PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients: feasibility, reliability, and validity.
The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. The PedsQL™ Cognitive Functioning Scale was developed as a brief generic symptom-specific instrument to measure cognitive functioning. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients. The 6-item PedsQL™ Cognitive Functioning Scale and the PedsQL™ 4.0 Generic Core Scales were completed by pediatric liver transplant recipients ages 8-18 years (n = 215) and parents of pediatric liver transplant recipients ages 2-18 years (n = 502). Both patient self-report and parent proxy-report were available for 212 cases. The 72-item Behavior Rating Inventory of Executive Function (BRIEF), a widely validated measure of executive functioning, was completed by 100 parents and 56 teachers on a subset of patients. The PedsQL™ Cognitive Functioning Scale demonstrated minimal missing responses (0.0%, child report, 0.67%, parent report), achieved excellent reliability (α = 0.88 child report, 0.94 parent report), distinguished between pediatric patients with liver transplants and healthy children supporting discriminant validity, and was significantly correlated with the PedsQL™ 4.0 Generic Core Scales and the BRIEF supporting construct and concurrent validity, respectively. Pediatric liver transplants recipients experienced cognitive functioning comparable to long-term pediatric cancer survivors. The results demonstrate the feasibility, reliability, discriminant, construct, and concurrent validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.


Novel molecularly imprinted magnetic nanoparticles for the selective extraction of protoberberine alkaloids in herbs and rat plasma.
In this work, a novel magnetic nanomaterial functionalized with a molecularly imprinted polymer was prepared for the extraction of protoberberine alkaloids. Molecularly imprinted polymers were made on the surface of Fe3 O4 nanoparticles by using berberine as template, acetonitrile/water as porogen, acrylamide as functional monomer and ethylene glycol dimethacrylate as cross-linker. The optimized molar ratio of template/functional monomer was 1:7. The polymeric magnetic nanoparticles were characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The stability and adsorption capacity of the molecularly imprinted polymers were investigated. The molecularly imprinted polymers were used as a selective sorbent for the magnetic molecularly imprinted solid-phase extraction and determination of jatrorrhizine, palmatine, and berberine. Extraction parameters were studied including loading pH, sample volume, stirring speed, and extraction time. Finally, a magnetic molecularly imprinted solid-phase extraction coupled to high-performance liquid chromatography method was developed. Under the optimized conditions, the method showed good linear range of 0.1-150 ng/mL for berberine and 0.1-100 ng/mL for jatrorrhizine and palmatine. The limit of detection was 0.01 ng/mL for berberine and 0.02 ng/mL for jatrorrhizine and palmatine. The proposed method has been applied to determine protoberberine alkaloids in Cortex phellodendri and rat plasma samples. The recoveries ranged from 87.33-102.43%, with relative standard deviation less than 4.54% in Cortex phellodendri and from 102.22-111.15% with relative standard deviation less than 4.59% in plasma.


Primary prevention of disc degeneration-related symptoms.
It has been shown previously that a history of low back pain often begins in childhood or adulthood. Indeed, the prevalence of severe back symptoms among schoolchildren is not insignificant. Possibilities for the primary prevention of intervertebral disc degeneration-related conditions are poorly reported in the literature despite the assumed socio-economical impact of the prevention of these conditions. In this review, the authors have collated published data on the prevalence and risk factors of childhood low back pain as well as the structure and results of published primary prevention programs. The prevalence of self-reported low back pain is 7-65% among children and it increases with age. Several lifestyle factors have been reported as significant risk factors for back pain, many of which are related to the schools. Current educational primary prevention programs in schools show no clear or long-term stable effect. Considering the growing evidence about the importance of normal and bad posture, an exercise-based posture correction program is suggested as a school-based primary prevention of disc degeneration-related symptoms. Further, prospective randomized studies with more than 20 years follow-up, however, are strongly required to confirm it.


Prospective cohort study of prone sleeping position and sudden infant death syndrome.
Studies of the link between prone sleeping position and sudden infant death syndrome have been criticised on grounds of recall bias and for not taking into account possible confounding effects. To avoid recall bias and to allow measurement of important biological factors a prospective cohort study of the cause of sudden infant death syndrome (SIDS) is being conducted. The infants included are those at high risk of the syndrome as assessed by a perinatal score. Of the 3110 members of the cohort born between January, 1988, and end of March, 1990, 23 infants later died of SIDS. Sleep position information was available for 15 of these. Matched analysis to control for the confounding effects of infant birthweight and maternal age indicated that prone sleeping position was associated with an increased risk of SIDS (OR 4.47 95% Cl [1.30-15.43]). The findings are strengthened by the results of a concurrent retrospective case-control study of 42 SIDS cases in which the prone position was also associated with an increased risk of SIDS (unadjusted OR 3.45 [1.59-7.49]).


Two ways of legumin-precursor processing in conifers. Characterization and evolutionary relationships of Metasequoia cDNAs representing two divergent legumin gene subfamilies.
Subunit monomers and oligomers of crystalloid-type legumins are major components of SDS-soluble fractions from Metasequoia glyptostroboides (Dawn redwood, Taxodiaceae) seed proteins. The subunits are made up of disulfide linked alpha-polypeptides and beta-polypeptides with molecular masses of 33 kDa and 23-25 kDa, respectively. Unusually for legumins, those from Metasequoia are glycosylated and the carbohydrate moieties are residing in the C-terminal region of the respective beta-polypeptides. A Metasequoia endosperm cDNA library has been constructed and legumin-encoding transcripts representing two divergent gene subfamilies have been characterized. Intersubfamily comparisons reveal 75% identity at the amino acid level and the values range from 53-35% when the legumin precursors deduced were compared with those from angiosperms. The predicted sequences together with data from amino acid sequencing prove that post-translational processing of Metasequoia prolegumins is directed to two different processing sites, each of them specific for one of the legumin subfamilies. The sites involved differ in their relative position and in the junction to be cleaved: Metasequoia legumin precursors MgLeg18 and MgLeg26 contain the conventional post-translational Asn-Gly processing site, which is generally regarded as highly conserved. In contrast, the MgLeg4 precursor is lacking this site and post-translational cleavage is directed to an unusual Asn-Thr processing site located in its hypervariable region, causing N-terminal extension of the beta-polypeptide relative to those hitherto known. Evidence is given that the unusual variant of processing also occurs in other conifers. Phylogenetic analysis reveals the precursors concerned as representatives of a distinct legumin subfamily, originating from duplication of an ancestral gene prior to or at the beginning of Taxodiaceae diversification.


The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study.
Diagnosis of sleep-disordered breathing requires overnight recordings, such as polygraphy or polysomnography. Considering the cost and low availability of these procedures, preselection of patients at high risk is recommended. We aimed to develop a screening tool allowing identification of individuals at risk of sleep-disordered breathing. We used the participants from the population-based HypnoLaus cohort in Lausanne, Switzerland, who had a clinical assessment and polysomnography at home, to build a clinical score (the NoSAS score) using multiple factor analysis and logistic regression to identify people likely to have clinically significant sleep-disordered breathing. The NoSAS score was externally validated in an independent sleep cohort (EPISONO). We compared its performance to existing screening scores (STOP-Bang and Berlin scores). We used the 2121 participants from the HypnoLaus cohort who were assessed between Sept 1, 2009, and June 30, 2013. The NoSAS score, which ranges from 0 to 17, allocates 4 points for having a neck circumference of more than 40 cm, 3 points for having a body-mass index of 25 kg/m(2) to less than 30 kg/m(2) or 5 points for having a body-mass index of 30 kg/m(2) or more, 2 points for snoring, 4 points for being older than 55 years of age, and 2 points for being male. Using a threshold of 8 points or more, the NoSAS score identified individuals at risk of clinically significant sleep-disordered breathing, with an area under the curve (AUC) of 0·74 (95% CI 0·72-0·76). It showed an even higher performance in the EPISONO cohort, with an AUC of 0·81 (0·77-0·85). The NoSAS score performed significantly better than did the STOP-Bang (AUC 0·67 [95% CI 0·65-0·69]; p<0·0001) and Berlin (0·63 [0·61-0·66]; p<0·0001) scores. The NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing. Because of its high discrimination power, the NoSAS score can help clinicians to decide which patients to further investigate with a nocturnal recording. Faculty of Biology and Medicine of the University of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, and Vaud Pulmonary League.


Biclustering Analysis of Co-regulation Patterns in Nuclear-Encoded Mitochondrial Genes and Metabolic Pathways.
Transcription of a large set of nuclear-encoded genes underlies biogenesis of mitochondria, regulated by a complex network of transcription factors and co-regulators. A remarkable heterogeneity can be detected in the expression of these genes in different cell types and tissues, and the recent availability of large gene expression compendiums allows the quantification of specific mitochondrial biogenesis patterns. We have developed a method to effectively perform this task. Massively correlated biclustering (MCbiclust) is a novel bioinformatics method that has been successfully applied to identify co-regulation patterns in large genesets, underlying essential cellular functions and determining cell types. The method has been recently evaluated and made available as a package in Bioconductor for R. One of the potential applications of the method is to compare expression of nuclear-encoded mitochondrial genes or larger sets of metabolism-related genes between different cell types or cellular metabolic states. Here we describe the essential steps to use MCbiclust as a tool to investigate co-regulation of mitochondrial genes and metabolic pathways.


The TRIM69-MST2 signaling axis regulates centrosome dynamics and chromosome segregation.
Stringent control of centrosome duplication and separation is important for preventing chromosome instability. Structural and numerical alterations in centrosomes are hallmarks of neoplastic cells and contribute to tumorigenesis. We show that a Centrosome Amplification 20 (CA20) gene signature is associated with high expression of the Tripartite Motif (TRIM) family member E3 ubiquitin ligase, TRIM69. TRIM69-ablation in cancer cells leads to centrosome scattering and chromosome segregation defects. We identify Serine/threonine-protein kinase 3 (MST2) as a new direct binding partner of TRIM69. TRIM69 redistributes MST2 to the perinuclear cytoskeleton, promotes its association with Polo-like kinase 1 (PLK1) and stimulates MST2 phosphorylation at S15 (a known PLK1 phosphorylation site that is critical for centrosome disjunction). TRIM69 also promotes microtubule bundling and centrosome segregation that requires PRC1 and DYNEIN. Taken together, we identify TRIM69 as a new proximal regulator of distinct signaling pathways that regulate centrosome dynamics and promote bipolar mitosis.


The extracranial facial nerve: high resolution three-dimensional Fourier transform MR imaging.
To investigate the use of high-resolution three-dimensional Fourier transform gradient-echo MR in evaluation of the extracranial facial nerve. Nine normal subjects and one clinical patient were scanned. Several imaging parameters, including echo time, field-of-view, and the use of Gd-DTPA, were manipulated to determine the optimal technique. Adequate results were obtained in less than 7 minutes acquisition time using a T1-weighted (50/5.3) gradient-echo technique, with a 30 degree flip angle, a 12-cm field of view, 128 x 256 matrix, and 28 or 60 1.0-mm-thick contiguous sections. Gd-DTPA administration was not found useful in identifying the normal extracranial facial nerve. The proximal extracranial facial nerve was seen as a branching low signal intensity tubular structure on 10 to 20 contiguous images in all five volunteers in which this optimal technique was employed. Postprocessing of the images to produce curved oblique planar reconstructed images was useful to display long segments of the facial nerve on a single image. Our experience with high resolution three-dimensional Fourier transform MR imaging indicates that it can consistently demonstrate the intraparotid facial nerve on multiple contiguous images.


Chloride methylation by plant pectin: an efficient environmentally significant process.
Atmospheric chloromethane (CH3Cl) plays an important role in stratospheric ozone destruction, but many uncertainties exist regarding the strengths of its sources and sinks and particularly regarding the processes generating this naturally occurring gas. Evidence is presented here that CH3Cl is produced in many terrestrial environments by a common mechanism. Abiotic conversion of chloride to CH3Cl occurs readily in plant material, with the widespread plant component pectin acting as a methyl donor. Significant CH3Cl emissions from senescent and dead leaves were observed at ambient temperatures; those emissions rose dramatically when temperatures increased. This ubiquitous process acting in terrestrial ecosystems and during biomass burning could contribute the bulk of atmospheric CH3Cl.


Thyroid hormone and the developing hypothalamus.
Thyroid hormone (TH) plays an essential role in normal brain development and function. Both TH excess and insufficiency during development lead to structural brain abnormalities. Proper TH signaling is dependent on active transport of the prohormone thyroxine (T4) across the blood-brain-barrier and into brain cells. In the brain T4 undergoes local deiodination into the more active 3,3',5-triiodothyronine (T3), which binds to nuclear TH receptors (TRs). TRs are already expressed during the first trimester of pregnancy, even before the fetal thyroid becomes functional. Throughout pregnancy, the fetus is largely dependent on the maternal TH supply. Recent studies in mice have shown that normal hypothalamic development requires intact TH signaling. In addition, the development of the human lateral hypothalamic zone coincides with a strong increase in T3 and TR mRNA concentrations in the brain. During this time the fetal hypothalamus already shows evidence for TH signaling. Expression of components crucial for central TH signaling show a specific developmental timing in the human hypothalamus. A coordinated expression of deiodinases in combination with TH transporters suggests that TH concentrations are regulated to prevent untimely maturation of brain cells. Even though the fetus depends on the maternal TH supply, there is evidence suggesting a role for the fetal hypothalamus in the regulation of TH serum concentrations. A decrease in expression of proteins involved in TH signaling towards the end of pregnancy may indicate a lower fetal TH demand. This may be relevant for the thyrotropin (TSH) surge that is usually observed after birth, and supports a role for the hypothalamus in the regulation of TH concentrations during the fetal period anticipating birth.


Arylamine N-acetyltransferases in mycobacteria.
Polymorphic Human arylamine N-acetyltransferase (NAT2) inactivates the anti-tubercular drug isoniazid by acetyltransfer from acetylCoA. There are active NAT proteins encoded by homologous genes in mycobacteria including M. tuberculosis, M. bovis BCG, M. smegmatis and M. marinum. Crystallographic structures of NATs from M. smegmatis and M. marinum, as native enzymes and with isoniazid bound share a similar fold with the first NAT structure, Salmonella typhimurium NAT. There are three approximately equal domains and an active site essential catalytic triad of cysteine, histidine and aspartate in the first two domains. An acetyl group from acetylCoA is transferred to cysteine and then to the acetyl acceptor e.g. isoniazid. M. marinum NAT binds CoA in a more open mode compared with CoA binding to human NAT2. The structure of mycobacterial NAT may promote its role in synthesis of cell wall lipids, identified through gene deletion studies. NAT protein is essential for survival of M. bovis BCG in macrophage as are the proteins encoded by other genes in the same gene cluster (hsaA-D). HsaA-D degrade cholesterol, essential for mycobacterial survival inside macrophage. Nat expression remains to be fully understood but is co-ordinated with hsaA-D and other stress response genes in mycobacteria. Amide synthase genes in the streptomyces are also nat homologues. The amide synthases are predicted to catalyse intramolecular amide bond formation and creation of cyclic molecules, e.g. geldanamycin. Lack of conservation of the CoA binding cleft residues of M. marinum NAT suggests the amide synthase reaction mechanism does not involve a soluble CoA intermediate during amide formation and ring closure.


Who gains clinical benefit from using insulin pump therapy? A qualitative study of the perceptions and views of health professionals involved in the Relative Effectiveness of Pumps over MDI and Structured Education (REPOSE) trial.
To explore health professionals' views about insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] and the types of individuals they thought would gain greatest clinical benefit from using this treatment. In-depth interviews with staff (n = 18) who delivered the Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial. Data were analysed thematically. Staff perceived insulin pumps as offering a better self-management tool to some individuals due to the drip feed of insulin, the ability to alter basal rates and other advanced features. However, staff also noted that, because of the diversity of features on offer, CSII is a more technically complex therapy to execute than multiple daily injections. For this reason, staff described how, alongside clinical criteria, they had tended to select individuals for CSII in routine clinical practice based on their perceptions about whether they possessed the personal and psychological attributes needed to make optimal use of pump technology. Staff also described how their assumptions about personal and psychological suitability had been challenged by working on the REPOSE trial and observing individuals make effective use of CSII who they would not have recommended for this type of therapy in routine clinical practice. Our findings add to those studies that highlight the difficulties of using patient characteristics and variables to predict clinical success using CSII. To promote equitable access to CSII, attitudinal barriers and prejudicial assumptions amongst staff about who is able to make effective use of CSII may need to be addressed.


Origin of Fermi-level pinning at GaAs surfaces and interfaces.
Through first-principles simulation methods, we assign the origin of Fermi-level pinning at GaAs surfaces and interfaces to the bistability between the As-As dimer and two As dangling bonds, which transform into each other upon charge trapping. This defect is shown to be naturally formed both at GaAs surfaces upon oxygen deposition and in the near-interface substoichiometric oxide. Using electron-counting arguments, we infer that the identified defect occurs in opposite charge states. The Fermi-level pinning then results from the amphoteric nature of this defect which drives the Fermi level to its defect level. These results account for the experimental characterization at both GaAs surfaces and interfaces within a unified picture, wherein the role of As antisites is elucidated.


Impulse processing: a dynamical systems model of incremental eye movements in the visual world paradigm.
The Visual World Paradigm (VWP) presents listeners with a challenging problem: They must integrate two disparate signals, the spoken language and the visual context, in support of action (e.g., complex movements of the eyes across a scene). We present Impulse Processing, a dynamical systems approach to incremental eye movements in the visual world that suggests a framework for integrating language, vision, and action generally. Our approach assumes that impulses driven by the language and the visual context impinge minutely on a dynamical landscape of attractors corresponding to the potential eye-movement behaviors of the system. We test three unique predictions of our approach in an empirical study in the VWP, and describe an implementation in an artificial neural network. We discuss the Impulse Processing framework in relation to other models of the VWP.


Economic issues in the use of office spirometry for lung health assessment.
The National Lung Health Education Program (United States) has recently recommended using office spirometry to screen for subclinical lung disease in adult smokers. No published studies evaluate the economic consequences of this recommendation. This review article outlines the issues that must be considered when evaluating the costs and health benefits of office spirometry. Much of the available data on the effectiveness of screening is from studies that included smoking cessation interventions, making it difficult to determine the effects of screening alone. The sensitivity and specificity of screening spirometry are not known, but may not be important in the economic model, because even false positive test results are beneficial if they lead to smoking cessation. Costs to be considered include those of spirometry itself, of implementing and maintaining screening and smoking cessation programs, and of their consequences, ie, reduced morbidity (lower short term health care costs) and mortality (perhaps higher long term health care costs). Despite these unique challenges, data are available to perform economic analyses regarding screening spirometry. Such analyses should play a role in future clinical policy making. Even modest quit rates attributable to screening spirometry may result in highly favourable cost effectiveness ratios.


Getting the message right on nature-based solutions to climate change.
Nature-based solutions (NbS)-solutions to societal challenges that involve working with nature-have recently gained popularity as an integrated approach that can address climate change and biodiversity loss, while supporting sustainable development. Although well-designed NbS can deliver multiple benefits for people and nature, much of the recent limelight has been on tree planting for carbon sequestration. There are serious concerns that this is distracting from the need to rapidly phase out use of fossil fuels and protect existing intact ecosystems. There are also concerns that the expansion of forestry framed as a climate change mitigation solution is coming at the cost of carbon rich and biodiverse native ecosystems and local resource rights. Here, we discuss the promise and pitfalls of the NbS framing and its current political traction, and we present recommendations on how to get the message right. We urge policymakers, practitioners and researchers to consider the synergies and trade-offs associated with NbS and to follow four guiding principles to enable NbS to provide sustainable benefits to society: (1) NbS are not a substitute for the rapid phase out of fossil fuels; (2) NbS involve a wide range of ecosystems on land and in the sea, not just forests; (3) NbS are implemented with the full engagement and consent of Indigenous Peoples and local communities in a way that respects their cultural and ecological rights; and (4) NbS should be explicitly designed to provide measurable benefits for biodiversity. Only by following these guidelines will we design robust and resilient NbS that address the urgent challenges of climate change and biodiversity loss, sustaining nature and people together, now and into the future.


High density electroencephalography in sleep research: potential, problems, future perspective.
High density EEG (hdEEG) during sleep combines the superior temporal resolution of EEG recordings with high spatial resolution. Thus, this method allows a topographical analysis of sleep EEG activity and thereby fosters the shift from a global view of sleep to a local one. HdEEG allowed to investigate sleep rhythms in terms of their characteristic behavior (e.g., the traveling of slow waves) and in terms of their relationship to cortical functioning (e.g., consciousness and cognitive abilities). Moreover, recent studies successfully demonstrated that hdEEG can be used to study brain functioning in neurological and neuro-developmental disorders, and to evaluate therapeutic approaches. This review highlights the potential, the problems, and future perspective of hdEEG in sleep research.


Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis.
Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 microg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = -0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis.


Treatment optimization in multiple sclerosis: report of an international consensus meeting.
Multiple sclerosis (MS) is a chronic disease for which there is currently no proven cure. Nevertheless, desperate views have changed to substantial optimism over recent years, as several lines of evidence have indicated that disease-modifying drugs (DMDs) have beneficial effects on neurological deterioration in MS. However, assessing the success of DMD therapy in an individual patient may not always be clear-cut for the doctor. In order to address this issue, an International Working Group of doctors experienced in treating patients with MS convened to discuss the optimization of DMD therapy, and the outcome of this consensus meeting is reported here. Participants developed statements that classify changes in relapses, disease progression and brain magnetic resonance imaging in a patient with MS who is taking DMD therapy, according to whether they are worthy of note, of some concern, or of serious concern and requiring a reassessment of current therapy. Based on these statements, the performance of standardized examinations to document changes in the disease enables a visual measure of the progress of an individual patient to be built up on an analogue model. This model provides a useful framework to help the neurologist to identify those patients for whom the therapeutic options should be reconsidered.


Gender-based violence and HIV sexual risk behavior: alcohol use and mental health problems as mediators among women in drinking venues, Cape Town.
Gender-based violence is a key determinant of HIV infection among women in South Africa as elsewhere. However, research has not examined potential mediating processes to explain the link between experiencing abuse and engaging in HIV sexual risk behavior. Previous studies suggest that alcohol use and mental health problems may explain how gender-based violence predicts sexual risk. In a prospective study, we examined whether lifetime history of gender-based violence indirectly affects future sexual risk behavior through alcohol use, depression and post-traumatic stress disorder (PTSD) in a high-risk socio-environmental context. We recruited a cohort of 560 women from alcohol drinking venues in a Cape Town, South African township. Participants completed computerized interviews at baseline and 4 months later. We tested prospective mediating associations between gender-based violence, alcohol use, depression, PTSD, and sexual risk behavior. There was a significant indirect effect of gender-based violence on sexual risk behavior through alcohol use, but not mental health problems. Women who were physically and sexually abused drank more, which in turn predicted more unprotected sex. We did not find a mediated relationship between alcohol use and sexual risk behavior through the experience of recent abuse or mental health problems. Alcohol use explains the link between gender-based violence and sexual risk behavior among women attending drinking venues in Cape Town, South Africa. Efforts to reduce HIV risk in South Africa by addressing gender-based violence must also address alcohol use.


A Rare Case of Pyonephrosis in an Infant Induced by Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae.
Pyonephrosis is a rare condition in both adult and pediatric population. Here, the author presents a rare case of pyonephrosis induced by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a 12-month-old girl presenting with a picture of urosepsis. The patient presented with febrile urinary tract infection and was unresponsive to intravenous meropenem. Physical examination revealed huge, firm and irregular right renal swelling. Ultrasound and computed tomography imaging revealed severely hydronephrotic right kidney, and laboratory investigations showed elevated C-reactive protein level (22.9 mg/dl). Emergency percutaneous nephrostomy tube was inserted, pus was drained (20 ml) and intravenous vancomycin and amikacin were started. Her general condition improved, and urine culture was negative. Functional assessment with dimercaptosuccinic acid renal scan revealed that the split renal function was 5% on the right and 95% on the left side, and the bladder outline was smooth with no reflux in voiding cystourethrogram. A right nephrectomy was done a week later using the anterior subcostal approach. The postoperative course was smooth. Histopathological examination was diagnostic for xanthogranulomatous pyelonephritis. No adverse events were reported in the follow-up over 12 months. It can be concluded that a high degree of suspicion, rapid initiation of appropriate antibiotics and drainage of pus are crucial in the management of pyonephrosis.


Transcranial direct current stimulation of the posterior parietal cortex modulates arithmetic learning.
The successful acquisition of arithmetic skills is an essential step in the development of mathematical competencies and has been associated with neural activity in the left posterior parietal cortex (PPC). It is unclear, however, whether this brain region plays a causal role in arithmetic skill acquisition and whether arithmetic learning can be modulated by means of non-invasive brain stimulation of this key region. In the present study we addressed these questions by applying transcranial direct current stimulation (tDCS) over the left PPC during a short-term training that simulates the typical path of arithmetic skill acquisition (specifically the transition from effortful procedural to memory-based problem-solving strategies). Sixty participants received either anodal, cathodal or sham tDCS while practising complex multiplication and subtraction problems. The stability of the stimulation-induced learning effects was assessed in a follow-up test 24 h after the training. Learning progress was modulated by tDCS. Cathodal tDCS (compared with sham) decreased learning rates during training and resulted in poorer performance which lasted over 24 h after stimulation. Anodal tDCS showed an operation-specific improvement for subtraction learning. Our findings extend previous studies by demonstrating that the left PPC is causally involved in arithmetic learning (and not only in arithmetic performance) and that even a short-term tDCS application can modulate the success of arithmetic knowledge acquisition. Moreover, our finding of operation-specific anodal stimulation effects suggests that the enhancing effects of tDCS on learning can selectively affect just one of several cognitive processes mediated by the stimulated area.


Sudden infant death syndrome-associated mutations in the sodium channel beta subunits.
Approximately 10% of sudden infant death syndrome (SIDS) cases may stem from potentially lethal cardiac channelopathies, with approximately half of channelopathic SIDS involving the Na(V)1.5 cardiac sodium channel. Recently, Na(V) beta subunits have been implicated in various cardiac arrhythmias. Thus, the 4 genes encoding Na(V) beta subunits represent plausible candidate genes for SIDS. This study sought to determine the spectrum, prevalence, and functional consequences of sodium channel beta-subunit mutations in a SIDS cohort. In this institutional review board-approved study, mutational analysis of the 4 beta-subunit genes, SCN1B to 4B, was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing of DNA derived from 292 SIDS cases. Engineered mutations were coexpressed with SCN5A in HEK 293 cells and were whole-cell patch clamped. One of the putative SIDS-associated mutations was similarly studied in adenovirally transduced adult rat ventricular myocytes. Three rare (absent in 200 to 800 reference alleles) missense mutations (beta3-V36M, beta3-V54G, and beta4-S206L) were identified in 3 of 292 SIDS cases. Compared with SCN5A+beta3-WT, beta3-V36M significantly decreased peak I(Na) and increased late I(Na), whereas beta3-V54G resulted in a marked loss of function. beta4-S206L accentuated late I(Na) and positively shifted the midpoint of inactivation compared with SCN5A+beta4-WT. In native cardiomyocytes, beta4-S206L accentuated late I(Na) and increased the ventricular action potential duration compared with beta4-WT. This study provides the first molecular and functional evidence to implicate the Na(V) beta subunits in SIDS pathogenesis. Altered Na(V)1.5 sodium channel function due to beta-subunit mutations may account for the molecular pathogenic mechanism underlying approximately 1% of SIDS cases.


Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity.
Inactivating PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome) mutations cause X-linked hypophosphatemia in humans and mice (Hyp) through overproduction of fibroblast growth factor 23 (FGF23) a phosphaturic factor, by osteocytes. Matrix extracellular phosphoglycoprotein (MEPE) is also elevated in Hyp and other hypophosphatemic disorders. In addition, the administration of an ASARM (acidic serine-aspartate rich MEPE-associated motif) peptide derived from MEPE causes phosphaturia and inhibits bone mineralization in mice, suggesting that MEPE also plays a role in phosphate homeostasis. Since recent studies found that MEPE binds specifically to PHEX in vitro, we tested the effect of recombinant-MEPE and its ASARM peptide on PHEX enzyme activity in vitro and FGF23 expression in bone marrow stromal cell cultures ex vivo. We found that both recombinant MEPE and synthetic phosphorylated ASARM peptide (ASARM-PO(4)) inhibit PHEX enzyme activities in an in vitro fluorescent-quenched PHEX enzyme activity assay. The ASARM-PO(4) peptide inhibits PHEX enzyme activity in a dose-dependent manner with a K(i) of 128 nM and V(max-i) of 100%. Recombinant MEPE also inhibits PHEX activity (K(i) = 2 nM and V(max-i) = 26%). Long-term bone marrow stromal cell cultures supplemented with 10 microM ASARM-PO(4) peptide resulted in significant elevation of FGF23 transcripts and inhibition of mineralization. These findings suggest that MEPE inhibits mineralization and PHEX activity and leads to increased FGF23 production. The resulting coordination of mineralization and release of a phosphaturic factor by MEPE may serve a physiological role in regulating systemic phosphate homeostasis to meet the needs for bone mineralization.


COVID-19 vaccines and the pandemic: lessons learnt for other neglected diseases and future threats.
Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a 'multiple shots on goal' approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible, vesicular stomatitis virus or adenovirus vectors, messenger RNA (mRNA), whole inactivated virus, nanoparticle and recombinant protein technologies, which led to multiple effective COVID-19 vaccines. The challenge of COVID-19 vaccine inequity, as COVID-19 spread globally, created a situation where cutting-edge mRNA technologies were preferentially supplied by multinational pharmaceutical companies to high-income countries while low and middle-income countries (LMICs) were pushed to the back of the queue and relied more heavily on adenoviral vector, inactivated virus and recombinant protein vaccines. To prevent this from occurring in future pandemics, it is essential to expand the scale-up capacity for both traditional and new vaccine technologies at individual or simultaneous hubs in LMICs. In parallel, a process of tech transfer of new technologies to LMIC producers needs to be facilitated and funded, while building LMIC national regulatory capacity, with the aim of several reaching 'stringent regulator' status. Access to doses is an essential start but is not sufficient, as healthcare infrastructure for vaccination and combating dangerous antivaccine programmes both require support. Finally, there is urgency to establish an international framework through a United Nations Pandemic Treaty to promote, support and harmonise a more robust, coordinated and effective global response.


Survival of Antarctic Cryptoendolithic Fungi in Simulated Martian Conditions On Board the International Space Station.
Dehydrated Antarctic cryptoendolithic communities and colonies of the rock inhabitant black fungi Cryomyces antarcticus (CCFEE 515) and Cryomyces minteri (CCFEE 5187) were exposed as part of the Lichens and Fungi Experiment (LIFE) for 18 months in the European Space Agency's EXPOSE-E facility to simulated martian conditions aboard the International Space Station (ISS). Upon sample retrieval, survival was proved by testing colony-forming ability, and viability of cells (as integrity of cell membrane) was determined by the propidium monoazide (PMA) assay coupled with quantitative PCR tests. Although less than 10% of the samples exposed to simulated martian conditions were able to proliferate and form colonies, the PMA assay indicated that more than 60% of the cells and rock communities had remained intact after the "Mars exposure." Furthermore, a high stability of the DNA in the cells was demonstrated. The results contribute to assessing the stability of resistant microorganisms and biosignatures on the surface of Mars, data that are valuable information for further search-for-life experiments on Mars. Endoliths-Eukaryotes-Extremophilic microorganisms-Mars-Radiation resistance.


Zonal organization of the climbing fiber projection to the flocculus and nodulus of the rabbit: a combined axonal tracing and acetylcholinesterase histochemical study.
The localization and termination of olivocerebellar fibers in the flocculus and nodulus of the rabbit were studied with anterograde axonal transport methods [wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) and tritiated leucine] and correlated with the compartments in the white matter of these lobules delineated with acetylcholinesterase histochemistry (Tan et al. J. Comp. Neurol., 1995, this issue). Olivocerebellar fibers originating from the caudal dorsal cap travel through floccular compartments FC2 and FC4 to terminate as climbing fibers in floccular zones FZII and FZIV. Fibers from the rostral dorsal cap and the ventrolateral outgrowth traverse compartments FC1 and FC3, which are interleaved with compartments FC2 and FC4, and terminate in zones FZI and FZIII. Fibers from the rostral pole of the medial accessory olive traverse the C2 compartment and terminate in the C2 zone. FZI-III extend into the adjoining folium (folium p) of the ventral paraflocculus. The C2 zone continues across folium p into other folia of the ventral paraflocculus and into the dorsal paraflocculus. Four compartments and five zones were distinguished in the nodulus. Medial compartment XC1 contains olivocerebellar fibers from the caudal dorsal cap and subnucleus beta that terminate in the XZI zone. Olivocerebellar fibers from the rostral dorsal cap and the ventrolateral outgrowth occupy XC2 and terminate in XZII. The XC4 compartment contains fibers from both the caudal dorsal cap and from the rostral dorsal cap and the ventrolateral outgrowth. The latter terminate in a central portion of the XZIV zone. The dorsomedial cell column projects to the XZIII zone, which is present only in the dorsal part of the nodulus. The rostral medial accessory olive projects to the XZV zone, which occupies the lateral border of the nodulus. These results confirm and extend the conclusions of Katayama and Nisimaru ([1988] Neurosci. Res. 5:424-438) on the zonal pattern in the olivo-nodular projection in the rabbit. Additional observations were made on the presence of a lateral A zone (Buisseret-Delmas [1988] Neurosci. Res. 5:475-493) in the hemisphere of lobules VI and VII. Retrograde labeling of the nucleo-olivary tract of Legendre and Courville ([1987] Neuroscience 21:877-891) was observed after WGA-HRP injections into the inferior olive including the rostral dorsal cap and the ventrolateral outgrowth. The anatomical and functional implications of these observations are discussed.


Prenatal exposure to bisphenol A and risk of allergic diseases in early life.
Prenatal exposure to bisphenol A (BPA) affects immune system and promotes allergy and asthma in mice, but findings in human studies are limited. We investigated whether prenatal exposure to BPA is associated with increased risk of allergic diseases in infants. We measured BPA concentrations in maternal urine samples collected at delivery from 412 women in Wuhan, China. The occurrence of allergic diseases including eczema and wheeze were assessed at age 6 mo through questionnaires. We used logistic regression to evaluate the association between urinary BPA levels and the risk of allergic diseases. Mothers of infants with allergic diseases had significantly higher urinary BPA levels than those of infants without allergic diseases (median: 2.35 vs. 4.55 µg/l, P = 0.03). Increased risk of infant allergic diseases was associated with creatinine-adjusted maternal urinary BPA concentrations. And this association was limited to females (odds ratio (OR) = 1.36; 95% confidence interval (CI): 1.10-1.79) rather than males. After stratification by maternal age, the association was only significant in infants of mothers who were younger than 25 y old (OR = 1.90; 95% CI: 1.09-3.29). Prenatal exposure to BPA may potentially increase the risk of allergic diseases at very early life in female infants.


Hopelessness as a Predictor of Suicide Ideation in Depressed Male and Female Adolescent Youth.
We examined hopelessness as a predictor of suicide ideation in depressed youth after acute medication treatment. A total of 158 depressed adolescents were administered the Children's Depression Rating Scale-Revised (CDRS-R) and Columbia Suicide Severity Rating Scale (C-SSRS) as part of a larger battery at baseline and at weekly visits across 6 weeks of acute fluoxetine treatment. The Beck Hopelessness Scale (BHS) was administered at baseline and week 6. A negative binomial regression model via a generalized estimating equation analysis of repeated measures was used to estimate suicide ideation over the 6 weeks of acute treatment from baseline measure of hopelessness. Depression severity and gender were included as covariates in the model. The negative binomial analysis was also conducted separately for the sample of males and females (in a gender-stratified analysis). Mean CDRS-R total scores were 60.30 ± 8.93 at baseline and 34.65 ± 10.41 at week 6. Mean baseline and week 6 BHS scores were 9.57 ± 5.51 and 5.59 ± 5.38, respectively. Per the C-SSRS, 43.04% and 83.54% reported having no suicide ideation at baseline and at week 6, respectively. The analyses revealed that baseline hopelessness was positively related to suicide ideation over treatment (p = .0027), independent of changes in depression severity. This significant finding persisted only for females (p = .0024). These results indicate the importance of early identification of hopelessness.


Chitosan as a Wound Dressing Starting Material: Antimicrobial Properties and Mode of Action.
Fighting bacterial resistance is one of the concerns in modern days, as antibiotics remain the main resource of bacterial control. Data shows that for every antibiotic developed, there is a microorganism that becomes resistant to it. Natural polymers, as the source of antibacterial agents, offer a new way to fight bacterial infection. The advantage over conventional synthetic antibiotics is that natural antimicrobial agents are biocompatible, non-toxic, and inexpensive. Chitosan is one of the natural polymers that represent a very promising source for the development of antimicrobial agents. In addition, chitosan is biodegradable, non-toxic, and most importantly, promotes wound healing, features that makes it suitable as a starting material for wound dressings. This paper reviews the antimicrobial properties of chitosan and describes the mechanisms of action toward microbial cells as well as the interactions with mammalian cells in terms of wound healing process. Finally, the applications of chitosan as a wound-dressing material are discussed along with the current status of chitosan-based wound dressings existing on the market.


Chronic Obstructive Pulmonary Disease: Clinical Implications for Patients With Lung Cancer
Chronic obstructive pulmonary disease (COPD) is the most common smoking-related illness. COPD often is underemphasized as a comorbidity except when considering issues surrounding surgical treatment options. This article aims to provide nurses with an overview of the pharmacologic and nonpharmacologic treatment implications of COPD. Definitions, differentials, and treatment considerations are provided, and clinical implications and resources are described. The added burden of dyspnea, fatigue, and psychological distress related to COPD may affect the overall outcome and quality of life (QOL) of patients with lung cancer. Attention to the prevention, assessment, and treatment of lung cancer and COPD and related symptomatology will help maximize patients' QOL.


Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.
To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation. Observational nationwide cohort study. Three Danish nationwide databases, August 2011 to October 2015. 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%). Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding. When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5.3%). All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting. No significant difference was found between NOACs and warfarin for ischaemic stroke. The risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin.


Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.
To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.


Mind the Gap: The Underrepresentation of Female Participants and Authors in Virtual Reality Research.
A common goal of human-subject experiments in virtual reality (VR) research is evaluating VR hardware and software for use by the general public. A core principle of human-subject research is that the sample included in a given study should be representative of the target population; otherwise, the conclusions drawn from the findings may be biased and may not generalize to the population of interest. In order to assess whether characteristics of participants in VR research are representative of the general public, we investigated participant demographic characteristics from human-subject experiments in the Proceedings of the IEEE Virtual Reality Conferences from 2015-2019. We also assessed the representation of female authors. In the 325 eligible manuscripts, which presented results from 365 human-subject experiments, we found evidence of significant underrepresentation of women as both participants and authors. To investigate whether this underrepresentation may bias researchers' findings, we then conducted a meta-analysis and meta-regression to assess whether demographic characteristics of study participants were associated with a common outcome evaluated in VR research: the change in simulator sickness following head-mounted display VR exposure. As expected, participants in VR studies using HMDs experienced small but significant increases in simulator sickness. However, across the included studies, the change in simulator sickness was systematically associated with the proportion of female participants. We discuss the negative implications of conducting experiments on non-representative samples and provide methodological recommendations for mitigating bias in future VR research.


Reduced CSF leak in complete calvarial reconstructions of microvascular decompression craniectomies using calcium phosphate cement.
Calcium phosphate cement provides a biomaterial that can be used for calvarial reconstruction in a retrosigmoid craniectomy for microvascular decompression (MVD). This study evaluates the outcomes of postoperative CSF leak and wound infection for patients undergoing a complete cranioplasty using calcium phosphate cement versus incomplete cranioplasty using polyethylene titanium mesh following a retrosigmoid craniectomy for MVD. The authors evaluated 211 cases involving patients who underwent first-time retrosigmoid craniectomies performed by a single attending surgeon fortrigeminal neuralgia from October 2008 to June 2014. From this patient population, 111 patients underwent calvarial reconstruction after retrosigmoid craniectomy using polyethylene titanium mesh, and 100 patients had reconstructions using calcium phosphate cement. A Pearson's chi-square test was used to compare postoperative complications of CSF leak and wound infection in these 2 types of cranioplasties. The polyethylene titanium mesh group included 5 patients (4.5%) with postoperative CSF leak or pseudomeningocele and 3 patients (2.7%) with wound infections. In the calcium phosphate cement group, no patients had a CSF leak, and 2 patients (2%) had wound infections. This represented a statistically significant reduction of postoperative CSF leak in patients who underwent calcium phosphate reconstructions of their calvarial defect compared with those who underwent polyethylene titanium mesh reconstructions (p = 0.03). No significant difference was seen between the 2 groups in the number of patients with postoperative wound infections. Calcium phosphate cement provides a viable alternative biomaterial for calvarial reconstruction of retrosigmoid craniectomy defects in patients who have an MVD. The application of this material provides a biocompatible barrier that reduces the incidence of postoperative CSF leaks.


New Approaches to Marine Conservation Through the Scaling Up of Ecological Data.
In an era of rapid global change, conservation managers urgently need improved tools to track and counter declining ecosystem conditions. This need is particularly acute in the marine realm, where threats are out of sight, inadequately mapped, cumulative, and often poorly understood, thereby generating impacts that are inefficiently managed. Recent advances in macroecology, statistical analysis, and the compilation of global data will play a central role in improving conservation outcomes, provided that global, regional, and local data streams can be integrated to produce locally relevant and interpretable outputs. Progress will be assisted by (a) expanded rollout of systematic surveys that quantify species patterns, including some carried out with help from citizen scientists; (b) coordinated experimental research networks that utilize large-scale manipulations to identify mechanisms underlying these patterns;


Barriers and Attitudes toward Breast Cancer Screening among Omani Women.
Breast cancer (BC) is the most common cancer accounting for 24.5% of Omani female cancer. Early detection of BC through regular breast cancer screening (BCS) has been found to decrease mortality rates. The aim of this study was to identify knowledge, attitudes and barriers of Omani women toward BCS. A cross-sectional study was conducted among adult Omani women attending the Sultan Qaboos University Hospital (SQUH). A total of 358 Omani women participated from 420 invited (response rate = 85.2%). Most women (92.1%) thought that BC could be cured if detected early, but less than half (46.8%) thought that they were at risk of BC if a relative had BC. The majority (81.1%) were aware that BCS was available in Oman, though less than half (48.5%) knew where to go for BCS and most (83.8%) had not undergone BCS before. The most common personal-related barriers to BCS were fear of BC diagnosis (40.8%), fear of treatment (52.1%) and embarrassment of the breast examination (46.6%). The most perceived system-related barriers to BCS were the concern over the availability of a male doctor (46.6%) or a non-Arabic speaking doctor (38.7%) and not recommended by the doctor (46.3%). Univariate binary logistic regression showed that attitudes toward BCS were influenced by their previous experiences of BCS (odds ratio [OR] = 2.28; 95% confidence interval [CI]: 1.18-4.41) and their willingness to participate in the future BCS [OR = 1.96; 95% CI: 1.14-3.37). Although Omani women showed an interest toward BCS, few had undergone BCS. Several cultural, practical and personal-related barriers were noted to interfere with BCS in Oman. Addressing these concerns through involving healthcare providers to reassure the women and implementing a national strategy of BCS could improve BCS screenings and early diagnosis of BC.


Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.
We recently reported a pump-probe method that uses a single laser pulse to introduce parahydrogen (p-H2) into a metal dihydride complex and then follows the time-evolution of the p-H2-derived nuclear spin states by NMR. We present here a theoretical framework to describe the oscillatory behaviour of the resultant hyperpolarised NMR signals using a product operator formalism. We consider the cases where the p-H2-derived protons form part of an AX, AXY, AXYZ or AA'XX' spin system in the product molecule. We use this framework to predict the patterns for 2D pump-probe NMR spectra, where the indirect dimension represents the evolution during the pump-probe delay and the positions of the cross-peaks depend on the difference in chemical shift of the p-H2-derived protons and the difference in their couplings to other nuclei. The evolution of the NMR signals of the p-H2-derived protons, as well as the transfer of hyperpolarisation to other NMR-active nuclei in the product, is described. The theoretical framework is tested experimentally for a set of ruthenium dihydride complexes representing the different spin systems. Theoretical predictions and experimental results agree to within experimental error for all features of the hyperpolarised 1H and 31P pump-probe NMR spectra. Thus we establish the laser pump, NMR probe approach as a robust way to directly observe and quantitatively analyse the coherent evolution of p-H2-derived spin order over micro-to-millisecond timescales.


Fructooligosaccharides prevent disorders of the femoral neck following gastrectomy in growing rats.
Gastrectomy-evoked osteopenia in the femoral metaphysis of rats can be prevented by the consumption of fructooligosaccharides (FOS). We examined the effect of FOS on the femoral neck. Twenty-eight 5-week-old male Sprague-Dawley rats were divided into two groups, sham-operated (SH) and gastrectomized (GX). One week after each operation, the rats were fed diets containing 0.5% calcium with or without 7.5% FOS for 4 weeks. After dietary treatment, the middle of the femoral neck was cross sectioned. Backscattered electron images of the sections were then taken to calculate the following morphometric parameters: (1) percent trabecular bone volume (%TBV), (2) percent cortical bone volume (%CBV), and (3) percent bone marrow cavity (%MV); all were determined relative to the entire scan area (SC). Calcium, phosphorus, and magnesium (weight percent) were then measured on the cortical bone by energy-dispersive X-ray analysis. Total bone volume (%BV = %TBV + %CBV) and %CBV were almost identical among the groups, except in GX rats. In GX rats, these variables were significantly (approximately 20% and 30%, respectively; P < 0.01) less than those in SH rats, whereas there were no changes in the other groups over the entire scan area. The calcium concentration close to the periosteal surface of cortical bone was markedly reduced by gastrectomy. This reduction was completely prevented by FOS consumption. These results suggest that FOS consumption prevents gastrectomy-evoked osteopenia regarding both volume and calcium concentration of the femoral neck.


Failure of angiography to accurately depict the extent of coronary artery narrowing in three fatal cases of percutaneous transluminal coronary angioplasty.
The angiographic and pathologic findings are described in three patients who died less than 24 h after failed percutaneous transluminal coronary angioplasty. In two of the three patients, coronary angiography performed before angioplasty disclosed apparently focal lesions in the left anterior descending and right coronary arteries. In these two patients quantitative angiographic analysis disclosed a minimal lumen cross-sectional area of 1.82 and 0.47 mm2, respectively, at the sites of apparently focal stenoses before angioplasty; corresponding percent lumen area narrowing measured 84% and 91%, respectively, by quantitative angiography at these two sites. In the third patient, coronary angioplasty was undertaken when the patient developed spontaneous occlusion of the right coronary artery several hours after diagnostic angiography. Retrospective quantitative angiographic analysis of the right coronary artery revealed a minimal lumen cross-sectional area of 1.14 mm2, with 85% lumen area narrowing at the site of subsequent total occlusion and angioplasty. In each of these three patients, necropsy examination disclosed that the distribution of coronary narrowing in the artery treated by angioplasty was in fact not focal; rather, in each of these three patients, the artery treated by angioplasty, as well as the extramural coronary arteries not treated by angioplasty, were severely narrowed by diffusely distributed atherosclerotic plaque. The angiographic and necropsy findings in these three patients document that coronary narrowing that remains occult by virtue of diffuse distribution may complicate evaluation of patients being considered for coronary angioplasty.


Neurological and neurodegenerative diseases are multifactorial and their causes are not well understood yet. Among the relevant risk factors, pesticides and the productive activities in which they are used are included. To evaluate the association of mortality from neurological diseases within the Province of Pavia (Italy) with the agricultural activities, as a proxy of pesticides exposure. Population data for 2012 were provided by the local health unit (ATS) and by the registry office of the Regional Health Service. Spatial analyses were carried out by both a classical and Bayesian approach, to obtain a mortality map of the relative risk for neurological diseases in the Province of Pavia. Spatial distribution of main agricultural activities within the same territory, used as proxy of pesticides use, was made possible by data from the Geoportale Territoriale of the Lombardy region. Finally, a comparison between spatial distribution of mortality from neurological diseases and spatial distribution of main agricultural activities has been conducted. Mortality for neurological diseases in the Province of Pavia in 2012 was 4.41 for men and 6.53 for women per 10,000 subjects living in this area. Female mortality for neurological diseases showed a cluster in the Oltrepò district, where viticulture and fruit/horticulture are more common than elsewhere. More precisely, Bayesian relative risk (RR) had higher values in comparison with the median RR of the Province (100.8), with a posterior probability (PP) between 0.75 and 0.95 (not significant). Similarly, mortality for Parkinson's disease in women showed RR greater than the median value of the Province (100.6), with PP between 0.25 and 0.75 (not significant). Notwithstanding the ecological nature of the study, our results suggest the need to further investigate the possible link between pesticides exposure or related activities and neurological and neurodegenerative diseases, particularly Parkinson's disease. An ad hoc study on a random sample of the population living in the Province of Pavia, with the collection of individual data by means of standardized questionnaire, would allow to control for biases usually present when an ecological study design is applied.


What happens during annual appraisal interviews? How leader-follower interactions unfold and impact interview outcomes.
Despite a wealth of research on antecedents and outcomes of annual appraisal interviews, the ingredients that make for a successful communication process within the interview itself remain unclear. This study takes a communication approach to highlight leader-follower dynamics in annual appraisal interviews. We integrate relational leadership theory and recent findings on leader-follower interactions to argue (a) how supervisors' task- and relation-oriented statements can elicit employee involvement during the interview process and (b) how these communication patterns affect both supervisors' and employees' perceptions of the interview. Moreover, we explore (c) how supervisor behavior is contingent upon employee contributions to the appraisal interview. We audiotaped 48 actual annual appraisal interviews between supervisors and their employees. Adopting a multimethod approach, we used quantitative interaction coding (N = 32,791 behavioral events) as well as qualitative open-axial coding to explore communication patterns among supervisors and their employees. Lag sequential analysis revealed that supervisors' relation-oriented statements triggered active employee contributions and vice versa. These relation-activation patterns were linked to higher interview success ratings by both supervisors and employees. Moreover, our qualitative findings highlight employee disagreement as a crucial form of active employee contributions during appraisal interviews. We distinguish what employees disagreed about, how the disagreement was enacted, and how supervisors responded to it. Overall employee disagreement was negatively related to ratings of supervisor support. We discuss theoretical implications for performance appraisal and leadership theory and derive practical recommendations for promoting employee involvement during appraisal interviews. (PsycINFO Database Record


Explosion yield estimation from pressure wave template matching.
A method for estimating the yield of explosions from shock-wave and acoustic-wave measurements is presented. The method exploits full waveforms by comparing pressure measurements against an empirical stack of prior observations using scaling laws. The approach can be applied to measurements across a wide-range of source-to-receiver distances. The method is applied to data from two explosion experiments in different regions, leading to mean relative errors in yield estimates of 0.13 using prior data from the same region, and 0.2 when applied to a new region.


Maintenance of efficacy and safety with subcutaneous golimumab among patients with active rheumatoid arthritis who previously received intravenous golimumab.
To evaluate the efficacy/safety of subcutaneous (SC) golimumab in patients with rheumatoid arthritis (RA) who previously received intravenous (IV) golimumab with or without methotrexate (MTX). Adult patients with RA (n = 643) with persistent disease despite MTX (≥ 15 mg/wk for ≥ 3 months) were randomized to IV placebo + MTX (n = 129) or IV golimumab 2-4 mg/kg (± MTX) every 12 weeks (n = 514). Patients who completed the study through Week 48 could participate in the longterm extension (LTE), comprising open-label golimumab 50 mg SC every 4 weeks (± MTX) for 24 weeks (LTE-0 to LTE-24) followed by 16 weeks of safety followup (LTE-24 to LTE-40; MTX could be adjusted). At Week 48, 28% (nominal p < 0.001 vs placebo), 11%, and 8% of patients who received IV golimumab + MTX, golimumab alone, and placebo + MTX, respectively, achieved ≥ 50% improvement in the American College of Rheumatology response criteria (ACR50). Among the 505 patients who entered the LTE and were still participating, the proportion of patients treated with golimumab 50 mg SC (± MTX) achieving an ACR50 response increased to 44% at both LTE-14 and LTE-24. ACR20, ACR70, and 28-joint Disease Activity Score using C-reactive protein exhibited similar response patterns as ACR50. Infections were the most commonly reported adverse events through the end of IV golimumab dosing (37% placebo + MTX, 45% golimumab, 51% golimumab + MTX) and with SC golimumab from LTE-0 through LTE-40 (35% golimumab, 36% golimumab + MTX). Concomitant MTX use yielded lower incidences of antibodies to SC golimumab and injection-related reactions. Clinical improvements observed in golimumab-treated patients were sustained or improved in patients switched from IV (2-4 mg/kg ± MTX) to open-label SC (50 mg ± MTX) golimumab. Both IV and SC golimumab demonstrated acceptable safety profiles (Clinicaltrials.gov NCT00361335).


Intrahepatic portal vein branches after extrahepatic portal vein occlusion. Experimental study.
Prehepatic portal hypertension caused by extrahepatic portal vein occlusion is a situation in which hepatocytes are not damaged by disease despite the fact that portal blood is unable to reach them due to portal vein occlusion. We explored the patency of intrahepatic portal vein branches after extrahepatic portal vein occlusion for the possibility of revascularization by splenoportal shunt. Prehepatic portal hypertension was induced in 8 mini-pigs by external compression of the portal vein with a device consisting of an inflatable silicone balloon mounted on a silicone cuff and attached to a subcutaneous chamber. Another device consisting of cannula and a subcutaneous chamber was placed into the splenic vein for portal pressure monitoring and portal venograms. Both devices were placed during laparotomy with their chambers positioned subcutaneously. Portal vein compression was initiated one week later and was accomplished in two steps. Extrahepatic portal vein occlusion and the patency of intrahepatic portal vein branches were confirmed by direct portal venography. Alteration of the intrahepatic portal bed was examined at necropsy after 4 weeks, checking for the presence of occlusion or thrombosis. Portal vein occlusion was achieved in 5 animals, while severe stenosis was demonstrated in the remaining three. Portal venograms demonstrated patency of the lobar portal vein branches filled by hepatopetal collaterals around the occluded portal vein. All intrahepatic branches were free of thrombus at gross examination. In the absence of the hepatic parenchymal disease, lobar intrahepatic portal vein branches remain patent despite truncal portal vein occlusion and are supplied by rapidly developed hepatopetal collaterals.


Parental chronic pain and internalizing symptoms in offspring: the role of adolescents' social competence - the HUNT study.
A growing body of research suggests that the children of parents with chronic pain are at risk for internalizing symptoms. The mechanisms of such associations have not been as thoroughly examined. The aim of the present study was to investigate whether adolescents' social competence mediates the association between parental chronic pain and offspring internalizing symptoms as well as whether these associations are moderated by adolescent gender. The current study was based on cross-sectional data from the Nord-Trøndelag Health Study (HUNT 3), a Norwegian population-based health survey conducted in 2006-2008. The present sample comprised adolescents who had both parents participating (n=9,681). Structural equation modeling was used for the data analysis. Our results indicated that the association between concurrent maternal and paternal chronic pain and offspring's symptoms of anxiety and depression was partly mediated by low social competence for girls (b(SE)=0.060 [0.030], P=0.043) but not for boys (b(SE)=-0.059 [0.040], P=0.146). This suggests that these associations are moderated by offspring gender. The study extends the existing literature on the possible pathways between parental chronic pain and internalizing symptoms in the offspring. Identifying protective factors in the pathways between parental chronic pain and mental distress in children could guide measures that promote the wellbeing of the child and family of chronic pain sufferers.


In vitro vs in silico detected SNPs for the development of a genotyping array: what can we learn from a non-model species?
There is considerable interest in the high-throughput discovery and genotyping of single nucleotide polymorphisms (SNPs) to accelerate genetic mapping and enable association studies. This study provides an assessment of EST-derived and resequencing-derived SNP quality in maritime pine (Pinus pinaster Ait.), a conifer characterized by a huge genome size ( approximately 23.8 Gb/C). A 384-SNPs GoldenGate genotyping array was built from i/ 184 SNPs originally detected in a set of 40 re-sequenced candidate genes (in vitro SNPs), chosen on the basis of functionality scores, presence of neighboring polymorphisms, minor allele frequencies and linkage disequilibrium and ii/ 200 SNPs screened from ESTs (in silico SNPs) selected based on the number of ESTs used for SNP detection, the SNP minor allele frequency and the quality of SNP flanking sequences. The global success rate of the assay was 66.9%, and a conversion rate (considering only polymorphic SNPs) of 51% was achieved. In vitro SNPs showed significantly higher genotyping-success and conversion rates than in silico SNPs (+11.5% and +18.5%, respectively). The reproducibility was 100%, and the genotyping error rate very low (0.54%, dropping down to 0.06% when removing four SNPs showing elevated error rates). This study demonstrates that ESTs provide a resource for SNP identification in non-model species, which do not require any additional bench work and little bio-informatics analysis. However, the time and cost benefits of in silico SNPs are counterbalanced by a lower conversion rate than in vitro SNPs. This drawback is acceptable for population-based experiments, but could be dramatic in experiments involving samples from narrow genetic backgrounds. In addition, we showed that both the visual inspection of genotyping clusters and the estimation of a per SNP error rate should help identify markers that are not suitable to the GoldenGate technology in species characterized by a large and complex genome.


Synbiotics decrease the incidence of septic complications in patients with severe SIRS: a preliminary report.
The purpose of this study was to evaluate if synbiotic therapy can correct the deteriorated gut flora and environment in patients with severe systemic inflammatory response syndrome (SIRS). Twenty-nine SIRS patients, who fulfilled a serum C-reactive protein (CRP) level >10 mg/dl, received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) (S group) and were compared with previous observations in 26 patients without synbiotics (NS group). Analysis of fecal flora confirmed that patients in the S group had significantly greater levels of beneficial Bifidobacterium, Lactobacillus, and total organic acids (particularly short-chain fatty acids) than those in the NS group. The incidence of infectious complications such as enteritis, pneumonia, and bacteremia was significantly lower in the S group than in the NS group. Synbiotics maintain the gut flora and environment and decrease the incidence of septic complications in patients with severe SIRS. Further randomized controlled study is necessary to determine the effects of synbiotics.


Self-etching adhesives increase collagenolytic activity in radicular dentin.
Endogenous matrix metalloproteinases (MMPs) release from crown dentin and their activation results in degradation of hybrid layers created by dentin adhesives. This study tested the hypothesis that instrumented intraradicular dentin possesses latent collagenolytic activity that is activated by mild self-etching adhesives. Root dentin shavings were produced from 50 cleaned and shaped, saline-irrigated root canals using Gates Glidden drills and rinsed with sodium azide to prevent bacterial growth. Dried dentin powder aliquots were treated with two clinically-relevant MMP inhibitors, 2% chlorhexidine for 10 minutes and 17% EDTA for 1 minute. Additional dentin powder was mixed with Clearfil Liner Bond 2V or Clearfil Tri-S Bond for 1 minute followed by extracting the adhesives with acetone. Dentin powder was also treated with 2% chlorhexidine for 10 minutes before or after adhesive application. Collagenolytic activities of the nine groups were assayed with a fluorometer in 96-well plates, by recording the changes in fluorescence before and after addition of fluorescein-labeled type I collagen. Epoxy resin-embedded powders were examined with TEM for the extent of demineralization. Instrumented, mineralized intraradicular dentin possessed low but detectable collagenolytic activity that was inhibited by chlorhexidine (p < 0.001) and EDTA (p < 0.001). Both adhesives partially demineralized the dentin powder and activated latent MMPs, with 14- to 15-fold increases in collagenolytic activities (p < 0.001) that were significantly (p < 0.001) but incompletely inactivated after 10 min application of chlorhexidine. Mild self-etching adhesives activate latent MMPs without denaturing these enzymes, and may adversely affect the longevity of bonded root canal fillings and posts.


Broad host range species in specialised pathogen groups should be treated with suspicion - a case study on Entyloma infecting Ranunculus.
Plant pathogenic smut fungi in the broader sense can be divided into the Ustilaginomycetes, which cause classical smut symptoms with masses of blackish spores being produced in a variety of angiosperms, and the Exobasidiomycetes, which are often less conspicuous, as many do not shed large amounts of blackish spores. The leaf-spot causing members of the genus Entyloma (Entylomatales, Exobasidiomycetes) belong to the latter group. Currently, 172 species that all infect eudicots are included in the genus. Vánky (2012) recognised five Entyloma species on species of Ranunculus s.lat. Two have been reported only from Ficaria verna s.lat., while three, E. microsporum, E. ranunculi-repentis, E. verruculosum, have been reported to have a broad host range, encompassing 30, 26, and 5 species of Ranunculus, respectively. This broad host range is in contrast to the generally high host specificity assumed for species of Entyloma, indicating that they may represent complexes of specialised species. The aim of this study was to investigate Entyloma on Ranunculus s.lat. using multigene phylogenies and morphological comparisons. Phylogenetic analyses on the basis of up to four loci (ITS, atp2, ssc1, and map) showed a clustering of Entyloma specimens according to host species. For some of these Entyloma lineages, names not currently in use were available and reinstated. In addition, Entyloma microsporum s.str. is neotypified. Six novel species are described in this study, namely, Entyloma jolantae on Ranunculus oreophilus, E. klenkei on R. marginatus, E. kochmanii on R. lanuginosus, E. piepenbringiae on R. polyanthemos subsp. nemorosus (type host) and R. repens, E. savchenkoi on R. paludosus, and E. thielii on R. montanus. For all species diagnostic bases and morphological characteristics are provided. The results in this study once more highlight the importance of detailed re-investigation of broad host-range pathogens of otherwise specialised plant pathogen groups.


Why have mortality rates for severe malnutrition remained so high?
A review of the literature that has appeared over the past five decades indicates that the median case fatality from severe malnutrition has remained unchanged over this period and is typically 20-30%, with the highest levels (50-60%) being among those with oedematous malnutrition. A likely cause of this continuing high mortality is faulty case-management. A survey of treatment centres worldwide (n = 79) showed that for acutely ill children, inappropriate diets that are high in protein, energy and sodium and low in micronutrients are commonplace. Practices that could have fatal consequences, such as prescribing diuretics for oedema, were found to be widespread. Evidence of outmoded and conflicting teaching manuals also emerged. Since low mortality levels from malnutrition can be achieved using appropriate treatment regimens, updated treatment guidelines, which are practical and prescriptive rather than descriptive, need to be implemented as part of a comprehensive training programme.


Plasma oxidative stress and total thiol levels in Crimean-Congo hemorrhagic fever.
In this study, we investigated the pro- and antioxidant status of patients with a pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) in terms of their role in its pathogenesis. During the study period, 34 children and 41 adults were diagnosed with CCHF. The control group consisted of healthy age- and gender-matched children and adults. Serum levels of the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and plasma total thiol (TTL) were evaluated and compared between groups. The difference in mean TAC values between CCHF patients and healthy controls was not statistically significant (P > 0.05). Mean TOS, OSI, and TTL values were significantly lower in CCHF patients than in healthy controls (P < 0.001). Comparisons between the 2 groups revealed that mean TOS and OSI values were significantly lower in adults with CCHF than in their healthy counterparts (P < 0.001). Similarly, mean TTL levels were lower in both children and adults with CCHF when compared separately with healthy controls (P < 0.05). There was no significant difference in the mean serum TTL levels between children and adults with CCHF (P > 0.05). Our results suggest that TTL may play a more important role in CCHF pathogenesis than the other parameters investigated. The mean TOS and OSI values were higher in the control group than in CCHF patients.


Nanohydroxyapatite Effect on the Degradation, Osteoconduction and Mechanical Properties of Polymeric Bone Tissue Engineered Scaffolds.
Statistical reports show that every year around the world approximately 15 million bone fractures occur; of which up to 10% fail to heal completely and hence lead to complications of non-union healing. In the past, autografts or allografts were used as the "gold standard" of treating such defects. However, due to various limitations and risks associated with these sources of bone grafts, other avenues have been extensively investigated through which bone tissue engineering; in particular engineering of synthetic bone graft substitutes, has been recognised as a promising alternative to the traditional methods. A selective literature search was performed. Bone tissue engineering offers unlimited supply, eliminated risk of disease transmission and relatively low cost. It could also lead to patient specific design and manufacture of implants, prosthesis and bone related devices. A potentially promising building block for a suitable scaffold is synthetic nanohydroxyapatite incorporated into synthetic polymers. Incorporation of nanohydroxyapatite into synthetic polymers has shown promising bioactivity, osteoconductivity, mechanical properties and degradation profile compared to other techniques previously considered. Scientific research, through extensive physiochemical characterisation, in vitro and in vivo assessment has brought together the optimum characteristics of nanohydroxyapatite and various types of synthetic polymers in order to develop nanocomposites of suitable nature for bone tissue engineering. The aim of the present article is to review and update various aspects involved in incorporation of synthetic nanohydroxyapatite into synthetic polymers, in terms of their potentials to promote bone growth and regeneration in vitro, in vivo and consequently in clinical applications.


Investigation of CO2 capture mechanisms of liquid-like nanoparticle organic hybrid materials via structural characterization.
Nanoparticle organic hybrid materials (NOHMs) have been recently developed that comprise an oligomeric or polymeric canopy tethered to surface-modified nanoparticles via ionic or covalent bonds. It has already been shown that the tunable nature of the grafted polymeric canopy allows for enhanced CO(2) capture capacity and selectivity via the enthalpic intermolecular interactions between CO(2) and the task-specific functional groups, such as amines. Interestingly, for the same amount of CO(2) loading NOHMs have also exhibited significantly different swelling behavior compared to that of the corresponding polymers, indicating a potential structural effect during CO(2) capture. If the frustrated canopy species favor spontaneous ordering due to steric and/or entropic effects, the inorganic cores of NOHMs could be organized into unusual structural arrangements. Likewise, the introduction of small gaseous molecules such as CO(2) could reduce the free energy of the frustrated canopy. This entropic effect, the result of unique structural nature, could allow NOHMs to capture CO(2) more effectively. In order to isolate the entropic effect, NOHMs were synthesized without the task-specific functional groups. The relationship between their structural conformation and the underlying mechanisms for the CO(2) absorption behavior were investigated by employing NMR and ATR FT-IR spectroscopies. The results provide fundamental information needed for evaluating and developing novel liquid-like CO(2) capture materials and give useful insights for designing and synthesizing NOHMs for more effective CO(2) capture.


Migraine and risk of cardiovascular disease in women.
Migraine with aura has been associated with an adverse cardiovascular risk profile and prothrombotic factors that, along with migraine-specific physiology, may increase the risk of vascular events. Although migraine with aura has been associated with increased risk of ischemic stroke, an association with cardiovascular disease (CVD) and, specifically, coronary events remains unclear. To evaluate the association between migraine with and without aura and subsequent risk of overall and specific CVD. Prospective cohort study of 27,840 US women aged 45 years or older who were participating in the Women's Health Study, were free of CVD and angina at study entry (1992-1995), and who had information on self-reported migraine and aura status, and lipid measurements. This report is based on follow-up data through March 31, 2004. The primary outcome measure was the combined end point of major CVD (first instance of nonfatal ischemic stroke, nonfatal myocardial infarction, or death due to ischemic CVD); other measures were first ischemic stroke, myocardial infarction, coronary revascularization, angina, and death due to ischemic CVD. At baseline, 5125 women (18.4%) reported any history of migraine; of the 3610 with active migraine (migraine in the prior year), 1434 (39.7%) indicated aura symptoms. During a mean of 10 years of follow-up, 580 major CVD events occurred. Compared with women with no migraine history, women who reported active migraine with aura had multivariable-adjusted hazard ratios of 2.15 (95% confidence interval [CI], 1.58-2.92; P<.001) for major CVD, 1.91 (95% CI, 1.17-3.10; P = .01) for ischemic stroke, 2.08 (95% CI, 1.30-3.31; P = .002) for myocardial infarction, 1.74 (95% CI, 1.23-2.46; P = .002) for coronary revascularization, 1.71 (95% CI, 1.16-2.53; P = .007) for angina, and 2.33 (95% CI, 1.21-4.51; P = .01) for ischemic CVD death. After adjusting for age, there were 18 additional major CVD events attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura did not have increased risk of any vascular events or angina. In this large, prospective cohort of women, active migraine with aura was associated with increased risk of major CVD, myocardial infarction, ischemic stroke, and death due to ischemic CVD, as well as with coronary revascularization and angina. Active migraine without aura was not associated with increased risk of any CVD event.


Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis.
Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery.


Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial.
Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive. We investigated the association between prediagnostic serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non-trial conditions. No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). beta-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk. In this large prospective study, high serum beta-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention.


Effects of herbivores on grassland plant diversity.
The role of herbivores in controlling plant species richness is a critical issue in the conservation and management of grassland biodiversity. Numerous field experiments in grassland plant communities show that herbivores often, but not always, increase plant diversity. Recent work suggests that the mechanisms of these effects involve alteration of local colonization of species from regional species pools or local extinction of species, and recent syntheses and models suggest that herbivore effects on plant diversity should vary across environmental gradients of soil fertility and precipitation.