as a reference. The target image used for atlas transformation consisted of a merged young and old-adult template specifically created for cross age-span normalization. Automated atlas transformation generated the Atlas Scaling Factor (ASF) defined as the volume-scaling factor required to match each individual to the atlas target. Because atlas normalization equates head size, the ASF should be proportional to TIV. A validation analysis was performed on 147 subjects to evaluate ASF as a proxy for manual TIV measurement. In addition, 19 subjects were imaged on multiple days to assess test-retest reliability. Results indicated that the ASF was (1) equivalent to manual TIV normalization (r = 0.93), (2) reliable across multiple imaging sessions (r = 1.00; mean absolute percentage of difference = 0.51%), (3) able to connect between-gender head size differences, and (4) minimally biased in demented older adults with marked atrophy. Hippocampal volume differences between nondemented (n = 49) and demented (n = 50) older adults (measured manually) were equivalent whether corrected using manual TIV or automated ASF (effect sizes of 1.29 and 1.46, respectively). To provide normative values, ASF was used to automatically derive estimated TIV (eTIV) in 335 subjects aged 15-96 including both clinically characterized nondemented (n = 77) and demented (n = 90) older adults. Differences in eTIV between nondemented and demented groups were negligible, thus failing to support the hypothesis that large premorbid brain size moderates Alzheimer's disease. Gender was the only robust factor that influenced eTIV. Men showed an approximately approximately 12% larger eTIV than women. These results demonstrate that atlas normalization using appropriate template images provides a robust, automated method for head size correction that is equivalent to manual TIV correction in studies of aging and dementia. Thus, atlas normalization provides a common framework for both morphometric and functional data analysis.


Antibodies reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein, in sera from children.
Recent data indicate that the Simian virus 40 (SV40) infection appears to be transmitted in humans independently from early SV40-contaminated antipolio vaccines. Serum antibodies against SV40 large T antigen (Tag) were analyzed in children/adolescents and young adults. To investigate antibodies reacting to SV40 Tag antigens, serum samples ( n = 812) from children and young adults were analyzed by indirect ELISAs using specific SV40 Tag mimotopes. Mimotopes were synthetic peptides corresponding to SV40 Tag epitopes. In sera ( n = 412) from healthy children up to 17 years old, IgG antibodies against SV40 Tag mimotopes reached an overall prevalence of 15%. IgM antibodies against SV40 Tag were detected in sera of children 6-8 months old confirming and extending the knowledge that SV40 seroconversion occurs early in life. In children/adolescents affected by different diseases ( n = 180) SV40 Tag had a prevalence of 18%, being the difference no significant compared to healthy subjects ( n = 220; 16%) of the same age. Our immunological data indicate that SV40 circulates in children and young adults, both in healthy conditions and affected by distinct diseases. The IgM detection in sera from healthy children suggests that the SV40 infection/seroconversion occurs early in life (>6 months). Our immunological data support the hypothesis that SV40, or a closely related still unknown polyomavirus, infects humans. The SV40 seroprevalence is lower than common polyomaviruses, such as BKPyV and JCPyV, and other new human polyomaviruses. In addition, our immunological surveillance indicates a lack of association between different diseases, considered herein, and SV40.


Measuring dlPFC Signals to Predict the Success of Merchandising Elements at the Point-of-Sale - A fNIRS Approach.
The (re-)launch of products is frequently accompanied by point-of-sale (PoS) marketing campaigns in order to foster sales. Predicting the success of these merchandising elements at the PoS on sales is of interest to research and practice, as the misinvestments that are based on the fragmented PoS literature are tremendous. Likewise, the predictive power of neuropsychological methods has been demonstrated in various research work. Nevertheless, the practical application of these neuropsychological methods is still limited. In order to foster the application of neuropsychological methods in research and practice, the current research work aims to explore, whether mobile functional near-infrared spectroscopy (fNIRS) - as a portable neuroimaging method - has the potential to predict the success of PoS merchandising elements by rendering significant neural signatures of brain regions of the dorsolateral prefrontal cortex (dlPFC), highlighting its potential to forecast shoppers' behaviour aka sales at the PoS. Building on previous research findings, the results of the given research work indicate that the neural signal of brain regions of the dlPFC, measured with mobile fNIRS, is able to predict actual sales associated with PoS merchandising elements, relying on the cortical relief effect. More precisely, the research findings support the hypothesis that the reduced neural activity of brain regions associated with the dlPFC can predict sales at the PoS, emphasising another crucial neural signature to predict shoppers' purchase behaviour, next to the frequently cited reward association system. The research findings offer an innovative perspective on how to design and evaluate PoS merchandising elements, indicating fruitful theoretical and practical implications.


Localisation of quantitative trait loci for quality attributes in a doubled haploid population of wheat (Triticum aestivum L.).
Selection of wheat germplasm for a range of quality traits has been a challenging exercise because of the cost of testing, the variation within testing data, and a poor understanding of the underlying genetics. The objective of this study was to identify quantitative trait loci (QTLs) underlying quality traits in wheat. A doubled haploid population comprising 190 lines from Chara/WW2449 was grown in two different environments and evaluated for various quality traits. A molecular map comprising 362 markers based upon simple sequence repeat, sequence tagged microsatellite, glutenin, and DArT loci was constructed and subsequently exploited to identify QTLs using a whole-genome approach. Fifteen QTLs that were consistent in the two different environments were identified for thousand kernel mass, grain protein content, milling yield, flour protein content, flour colour, flour water absorption, dough development time, dough strength (extensograph height and resistance at 5 cm), and dough extensibility (extensograph length) using the whole genome average interval mapping approach. The amount of genetic variation explained by individual QTLs ranged from 3% to 49%. A number of QTLs associated with dough strength, dough extensibility, dough development time, and flour water absorption were located close to the glutenin Glu-B1 locus on chromosome 1B. Identification of the chromosomal location and effect of the QTLs influencing wheat quality may hasten the development of superior wheats for target markets via marker-assisted selection.


Beam-width-dependent filtering properties of strong volume holographic gratings.
The finite dimension of the incident beam used to read out volume holographic gratings has interesting effects on their filtering properties. As the readout beam gets narrower, there is more deviation from the ideal response predicted for monochromatic plane waves. In this paper we experimentally explore beam-width-dependent phenomena such as wavelength selectivities, angular selectivities, and diffracted beam profiles. Volume gratings in both reflection and transmission geometries are investigated near 1550 nm. Numerical simulations utilizing the technique of Fourier decomposition provide a satisfactory explanation and confirm that the spread of spatial harmonics is the main contributing factor.


Alteration of fibrin hydrogel gelation and degradation kinetics through addition of azo dyes.
Fibrin is a degradable biopolymer with an excellent clinical safety profile. Use of higher mechanical strength fibrin hydrogels is limited by the rapid rate of fibrin polymerization. We recently demonstrated the use of higher mechanical strength (fibrinogen concentrations >30 mg/ml) fibrin scaffolds for surgical implantation of cells. The rapid polymerization of fibrin at fibrinogen concentrations impaired our ability to scale production of these fibrin scaffolds. We serendipitously discovered that the azo dye Trypan blue (TB) slowed fibrin gelation kinetics allowing for more uniform mixing of fibrinogen and thrombin at high concentrations. A screen of closely related compounds identified similar activity for Evans blue (EB), an isomer of TB. Both TB and EB exhibited a concentration dependent increase in clot time, though EB had a larger effect. While gelation time was increased by TB or EB, overall polymerization time was unaffected. Scanning electron microscopy showed similar surface topography, but transmission electron microscopy showed a higher cross-linking density for gels formed with TB or EB versus controls. Based on these data we conclude that addition of TB or EB during thrombin mediated fibrin polymerization slows the initial gelation time permitting generation of larger more uniform fibrin hydrogels with high-mechanical strength.


Developmental control of the melanocortin-4 receptor by MRAP2 proteins in zebrafish.
The melanocortin-4 receptor (MC4R) is essential for control of energy homeostasis in vertebrates. MC4R interacts with melanocortin receptor accessory protein 2 (MRAP2) in vitro, but its functions in vivo are unknown. We found that MRAP2a, a larval form, stimulates growth of zebrafish by specifically blocking the action of MC4R. In cell culture, this protein binds MC4R and reduces the ability of the receptor to bind its ligand, α-melanocyte-stimulating hormone (α-MSH). A paralog, MRAP2b, expressed later in development, also binds MC4R but increases ligand sensitivity. Thus, MRAP2 proteins allow for developmental control of MC4R activity, with MRAP2a blocking its function and stimulating growth during larval development, whereas MRAP2b enhances responsiveness to α-MSH once the zebrafish begins feeding, thus increasing the capacity for regulated feeding and growth.


Effects of air pollution on heart rate variability: the VA normative aging study.
Reduced heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with air pollution, especially fine particulate matter [< 2.5 microm in aerodynamic diameter (PM2.5)]. We examined the relationship between HRV [standard deviation of normal-to-normal intervals (SDNN), power in high frequency (HF) and low frequency (LF), and LF:HF ratio] and ambient air pollutants in 497 men from the Normative Aging Study in greater Boston, Massachusetts, seen between November 2000 and October 2003. We examined 4-hr, 24-hr, and 48-hr moving averages of air pollution (PM2.5, particle number concentration, black carbon, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide). Controlling for potential confounders, HF decreased 20.8% [95% confidence interval (CI), 4.6-34.2%] and LF:HF ratio increased 18.6% (95% CI, 4.1-35.2%) per SD (8 microg/m3) increase in 48-hr PM2.5. LF was reduced by 11.5% (95% CI, 0.4-21.3%) per SD (13 ppb) increment in 4-hr O3. The associations between HRV and PM2.5 and O3 were stronger in people with ischemic heart disease (IHD) and hypertension. The associations observed between SDNN and LF and PM2.5 were stronger in people with diabetes. People using calcium-channel blockers and beta-blockers had lower associations between O3 and PM2.5 with LF. No effect modification by other cardiac medications was found. Exposures to PM2.5 and O3 are associated with decreased HRV, and history of IHD, hypertension, and diabetes may confer susceptibility to autonomic dysfunction by air pollution.


Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.


Musculoskeletal health of Indigenous Australians.
Research on non-communicable diseases (NCD) in Indigenous Australians has mostly focused on diabetes mellitus and chronic kidney or cardiovascular disease. Osteoporosis, characterised by low bone mass and structural deterioration of bone tissue, and sarcopenia, the age-related loss of muscle mass and strength, often co-exist with these common NCDs-the combination of which will disproportionately increase bone fragility and fracture risk and negatively influence cortical and trabecular bone. Furthermore, the social gradient of NCDs, including osteoporosis and fracture, is well-documented, meaning that specific population groups are likely to be at greater risk of poorer health outcomes: Indigenous Australians are one such group. This review summarises the findings reported in the literature regarding the muscle and bone health of Indigenous Australians. There are limited data regarding the musculoskeletal health of Indigenous Australians; however, areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) is reported to be greater at the hip compared to non-Indigenous Australians. Falls are the leading cause of injury-related hospitalisations in older Australians, particularly Indigenous Australians, with a great proportion suffering from fall-related fractures. Despite sparse data, it appears that Indigenous men and women have a substantially higher risk of hip fracture at a much younger age compared to non-Indigenous Australians. Data on more detailed musculoskeletal health outcomes are required in Indigenous Australians to better understand fracture risk and to formulate evidence-based strategies for fracture prevention and to minimise the risk of falls.


Structural events in the photocycle of green fluorescent protein.
Picosecond time-resolved mid-infrared absorption changes of the wild type green fluorescent protein from Aequorea victoria are reported on structural events during the photocycle. Concomitant with rapid H/D transfer following excitation of the neutral A state at 400 nm, a transient signal at 1721/1711 cm(-1) (H/D) developed belonging to protonated glutamate 222, which was definitively assigned using the E222D mutant from the altered proton-transfer kinetics to aspartate in addition to the altered band position and intensity in the spectra. A transient at 1697 cm(-1), assigned to a structural perturbation of glutamine 69, had a H/D kinetic isotope effect of >32, showing the conformational dynamics to be sensitive to the active site H/D vibrations. The kinetic data up to 2 ns after excitation in the 1250-1800 cm(-1) region in D2O provided 10 and 75 ps time constants for the excited-state deuteron transfer and the associated A1* - A1 and A2* - A2 difference spectra and showed the radiative intermediate I state vibrations and the transient accumulation of the long-lived ground-state intermediate I2. Assignments of chromophore modes for the A1, A2, and I2 ground states are proposed on the basis of published model compound studies (Esposito, A. P.; Schellenberg, P.; Parson, W. W.; Reid, P. J. J. Mol. Struct. 2001, 569, 25 and He, X.; Bell, A. F.; Tonge, P. J. J. Phys. Chem. B 2002, 106, 6056). Tentative assignments for the singlet-state intermediates A1*, A2*, and I* are discussed. An unexpected and unassigned band that may be a C=C chromophore vibration was observed in the ground state (1665 cm(-1)) as well as in all photocycle intermediates. Optical dumping of the transient I population was achieved using an additional 532 nm pulse and the directly obtained I2 - I* difference spectrum was highly similar to the I2 - I* photocycle spectrum. The pump-dump-probe spectrum differed from the pump-probe photocycle difference spectrum with respect to the intensity of the phenol 1 mode at 1578 cm(-1), suggesting stronger delocalization of the negative charge onto the phenolic ring of the anionic chromophore in the dumped I2 state. Indication for structural heterogeneity of the chromophore, Glu 222, and the chromophore environment was found in the two parallel proton-transfer reactions and their distinct associated ground- and intermediate-state vibrations. Vibrational spectral markers at 1695 cm(-1) assigned to Gln 69, at 1631 cm(-1) belonging to a C=C mode, and at 1354 cm(-1) belonging to a phenolate vibration further indicated the I2 and I* states to be unrelaxed.


Television and video game exposure and the development of attention problems.
Television viewing has been associated with greater subsequent attention problems in children. Few studies have examined the possibility of a similar association between video games and attention problems, and none of these has used a longitudinal design. A sample of 1323 middle childhood participants were assessed during a 13-month period by parent- and child-reported television and video game exposure as well as teacher-reported attention problems. Another sample of 210 late adolescent/early adult participants provided self-reports of television exposure, video game exposure, and attention problems. Exposure to television and video games was associated with greater attention problems. The association of television and video games to attention problems in the middle childhood sample remained significant when earlier attention problems and gender were statistically controlled. The associations of screen media and attention problems were similar across media type (television or video games) and age (middle childhood or late adolescent/early adult). Viewing television and playing video games each are associated with increased subsequent attention problems in childhood. It seems that a similar association among television, video games, and attention problems exists in late adolescence and early adulthood. Research on potential risk factors for attention problems should be expanded to include video games in addition to television.


Contemporary Outcomes Following Coronary Artery Bypass Graft Surgery for Left Main Disease.
Although results of percutaneous coronary intervention (PCI) have been steadily improving, whether surgical outcomes have improved over time is not fully elucidated. This study sought to compare the current outcomes of patients undergoing coronary artery bypass grafting (CABG) with prior surgical results, in the context of randomized trials including the left main (LM) coronary artery stem. The authors performed a propensity-matched analysis of patients randomized to CABG in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) (enrollment period 2005 to 2007) and EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) (enrollment period 2010 to 2014) trials. All patients had left main (LM) disease with or without multivessel disease. Adjustment was based on 15 clinical and angiographic variables, including anatomic SYNTAX score, with a 2:1 ratio for the EXCEL and SYNTAX trials, collectively analyzing 909 subjects (n = 580 and n = 329, respectively). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, or ischemia-driven revascularization at 3 years. Baseline characteristics, anatomic SYNTAX score, number and types of grafts, and duration of hospitalization for the procedures were similar in both groups. CABG procedures in the EXCEL compared with the SYNTAX trial were more often off-pump (29.6% vs. 15.4%; p < 0.001), and guideline-directed medical therapies were used more frequently in the EXCEL surgical cohort. The primary endpoint occurred in 14.0% and 20.9% (p = 0.008) of patients in the EXCEL and SYNTAX trials, respectively. With the exception of MI (4.1% vs. 3.7%), all nonhierarchical events tended to contribute to the improved outcomes in the more recent trial: all-cause death (5.5% vs. 8.5%), stroke (3.1% vs. 5.1%), and ischemia-driven revascularization (7.1% vs. 9.4%) in the EXCEL and SYNTAX trials, respectively. Over a 5- to 7-year period, significant improvement in event-free survival after surgical revascularization for LM disease at 3 years was noted between the SYNTAX and EXCEL trials, consistent with improving results with cardiac surgery over time. (Synergy Between PCI With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972; Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776).


Gap junctions between cultured astrocytes: immunocytochemical, molecular, and electrophysiological analysis.
The properties of astroglial gap junction channels and the protein that constitutes the channels were characterized by immunocytochemical, molecular biological, and physiological techniques. Comparative immunocytochemical labeling utilizing different antibodies specific for liver connexin 32 and connexin 26 and antibodies to peptides corresponding to carboxy-terminal sequences of the heart gap junction protein (connexin 43) indicates that the predominant gap junction protein in astrocytes is connexin 43. The expression of this connexin in cultured astrocytes was also established by Western and Northern blot analyses. Cultured astrocytes expressed connexin 43 mRNA and did not contain detectable levels of the mRNAs encoding connexin 32 or connexin 26. Further, the cells contained the same primary connexin 43 translation product and the same phosphorylated forms as heart. Finally, electrophysiological recordings under voltage-clamp conditions revealed that astrocyte cell pairs were moderately well coupled, with an average junctional conductance of about 13 nS. Single-channel recordings indicated a unitary junctional conductance of about 50-60 pS, which is of the same order as that found in cultured rat cardiac myocytes, where the channel properties of connexin 43 were first described. Thus, physiological properties of gap junction channels appear to be determined by the connexin expressed, independent of the tissue type.


Biomechanical Profiles When Towing a Sled and Wearing a Weighted Vest Once Cleared for Sports Post-ACL Reconstruction.
Though rehabilitation attempts to correct "stiff knee gait" and control for dynamic limb valgus after anterior cruciate ligament reconstruction (ACLR), impaired biomechanics often persist when an individual is cleared to return to sport (RTS). Reduced knee extension moments (KEMs) and knee flexion angles (KFAs) often continue. While at the hip, increased hip adduction angles (HADDAs) and hip internal rotation angles (HIRAs) often persist in spite of dynamic hip stabilization exercises. Sled towing and weighted vest tasks increase KEM and hip extension moments (HEMs) in healthy individuals, yet biomechanical profiles during these tasks after ACLR are unknown. Weighted gait will increase KEM, HEM, hip abduction moments (HABDMs), and hip external rotation moments (HERMs) and will not increase unwanted biomechanics (limb asymmetries, HIRA, HADDA) compared with normal gait. Controlled laboratory study. Level 4. Fourteen men and 24 women who were 5 to 12 months after ACLR, had no concomitant ligament injuries, and were cleared to RTS were recruited. Sexes were evaluated independently given the sex-specific incidence to ACL injury, reinjury, and gait responses to certain interventions. Joint moment impulses and peak angles over the first 25% of stance were compared between limbs and across tasks (eg, unweighted gait, sled 50% body weight [BW], and vest 50% BW). Men showed that weighted gait increased KEM, HEM, HERM, HADBM (vest only), HADDA, HIRA (sled only), and KFA. Asymmetrical KEM and KFA existed across tasks. Women showed that weighted gait increased KEM, HEM, HERM, HADBM (vest only), HFA (sled only), HADDA, and KFA. Asymmetrical KEM, HEM, HIRA, and KFA (sled only) existed across tasks. Weighted gait generally increased joint moments. Unwanted biomechanics were unique for each weighted gait task. Though joint moments increased, both tasks created unwanted biomechanics after ACLR. Persistent hip (women only) and KEM asymmetries across tasks when cleared to RTS are concerning given the relationship among these biomechanics and decreased functional performance.


Will exhaled nitric oxide monitoring become routine in managing asthma?
In this editorial, we outline the rationale for a new approach to the assessment of airway disease based on measurement of airway inflammation using noninvasive markers (inflammometry). Our focus is on measurement of exhaled nitric oxide (FE(NO)), as this technique is simple and affordable, and is applicable in a wide variety of clinical settings. Studies have shown that raised FE(NO) is a useful marker of corticosteroid-responsive airway disease; low FE(NO) may identify patients who can safely reduce or withdraw corticosteroids. However, the optimum use of FE(NO) in clinical practice remains to be established.


Community size as a factor in health partnerships in community parks and recreation, 2007.
Although partnerships between park and recreation agencies and health agencies are prevalent, little research has examined partnership characteristics and effectiveness among communities of different sizes. The objective of this study was to determine whether park and recreation leaders' perceptions of partnership characteristics, effectiveness, and outcomes vary by community size. A web-based survey was completed in 2007 by 1,217 National Recreation and Park Association members. Community size was divided into 4 categories: very small, small, medium, and large. Questions measured agencies' recognition of the need for partnerships, their level of experience, and the effectiveness and outcomes of partnerships. Larger communities were significantly more likely to recognize the need for and have more experience with partnerships than smaller communities. Very small and large communities partnered significantly more often with senior services, nonprofit health promotion agencies, and public health agencies than did small and medium ones. Large and small communities were significantly more likely than very small and medium communities to agree that their decision making in partnerships is inclusive and that they have clearly defined goals and objectives. Large communities were significantly more likely than very small communities to report that their partnership helped leverage resources, make policy changes, meet their mission statement, and link to funding opportunities. Community size shapes partnership practices, effectiveness, and outcomes. Very small communities are disadvantaged in developing and managing health partnerships. Increasing education, training, and funding opportunities for small and rural park and recreation agencies may enable them to more effectively partner with organizations to address community health concerns.


Transdermal nicotine for analgesia after radical retropubic prostatectomy.
Previous animal and human studies suggested that nicotine might have an antinociceptive effect. We hypothesized that the preoperative application of a 7 mg nicotine patch would result in reduced postoperative analgesic requirements in patients undergoing radical retropubic prostatectomy (RRP) under general anesthesia. Nonsmokers undergoing RRP under general anesthesia were enrolled in this prospective, double-blind, placebo-controlled study. Patients were randomly assigned to receive a patch of 7 mg nicotine or placebo applied behind the ear 30-60 min before induction of anesthesia. The anesthetic technique was standardized. Postoperative analgesia was provided with a standardized morphine patient-controlled analgesia and 6 hourly ketorolac 15 mg IV. Data were collected in the postanesthesia care unit and at 6, 12, and 24 h after surgery. Ninety patients were included in the analysis: 44 in the nicotine group and 46 in the placebo group. The groups did not differ significantly with respect to age, height, weight, ASA class, length of surgery, or amounts of intraoperative fentanyl received. The nicotine group showed significantly lower cumulative morphine consumption at 24 h (mean +/- sd): 33.3 +/- 30.8 mg vs 44.7 +/- 26.4 mg (P = 0.0059, time x treatment P = 0.0031). However, the repeated measures tests found no difference in amount of pain reported on coughing or at rest, either as treatment effects or in interaction with time. In post hoc comparisons, there was no significant difference in amount of pain reported on coughing or at rest at any of the times assessed. There were also no significant differences between the groups in the incidence of postoperative nausea and vomiting or the need for rescue antiemetics. However, the maximum nausea verbal rating scale score was higher in the nicotine than in the placebo group (median, 25th to 75th percentiles = 4, 0-6 vs 0, 0-6, P = 0.0158). There was a significant negative correlation between the 24 h plasma nicotine levels and postoperative morphine consumption in the postanesthesia care unit (P = 0.049), as well as at 6, 12, and 24 h (P = 0.002). The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in opioid consumption in patients undergoing RRP under general anesthesia. Despite this reduction in opioid use, there was no reduction in pain scores or postoperative nausea and vomiting with the use of transdermal nicotine.


Large-scale evaluation of multimodal biometric authentication using state-of-the-art systems.
We examine the performance of multimodal biometric authentication systems using state-of-the-art Commercial Off-the-Shelf (COTS) fingerprint and face biometric systems on a population approaching 1,000 individuals. The majority of prior studies of multimodal biometrics have been limited to relatively low accuracy non-COTS systems and populations of a few hundred users. Our work is the first to demonstrate that multimodal fingerprint and face biometric systems can achieve significant accuracy gains over either biometric alone, even when using highly accurate COTS systems on a relatively large-scale population. In addition to examining well-known multimodal methods, we introduce new methods of normalization and fusion that further improve the accuracy.


Oxidative stress and inflammatory process in patients with atrial fibrillation: the role of left atrium distension.
Atrial fibrillation has been associated with increased oxidative stress, elevated inflammatory status and endothelial dysfunction. However, the underlying mechanisms regulating the expression of inflammatory markers or oxidative stress status are unclear. We searched for clinical determinants of oxidative stress status, endothelial function and inflammatory process in patients with chronic atrial fibrillation. Sixty nine patients with chronic atrial fibrillation at a stable clinical state were recruited. Ejection fraction of the left ventricle and the dimensions of the left atrium were determined echocardiographically. Flow mediated dilatation (FMD) was evaluated in the brachial artery, while serum oxidized LDL (ox-LDL), matrix metalloproteinase-9 (MMP-9), soluble CD40-ligand (sCD40L) and C-reactive protein (CRP) were measured. FMD was correlated with CRP (r=-0.423, p=0.028), independently of other clinical parameters (beta(SE): -0.0039(0.00159), p=0.022). Ox-LDL was significantly correlated with left atrium diameter(r=0.358, p=0.005) independently of other clinical variables (beta(SE):1.288(0.455), p=0.007). The only independent predictors of MMP-9 were sCD40L (beta(SE):17.232(7.654), p=0.028), CRP (beta(SE):4.249(2.186), p=0.05) and gender (beta(SE):204.657(68.153), p=0.004), but not left atrium dimensions. Independent predictors of CRP were hypertension (beta(SE): 8.531(3.973), p=0.036), sCD40L (beta(SE): 0.779(0.408), p=0.06) and age (beta(SE): 0.381(0.201), p=0.063). There is a strong link between inflammation and endothelial function, in patients with atrial fibrillation. The maximum diameter of left atrium is the only independent predictor of oxidized LDL, suggesting that left atrium distension may predict oxidative stress status in these patients.


Congestion transition in air traffic networks.
Air Transportation represents a very interesting example of a complex techno-social system whose importance has considerably grown in time and whose management requires a careful understanding of the subtle interplay between technological infrastructure and human behavior. Despite the competition with other transportation systems, a growth of air traffic is still foreseen in Europe for the next years. The increase of traffic load could bring the current Air Traffic Network above its capacity limits so that safety standards and performances might not be guaranteed anymore. Lacking the possibility of a direct investigation of this scenario, we resort to computer simulations in order to quantify the disruptive potential of an increase in traffic load. To this end we model the Air Transportation system as a complex dynamical network of flights controlled by humans who have to solve potentially dangerous conflicts by redirecting aircraft trajectories. The model is driven and validated through historical data of flight schedules in a European national airspace. While correctly reproducing actual statistics of the Air Transportation system, e.g., the distribution of delays, the model allows for theoretical predictions. Upon an increase of the traffic load injected in the system, the model predicts a transition from a phase in which all conflicts can be successfully resolved, to a phase in which many conflicts cannot be resolved anymore. We highlight how the current flight density of the Air Transportation system is well below the transition, provided that controllers make use of a special re-routing procedure. While the congestion transition displays a universal scaling behavior, its threshold depends on the conflict solving strategy adopted. Finally, the generality of the modeling scheme introduced makes it a flexible general tool to simulate and control Air Transportation systems in realistic and synthetic scenarios.


For your interest? The ethical acceptability of using non-invasive prenatal testing to test 'purely for information'.
Non-invasive prenatal testing (NIPT) is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, information from NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare parents to raise a child with a genetic condition. NIPT can also be used by women and couples to test purely 'for information'. Here, no particular action is envisaged following the test; it is motivated entirely by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT 'purely for information', including the competing interests of the prospective parents and the future child, and the acceptability of testing for 'frivolous' reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult-onset conditions, carrier status or non-serious traits presenting in childhood would be unacceptable.


Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E(2)P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump.
Nigella sativa seed oil was found to contain a modulator of Na,K-ATPase. Separation analyses combined with (1)H NMR and GCMS identified the inhibitory fraction as a mixture of oleic and linoleic acids. These two fatty acids are specifically concentrated in several medicinal plant oils, and have particularly been implicated in decreasing high blood pressure. The ouabain binding site on Na,K-ATPase has also been implicated in blood pressure regulation. Thus, we aimed to determine how these two molecules modify pig kidney Na,K-ATPase. Oleic and linoleic acids did not modify reactions involving the E(1) (Na(+)) conformations of the Na,K-ATPase. In contrast, K(+) dependent reactions were strongly modified after treatment. Oleic and linoleic acids were found to stabilize a pump conformation that binds ouabain with high affinity, i.e., an ion free E(2)P form. Time-resolved binding assays using anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with γ-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma levels of oleic and linoleic acids are important in the modulation of the sensitivity of the sodium pump to cardiac glycosides. Given the possible involvement of the cardiac glycoside binding site on Na,K-ATPase in the regulation of hypertension, we suggest oleic acid to be a specific chaperon that modulates interaction of cardiac glycosides with the sodium pump.


Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children's Hospital.
A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting. We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases. We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection. We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up.


Construction of a survey to assess workload and fatigue among AMT operators in Mexico.
Operators of machinery classified as Advanced Manufacturing Technology (AMT) are exposed to high levels of workload and fatigue. However, only few studies have been conducted on this topic in Hispanic-American countries workers. Several instruments be used to assess workload and fatigue; however, only few of them have been adapted to Spanish language. This paper reports on the development and validity testing of a survey instrument in Spanish, aiming to subjectively assess workload and fatigue among AMT operators in Mexico. After an exhaustive literature review in search of already available measurement instruments, they were adapted for content and later translated into Spanish; a pilot test was conducted to evaluate validity and reliability; afterwards appropriate modifications were made to the testing instruments. Final version of the instrument was applied to a group of 121 operators of CNC lathes. Reliability was analyzed using KMO and Cronbach alpha indices. For the assessment of workload, both NASA-TLX and ISTAS 21 methods were incorporated to the survey instrument. As for fatigue assessment tools, these were SOFI-S, FAS and OFER questionnaires. RESULTS show KMO value and Cronbach alpha above 0.6.Conclusions. The survey instrument as designed, allows the collection of reliable and valid data regarding workload and fatigue among AMT operators in Mexico.


CpG islands recruit a histone H3 lysine 36 demethylase.
In higher eukaryotes, up to 70% of genes have high levels of nonmethylated cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over 20 years ago, but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, except that they are refractory to epigenetic silencing by DNA methylation. Here we show that CpG islands directly recruit the H3K36-specific lysine demethylase enzyme KDM2A. Nucleation of KDM2A at these elements results in removal of H3K36 methylation, creating CpG island chromatin that is uniquely depleted of this modification. KDM2A utilizes a zinc finger CxxC (ZF-CxxC) domain that preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated, thus constraining KDM2A to nonmethylated CpG islands. These data expose a straightforward mechanism through which KDM2A delineates a unique architecture that differentiates CpG island chromatin from bulk chromatin.


LGBT people and suicidality in youth: A qualitative study of perceptions of risk and protective circumstances.
Evidence suggests that lesbian, gay, bisexual and trans (LGBT) people are more likely to attempt to take their own lives in their youth when compared to heterosexual and/or cisgender people. This study draws on in-depth interviews with 17 LGBT individuals living in England, and explores the narratives used by participants to better understand their perceptions of risk and protective circumstances to explain suicide attempts in youth. Using a Goffman-informed thematic analysis, results identified three key themes that were linked to attempts to end life in youth. The first theme considers the conflicts resulting from first disclosure of sexual orientation and/or gender identity/trans status and being 'out' to others. The second theme explores participants' accounts of their concurrent mental health issues and how diagnoses of the mental health issues helped them make sense of their own experiences of attempted suicide. The final theme explores the experience of grieving over lost relationships and how that grief is received by others, including health professionals. Our results indicate that some LGBT individuals have effectively, although often arduously, navigated suicidal crises by utilising various approaches to coping. We provide a rich and layered picture of LGBT suicide risk in youth and potential resilience scenarios, although these are a reflection of our specific group of participants' experiences and realities. We argue that it is important to understand how LGBT individuals with a history of suicide attempts narrate and make sense of their experiences in early life and we suggest that the early negative experiences continue to have an effect on LGBT adults today.


Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development.
Intestinal stem cells (ISCs) are regulated by the mesenchymal environment via physical interaction and diffusible factors. We examined the role of Indian hedgehog (Ihh) in mesenchymal organization and the mechanisms by which perturbations in epithelial-mesenchymal interactions affect ISC fate. We generated mice with intestinal epithelial-specific disruption of Ihh. Gross and microscopic anatomical changes were determined using histologic, immunohistochemical, and in situ hybridization analyses. Molecular mechanisms were elucidated by expression profiling and in vitro analyses. Deletion of intestinal epithelial Ihh disrupted the intestinal mesenchymal architecture, demonstrated by loss of the muscularis mucosae, deterioration of the extracellular matrix, and reductions in numbers of crypt myofibroblasts. Concurrently, the epithelial compartment had increased Wnt signaling, disturbed crypt polarity and architecture, defective enterocyte differentiation, and increased and ectopic proliferation that was accompanied by increased numbers of ISCs. Mechanistic studies revealed that Hh inhibition deregulates bone morphogenetic protein signaling, increases matrix metalloproteinase levels, and disrupts extracellular matrix proteins, fostering a proliferative environment for ISCs and progenitor cells. Ihh regulates ISC self-renewal and differentiation. Intestinal epithelial Ihh signals to the mesenchymal compartment to regulate formation and proliferation of mesenchymal cells, which in turn affect epithelial proliferation and differentiation. These findings provide a basis for analyses of the role of the muscularis mucosae in ISC regulation.


Human glioma growth is controlled by microRNA-10b.
MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas.


Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions.
Mass spectrometry based metabolomics has become a promising complement and alternative to transcriptomics and proteomics in many fields including in vitro systems pharmacology. Despite several merits, metabolomics based on liquid chromatography mass spectrometry (LC-MS) is a developing area that is yet attached to several pitfalls and challenges. To reach a level of high reliability and robustness, these issues need to be tackled by implementation of refined experimental and computational protocols. This study illustrates some key pitfalls in LC-MS based metabolomics and introduces an automated computational procedure to compensate for them. Non-cancerous mammary gland derived cells were exposed to 27 chemicals from four pharmacological classes plus a set of six pesticides. Changes in the metabolome of cell lysates were assessed after 24 h using LC-MS. A data processing pipeline was established and evaluated to handle issues including contaminants, carry over effects, intensity decay and inherent methodology variability and biases. A key component in this pipeline is a latent variable method called OOS-DA (optimal orthonormal system for discriminant analysis), being theoretically more easily motivated than PLS-DA in this context, as it is rooted in pattern classification rather than regression modeling. The pipeline is shown to reduce experimental variability/biases and is used to confirm that LC-MS spectra hold drug class specific information. LC-MS based metabolomics is a promising methodology, but comes with pitfalls and challenges. Key difficulties can be largely overcome by means of a computational procedure of the kind introduced and demonstrated here. The pipeline is freely available on www.github.com/stephanieherman/MS-data-processing.


A false start in the race against doping in sport: concerns with cycling's biological passport.
Professional cycling has suffered from a number of doping scandals. The sport's governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling's biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist's system. Instead, the biological passport tracks biological variables in a cyclist's blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports.


Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism.
Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m2.7, P<0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m2.7, P<0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.


Genetic analysis of biological pathway data through genomic randomization.
Genome Wide Association Studies (GWAS) are a standard approach for large-scale common variation characterization and for identification of single loci predisposing to disease. However, due to issues of moderate sample sizes and particularly multiple testing correction, many variants of smaller effect size are not detected within a single allele analysis framework. Thus, small main effects and potential epistatic effects are not consistently observed in GWAS using standard analytical approaches that consider only single SNP alleles. Here, we propose unique methodology that aggregates variants of interest (for example, genes in a biological pathway) using GWAS results. Multiple testing and type I error concerns are minimized using empirical genomic randomization to estimate significance. Randomization corrects for common pathway-based analysis biases, such as SNP coverage and density, linkage disequilibrium, gene size and pathway size. Pathway Analysis by Randomization Incorporating Structure (PARIS) applies this randomization and in doing so directly accounts for linkage disequilibrium effects. PARIS is independent of association analysis method and is thus applicable to GWAS datasets of all study designs. Using the KEGG database as an example, we apply PARIS to the publicly available Autism Genetic Resource Exchange GWAS dataset, revealing pathways with a significant enrichment of positive association results.


Retinal Vascular Network Topology Reconstruction and Artery/Vein Classification via Dominant Set Clustering.
The estimation of vascular network topology in complex networks is important in understanding the relationship between vascular changes and a wide spectrum of diseases. Automatic classification of the retinal vascular trees into arteries and veins is of direct assistance to the ophthalmologist in terms of diagnosis and treatment of eye disease. However, it is challenging due to their projective ambiguity and subtle changes in appearance, contrast, and geometry in the imaging process. In this paper, we propose a novel method that is capable of making the artery/vein (A/V) distinction in retinal color fundus images based on vascular network topological properties. To this end, we adapt the concept of dominant set clustering and formalize the retinal blood vessel topology estimation and the A/V classification as a pairwise clustering problem. The graph is constructed through image segmentation, skeletonization, and identification of significant nodes. The edge weight is defined as the inverse Euclidean distance between its two end points in the feature space of intensity, orientation, curvature, diameter, and entropy. The reconstructed vascular network is classified into arteries and veins based on their intensity and morphology. The proposed approach has been applied to five public databases, namely INSPIRE, IOSTAR, VICAVR, DRIVE, and WIDE, and achieved high accuracies of 95.1%, 94.2%, 93.8%, 91.1%, and 91.0%, respectively. Furthermore, we have made manual annotations of the blood vessel topologies for INSPIRE, IOSTAR, VICAVR, and DRIVE datasets, and these annotations are released for public access so as to facilitate researchers in the community.


The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading.
The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Applying interaction proteomics coupled to mass spectrometry to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association with a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ + vs ERβ - cells, and before and after AGO2 knock-down in ERβ + cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may also be able to directly control mRNA translation efficiency and stability. These results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions.


Stigma associated with mental illness: perspectives of university students in Qatar.
Stigma in relation to mental illness is one of the main factors inhibiting people from seeking help. Studies have been undertaken looking into the knowledge, attitudes, and beliefs (KAB) about mental illness among residents in Qatar; however, none have looked specifically at students in higher education. The aim of this study was to understand the KAB toward mental illness among students at a Qatari university and determine if there are any differences based on gender, nationality, and college type. A convenience sample of students from all genders, colleges, and nationalities was approached to participate in a survey that consisted of four sections: demographic, beliefs, attitudes, and help-seeking and treatment preferences associated with mental illness. Chi-square testing was performed to test for differences in the distribution of proportions of our primary outcomes (students' beliefs, attitudes, and help-seeking and treatment preferences). A total of 282 students completed the survey. The majority of the participating students were females (59.3%), non-Qataris (64.3%), and enrolled in science-based colleges (62.7%). Beliefs reflecting poor mental health literacy, such as "medications to treat mental illness can cause addiction", "mental illness is not like any other illness", or that "mental illness is a punishment from God", were reported by a majority of students (84.4%, 56.7%, and 50.2%, respectively). Stigmatizing attitudes that were endorsed by a majority of students included believing that people with mental illness cannot have regular jobs (60.2%), that people with mental illness are dangerous (65.7%), and that they would not marry someone with a mental illness (88.9%). Additionally, 33.6% of students indicated they would be ashamed to mention if someone in their family or they themself, had a mental illness. A vast majority of students (86.3%) indicated to prefer family and friend's support as treatment options. Significant differences in KAB about mental illness between genders, colleges, and college type were found only for a few items. The findings of this study suggest that a high percentage of students reported KAB about mental illness, that are considered stigmatizing. Students' KAB about mental illness was consistent with that reported by the general population in Qatar. Nevertheless, the sample was small and as such, larger studies from a randomly selected population are needed to confirm these findings.


Phylogenomic reconstruction indicates mitochondrial ancestor was an energy parasite.
Reconstruction of mitochondrial ancestor has great impact on our understanding of the origin of mitochondria. Previous studies have largely focused on reconstructing the last common ancestor of all contemporary mitochondria (proto-mitochondria), but not on the more informative pre-mitochondria (the last common ancestor of mitochondria and their alphaproteobacterial sister clade). Using a phylogenomic approach and leveraging on the increased taxonomic sampling of alphaproteobacterial and eukaryotic genomes, we reconstructed the metabolisms of both proto-mitochondria and pre-mitochondria. Our reconstruction depicts a more streamlined proto-mitochondrion than these predicted by previous studies, and revealed several novel insights into the mitochondria-derived eukaryotic metabolisms including the lipid metabolism. Most strikingly, pre-mitochondrion was predicted to possess a plastid/parasite type of ATP/ADP translocase that imports ATP from the host, which posits pre-mitochondrion as an energy parasite that directly contrasts with the current role of mitochondria as the cell's energy producer. In addition, pre-mitochondrion was predicted to encode a large number of flagellar genes and several cytochrome oxidases functioning under low oxygen level, strongly supporting the previous finding that the mitochondrial ancestor was likely motile and capable of oxidative phosphorylation under microoxic condition.


Ellipsometric measurement technique for a modified Otto configuration used for observing surface-plasmon resonance.
In order to carry out precise measurements of the thickness of a dielectric layer deposited on a metal surface, we have introduced an ellipsometric measurement technique (EMT) to the modified Otto's configuration (MOC) that is used for observing surface plasmon resonance (SPR). For that purpose, we have measured the thickness of the Au layer by the EMT at four different locations on an elliptic fringe pattern obtained from the MOC basing on a four-layer structure model: prism (BK7)-air-Ausubstrate (BK7). Then, we have measured that of a TiO(2) layer deposited on the Au layer by the EMT basing on a five-layer structure model: prism (BK7)-air-TiO(2)-Au-substrate (BK7). We have found experimentally that the combination of EMT and MOC is effective for measuring the thickness of the dielectric layer on the metal.


Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. I. Lung epithelial morphogenesis.
The role of Ca2+-dependent cell-cell adhesion molecules, E- and P-cadherins, in the histogenesis of mouse embryonic lung was studied. All epithelial cells of the lung express both E- and P-cadherin at the early developmental stage. P-cadherin, however, gradually disappears during development, initially from the main bronchi and eventually from all epithelial cells. When a monoclonal antibody to E-cadherin (ECCD-1) was added to monolayer cultures of lung epithelial cells, it induced a partial disruption of their cell-cell adhesion, while a monoclonal antibody to P-cadherin (PCD-1) showed a subtle effect. A mixture of the two antibodies, however, displayed a synergistic effect. We then tested the effect of the antibodies on the morphogenesis of lung primordia using an organ culture system. In control media, the explants formed typical bronchial trees. In the presence of ECCD-1, the explants grew up at the same rate as in the control, but their morphogenesis was affected. The control explants formed round epithelial lobules with an open luminal space at the tips of the bronchial trees, whereas the lobules of explants incubated with ECCD-1 tended to be flat and devoid of the luminal space. PCD-1 showed a similar but very small effect. A mixture of the two antibodies, however, showed a stronger effect: the branching of epithelia was partially suppressed and the arrangement of epithelial cells was distorted in many places. These results suggest that E- and P-cadherin have a synergistic role in the organization of epithelial cells in lung morphogenesis.


IGF-I CA19 repeat polymorphisms and cancer risk: a meta-analysis.
IGF-I CA repeat polymorphisms, especially the allele containing CA19 repeats, have been reported to be associated with the risk for various types of cancers. However, the results still remain controversial and ambiguous. This meta-analysis was performed to evaluate the association between IGF-I CA19 repeat polymorphisms and the risk of cancer. Total 18 studies with IGF-I CA19 repeat genotyping on 9,873 patients and 15,607 controls were analyzed. We used random-effects model with a pooled OR of 0.69 (95% CI = 0.60-0.79) for the recessive genetic model, 0.97 (95% CI = 0.86-1.10) for the dominant genetic model, 0.99 (95% CI = 0.86-1.14) for the homozygote comparison and 1.06 (95% CI = 0.91-1.23) for the heterozygote comparison. In the subgroup analysis of recessive model, OR (95% CI) was 0.65 (0.52-0.80) in breast cancer, 0.68 (0.53-0.86) in prostate cancer, and 0.71 (0.52-0.96) in Caucasian. In conclusion, IGF-1 CA19 repeat polymorphisms are unlikely to be a major determinant of susceptibility to cancer. However, the subgroup analysis of recessive model indicates that IGF-I CA19 repeat polymorphisms may reduce the risk of certain types of cancer or in a specific population.


Acupuncture for peripheral joint osteoarthritis: a systematic review and meta-analysis.
To evaluate the evidence for the effectiveness of acupuncture in peripheral joint osteoarthritis (OA). Systematic searches were conducted on Medline, Embase, AMED, Cochrane Library, CINAHL, British Nursing Index, PsychINFO and CAMPAIN until July 2005. Hand-searches included conference proceedings and our own files. There were no restrictions regarding the language of publication. All randomized controlled trials (RCTs) of acupuncture for patients with peripheral joint OA were considered for inclusion. Trials assessing needle acupuncture with or without electrical stimulation were considered if sham- or placebo-controlled or controlled against a comparator intervention. Trials testing other forms of acupuncture were excluded. Methodological quality was assessed and, where possible, meta-analyses were performed. Thirty-one possibly relevant studies were identified and 18 RCTs were included. Ten trials tested manual acupuncture and eight trials tested electro-acupuncture. Overall, ten studies demonstrated greater pain reduction in acupuncture groups compared with controls. The meta-analysis of homogeneous data showed a significant effect of manual acupuncture compared with sham acupuncture (standardized mean difference 0.24, 95% confidence interval 0.01-0.47, P = 0.04, n = 329), which is supported by data for knee OA. The extent of heterogeneity in trials of electro-acupuncture prevented a meaningful meta-analysis. Sham-controlled RCTs suggest specific effects of acupuncture for pain control in patients with peripheral joint OA. Considering its favourable safety profile acupuncture seems an option worthy of consideration particularly for knee OA. Further studies are required particularly for manual or electro-acupuncture in hip OA.


The Foraging Ecology of the Endangered Cape Verde Shearwater, a Sentinel Species for Marine Conservation off West Africa.
Large Marine Ecosystems such as the Canary Current system off West Africa sustains high abundance of small pelagic prey, which attracts marine predators. Seabirds are top predators often used as biodiversity surrogates and sentinel species of the marine ecosystem health, thus frequently informing marine conservation planning. This study presents the first data on the spatial (GPS-loggers) and trophic (stable isotope analysis) ecology of a tropical seabird-the endangered Cape Verde shearwater Calonectris edwardsii-during both the incubation and the chick-rearing periods of two consecutive years. This information was related with marine environmental predictors (species distribution models), existent areas of conservation concern for seabirds (i.e. marine Important Bird Areas; marine IBAs) and threats to the marine environment in the West African areas heavily used by the shearwaters. There was an apparent inter-annual consistency on the spatial, foraging and trophic ecology of Cape Verde shearwater, but a strong alteration on the foraging strategies of adult breeders among breeding phases (i.e. from incubation to chick-rearing). During incubation, birds mostly targeted a discrete region off West Africa, known by its enhanced productivity profile and thus also highly exploited by international industrial fishery fleets. When chick-rearing, adults exploited the comparatively less productive tropical environment within the islands of Cape Verde, at relatively close distance from their breeding colony. The species enlarged its trophic niche and increased the trophic level of their prey from incubation to chick-rearing, likely to provision their chicks with a more diversified and better quality diet. There was a high overlap between the Cape Verde shearwaters foraging areas with those of European shearwater species that overwinter in this area and known areas of megafauna bycatch off West Africa, but very little overlap with existing Marine Important Bird Areas. Further investigation on the potential nefarious effects of fisheries on seabird communities exploiting the Canary Current system off West Africa is needed. Such negative effects could be alleviated or even dissipated if the 'fisheries-conservation hotspots' identified for the region, would be legislated as Marine Protected Areas.


Experiences of everyday life in men with alcohol dependency--a qualitative study.
The aim of the present study is to describe and understand the meaning of living with alcohol dependency (AD) as a man. Studies point out a high prevalence of AD in men and the reasons for, and consequences of, that are complex. However, today there is a lack of knowledge about men's lived experiences of having AD. In-depth interviews were conducted with 15 alcohol dependent men and analyzed using a phenomenological-hermeneutic approach. In the comprehensive understanding, findings from the naïve understanding and the structural analysis were interpreted with help from both gender and caring theoretical perspectives. "A Fallible Man" and "A Man with Powerfulness" were disclosed as two main gender formations influencing senses of well-being. A Fallible Man involved varying experiences of restrictions, being in control, and meaninglessness. Being in control promoted a sense of well-being. A Man with Powerfulness involved energetic activity, and the development and maintaining of interests as well as risk-taking. Being powerful diminished feelings of meaninglessness, cravings, and social alienation. The results show, among other things, that the men live an incompatible life and, because of that, need support and guidance to find a more meaningful life. This can be accomplished if caregivers allow men to be in focus and involved in planning their own care. To avoid limiting the men while they are in treatment, the health care professionals also need to focus on the men's everyday life. This focus involves acknowledging the men's individual experiences of what enriches and limits their everyday lives.


Acute myocardial infarction following ingestion of a non-selective non-steroidal anti-inflammatory drug.
While selective non-steroidal anti-inflammatory drugs, namely cyclo-oxygenase-2 (COX 2) inhibitors, are known to be associated with acute myocardial infarction, little is known about the cardiovascular safety of the non-selective non-steroidal anti-inflammatory drugs. We report the case of a 44-year-old man who developed anaphylactic reaction and acute inferior myocardial infarction following ingestion of a non-selective anti-inflammatory drug, diclofenac sodium. Coronary angiography revealed a large thrombus in the right coronary artery which was partially removed by intracoronary catheter aspiration. Complete resolution of the remaining thrombus was achieved after treatment with an oral anticoagulant.


Structure and dynamics of water molecules confined in triglyceride oils.
Though it is commonly known that a small amount of water can be present in triglyceride oil, a molecular picture of how water molecules organize in the oil phase is lacking. We investigate the hydrogen-bond configuration and dynamics of water in triacetin, tributyrin and trioctanoin using linear infrared and time-resolved two-dimensional infrared (2DIR) spectroscopy of the water hydroxyl stretch vibration. We identify water molecules with a single strong hydrogen bond to the triglyceride, water molecules with two weaker hydrogen bonds to the triglycerides, and water clusters. These species do not interconvert on the 20 ps timescale of the experiment, as evidenced by the absence of cross-peaks in the 2DIR spectrum. The vibrational response of water molecules with a single strong hydrogen bond to the triglyceride depends strongly on the excitation frequency, revealing the presence of different subspecies of singly-bound water molecules that correspond to different hydrogen-bond locations. In contrast, the water molecules with two weaker hydrogen bonds to the triglyceride correspond to a single, specific hydrogen-bond configuration; these molecules likely bridge the carbonyl groups of adjacent triglyceride molecules, which can have considerable influence on liquid triglyceride properties.


Cutting Brussels sprouts: collaboration involving persons with dementia.
How people with dementia collaborate with other people is an area in need of more research and conceptualizations. Collaboration introduces a number of new possibilities and demands concerning cognitive and linguistic abilities and it is suggested that a theoretical framework that emphasize that cognitive resources are not exclusively individual, but are part of cognitive and communicative context. In this article focus is on joint activities and their collaborative organization is analyzed using an example involving persons with dementia working together with staff preparing a meal. The analysis shows that persons with dementia are able to collaborate in fairly advanced activities if they are supported in such a way that they can make use of the cognitive and linguistic resources of others, in particular cognitive functions having to do with planning and execution of actions. The organization of artifacts like kitchen tools can function as an external memory support. The results support a theoretical framework that help to understand what people can do together rather than focus on individual abilities. The results also indicate that is possible to learn how to organize collaboration involving persons with dementia by understanding how other persons abilities as well as artifacts can be used as external resources for support of cognitive and linguistic abilities.


Osteoarthritis.
Osteoarthritis (OA) is a chronic degenerative disorder of multifactorial etiology characterized by loss of articular cartilage and periarticular bone remodelling. OA causes joint pain, typically worse with weight-bearing and activity as well as can manifest with stiffness after inactivity. It can present as localized, generalized or as erosive osteoarthritis. Primary osteoarthritis is mostly related to aging, whereas, secondary osteoarthritis is caused by another disease or condition. X-rays, arthrocentesis and arthroscopy remain the main diagnostic tools. Blood tests are performed to exclude diseases that can cause secondary osteoarthritis. The treatment of osteoarthritis includes non-pharmacological management, pharmacological treatment in the form of drugs which can modify symptoms, symptomatic slow acting drugs for OA or structure modifying OA drugs depending upon the clinical requirement of the patient. Patients with persistent pain and progressive limitation of daily activities despite medical management may be the candidates for surgery.