Management of accidental dural puncture and post-dural puncture headache after labour: a Nordic survey.
a major risk with epidural analgesia is accidental dural puncture (ADP), which may result in post-dural puncture headache (PDPH). This survey was conducted to explore the incidence of ADP, the policy for management of PDPH and the educational practices in epidural analgesia during labour in the Nordic countries. a postal questionnaire was sent to the anaesthesiologist responsible for Obstetric anaesthesia service in all maternity units (n=153) with questions relating to the year 2008. the overall response rate was 93%. About 32% (22-47%) of parturients received epidural analgesia for labour. There were databases for registering obstetric epidural complications in 13% of Danish, 24% of Norwegian and Swedish, 43% of Finnish and 100% of hospitals in Iceland. The estimated incidence of ADP was 1% (n approximately 900). Epidural blood patch (EBP) was performed in 86% (n≈780) of the parturients. The most common time interval from diagnosis to performing EBP was 24-48 h. The success rate for EBP was >75% in 67% (62-79%) of hospitals. The use of diagnostic CT/MRI before the first or the second EBP was exceptional. No major complication was reported. Teaching of epidurals was commonest (86%) in the non-obstetric population and 53% hospitals desired a formal training programme in obstetric analgesia. we found the incidence of ADP to be approximately 1%. EBP was the commonest method used for its management, and the success rate was high in most hospitals. Formal training in epidural analgesia was absent in most countries and trainees first performed it in the non-obstetric population.


Mediterranean dietary traditions for the molecular treatment of human cancer: anti-oncogenic actions of the main olive oil's monounsaturated fatty acid oleic acid (18:1n-9).
The final proof about the specific mechanisms by which the different components of olive oil, the principal source of fat in a typical "Mediterranean diet", exert their potential protective effects on the promotion and progression of several human cancers requires further investigations. A recent discovery that dietary fatty acids can interact with the human genome by regulating the amount and/or activity of transcription factors has opened a whole new line of research aimed to molecularly corroborate the ant-cancer benefits of the olive oil-based Mediterranean diet and the underlying mechanisms. Our most recent findings reveal that oleic acid (OA; 18:1n-9), the main olive oil's monounsaturated fatty acid, can suppress the overexpression of HER2 (erbB-2), a well-characterized oncogene playing a key role in the etiology, invasive progression and metastasis in several human cancers. First, exogenous supplementation with physiological concentrations of OA significantly down-regulates HER2-coded p185(Her-2/neu) oncoprotein in human cancer cells naturally harboring amplification of the HER gene. Second, OA exposure specifically represses the transcriptional activity of the human HER2 gene promoter in tumor-derived cell lines naturally exhibiting HER2 gene amplification and p185(Her-2/neu) protein overexpression but not in cancer cells expressing physiological levels of HER2. Third, OA treatment induces the up-regulation of the Ets protein PEA3 (a transcriptional repressor of the HER2 gene promoter) solely in cancer cells naturally displaying HER2 gene amplification. Fourth, HER2 gene promoter bearing a PEA3 site-mutated sequence cannot be negatively regulated by OA, while treatment with OA fails to repress the expression of a human full-length HER2 cDNA controlled by a SV40 viral promoter. Fifth, OA-induced inhibition of HER2 promoter activity does not occur if HER2 gene-amplified cancer cells do no concomitantly exhibit high levels of Fatty Acid Synthase (FASN; Oncogenic antigen-519) as specific depletion of FASN, which itself similarly suppresses HER2 overexpression by inducing PEA3-dependent repression of HER2 gene promoter, strongly antagonizes the inhibitory effects of OA on HER2 gene promoter activity. Considering that OA treatment efficiently blocks FASN activity and down-regulates FASN protein expression, it is reasonable to suggest that an accumulation of supra-physiological concentrations of the FASN substrate malonyl-CoA, due to its reduced utilization by FASN in the presence of exogenous OA, appears to act as an indicator of "cell fuel" availability capable to suppress HER2 expression via formation of inhibitory "PEA3 protein-PEA3 DNA binding site" complexes on the endogenous HER2 promoter. Indeed, malonyl-CoA on its own dramatically decreases HER2 promoter activity, while OA or malonyl-CoA similarly up-regulates PEA3 gene promoter activity. This previously unrecognized ability of OA to directly affect the expression of a cluster of interrelated human cancer genes (i.e., HER2, FASN and PEA3) should open a new line of research aimed to explore the anti-cancer effects of OA. Certainly, an appropriate dietary intervention reproducing this prominent anti-oncogenic feature of the "Mediterranean diet" must be carried out in animal models and human pilot studies in the future. Only then we will know whether the old "Mediterranean dietary traditions" will become a new molecular approach in the management of cancer disease.


How to govern the digital transformation of health services.
The impact of digitalization of health services has been profound and is expected to be even more profound in the future. It is important to evaluate whether digital health services contribute to health system goals in an optimal way. This should be done at the level of the service, not the 'digital transformation'. Decisions to adopt new digital health services, at different levels of the health care system, are ideally based on evidence regarding their performance in light of health system goals. In order to evaluate this, a broad perspective should be taken in evaluations of digital health services. Attainment of the broad health system goals, including quality, efficiency and equity, are objectives against which to judge new digital health services. These goals in a broad sense are unaltered by the process of digitalization. Governance should be designed and tailored in such a way to capture all relevant changes in an adequate way. When evaluating digital health services many specific aspects need to be considered. Like for other innovations and (new) technologies, such promises may or may not materialize and potential benefits may also be accompanied by unintended and/or negative (side) effects in the short or long term. Hence, the introduction, implementation, use and funding of digital health technologies should be carefully evaluated and monitored. Governments should play a more active role in the further optimization both of the process of decision making (both at the central and decentral level) and the related outcomes. They need to find a balance between centralized and decentralized activity. Moreover, the broader preparation of the health care system to be able to deal with digitalization, from education, through financial and regulatory preconditions, to implementation of monitoring systems to monitor its effects on health system performance remains important.


Vitiligo: a possible model of degenerative diseases.
Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects.


Five-degrees-of-freedom measurement system based on a monolithic prism and phase-sensitive detection technique.
This paper presents a method for measuring five-degrees-of-freedom errors of a moving stage with a monolithic prism and phase-sensitive detection technique. It consists of a pigtailed laser diode, three position-sensitive detectors (PSDs), a monolithic prism, and additional optical and electronic components. The monolithic prism mounted on the moving stage generates three beams that are detected by three PSDs, respectively, so that the straightness, pitch, yaw, and roll errors can be simultaneously measured. Theoretical analysis of each error measurement process is presented. To reduce the influence of disturbing light, the laser diode is modulated by a sinusoidal wave current, and a phase-sensitive detection technique is developed to demodulate the signals. Compared with a laser interferometer, the deviation errors when measuring the horizontal and vertical straightness errors are better than ±0.25 and ±0.4 μm, respectively. The deviation errors for the pitch, yaw, and roll are better than ±0.5, ±0.3, and ±2 arc sec, respectively, in comparison with an autocollimator. The system can be assembled to measure five error components of machine tools in an industrial environment.


Rehabilitation service models for people with physical and/or mental disability living in low- and middle-income countries: A systematic review.
To compare models of rehabilitation services for people with mental and/or physical disability in order to determine optimal models for therapy and interventions in low- to middle-income countries. CINAHL, EMBASE, MEDLINE, CENTRAL, PsycINFO, Business Source Premier, HINARI, CEBHA and PubMed. Systematic reviews, randomized control trials and observational studies comparing >2 models of rehabilitation care in any language. Date extraction: Standardized forms were used. Methodological quality was assessed using AMSTAR and quality of evidence was assessed using GRADE. Twenty-four systematic reviews which included 578 studies and 202,307 participants were selected. In addition, four primary studies were included to complement the gaps in the systematic reviews. The studies were all done at various countries. Moderate- to high-quality evidence supports the following models of rehabilitation services: psychological intervention in primary care settings for people with major depression, admission into an inpatient, multidisciplinary, specialized rehabilitation unit for those with recent onset of a severe disabling condition; outpatient rehabilitation with multidisciplinary care in the community, hospital or home is recommended for less severe conditions; However, a model of rehabilitation service that includes early discharge is not recommended for elderly patients with severe stroke, chronic obstructive pulmonary disease, hip fracture and total joints. Models of rehabilitation care in inpatient, multidisciplinary and specialized rehabilitation units are recommended for the treatment of severe conditions with recent onset, as they reduce mortality and the need for institutionalized care, especially among elderly patients, stroke patients, or those with chronic back pain. Results are expected to be generalizable for brain/spinal cord injury and complex fractures.


[Pyogenic granuloma developing rapidly after excision of corneal/conjunctival intraepithelial neoplasia].
Pyogenic granuloma is a benign tumor presenting with a smooth hemorrhagic surface that develops on the ocular surface after trauma or ophthalmic surgery. Abnormal wound healing due to physical and/or chemical stimulation may contribute to the pathogenesis of the tumor. We herein report the usefulness of brushing cytology for diagnosis of pyogenic granuloma, which rapidly developed after surgical resection of corneal/conjunctial intraepithelial neoplasia (CIN). A 70-year-old man presented with a flat tumor on the left lower conjunctiva in conjunction with the cornea. The patient underwent excision of the tumor and cryotherapy. The primary tumor was histologically diagnosed with CIN. A hemorrhagic mass developed on the conjunctiva one month after the excision. Brushing cytology demonstrated vascular endothelial cells with spindle-shaped nuclei mixed with prominent neutrophils without abnormal squamous epithelial cells. The secondary tumor was diagnosed as pyogenic granuloma. It is possible to diagnose a secondary tumor based on information of the clinical course, slit-lamp examination and brushing cytology before the excision of CIN.


Genomic insights into the circulation of pandemic fluoroquinolone-resistant extra-intestinal pathogenic Escherichia coli ST1193 in Vietnam.
Extra-intestinal pathogenic Escherichia coli (ExPEC) ST1193, a globally emergent fluoroquinolone-resistant clone, has become an important cause of bloodstream infections (BSIs) associated with significant morbidity and mortality. Previous studies have reported the emergence of fluoroquinolone-resistant ExPEC ST1193 in Vietnam; however, limited data exist regarding the genetic structure, antimicrobial resistance (AMR) determinants and transmission dynamics of this pandemic clone. Here, we performed genomic and phylogenetic analyses of 46 ST1193 isolates obtained from BSIs and healthy individuals in Ho Chi Minh City, Vietnam, to investigate the pathogen population structure, molecular mechanisms of AMR and potential transmission patterns. We further examined the phylogenetic structure of ST1193 isolates in a global context. We found that the endemic E. coli ST1193 population was heterogeneous and highly dynamic, largely driven by multiple strain importations. Several well-supported phylogenetic clusters (C1-C6) were identified and associated with distinct blaCTX-M variants, including blaCTXM-27 (C1-C3, C5), blaCTXM-55 (C4) and blaCTXM-15 (C6). Most ST1193 isolates were multidrug-resistant and carried an extensive array of AMR genes. ST1193 isolates also exhibited the ability to acquire further resistance while circulating in Vietnam. There were phylogenetic links between ST1193 isolates from BSIs and healthy individuals, suggesting these organisms may both establish long-term colonization in the human intestinal tract and induce infections. Our study uncovers factors shaping the population structure and transmission dynamics of multidrug-resistant ST1193 in Vietnam, and highlights the urgent need for local One Health genomic surveillance to capture new emerging ExPEC clones and to better understand the origins and transmission patterns of these pathogens.


Ferredoxin from sweet pepper (Capsicum annuum L.) intensifying harpin(pss)-mediated hypersensitive response shows an enhanced production of active oxygen species (AOS).
The hypersensitive response (HR) is a form of cell death associated with plant resistance to pathogen infection. Harpin(pss), an elicitor from the bacterium Pseudomonas syringae pv. syringae, induces a HR in non-host plants. Previously, we reported an amphipathic protein from sweet pepper interfering with harpin(pss)-mediated HR. In this report, we isolated and characterized a cDNA clone encoded that amphipathic protein from sweet pepper. This protein is designated as PFLP (plant ferredoxin-like protein) by virtue of its high homology with plant ferredoxin protein containing an N-terminal signal peptide responsible for chloroplast targeting and a putative 2Fe-2S domain responsible for redox activity. Recombinant PFLP obtained from Escherichia coli was able to significantly increase active oxygen species (AOS) generation when mixed with harpin(pss) in tobacco suspension cells. It also showed enhanced HR when co-infiltrated with harpin(pss) in tobacco leaves. We used a transgenic tobacco suspension cells system that constitutively expresses the Pflp gene driven by the CaMV 35S promoter to study the function of PFLP in enhancing harpin(pss)-mediated hypersensitive cell death in vivo. In response to harpin(pss), suspension cells derived from Pflp transgenic tobacco showed a significant increase both in the generation of AOS and in cell death as compared to the wild type. AOS inhibitors diphenylene iodonium chloride (DPI) and lanthanum chlorate (LaCl3) were used to study the involvement of AOS in harpin(pss)-induced cell death. Our results demonstrate enhanced generation of AOS is necessary to cause enhanced hypersensitive cell death in Pflp transgenic tobacco cells and it is plasma membrane-bound NADPH-oxidase-dependent. Sub-cellular localization studies showed that PFLP is present in the cytoplasm and chloroplast of Pflp transgenic tobacco cells, but only in the chloroplast, not in the cytoplasm, of wild-type tobacco cells. It is possible that PFLP can change the redox state of the cell upon harpin(pss) inoculation to increase AOS generation and hypersensitive cell death. Overall, this study will provide a new insight in the functional properties of ferredoxin in hypersensitive cell death.


Essential tremor-Parkinson's disease: A double whammy.
Surprisingly little has been written about the combined clinical entity, essential tremor-Parkinson's disease (ET-PD), which is the result of a double disease hit. We carefully quantified tremor burden using a wide range of measures (tremor severity, tremor-related disability, tremor-related quality of life) and furthermore, studied additional motor and non-motor features in ET-PD. In this prospective, clinical-epidemiological study, we performed a standardized, structured clinical evaluation of 27 ET-PD patients, comparing them to age-matched samples of 35 PD and 109 ET patients. The number of hours/day shaking was lowest in PD (median=3.0), intermediate in ET (median=10.0) and highest in ET-PD (median=14.0) (p<0.001). All measures of mobility and balance (Berg Balance test, Activities-specific Balance Confidence Scale, Timed Up and Go test) worsened across groups in a stepwise manner from ET to PD to ET-PD (p<0.05). Mini-mental state test scores worsened (p=0.002) and daytime sleepiness increased (p=0.002) across groups from ET to PD to ET-PD. The ET-PD patient seems to be more than just a PD patient with a little more kinetic tremor. Aside from a significantly greater tremor burden, ET-PD patients exhibited more cognitive and sleep problems and more mobility and balance problems than patients with isolated PD.


Reduced mortality and CD4 cell loss among carriers of the interleukin-10 -1082G allele in a Zimbabwean cohort of HIV-1-infected adults.
To evaluate the effect on HIV progression of single nucleotide polymorphisms in promoters of the genes for tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 and known to influence cytokine production. Survival was documented for 4.3 years after baseline for 198 HIV-1-infected and 180 HIV-uninfected individuals from the Mupfure Schistosomiasis and HIV Cohort in rural Zimbabwe. Polymorphisms determined were -592C>A and -1082A>G for IL-10 and -238G>A and -308G>A for TNF-alpha. CD4 cell counts, plasma HIV RNA, soluble TNF receptor II (sTNF-rII), IL-8 and IL-10 were also measured. Mortality was lower in carriers of the IL-10 -1082G high-producer allele (hazard ratio, 0.47; P < 0.01). CD4 cell count decrease in participants reporting for the follow-up at 3 years was attenuated in carriers of this allele (P < 0.01). In univariate analysis, plasma IL-10, IL-8, and sTNF-rII correlated negatively with CD4 cell count, positively with HIV RNA, and higher levels predicted mortality. In multivariate analysis only sTNF-rII was an independent predictor of HIV progression markers and mortality. Indeed, sTNF-rII predicted mortality (P < 0.01) at a level of significance comparable to HIV RNA (P < 0.01) and CD4 cell count (P < 0.05). In carriers of IL-10 -1082G, an allele linked to increased IL-10 production, survival was doubled and CD4 cell decrease was attenuated compared with noncarriers. Only sTNF-rII and not plasma IL-10 was an independent predictor of HIV progression markers and mortality. This study supports immune activation as a driving force in HIV pathogenesis and indicates a protective role of IL-10 -1082G that should be evaluated in other cohorts.


Nonenzymatic sugar production from biomass using biomass-derived γ-valerolactone.
Widespread production of biomass-derived fuels and chemicals will require cost-effective processes for breaking down cellulose and hemicellulose into their constituent sugars. Here, we report laboratory-scale production of soluble carbohydrates from corn stover, hardwood, and softwood at high yields (70 to 90%) in a solvent mixture of biomass-derived γ-valerolactone (GVL), water, and dilute acid (0.05 weight percent H2SO4). GVL promotes thermocatalytic saccharification through complete solubilization of the biomass, including the lignin fraction. The carbohydrates can be recovered and concentrated (up to 127 grams per liter) by extraction from GVL into an aqueous phase by addition of NaCl or liquid CO2. This strategy is well suited for catalytic upgrading to furans or fermentative upgrading to ethanol at high titers and near theoretical yield. We estimate through preliminary techno-economic modeling that the overall process could be cost-competitive for ethanol production, with biomass pretreatment followed by enzymatic hydrolysis.


Regional cerebral blood flow in children with autism spectrum disorders: a quantitative ⁹⁹mTc-ECD brain SPECT study with statistical parametric mapping evaluation.
Autism spectrum disorders (ASD), which include autism, asperger syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS), are devastating neurodevelopmental disorders of childhood resulting in deficits in social interaction, repetitive patterns of behaviors, and restricted interests and activities. Single photon emission computed tomography (SPECT) is a common technique used to measure regional cerebral blood flow (rCBF). Several studies have measured rCBF in children with ASD using SPECT, however, findings are discordant. In addition, the majority of subjects used in these studies were autistic. In this study, we aimed to investigate changes in rCBF in children with ASD using SPECT. A Technetium-99m-ethyl cysteinate dimmer (⁹⁹m)Tc-ECD) brain SPECT study was performed on an ASD group consisting of 23 children (3 girls and 20 boys; mean age (7.2 ± 3.0) years) who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria and an age-matched control group with 8 children (1 girl and 7 boys, mean age (5.5 ± 2.4) years). Image data were evaluated with Statistical Parametric Mapping, 5th version (SPM5). A Student's t test for unpaired data was used to compare rCBF and asymmetry in the autism and corresponding control group. The covariance analysis, taking age as covariance, was performed between the ASD and control group. There was a significant reduction in rCBF in the bilateral frontal lobe (frontal poles, arcula frontal gyrus) and the bilateral basal ganglia in the autism group, and a reduction in the bilateral frontal, temporal, parietal, legumina nucleus and cerebellum in the AS group compared to the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group was observed. Inner-group comparison analysis revealed that rCBF decreased significantly in the bilateral frontal lobe (42.7%), basal nucleus (24.9%) and temporal lobe (22.8%) in the autism group, and in the bilateral cerebellum (22.8%), basal nucleus (19.3%) and right thalamencephalon (16.6%) in the AS group (P < 0.05). The decrease in rCBF in ASD is a global event, which involves the bilateral frontal, temporal, limbic system and basal ganglias. Asymmetry of hemispheric hypoperfusion was more obvious in the AS group than the autism group, which indicates a different neurobiological mechanism from that of autism.


Parasite species of the endangered Iberian wolf (Canis lupus signatus) and a sympatric widespread carnivore.
Parasites have a profound impact on wildlife population dynamics. However, until some years ago, studies on the occurrence and prevalence of wildlife parasites were neglected comparatively with the studies on humans and domestic animals. In this study, we determined the parasite prevalence of two sympatric wild canids: the endangered Iberian wolf (Canis lupus signatus) and the widespread red fox (Vulpes vulpes), in central Portugal. From November 2014 to July 2015, fresh fecal samples from both species were collected monthly in several transects distributed throughout the study area. All samples were submitted to several coprological techniques. In total, 6 helminth parasites (Crenosoma vulpis, Angiostrongylus vasorum, Toxocara canis, Trichuris vulpis, Ancylostomatidae, Toxascaris leonina), and a protozoa (Balantidium coli) were identified based on size and morphology. The red fox was infected by seven different parasites while the Iberian wolf was infected by four. All parasites present in wolf were also present in the red fox. C. vulpis had the higher prevalence in red fox, while Ancylostomatidae were the most prevalent parasites in wolf. To our knowledge, this is the first study in this isolated subpopulation of the Iberian wolf. Our results show that both carnivores carry parasites that are of concern as they are pathogenic to humans and other wild and domestic animals. We suggest that surveillance programs must also include monitoring protocols of wildlife; particularly endangered species.


Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome.
The aim of this study was to clarify the significance of DNA methylation alterations during gastric carcinogenesis. Single-CpG resolution genome-wide DNA methylation analysis using the Infinium assay was performed on 109 samples of non-cancerous gastric mucosa (N) and 105 samples of tumorous tissue (T). DNA methylation alterations in T samples relative to N samples were evident for 3861 probes. Since N can be at the precancerous stage according to the field cancerization concept, unsupervised hierarchical clustering based on DNA methylation levels was performed on N samples (βN) using the 3861 probes. This divided the 109 patients into three clusters: A (n = 20), B1 (n = 20), and B2 (n = 69). Gastric carcinomas belonging to Cluster B1 showed tumor aggressiveness more frequently than those belonging to Clusters A and B2. The recurrence-free and overall survival rates of patients in Cluster B1 were lower than those of patients in Clusters A and B2. Sixty hallmark genes for which βN characterized the epigenetic clustering were identified. We then focused on DNA methylation levels in T samples (βT) of the 60 hallmark genes. In 48 of them, including the ADAM23, OLFM4, AMER2, GPSM1, CCL28, DTX1 and COL23A1 genes, βT was again significantly correlated with tumor aggressiveness, and the recurrence-free and/or overall survival rates. Multivariate analyses revealed that βT was a significant prognostic factor, being independent of clinicopathological parameters. These data indicate that DNA methylation profiles at the precancerous stage may be inherited by gastric carcinomas themselves, thus determining tumor aggressiveness and patient outcome.


A scheme to polarize nuclear-spin of atoms by a sequence of short laser pulses: application to the muonium.
We theoretically show that a sequence of short laser pulses can efficiently polarize nuclear-spin of atoms/ions. This is a variant of optical pumping with an important difference that a sequence of short laser pulses is used instead of a continuous-wave laser. Such a replacement is particularly useful if the pumping wavelength is in the ultraviolet or vacuum-ultraviolet region where obtaining a continuous-wave light source with a sufficient intensity is very difficult. Because of the use of short laser pulses neither hyperfine transitions nor fine structure transitions are spectrally resolved, which is quite in contrast to the standard optical pumping scheme by a continuous-wave laser. As an example we apply the scheme to polarize the muonium (μ(+)e(-), lifetime 2.2 μs), for which the pumping wavelength is 122 nm. From numerical solutions of a set of density matrix equations, we find that the use of only a single, two, and five pulses with a ps duration at the peak intensity of 2×10(8) W/cm(2) and a 5 ns time interval results in the degrees of spin-polarization of 33, 50, and 80 %, respectively, within the time scale of a few tens of ns.


Evaluation of dendritic cell immunogenicity after activation and chemical fixation: a mixed lymphocyte reaction model.
Dendritic cells (DC) are central to the control of adaptive immunity. Their ability to activate antigen-specific T cells depends on their maturation state. Many microbial and inflammatory products have stimulated DC maturation. This in vitro study used assays of phenotype and function to examine the potential of bacillus Calmette-Guerin, muramyl dipeptide, and CpG-rich oligodeoxynucleotides to stimulate DC maturation. A chemical fixation method was developed to reliably assess the functional potential of stimulated DC within a mixed lymphocyte reaction model. Using this method, it was shown that bacillus Calmette-Guerin provides a maturation signal as effective as the prototype DC stimulant interleukin-1beta. Furthermore, weaker stimuli such as muramyl dipeptide and CpG-rich oligodeoxynucleotides also are able to induce functional maturation of DC. Using chemical fixation, it was possible to generate stable DC in an immature or a mature state. These observations have importance for our understanding of the regulation of adaptive immunity and for the design of DC-based immunotherapeutic strategies.


Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart.
The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease. In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI). Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 μg HGF and 2 to 8 μg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging. The IGF-1/HGF activated c-kit positive-CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive-CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI. In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.


Genetic and environmental effects on the scaling of metabolic rate with body size.
Metabolic rate (MR) often scales with body mass (BM) following a power function of the form MR=aBM b , where log(a) is the allometric intercept and b is the allometric exponent (i.e. slope on a log-log scale). The variational properties of b have been debated, but very few studies have tested for genetic variance in b, and none have tested for a genotype-by-environment (G×E) interaction in b Consequently, the short-term evolutionary potentials of both b and its phenotypic plasticity remain unknown. Using 10 clones of a population of Daphnia magna, we estimated the genetic variance in b and assessed whether a G×E interaction affected b We measured MR on juveniles of different sizes reared and measured at three temperatures (17, 22 and 28°C). Overall, b decreased with increasing temperature. We found no evidence of genetic variance in b at any temperature, and thus no G×E interaction in b However, we found a significant G×E interaction in size-specific MR. Using simulations, we show how this G×E interaction can generate genetic variation in the ontogenetic allometric slope of animals experiencing directional changes in temperature during growth. This suggests that b can evolve despite having limited genetic variation at constant temperatures.


Neighborhood conditions and celiac disease risk among children in Sweden.
To investigate celiac disease (CD) clustering at different geographical levels and to examine the association between neighborhood demographic and socioeconomic conditions and the risk of neighborhood CD. We included 2080 children diagnosed with CD between 1998 and 2003, identified from 43 of the 47 reporting hospitals in Sweden. A total of 8036 small area market statistics (SAMS) areas were included; these were nested in 253 municipalities that were further nested into eight 'nomenclature of territorial units for statistics' (NUTS) 2 regions. We performed multilevel logistic regression analyses. We found the highest geographical variation in CD incidence at the municipality level, compared to the region level. The probability of having CD increased in the statistical areas of (SAMS) areas with higher average annual work income, with an odds ratio (OR) of 2.24 and 95% CI of 1.76-2.85. Reduced CD risk in neighborhoods was associated with higher average age (OR 0.96; 95% CI 0.95-0.97), higher proportion of residents with a university education (OR 0.98; 95% CI 0.97-0.99), and higher level of industrial and commercial activity (OR 0.59; 95% CI 0.44-0.82). We found no significant association between CD risk and population density, proportion of Nordic to non-Nordic inhabitants, nor share of the population with only a compulsory education. Neighborhood composition influences cd risk this is one of the first attempts to identify factors explaining geographical variation in CD.


Black Heterogeneity in Cancer Mortality: US-Blacks, Haitians, and Jamaicans.
The quantitative intraracial burden of cancer incidence, survival and mortality within black populations in the United States is virtually unknown. We computed cancer mortality rates of US- and Caribbean-born residents of Florida, specifically focusing on black populations (United States, Haiti, Jamaica) and compared them using age-adjusted mortality ratios obtained from Poisson regression models. We compared the mortality of Haitians and Jamaicans residing in Florida to populations in their countries of origin using Globocan. We analyzed 185,113 cancer deaths from 2008 to 2012, of which 20,312 occurred in black populations. The overall risk of death from cancer was 2.1 (95% CI: 1.97-2.17) and 1.6 (95% CI: 1.55-1.71) times higher for US-born blacks than black Caribbean men and women, respectively (P < .001). Race alone is not a determinant of cancer mortality. Among all analyzed races and ethnicities, including Whites and Hispanics, US-born blacks had the highest mortality rates while black Caribbeans had the lowest. The biggest intraracial difference was observed for lung cancer, for which US-blacks had nearly 4 times greater mortality risk than black Caribbeans. Migration from the islands of Haiti and Jamaica to Florida resulted in lower cancer mortality for most cancers including cervical, stomach, and prostate, but increased or stable mortality for 2 obesity-related cancers, colorectal and endometrial cancers. Mortality results in Florida suggest that US-born blacks have the highest incidence rate of "aggressive" prostate cancer in the world, rather than Caribbean men.


Empathic neural responses to others' pain are modulated by emotional contexts.
Recent brain imaging studies indicate that empathy for pain relies upon both the affective and/or the sensorimotor nodes of the pain matrix, and empathic neural responses are modulated by stimulus reality, personal experience, and affective link with others. The current work investigated whether and how empathic neural responses are modulated by emotional contexts in which painful stimulations are perceived. Using functional magnetic resonance imaging (fMRI), we first showed that perceiving a painful stimulation (needle penetration) applied to a face with neutral expression induced activation in the anterior cingulate cortex (ACC) relative to nonpainful stimulation (Q-tip touch). However, when observation of the painful stimuli delivered to a neutral face was intermixed with observation of painful or happy faces, the ACC activity decreased while the activity in the face area of the secondary somatosensory cortex increased to the painful stimulation. Moreover, the secondary somatosensory activity associated with the painful stimulation decreased when the painful stimulation was applied to faces with happy and painful expressions. The findings suggest that observing painful stimuli in an emotional context weakens affective responses but increases sensory responses to perceived pain and implies possible interactions between the affective and sensory components of the pain matrix during empathy for pain.


Advancing research on emergency care systems in low-income and middle-income countries: ensuring high-quality care delivery systems.
Emergency care systems (ECS) address a wide range of acute conditions, including emergent conditions from communicable diseases, non-communicable diseases, pregnancy and injury. Together, ECS represent an area of great potential for reducing morbidity and mortality in low-income and middle-income countries (LMICs). It is estimated that up to 54% of annual deaths in LMICs could be addressed by improved prehospital and facility-based emergency care. Research is needed to identify strategies for enhancing ECS to optimise prevention and treatment of conditions presenting in this context, yet significant gaps persist in defining critical research questions for ECS studies in LMICs. The Collaborative on Enhancing Emergency Care Research in LMICs seeks to promote research that improves immediate and long-term outcomes for clients and populations with emergent conditions. The objective of this paper is to describe systems approaches and research strategies for ECS in LMICs, elucidate priority research questions and methodology, and present a selection of studies addressing the operational, implementation, policy and health systems domains of health systems research as an approach to studying ECS. Finally, we briefly discuss limitations and the next steps in developing ECS-oriented interventions and research.


Transcriptomic effects of adenosine 2A receptor deletion in healthy and endotoxemic murine myocardium.
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2. Few canonical paths were impacted, with altered Gnb1, Prkar2b, Pde3b and Map3k2 (among others) implicating modified G protein/cAMP/PKA and cGMP/NOS signalling. Lipopolysaccharide (LPS; 20 mg/kg) challenge for 24 h modified >4100 transcripts in wild-type (WT) myocardium (≥1.5-fold change, FDR < 1 %); the most induced are Lcn2 (+590); Saa3 (+516); Serpina3n (+122); Cxcl9 (+101) and Cxcl1 (+89) and the most repressed are Car3 (-38); Adipoq (-17); Atgrl1/Aplnr (-14); H19 (-11) and Itga8 (-8). Canonical responses centred on inflammation, immunity, cell death and remodelling, with pronounced amplification of toll-like receptor (TLR) and underlying JAK-STAT, NFκB and MAPK pathways, and a 'cardio-depressant' profile encompassing suppressed ß-adrenergic, PKA and Ca2+ signalling, electromechanical and mitochondrial function (and major shifts in transcripts impacting function/injury including Lcn2, S100a8/S100a9, Icam1/Vcam and Nox2 induction, and Adipoq, Igf1 and Aplnr repression). Endotoxemic responses were selectively modified by A2AR KO, supporting inflammatory suppression via A2AR sensitive shifts in regulators of NFκB and JAK-STAT signalling (IκBζ, IκBα, STAT1, CDKN1a and RRAS2) without impacting the cardio-depressant gene profile. Data indicate A2ARs exert minor effects in un-stressed myocardium and selectively suppress NFκB and JAK-STAT signalling and cardiac injury without influencing cardiac depression in endotoxemia.


Effects of cryopreservation at -80 degrees C on the formulation and pathogenicity of the obligate aphid pathogen Pandora nouryi.
Cryopreservation at -80 degrees C is an alternative to liquid nitrogen storage for Entomophthorales. However, detailed studies about its effects on fungal pathogenicity and formulation are very limited. In the present study, the obligate aphid pathogen Pandora nouryi was formulated as mycelia grown on millet-gel granules after preservation as primary spores at -80 degrees C for 3-18 months, although its ability to produce infectious conidia gradually diminished. The sporulation capacity of this granular formulation was reduced to 18.5 x 10(4) conidia/mg after 18 months of storage, which was still higher than that of mycotized aphids. The half-decline time of sporulation capacity was computed as 13.6 months. The infectivity to the green peach aphid Myzus persicae had no significant decline in 12 months. The ability to yield resting spores within host carcasses remained unchanged, and the probability of resting spore formation increased with the conidial concentrations that infect aphids. Therefore, cryopreservation at -80 degrees C exerted a marginal impact on formulation and pathogenicity of P. nouryi and can substitute for costly liquid nitrogen storage in routine laboratory studies. The potential of the formulation in aphid biocontrol can be maintained although there is a risk of losing fungal sporulation ability in long-term preservation.


The estimated cost of dementia in Japan, the most aged society in the world.
Dementia has become a global critical issue. It is estimated that the global cost of dementia was 818 billion USD in 2015. The situation in Japan, which is the most aged country in the world, should be critical. However, the societal cost of dementia in Japan has not yet been estimated. This study was designed to estimate cost of dementia from societal perspective. We estimated the cost from societal perspective with prevalence based approach. Main data sources for the parameters to estimate the costs are the National Data Base, a nationwide representative individual-level database for healthcare utilization, the Survey of Long-Term Care Benefit Expenditures, a nationwide survey based on individual-level secondary data for formal long-term care utilization, and the results of an informal care time survey for informal care cost. We conducted the analyses with 'probabilistic modeling' using the parameters obtained to estimate the costs of dementia. We also projected future costs. The societal costs of dementia in Japan in 2014 were estimated at JPY 14.5 trillion (se 66.0 billion). Of these, the costs for healthcare, long-term care, and informal care are JPY 1.91 trillion (se 4.91 billion), JPY 6.44 trillion (se 63.2 billion), and JPY 6.16 trillion (se 12.5 billion) respectively. The cost per person with dementia appeared to be JPY5.95 million (se 27 thousand). The total costs would reach JPY 24.3 trillion by 2060, which is 1.6 times higher than that in 2014. The societal cost of dementia in Japan appeared to be considerable. Interventions to mitigate this impact should be considered.


Branching and alignment in reverse worm-like micelles studied with simultaneous dielectric spectroscopy and RheoSANS.
Topology and branching play an important but poorly understood role in controlling the mechanical and flow properties of worm-like micelles (WLMs). To address the challenge of characterizing branching during flow of WLMs, dielectric spectroscopy, rheology, and small-angle neutron scattering (dielectric RheoSANS) experiments are performed simultaneously to measure the concurrent evolution of conductivity, permittivity, stress, and segmental anisotropy of reverse WLMs under steady-shear flow. Reverse WLMs are microemulsions comprised of the phospholipid surfactant lecithin dispersed in oil with water solubilized in the micelle core. Their electrical properties are independently sensitive to the WLM topology and dynamics. To isolate the effects of branching, dielectric RheoSANS is performed on WLMs in n-decane, which show fast breakage times and exhibit a continuous branching transition for water-to-surfactant ratios above the corresponding maximum in zero-shear viscosity. The unbranched WLMs in n-decane exhibit only subtle decreases in their electrical properties under flow that are driven by chain alignment and structural anisotropy in the plane perpendicular to the electric field and incident neutron beam. These results are in qualitative agreement with additional measurements on a purely linear WLM system in cyclohexane despite differences in breakage kinetics and a stronger tendency for the latter to shear band. In contrast, the branched micelles in n-decane (higher water content) undergo non-monotonic changes in permittivity and more pronounced decreases in conductivity under flow. The combined steady-shear electrical and microstructural measurements are capable, for the first time, of resolving branch breaking at low shear rates prior to alignment-driven anisotropy at higher shear rates.


Incidence and Risk Factors of Osteonecrosis of the Jaw in Advanced Cancer Patients after Treatment with Zoledronic Acid or Denosumab: A Retrospective Cohort Study.
Zoledronic acid and denosumab are two antiresorptive drugs currently in use for treating osteoporosis. They have different mechanisms of action, but both have been shown to delay the onset of skeletal-related events in patients with advanced cancer. However, medication-related osteonecrosis of the jaw (MRONJ) has been reported in cancer patients treated with zoledronic acid or denosumab. We studied 155 patients with several types of advanced cancer who were treated with zoledronic acid or denosumab in our hospital during the period from April 2010 through March 2013. Thirteen of these 155 patients (8.4%) developed MRONJ. MRONJ development was significantly associated with the number of zoledronic acid or denosumab infusions (p<0.001) and the duration of zoledronic acid or denosumab therapy (p<0.001). Logistic regression analysis showed that diabetes [odds ratio (OR)=6.699, 95% confidence interval (CI), 1.435-31.277, p=0.016], anemia [OR=14.559, 95% CI, 2.161-98.069, p=0.006], and pus discharge [OR=6.491, 95% CI, 1.514-27.835, p=0.012] significantly increased the risk of developing MRONJ. However, the risk of MRONJ was significantly lower [OR=0.137, 95% CI, 0.020-0.944, p=0.043] when patients received periodical dentistry maintenance. Diabetes, anemia, and pus discharge may also play roles in its development. These findings suggest that the active inclusion of dentistry maintenance in bisphosphonate or denosumab treatment of cancer patients can reduce MRONJ development.


Recent trends in the initial therapy for newly diagnosed prostate cancer in Japan.
The objective of the present study was to investigate the trends over time in the initial treatment of prostate cancer in Japan. A total of 8291 patients with newly diagnosed prostate cancer whose treatment started in 2010 were registered in a multi-institutional observational study undertaken nationwide across Japan by the Japan Prostate Cancer Study Group. Each patient's background characteristics and initial treatment were recorded. The median age at diagnosis was 71 years. The proportion of T1c disease was 40.5% and that of M1 disease was 10.4%. The prostate-specific antigen level was <10 ng/ml in 52.0% of the patients. High-, intermediate- and low-risk patients as determined by D'Amico's classification system made up 19.3, 29.8 and 25.9% of the cases, respectively. The initial treatment was androgen depletion therapy in 40.2%, radical prostatectomy in 32.0% (17.3% of these involved laparoscopic prostatectomy), radiation in 21.0% (46.4% of these involved brachytherapy). In cases of organ-confined disease, radical prostatectomy was selected in 39.5%, androgen depletion therapy in 28.0% and radiation in 23.9%. In D'Amico's low-risk group, the proportion treated with radiation was nearly equal to that treated with radical prostatectomy (30.2 and 32.7%, respectively); 73.2% of the radiation treatments involved brachytherapy. Compared with previous Japanese studies, radiation use was increased by ∼10%. This increased proportion of radiation use was a typical trend in initial therapy for newly diagnosed prostate cancer cases in Japan. Although androgen depletion therapy use was decreased, it was selected in a high proportion of the patients irrespective of the disease stage.


Corpus callosum size correlates with asymmetric performance on a dichotic listening task in healthy aging but not in Alzheimer's disease.
Alzheimer's disease (AD) involves not only gray matter but also white matter pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased CC size may indicate reduced functional interhemispheric connectivity, differences in callosal size may have cognitive consequences that may become specifically apparent in neuropsychological tasks that tap hemispheric laterality. In the present study, we examined callosal functioning with a dichotic listening task in 25 Alzheimer patients, 20 healthy elderly and 20 healthy elderly with subjective memory complaints. We found decreased performance, increased ear asymmetry, and decreased callosal size in the AD group compared to healthy elderly. As expected, in the healthy elderly, we found significant negative correlations between ear asymmetry and callosal size, specifically in the anterior and posterior callosal subareas. While the association with the posterior subareas (isthmus and splenium) points at involvement of temporal areas mediating language processing, the association with the anterior subarea (the rostrum and genu) points at involvement of frontal areas mediating attention and executive functions. Remarkably however, in contrast to the healthy elderly, callosal size was not related to ear asymmetry in the AD group. The absence of an association between callosal atrophy and ear asymmetry implies that other pathological processes, next to reduced callosal functioning, attribute to ear asymmetry in AD. Difficulties to attend specifically to the left ear during dichotic listening in some of the AD patients, points at decreased attention and executive functions and suggests that pathology of specifically the frontal areas is involved.


Aberrant promoter methylation of multiple genes during multistep pathogenesis of colorectal cancers.
Aberrant methylation of 5'gene promoter regions associated with gene silencing is an epigenetic phenomenon responsible for silencing of tumor suppressor genes in many cancer types. The aims of our study were to study the role of methylation of a large panel of genes during multistage pathogenesis and to correlate our findings with patient age and other clinico-pathological features. We investigated the aberrant promoter methylation profile of 19 genes in 92 colorectal cancers (CRCs) and corresponding nonmalignant epithelia (NME) (n = 57), and selected 15 genes for studying 26 colorectal adenomas (CAs). On the Basis of our results, the genes could be divided into 3 groups. Group 1 consisted of 13 genes whose methylation was tumor-specific. For 8 of these genes, the methylation frequencies in CAs were similar to those of CRCs, but significantly different from the frequencies in NME. Group 2, consisting of 2 genes demonstrating little or no methylation, were present in any sample type. In Group 3, consisting of 4 genes, relatively frequent methylation was present in both CRCs and NME, and the differences between these specimen types were not significant. Methylation of Group 1 genes were tightly correlated with each other, and these genes demonstrated increased methylation frequencies in CRCs with increasing age. Methylation was not correlated with other clinico-pathological features. In general, methylation frequencies of CAs were intermediate between CRCs and NME. Our study constitutes the most comprehensive methylation profile of CRCs, demonstrates that methylation commences early during CRC pathogenesis and is an age-related phenomenon.


Price smoking participation elasticity in Colombia: estimates by age and socioeconomic level.
Tobacco prevalence in Colombia is small compared with other Latin America despite the nation's tobacco taxes being among the lowest in the region. However, tobacco taxes have increased several times during the last decade, and large increases in 2010 and 2016 impacted consumer prices. This paper aims to estimate the price smoking participation elasticity (PPE) in Colombia, with specific reference to regional increases in consumer prices after 2010 tax policy changes. The PPE is computed using logistic regression based on individual-level data from the National Psychoactive Substances Consumption Survey for 2008 and 2013. Our specific focus is state-level variation in Colombian cigarette prices between 2008 and 2013 induced by the tax hike in 2010. The estimated PPE in Colombia is around -0.66 (p value=0.046). We find almost no differences across socioeconomic level, but price sensitivity was greater for women than men, and for relatively older individuals (ages 51-64). PPE for Colombia is above estimates for comparable middle-income countries such as Mexico. As a result, current estimates for health gains of tax policies are likely to be underestimated. Moreover, in contrast with the literature, we find that the PPE for the youth (≤25 years) is lower than older age groups, and there is no evidence of a prominent socio-economic status (SES) gradient.


Public Perceptions of Aquaculture: Evaluating Spatiotemporal Patterns of Sentiment around the World.
Aquaculture is developing rapidly at a global scale and sustainable practices are an essential part of meeting the protein requirements of the ballooning human population. Locating aquaculture offshore is one strategy that may help address some issues related to nearshore development. However, offshore production is nascent and distinctions between the types of aquatic farming may not be fully understood by the public-important for collaboration, research, and development. Here we evaluate and report, to our knowledge, the first multinational quantification of the relative sentiments and opinions of the public around distinct forms of aquaculture. Using thousands of newspaper headlines (Ntotal = 1,596) from developed (no. countries = 26) and developing (42) nations, ranging over periods of 1984 to 2015, we found an expanding positive trend of general 'aquaculture' coverage, while 'marine' and 'offshore' appeared more negative. Overall, developing regions published proportionally more positive than negative headlines than developed countries. As case studies, government collected public comments (Ntotal = 1,585) from the United States of America (USA) and New Zealand mirrored the media sentiments; offshore perception being particularly negative in the USA. We also found public sentiment may be influenced by local environmental disasters not directly related to aquaculture (e.g., oil spills). Both countries voiced concern over environmental impacts, but the concerns tended to be more generalized, rather than targeted issues. Two factors that could be inhibiting informed discussion and decisions about offshore aquaculture are lack of applicable knowledge and actual local development issues. Better communication and investigation of the real versus perceived impacts of aquaculture could aid in clarifying the debate about aquaculture, and help support future sustainable growth.


Persistence of Lineage IV Peste-des-petits ruminants virus within Israel since 1993: An evolutionary perspective.
Peste-des-petits ruminants (PPR) is one of the most important infectious diseases of domesticated small ruminants. From the initial identification in 1942 in West Africa, PPR virus (PPRV) has spread throughout much of the developing world. PPRV is now considered endemic throughout Africa, with the notable exception of South Africa, the Middle-East and Israel, as well as South-, East-, and Central Asia. Despite this widespread dispersal, the evolution and transmission of PPRV in endemic populations is not well understood. This understanding will be critical in the planning of rational measures to eradicate PPRV by the planned time as defined by the FAO and OIE. To further advance the understanding of the evolution of PPRV the full genome sequence of 18 viruses isolated from Israel from consecutive years between 1997-2014 were generated. This data set is unique and crucial for the understanding of the evolution of PPRV, as it represents the first set of full-length sequence data available from consecutive years from a single geographic location. Analysis of these full genome sequences shows 96.2-99.9% nucleotide conservation across the Israel isolates and further demonstrates the strong purifying selection pressures on PPRV within Israel and globally. Four amino acid substitutions indicative of putative positive selection were additionally identified within the Israel isolates. The mean substitution rate per site per year was estimated to be 9.22 x 10-4 (95% HPD 6.206 x 10-4-1.26 x 10-3). Using Bayesian and phylogenetic analyses we further demonstrate that the PPRV isolates from Israel belongs to linage IV and form a single strong regional cluster within all other lineage IV viruses circulating worldwide implying a single incursion into Israel.


Athlete-Opponent Interdependency Alters Pacing and Information-Seeking Behavior.
The influence of interdependency between competitors on pacing decision-making and information-seeking behavior has been explored. This has been done by only altering instructions, and thereby action possibilities, while controlling environment (i.e., competitor behavior) and exercise task. Twelve participants performed a 4-km time trial on a Velotron cycle ergometer in a randomized, counterbalanced order alone with no virtual opponent (NO), against a virtual opponent with no restrictions (low athlete-opponent interdependency [OP-IND]), or against a virtual opponent who the participant was permitted to overtake only once during the trial (high athlete-opponent interdependency [OP-DEP]). Information-seeking behavior was evaluated using an SMI eye tracker. Differences in pacing, performance, and information-seeking behavior were examined using repeated-measures ANOVA (P < 0.05). Neither mean power output (NO, 298 ± 35 W; OP-IND, 297 ± 38 W; OP-DEP, 296 ± 37 W) nor finishing time (NO, 377.7 ± 17.4 s; OP-IND, 379.3 ± 19.5 s; OP-DEP, 378.5 ± 17.7 s) differed between experimental conditions. However, power output was lower in the first kilometer of OP-DEP compared with the other experimental conditions (NO, 332 ± 59 W; OP-IND, 325 ± 62 W; OP-DEP, 316 ± 58 W; both P < 0.05), and participants decided to wait longer before they overtook their opponent (OP-IND, 137 ± 130 s; OP-DEP, 255 ± 107 s; P = 0.040). Moreover, total fixation time spent on the avatar of the virtual opponent increased when participants were only allowed to overtake once (OP-IND, 23.3 ± 16.6 s; OP-DEP, 55.8 ± 32.7 s; P = 0.002). A higher interdependency between athlete and opponent altered pacing behavior in terms of in-race adaptations based on opponent's behavior, and it induced an increased attentional focus on the virtual opponent. Thus, in the context of exercise regulation, attentional cues are likely to be used in an adaptive way according to their availability and situational relevance, consistent with a decision-making framework based on the interdependence of perception and action.


Maternal, dominance and additive genetic effects in Nile tilapia; influence on growth, fillet yield and body size traits.
There are only few studies of dominance effects in non-inbred aquaculture species, since commonly used mating designs often have low power to separate dominance, maternal and common environmental effects. Here, a factorial design with reciprocal cross, common rearing of eggs and subsequent lifecycle stages and pedigree assignment using DNA microsatellites was used to separate these effects and estimate dominance (d2) and maternal (m2) ratios in Nile tilapia for six commercial traits. The study included observations on 2524 offspring from 155 full-sib families. Substantial contributions of dominance were observed (P < 0.05) for body depth (BD) and body weight at harvest (BWH) with estimates of d2 = 0.27 (s.e. 0.09) and 0.23 (s.e. 0.09), respectively in the current breeding population. In addition the study found maternal variance (P < 0.05) for BD, BWH, body thickness and fillet weight explaining ~10% of the observed phenotypic variance. For fillet yield (FY) and body length (BL), no evidence was found for either maternal or dominance variance. For traits exhibiting maternal variance, including this effect in evaluations caused substantial re-ranking of selection candidates, but the impact of including dominance effects was notably less. Breeding schemes may benefit from utilising maternal variance in increasing accuracy of evaluations, reducing bias, and developing new lines, but the utilisation of the dominance variance may require further refinement of parameter estimates.


Polybrominated diphenylethers (PBDEs) alter larval settlement of marine benthic polychaetes.
Polybrominated diphenylethers (PBDEs) are found ubiquitously in marine environments worldwide. Sediment is the major sink of PBDEs, with the congener BDE 47 being most abundant. In this study, laboratory experiments were carried out to test the hypothesis that contamination of BDE 47 at environmentally realistic sediment concentrations can alter polychaete larval settlement. Using multiple-choice experiment, settlement of three polychaete species (Pseudopolydora vexillosa, Polydora cornuta, and Capitella sp. I) on four types of spiked sediment was studied and compared: (i) low BDE 47 concentration (0.5 ng g(-1) dry weight); (ii) high BDE 47 concentration (3.0 ng g(-1) dry weight), (iii) hexane (solvent control), and (iv) natural sediment (control). Our results showed that settlement of P. vexillosa and Capitella sp. I larvae was significantly promoted, while settlement of P. cornuta reduced, at high BDE 47 concentration in sediment compared with the respective controls under both short- (24 h) and long-term (4 week) exposures. After 4 weeks, body burden of BDE 47 in all polychaete species was directly related to the spike concentration, and body length of settled juveniles of P. vexillosa and Capitella sp. I at the high-concentration treatment was significantly longer compared with that of other treatments and controls. For the first time, we demonstrated that environmentally realistic concentrations of BDE 47 in sediment can affect polychaete settlement in species-specific and dose-dependent manners. Given the global contamination of PBDE in marine sediment, BDE 47 may potentially alter the settlement pattern of marine polychaetes and hence their benthic composition over large areas.


Light-mediated inhibition of protein synthesis.
The regulation of protein synthesis is vital for a host of cell biological processes, but investigating roles for protein synthesis have been hindered by the inability to selectively interfere with it. To inhibit protein synthesis with spatial and temporal control, we have developed a photo-releasable anisomycin compound, N-([6-bromo-7-hydroxycoumarin-4-yl]methyloxycarbonyl)anisomycin (Bhc-Aniso), that can be removed through exposure to UV light. The area of protein synthesis inhibition can be restricted to a small light-exposed region or, potentially, the volume of two-photon excitation if a pulsed IR laser is the light source. We have tested the compound's effectiveness with an in vitro protein-translation system, CHO cells, HEK293 cells, and neurons. The photo-released anisomycin can inhibit protein synthesis in a spatially restricted manner, which will enable the specific inhibition of protein synthesis in subsets of cells with temporal and spatial precision.


Silicosis surveillance in Ontario from 1979 to 1992.
This paper reports the detection rates of silicosis among silica-exposed persons first exposed to dust in 1950 or later and still employed in 1979 or later in the province of Ontario. The rate varied strongly with latency, being less than two new cases per 10 000 examinations during the first two decades from first exposure, reaching two new cases per 1000 examinations at 27 years from first exposure, and averaging between two and four new cases per 1000 examinations thereafter. A Poisson regression analysis found that the silicosis rate in the interval after 30 years from first exposure was more than 16 times higher than the rate prior to 20 years from first exposure. There was no significant difference in the diagnosis rates among the workers in the mining, primary metal, and nonmetallic mineral industries sectors. The rate of silicosis was higher among smokers than among never smokers (rate ratio 1.54).


Inclusion of soil arsenic bioaccessibility in ecological risk assessment and comparison with biological effects.
The purpose of this study was to conduct an ecological risk assessment (ERA) for meadow voles (Microtus pennslvanicus) found at three arsenic contaminated sites in Nova Scotia, Canada (as well as two background locations) and to compare the numeric results to measured biomarkers of exposure and effect. The daily intake of arsenic by meadow voles was determined by three separate calculations: estimated daily intake (EDI), bioaccessible estimated daily intake (BEDI, with bioaccessibility of soil included), and actual daily intake (ADI, which is calculated with arsenic concentrations in the stomach contents). The median bioaccessibility of arsenic in soils from the contaminated locations was significantly greater than at background locations. The bioaccessible arsenic concentration in soil from all samples (both contaminated and background) was significantly less than the total concentration. Use of site-specific bioaccessibility (hazard quotients=38 at Upper Seal Harbour (USH); 60 at Lower Seal Harbour (LSH); and 120 at Montague tailings (MONT)) and stomach arsenic contents (hazard quotients=2.1 at USH; 7.9 at LSH; and 6.7 at MONT) in the ERA resulted in lower numeric risk than compared to risk calculated with 100% bioavailability (hazard quotient=180 at USH; 75 at LSH; and 680 at MONT). Further, the use of bioaccessibility on the calculation of risk was aligned with biomarker results (changes in glutathione and micronucleated erythrocytes) in voles captured at the sites. This study provides evidence that using site-specific bioaccessibility in ERAs may provide a more realistic level of conservatism, thereby enhancing the accuracy of predicting risk to wildlife receptors. Furthermore, when numeric risk assessments are combined with site-specific biological data (i.e., biomarkers of exposure and effect), both lines of evidence can be used to make informed decisions about ecological risk and site management.


Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.
Epilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ). After the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm2) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue. These results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.


Complexity and specificity of experimentally-induced expectations in motion perception.
Our perceptions are fundamentally altered by our expectations, i.e., priors about the world. In previous statistical learning experiments (Chalk, Seitz, & Seriès, 2010), we investigated how such priors are formed by presenting subjects with white low contrast moving dots on a blank screen and using a bimodal distribution of motion directions such that two directions were more frequently presented than the others. We found that human observers quickly and automatically developed expectations for the most frequently presented directions of motion. Here, we examine the specificity of these expectations. Can one learn simultaneously to expect different motion directions for dots of different colors? We interleaved moving dot displays of two different colors, either red or green, with different motion direction distributions. When one distribution was bimodal while the other was uniform, we found that subjects learned a single bimodal prior for the two stimuli. On the contrary, when both distributions were similarly structured, we found evidence for the formation of two distinct priors, which significantly influenced the subjects' behavior when no stimulus was presented. Our results can be modeled using a Bayesian framework and discussed in terms of a suboptimality of the statistical learning process under some conditions.


Examination of the regression model to quantify the degree of low back pain and lower limb symptoms in patients with lumbar disc herniation by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).
The Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was created to evaluate specific treatment outcomes in terms of physical functioning, social ability, and mental health in patients with back pain-related diseases. In this study, we investigated whether the JOABPEQ could be used to construct a regression model to quantify low back pain and lower limb symptoms in patients with lumbar disc herniation (LDH). We reviewed 114 patients with LDH scheduled to undergo surgery at our hospital. We measured the degrees of 1) lower back pain, 2) lower limb pain, and 3) lower limb numbness using the visual analog scale before the surgery. All answers and physical function data were subjected to partial least squares regression analysis. The degrees of lower back and lower limb pain could be used as a regression model from the JOABPEQ and had a significant causal relationship with them. However, the degree of lower limb numbness could not be used for the same. Based on our results, the questions of the JOABPEQ can be used to multilaterally understand the degree of lower back pain and lower limb pain in patients with LDH. However, the degree of lower limb numbness has no causal relationship, so actual measurement is essential.


Trichoderma harzianum enhances antioxidant defense of tomato seedlings and resistance to water deficit.
Some plant-symbiotic strains of the genus Trichoderma colonize roots and induce profound changes in plant gene expression that lead to enhanced growth, especially under biotic and abiotic stresses. In this study, we tested the hypothesis that one of the protective mechanisms enhanced by T. harzianum T22 colonization is the antioxidant defense mechanism. Having established that strain T22 modulates the expression of the genes encoding antioxidant enzymes, the status of antioxidant defense of tomato seedlings in response to colonization by T22 and water deficit was investigated. Total ascorbate or glutathione levels were not affected by either stimuli, but under water deficit, antioxidant pools became more oxidized (lower ratios of reduced to oxidized forms), whereas colonized plants maintained redox state as high as or higher than unstressed and untreated plants. The enhanced redox state of colonized plants could be explained by their higher activity of ascorbate and glutathione-recycling enzymes, higher activity of superoxide dismutase, catalase, and ascorbate peroxidase, in both root and shoot throughout the experiment. Similar enzymes were induced in uncolonized plants in response to water-deficit stress but to a lower extent when compared with colonized plants. This orchestrated enhancement in activity of reactive oxygen species (ROS)-scavenging pathways in colonized plants in response to stress supports the hypothesis that enhanced resistance of colonized plants to water deficit is at least partly due to higher capacity to scavenge ROS and recycle oxidized ascorbate and glutathione, a mechanism that is expected to enhance tolerance to abiotic and biotic stresses.


The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk.
The apolipoprotein B (apoB)/apoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-I ratio was superior to any of the cholesterol ratios - total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C - in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-I ratio. Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40 years of age. After a mean follow-up of 98 months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study. High apoB and a high apoB/apoA-I ratio were strongly related to increased coronary risk, while high apoA-I was inversely related to risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6 mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-I in risk models did not further improve the strong predictive value of apoB/apoA-I. These results indicate that the apoB/apoA-I ratio is at present the best single lipoprotein-related variable to quantitate coronary risk. Given the additional advantages apolipoproteins possess - fasting samples are not required, apoB/apoA-I is a better index of the adequacy of statin therapy than LDL-C, and the measurement of apoB and apoA-I are standardized, whereas LDL-C and HDL-C are not - there would appear to be considerable advantage to integrating apolipoproteins into clinical practice.


All-atom molecular dynamics simulation of photosystem II embedded in thylakoid membrane.
The molecular dynamics simulation is reported. The latest data on photosystem II structure, a thylakoid membrane model with the same lipid class distribution and fatty acid composition as the native thylakoid membrane, are used. The results indicate that the transfer of water, oxygen and protons has different pathways. The root mean square (rms)-fluctuation analysis of trajectory revealed that the residues surrounding the oxygen-evolving center (OEC) show small fluctuations and that most of the water molecules there show large fluctuation and are on proposed pathways for water and oxygen transfer. The water molecules near the OEC having small fluctuation could be involved in proton transfer. We assume that each kind of pathway characterized in this study plays a role in photosynthesis.


In Search for Genes Related to Atherosclerosis and Dyslipidemia Using Animal Models.
Atherosclerosis is a multifactorial chronic disease that affects large arteries and may lead to fatal consequences. According to current understanding, inflammation and lipid accumulation are the two key mechanisms of atherosclerosis development. Animal models based on genetically modified mice have been developed to investigate these aspects. One such model is low-density lipoprotein (LDL) receptor knockout (KO) mice (ldlr-/-), which are characterized by a moderate increase of plasma LDL cholesterol levels. Another widely used genetically modified mouse strain is apolipoprotein-E KO mice (apoE-/-) that lacks the primary lipoprotein required for the uptake of lipoproteins through the hepatic receptors, leading to even greater plasma cholesterol increase than in ldlr-/- mice. These and other animal models allowed for conducting genetic studies, such as genome-wide association studies, microarrays, and genotyping methods, which helped identifying more than 100 mutations that contribute to atherosclerosis development. However, translation of the results obtained in animal models for human situations was slow and challenging. At the same time, genetic studies conducted in humans were limited by low sample sizes and high heterogeneity in predictive subclinical phenotypes. In this review, we summarize the current knowledge on the use of KO mice for identification of genes implicated in atherosclerosis and provide a list of genes involved in atherosclerosis-associated inflammatory pathways and their brief characteristics. Moreover, we discuss the approaches for candidate gene search in animals and humans and discuss the progress made in the field of epigenetic studies that appear to be promising for identification of novel biomarkers and therapeutic targets.


Cognitive, psychophysical, and neural correlates of vulvar pain in primary and secondary provoked vestibulodynia: a pilot study.
Provoked vestibulodynia (PVD) is a common condition characterized by localized, provoked pain that can be present since first vaginal penetration attempt (primary) or can develop after a period of pain-free penetration (secondary). Research has demonstrated psychosocial and psychophysical differences between women with these subtypes of PVD, but the question of whether neural responses to pain also differ remains to be investigated. This study aims to examine whether cognitive, psychophysical, and neural responses to vulvar pressure pain differ between women with PVD1 and PVD2. Women with PVD1 and PVD2 were compared for group differences using multiple modalities, including questionnaires, psychophysical testing, and neuroimaging. Pain ratings were held constant across groups, rather than amount of pressure applied. Demographics, sexual functioning, four questionnaires examining anxiety and catastrophizing, quantitative sensory testing at the vulvar vestibule using a vulvalgesiometer, and functional and structural magnetic resonance imaging (MRI). Findings suggest that women with PVD1 are more anxious and that they catastrophize more about their vulvar and nonvulvar pain than women with PVD2. Overall, MRI results demonstrated structural and functional similarities to other chronic pain findings for both groups of women. Gray matter (GM) density also differed between groups: women with PVD1 showed significant decreases in GM throughout areas associated with pain processing. Functionally, between-groups differences were found during painful vulvar stimulation despite lower pressures applied to the vulva for women with PVD1 because of their heightened sensitivity; the determination of the level of vulvar pressure to elicit pain was based on subjective ratings. Findings are limited by sample size and liberal alpha values; however, future research is certainly warranted based on the preliminary findings of this study suggesting both similarities and differences between PVD1 and PVD2. Overall, women with PVD1 seem to fare worse on several pain-related and psychosocial variables compared with women with PVD2.


Regional differences in presence of Shiga toxin-producing Escherichia coli virulence-associated genes in the environment in the North West and East Anglian regions of England.
Shiga toxin-producing Escherichia coli is carried in the intestine of ruminant animals, and outbreaks have occurred after contact with ruminant animals or their environment. The presence of STEC virulence genes in the environment was investigated along recreational walking paths in the North West and East Anglia regions of England. In all, 720 boot sock samples from walkers' shoes were collected between April 2013 and July 2014. Multiplex PCR was used to detect E. coli based on the amplification of the uidA gene and investigate STEC-associated virulence genes eaeA, stx1 and stx2. The eaeA virulence gene was detected in 45·5% of the samples, where stx1 and/or stx2 was detected in 12·4% of samples. There was a difference between the two regions sampled, with the North West exhibiting a higher proportion of positive boot socks for stx compared to East Anglia. In univariate analysis, ground conditions, river flow and temperature were associated with positive boot socks. The detection of stx genes in the soil samples suggests that STEC is present in the English countryside and individuals may be at risk for infection after outdoor activities even if there is no direct contact with animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Several outbreaks within the UK have highlighted the danger of contracting Shiga toxin-producing Escherichia coli from contact with areas recently vacated by livestock. This is more likely to occur for STEC infections compared to other zoonotic bacteria given the low infectious dose required. While studies have determined the prevalence of STEC within farms and petting zoos, determining the risk to individuals enjoying recreational outdoor activities that occur near where livestock may be present is less researched. This study describes the prevalence with which stx genes, indicative of STEC bacteria, were found in the environment in the English countryside.


Laser capture microdissection in Ectocarpus siliculosus: the pathway to cell-specific transcriptomics in brown algae.
Laser capture microdissection (LCM) facilitates the isolation of individual cells from tissue sections, and when combined with RNA amplification techniques, it is an extremely powerful tool for examining genome-wide expression profiles in specific cell-types. LCM has been widely used to address various biological questions in both animal and plant systems, however, no attempt has been made so far to transfer LCM technology to macroalgae. Macroalgae are a collection of widespread eukaryotes living in fresh and marine water. In line with the collective effort to promote molecular investigations of macroalgal biology, here we demonstrate the feasibility of using LCM and cell-specific transcriptomics to study development of the brown alga Ectocarpus siliculosus. We describe a workflow comprising cultivation and fixation of algae on glass slides, laser microdissection, and RNA amplification. To illustrate the effectiveness of the procedure, we show qPCR data and metrics obtained from cell-specific transcriptomes generated from both upright and prostrate filaments of Ectocarpus.


In vitro innate immune cell based models to assess whole cell Bordetella pertussis vaccine quality: a proof of principle.
Lot release testing of vaccines is primarily based on animal models that are costly, time-consuming and sometimes of questionable relevance. In order to reduce animal use, functional in vitro assays are being explored as an alternative approach for the current lot release testing paradigm. In this study, we present an evaluation of APC platforms assessing innate immune activation by whole cell Bordetella pertussis (wP) vaccines. Primary monocytes, monocyte-derived DC (moDC) and human monocyte/DC cell lines (MonoMac6 and MUTZ-3) were compared for their capacity to respond to wP vaccines of varying quality. To produce such vaccines, the production process of wP was manipulated, resulting in wP vaccines covering a range of in vivo potencies. The responses of MUTZ-3 cells and primary monocytes to these vaccines were marginal and these models were therefore considered inappropriate. Importantly, moDC and MonoMac6 cells responded to the wP vaccines and discriminated between vaccines of varying quality, although slight variations in the responses to wP vaccines of similar quality were also observed. This study provides a proof of principle for the use of in vitro APC platforms as part of a new strategy to assess wP vaccine lot consistency, though careful standardisation of assay conditions is necessary.


Phyllodes tumors of the breast: the role of pathologic parameters.
We aimed to establish whether morphologic parameters were prognostically important in a large series of breast phyllodes tumors in Asian women. Of 335 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital, Singapore, between January 1992 and December 2002, 250 (74.6%) were benign, 54 (16.1%) borderline, and 31 (9.3%) malignant, based on histologic review of archival slides. Of the women, 43 (12.8%) experienced recurrences during the follow-up period. Recurrent disease was correlated with grade or classification (P = .028), stromal atypia (P = .016), stromal hypercellularity (P = .046), and permeative microscopic borders (P = .021). Multivariate analysis revealed that independent predictors of recurrence were pseudoangiomatous stromal hyperplasia (PASH) and margin status, whereby the presence of PASH and complete or negative margins reduced recurrence hazards by 51.3% and 51.7% respectively. The 7 women who died of disease during follow-up had malignant phyllodes tumor at the outset and experienced recurrences, and death was preceded by distant metastases.


Feline shoulder luxation: a cadaveric study of injury and repair using ligament prostheses.
To describe the range of motion and clinical stability of the feline shoulder following experimental injury and repair using a prosthetic suture technique. Eighteen feline cadaveric thoracic limbs were randomly allocated into three groups: medial injury, lateral injury or bilateral injury. Joint range of motion and clinical stability in all directions was recorded before and after specific anatomic structures were sectioned and following surgical repair using a prosthetic suture technique. Results were compared between intact, injured and repaired limbs for each injury type. There was a significant difference in joint range of motion in specific limb directions between intact and injured joints and between injured and repaired joints. There was no difference in joint range of motion between intact and repaired joints. Four of six medially injured joints were deemed clinically stable and five of six laterally injured joints were deemed clinically stable. All bilaterally injured joints were deemed unstable. The relative contributions of shoulder stabilisers to joint range of motion and clinical stability provide a reference for clinical cases with suspected shoulder instability. The prosthetic suture repair technique described was effective at returning the shoulder joint to a normal range of motion in this ex vivo model.


Lethal pathogens, non-lethal synergists and the evolutionary ecology of resistance.
Mixed pathogenic infections are known to have profound effects on the ecological and evolutionary diversity of both hosts and parasites. Although a variety of mechanisms have been proposed by which hosts can withstand parasitic infections, the role of multiple infections and the trade-off in multiple defence strategies remain relatively unexplored. We develop a stage-structured host-pathogen model to explore the ecological and evolutionary dynamics of host resistance to different modes of infection. In particular, we investigate how the evolution of resistance is influenced through infection by a lethal pathogen and a non-lethal synergist (that only acts to enhance the infectivity of the pathogen). We extend our theoretical framework to explore how trade-offs in the ability to withstand infection by the lethal pathogen and the ability to tolerate the synergist affect the likelihood of coexistence and the evolution of polymorphic host strategies. We show how the underlying structure of the trade-off surface is crucial in the maintenance of resistance polymorphisms. Further, depending on the shape of the trade-off surface, we predict that different levels of host resistance will show individual responses to the presence of non-lethal synergists. Our results are discussed in the wider context of recent developments in understanding the evolution of resistance to pathogen infections and resistance management.


'Furuncular myiasis of the breast caused by the larvae of the Tumbu fly (Cordylobia anthropophaga)'.
Cutaneous myiasis of the breast due to infestation by the larva of Cordylobia anthropophaga is rare. To the best of our knowledge, only one case has been reported in the English literature. This rarity calls for an awareness of its possibility as a cause of furuncular breast lesions, especially in areas where the C. anthropophaga (Tumbu fly) is endemic or in patients returning from such areas. As it can be easily confused with other furuncular breast lesions (like tuberculosis, mycosis, actinomycosis, furunculosis, chronic breast abscess and fungating malignancies), this awareness is important to avoid misdiagnosis or delay in diagnosis. We present a case of furuncular breast myiasis due to the larvae of C. anthropophaga earlier misdiagnosed as mastitis in a patient living in tropical Africa (Nigeria) where the Tumbu fly is endemic. We report a 70 year old woman who presented with a week history of itchy multiple discharging sinuses of the right breast. The sinuses contained wriggling larvae of C. anthropophaga. Fourteen larvae were extracted from the breast and the sinuses healed quite well after the extraction. Cutaneous myiasis of the breast is rare, hence, an awareness of its clinical features is necessary when a patient presents with furuncular skin lesions especially in endemic areas or people returning from such areas. Diagnosis is mainly clinical and lesions heal well after the extraction of the larvae. Preventive measures such as ironing after drying of dresses and a good personal hygiene are crucial in controlling C. anthropophaga infestation.


Added value of online satellite data transmission for flood forecasting: warning systems in medium-size catchments.
The present paper deals with the implementation of online data transferred via LEO satellite communication in a flood forecasting system. Although the project is ongoing, it is already recognised that the information chain: "measurement-transmission-forecast-alert" can be shortened, i.e., the flood danger can be more rapidly communicated to the population at risk. This gain is particularly valuable for medium size catchments where the concentration time (basin time of response to rainfall) is short.


Dissociative and metacognitive factors in hallucination-proneness when controlling for comorbid symptoms.
Recent studies have linked hallucination-proneness to dysfunctional metacognitive beliefs, dissociation, and disrupted capacity to discriminate between internal and external cognitive events (reality discrimination). This study addressed a number of methodological limitations of previous research by investigating the relationship between hallucination-proneness and the aforementioned variables while controlling for comorbid symptoms. A large sample of nonclinical participants was screened on measures of hallucination-proneness, cognitive intrusions, paranoid ideation, metacognitive beliefs, and dispositional mindfulness (including measures of dissociation-like experiences). In addition, a signal detection task was used to investigate reality discrimination in four subgroups of participants selected on the basis of their scores on hallucination-proneness and intrusions. Regression analyses for the self-report data were conducted to investigate the predictors of hallucination-proneness and paranoia when controlling for comorbid symptoms. Also, between-group differences on the behavioural data were tested to determine whether perturbed reality discrimination is specifically associated with hallucination-proneness rather than cognitive intrusions. Results revealed that metacognitive beliefs are more strongly associated with intrusions and paranoia than hallucination-proneness, whereas hallucination-proneness is related to perturbed reality discrimination and dissociation. These results clarify previous research on metacognitive dysfunction in hallucination-proneness, and highlight the importance of controlling for the covariation among symptoms when investigating the cognitive processes underlying psychotic experiences.


Regulation of learning and memory by meningeal immunity: a key role for IL-4.
Proinflammatory cytokines have been shown to impair cognition; consequently, immune activity in the central nervous system was considered detrimental to cognitive function. Unexpectedly, however, T cells were recently shown to support learning and memory, though the underlying mechanism was unclear. We show that one of the steps in the cascade of T cell-based support of learning and memory takes place in the meningeal spaces. Performance of cognitive tasks led to accumulation of IL-4-producing T cells in the meninges. Depletion of T cells from meningeal spaces skewed meningeal myeloid cells toward a proinflammatory phenotype. T cell-derived IL-4 was critical, as IL-4(-/-) mice exhibited a skewed proinflammatory meningeal myeloid cell phenotype and cognitive deficits. Transplantation of IL-4(-/-) bone marrow into irradiated wild-type recipients also resulted in cognitive impairment and proinflammatory skew. Moreover, adoptive transfer of T cells from wild-type into IL-4(-/-) mice reversed cognitive impairment and attenuated the proinflammatory character of meningeal myeloid cells. Our results point to a critical role for T cell-derived IL-4 in the regulation of cognitive function through meningeal myeloid cell phenotype and brain-derived neurotrophic factor expression. These findings might lead to the development of new immune-based therapies for cognitive impairment associated with immune decline.


Changes in Atmospheric Circulation and Ocean Ice Cover over the North Atlantic During the Last 41,000 Years.
High-resolution, continuous multivariate chemical records from a central Greenland ice core provide a sensitive measure of climate change and chemical composition of the atmosphere over the last 41,000 years. These chemical series reveal a record of change in the relative size and intensity of the circulation system that transported air masses to Greenland [defined here as the polar circulation index (PCI)] and in the extent of ocean ice cover. Massive iceberg discharge events previously defined from the marine record are correlated with notable expansions of ocean ice cover and increases in PCI. During stadials without discharge events, ocean ice cover appears to reach some common maximum level. The massive aerosol loadings and dramatic variations in ocean ice cover documented in ice cores should be included in climate modeling.