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IntroductionChronic rhinosinusitis with nasal polyposis is an inflammatory disease that, although not directly linked to allergy, often displays a Th2-skewed inflammation characterized by elevated local IgE and IL-5 levels. The nasal cavity is constantly exposed to bacteria and viruses that may trigger epithelial inflammatory responses. To gain more insight into mechanisms by which such a biased inflammation might arise, we have investigated the epithelial expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship to disease and microbial triggers.MethodsEpithelial cells were obtained from polyp tissues of nasal polyposis patients and from inferior turbinates of non-diseased controls. Cells were exposed to various TLR-specific triggers to study the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the potential regulatory mechanisms through the expression profile the transcription factors ATF-3, DUSP-1, EGR-1, and NFKB-1.ResultsThe TLR3 agonist and viral analogue poly(I: C) induced TSLP mRNA 13.0 +/- 3.1 fold (p ConclusionThe TLR3 induced expression of TSLP introduces a mechanism by which the Th2-skewed tissue environment might arise in nasal polyps and invites a further evaluation of the potential contribution of current or past viral infections to polyposis pathogenesis.

The application of stem cells in the treatment of various degenerative diseases is highly promising. However, cell-based therapy could be limited by the problem of low viability of grafted cells and uncertainty about their fate. The combination of molecular imaging and contrast-enhanced MRI may give more insight into the survival and behavior of grafted stem cells. We explore hair-follicle-bulge-derived stem cells (HFBSCs) as a potential candidate for autologous cell-based therapy. HFBSCs are transduced with a lentiviral construct with genes coding for bioluminescent (Luc2) and fluorescent (copGFP) reporter proteins, and subsequently loaded with magnetic nanoparticles to enable MRI visualization. Thus, we investigate for the first time if lentiviral transduction and cellular loading with nanoparticles have a cytotoxic effect upon these stem cells. Transduction efficiency, proliferation rate, cell viability and reporter protein co-expression during long-term culture of transduced HFBSCs were studied using fluorescence and bioluminescence microscopy. In addition, the effect of TMSR50 nanoparticles on proliferation and viability was investigated using the MTS assay and bioluminescence microscopy. The amount of TMSR50-loaded HFBSCs needed to reach signal threshold for MRI was assessed using an agarose phantom. Transduction with the Luc2-copGFP construct did not influence senescence, proliferation, doubling time, and differentiation of the HFBSCs. CopGFP expression was visible immediately after transduction and persisted for at least 15 passages, concomitantly with Luc2 expression. Cellular loading with TMSR50 nanoparticles did not affect cell viability and proliferation. The results imply that combined MRI and bioluminescence imaging may enable in vivo localization and long-term monitoring of grafted viable HFBSCs. Copyright © 2016 John WileySons, Ltd.

Children with obesity show differences in brain structure, executive function and appetitive traits when compared with lean peers. Little is known on the relationship between brain structure and these traits.To investigate the relationship between differences in brain structure and executive function and appetitive traits, in obese and lean adolescents.MRI was used to measure cortical thickness and subcortical volumes. Executive function was measured by a Stop Signal-and a Choice Delay Task. Appetitive traits were measured using the Child Eating Behaviour Questionnaire.Adolescents with obesity had greater volumes of the pallidum; 1.78 mL (SE 0.03, p=0.014), when compared with controls; 1.65 mL (SE 0.02). In the group with obesity, greater pallidum volume was positively associated with the ability to delay reward in the Choice Delay Task (p=0.012).The association between pallidum volumes and Choice Delay Task in obese adolescents supports the hypothesis that the pallidum plays an important role in executive dysfunction in obese children.

In holography, we create a “holistic” representation of a light wave from the coherent superposition of measurement and reference beams. We shift the light phase to detect the complex amplitude. This sounds a lot like interferometry! Here I explore how advances in digital signal processing are driving a convergence of the two techniques. Article not available.

Cell walls are essential organelles for fungi; they define cell shape during growth and provide osmotic integrity and protection against harmful influences in the growth environment. Fungal walls also play an important role in developing fungal infections as they form the first contact between the pathogen and the host immune system. In many ascomycetes, the cell wall consists of a polysaccharide matrix surrounded by a layer of covalently bound glycoproteins. With the complete genome sequences being available for many species, cell wall research in recent years has largely focused on identifying and elucidating the functions of cell wall proteins. In this chapter, we discuss, with a main focus on proteomics, new insights and advances in fungal cell wall research.

Low T3 States Nonthyroidal Illness Syndrome With Low Serum T4 Physiologic Interpretations of NTIS Serum Hormone Levels and Tissue Hormone Supplies in NTIS Is There Evidence for Substances in Serum Which Can Affect T4 Binding to Proteins? TSH Levels Thyroid Hormone Turnover T4 Entry Into Cells and Generation of T3 Thyroid Hormone in Tissues Organ Specific Responses In NTIS Are Patients With NTIS Clinically Hypothyroid? Mechanism of Thyroid Hormone Suppression in NTIS Cytokines in NTIS Other Factors Altering Serum T4 Supply Diagnosis Is Thyroid Hormone Treatment of NTIS Advantageous or Disadvantageous? If Thyroid Hormone Replacement Is Given, What Should It Be? Additional Supportive Hormonal Therapy to Consider Conclusions

Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Conclusions: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.

This study provides a comprehensive framework to mitigate or prevent forest and land (or wildland) fire disaster in Malaysia. This system supports emergency response and preparedness for wildland fire by means of integrated modelling, monitoring and mapping of fire danger. In this framework, multi-sensor applications for monitoring fire danger and fire activity are linked with decision-aid models in a Geographic Information System (GIS) environment to generate information required for wildland fire management. Using a customized version of the spatial Fire Management System software, components of the Malaysia Fire Danger Rating System (FDRS) are calculated to provide fire weather, fire behaviour and wildfire threat information. Wildfire threat ratings (WTRs) are assessed on the basis of fire occurrence risk, potential fire behaviour, suppression capability and values at risk. Outputs from the Malaysia FDRS were integrated with hotspots extracted from remote sensing data to generate combined maps of activ...

Low donor supply and the high demand for transplantable organs is an international problem. The efficiency of organ procurement is often expressed by donor conversion rates (DCRs). These rates differ among countries, but a uniform starting point for defining a potential heart-beating donor is lacking. Imprecise definitions cause confusion; therefore, we call for a reproducible method like imminent brain death (IBD), which contains criteria in detail to determine potential heart-beating donors. Medical charts of 4814 patients who died on an ICU in Dutch university hospitals between January 2007 and December 2009 were reviewed for potential heart-beating donors. We compared two starting points: 'Severe Brain Damage' (SBD) (old definition) and IBD (new definition), which differ in the number of absent brainstem reflexes. Of the potential donors defined by IBD 45.6% fulfilled the formal brain death criteria, compared with 33.6% in the larger SBD group. This results in a higher DCR in the IBD group (40% vs. 29.5%). We illustrated important differences in DCRs when using two different definitions, even within one country. To allow comparison among countries and hospitals, one universal definition of a potential heart-beating donor should be used. Therefore, we propose the use of IBD.

Introduction Although sperm procurement and preservation has been become commonplace in situations in which infertility can be easily foreseen, peri- or postmortem sperm procurement for reproductive use in unexpected coma or death is not generally accepted. There are no laws and regulations for this kind of intervention in all countries and they may also differ from country to country. Intensive care specialists can be confronted with a request for peri- or postmortem sperm procurement, while not being aware of the country-specific provisions. Case description A young male patient who suffered 17 L blood loss and half an hour of cardiopulmonary resuscitation was admitted to a university hospital for an ill-understood unstoppable abdominal bleed. After rapid deterioration of the neurological situation, due to severe post-anoxic damage, the decision was made to withdraw life-sustaining treatment. At that moment the partner of the patient asked for perimortem sperm procurement, which was denied, on the basis of the ethical reasoning that consent of the man involved was lacking. Retrospectively the decision was right according to Dutch regulations; however, with more time for elaborate ethical reasoning, the decision outcome, without the awareness of an existing prohibition, also could have been different. Conclusions Guidelines and laws for peri- or postmortem sperm procurement differ from country to country, so any intensive care specialist should have knowledge from the latest legislation for this specific subject in his/her country. An overview is provided. A decision based on ethical reasoning may appear satisfying, but can unfortunately be in full contrast with the existing laws.

The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analysed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation.

Summary Background Successful donation of organs after cardiac death (DCD) requires identification of patients who will die within 60 min of withdrawal of life-sustaining treatment (WLST). We aimed to validate a straightforward model to predict the likelihood of death within 60 min of WLST in patients with irreversible brain injury. Methods In this multicentre, observational study, we prospectively enrolled consecutive comatose patients with irreversible brain injury undergoing WLST at six medical centres in the USA and the Netherlands. We assessed four clinical characteristics (corneal reflex, cough reflex, best motor response, and oxygenation index) as predictor variables, which were selected on the basis of previous findings. We excluded patients who had brain death or were not intubated. The primary endpoint was death within 60 min of WLST. We used univariate and multivariable logistic regression analyses to assess associations with predictor variables. Points attributed to each variable were summed to create a predictive score for cardiac death in patients in neurocritical state (the DCD-N score). We assessed performance of the score using area under the curve analysis. Findings We included 178 patients, 82 (46%) of whom died within 60 min of WLST. Absent corneal reflexes (odds ratio [OR] 2·67, 95% CI 1·19–6·01; p=0·0173; 1 point), absent cough reflex (4·16, 1·79–9·70; p=0·0009; 2 points), extensor or absent motor responses (2·99, 1·22–7·34; p=0·0168; 1 point), and an oxygenation index score of more than 3·0 (2·31, 1·10–4·88; p=0·0276; 1 point) were predictive of death within 60 min of WLST. 59 of 82 patients who died within 60 min of WLST had DCD-N scores of 3 or more (72% sensitivity), and 75 of 96 of those who did not die within this interval had scores of 0–2 (78% specificity); taking into account the prevalence of death within 60 min in this population, a score of 3 or more was translated into a 74% chance of death within 60 min (positive predictive value) and a score of 0–2 translated into a 77% chance of survival beyond 60 min (negative predictive value). Interpretation The DCD-N score can be used to predict potential candidates for DCD in patients with non-survivable brain injury. However, this score needs to be tested specifically in a cohort of potential donors participating in DCD protocols. Funding None.

Analyzing governments' expenditure when it comes to military engagement is a challenging task. As governments are neither transparent nor eager to come forward with the necessary information, researchers make a lot of assumptions that require extensive justification. This article details a range of relevant cost channels and describes the difficulties in estimating their respective sizes. But when worked-up in a careful and deliberate way, it is possible to obtain reasonable estimates of the budgetary effects of military engagements. Following the outlined methodology creates an opportunity to improve openness, which will benefit researchers, policymakers, and the public at large.

As brain death is a difficult concept for the lay public to understand, we hypothesized that allowing relatives of the patient to be present during brain death determination would improve their understanding of this condition and would eventually lead to an increased consent rate for organ donation.A prospective multicenter trial was conducted in five Dutch hospitals. Relatives were given the opportunity to be present during brain death testing. The family consent rate for organ donation was the primary endpoint examined, and the degree of the relatives' understanding of brain death was the secondary endpoint.Between April 2010 and July 2011, we included the relatives of 8 patients in this study. The relatives witnessed brain death testing during this time. This sample size was too small to draw valid statistical conclusions. However, we have documented some noteworthy experiences of the relatives.Although, the hypothesis behind this study had promise, we were unable to reach our predefined goal. The possible causes for this shortcoming included the rarity of patients with brain death, the common practice in the Netherlands of obtaining consent for organ donation before brain death testing and the uneasiness of the staff in the presence of the patients' relatives during brain death determination. Although, we cannot draw a conclusion from statistical evidence, we would recommend that relatives be given the opportunity to be present during brain death testing and, specifically, during the apnea test.

In stem cell cultures from adult human tissue, undesirable contamination with fibroblasts is frequently present. The presence of fibroblasts obscures the actual number of stem cells and may result in extracellular matrix production after transplantation. Identification of fibroblasts is difficult because of the lack of specific fibroblast markers. In our laboratory, we isolate and expand neural-crest-derived stem cells from human hair follicle bulges and investigate their potential to differentiate into neural cells. To establish cellular identities, we perform immunohistochemistry with antibodies specific for glial and neuronal markers, and use fibroblasts as negative control. We frequently observe that human adult dermal fibroblasts also express some glial and neuronal markers. In this study, we have sought to determine whether our observations represent actual expression of these markers or result from cross-reactivity. Immunohistochemistry was performed on human adult dermal fibroblasts using acknowledged glial and neuronal antibodies followed by verification of the data using RT-qPCR. Human adult dermal fibroblasts showed expression of the glia-specific markers SOX9, glial fibrillary acidic protein and EGR2 (KROX20) as well as for the neuron-specific marker class III β-tubulin, both at the protein and mRNA level. Furthermore, human adult dermal fibroblasts showed false-positive immunostaining for S100β and GAP43 and to a lower extent for OCT6. Our results indicate that immunophenotyping as a tool to determine cellular identity is not as reliable as generally assumed, especially since human adult dermal fibroblasts may be mistaken for neural cells, indicating that the ultimate proof of glial or neuronal identity can only be provided by their functionality.

Objective: To describe changes in the health service delivery process experienced by professionals, patients and informal caregivers during implementation of a national programme to improve quality of care of geriatric rehabilitation by improving integration of health service delivery processes.Study setting: Sixteen skilled nursing facilities.Study design: Prospective study, comparing three consecutive cohorts.Data collection: Professionals (elderly care physicians, physiotherapists and nursing staff) rated four domains of health service delivery at admission and at discharge of 1075 patients. In addition, these patients [median age 79 (Interquartile range 71–85) years, 63% females] and their informal caregivers rated their experiences on these domains 4 weeks after discharge.Principal findings: During the three consecutive cohorts, professionals reported improvement on the domain team cooperation, including assessment for intensive treatment and information transfer among professionals. Fewer improvements were reported within the domains alignment with patients’ needs, care coordination and care quality. Between the cohorts, according to patients (n = 521) and informal caregivers (n = 319) there were no changes in the four domains of health service delivery.Conclusion: This national programme resulted in small improvements in team cooperation as reported by the professionals. No effects were found on patients’ and informal caregivers’ perceptions of health service delivery.

Prototype comparator devices have been designed and constructed for the calibration of thermometers on-site and in situ. The uncertainties that can be obtained using this device can be compared with those of block calibrators. The system has reduced stem conduction losses by limiting gradients and consequent heat flows. Presently, the range of the prototype applications is limited to between −90 °C and +150 °C. The article shows details on the construction, discusses evaluation tests and calibration results, and gives example uncertainty budgets.

Many collectors avoid collecting cacti (Cactaceae) and other succulent plants because they are unsure of how to preserve cacti as herbarium specimens. However, preserved specimens of cacti are valuable and crucial for research and conservation. This paper addresses techniques for collection and processing of cacti to make herbarium specimens, with particular reference to the use of ethanol to aid drying.

In this article, we estimate the total costs of the German participation in the Afghanistan war, both past and future. This is a hugely complex and uncertain calculation, which depends on several important assumptions. These assumptions pertain to the different cost channels and the shares of these channels that can be attributed to the German participation in the war. By calculating the costs of the German participation, we provide a framework for other researchers to do the same with respect to other countries. The article can function as a roadmap for researchers focusing on this topic. In the end we find that, in the most realistic of several possible scenarios regarding the duration and intensity of the German participation in the war in Afghanistan, the German share of the net present value of the total costs of the war ranges from 26 billion Euro to 47 billion Euro. This large range reflects the uncertainties with which the costs must be estimated. On an annual basis, we estimate that the German participation in the war costs between 2.5 and 3 billion Euro. This contrasts with the official war budget, which is little over 1 billion Euro for 2010, showing that governments may not adequately represent the costs of military action.

SUMMARY While previous research has looked at the determinants of the quality of institutions, not much research has been done that looks at the determinants of institutional change. This paper examines what determines the probability of an improvement in political freedoms. Several path-dependent variables, such as the history of political freedom, are clearly influential. In addition to that, economic openness and improvements in ethnolinguistically similar neighbouring countries turn out to significantly influence the probability of improvement. In Africa, an improvement of political freedom is associated with a 20.1% increase in the probability of improvement in neighbouring countries, keeping everything else constant. This result is robust to the inclusion of different variables, as well as different estimation techniques.

Historically, three varieties or subspecies were recognized within Eriastrum eremicum; these were distinguished by characters such as the number of leaf lobes, the length of the corolla, and the corolla symmetry. This study used traditional multivariate analysis along with spatial and geostatistical analyses of morphometric data to scan for geographic trends in these morphological characters. In addition to the typical form of E. eremicum in the Mojave Desert of California, both multivariate and spatial statistics revealed a distinct group of populations in southwest Utah, and another group in southern Arizona. These results suggest that there are some geographic clusters of similar plant morphology within this species, and that three subspecies should be recognized. Plants from southwest Utah are here placed in Eriastrum eremicum subsp. zionis comb. nov., and plants from Arizona are recognized as Eriastrum eremicum subsp. yageri (M. E. Jones) H. L. Mason.

Summary The rapid increase of ~omics datasets generated by microarray, mass spectrometry and next generation sequencing technologies requires an integrated platform that can combine results from different ~omics datasets to provide novel insights in the understanding of biological systems. MADMAX is designed to provide a solution for storage and analysis of complex ~omics datasets. In addition, analysis results (such as lists of genes) can be merged to reveal candidate genes supported by all datasets. The system constitutes an ISA-Tab compliant LIMS part, which is linked to the different analysis pipelines. A pilot study of different type of ~omics data in Brassica rapa demonstrates the possible use of MADMAX. The web-based user interface provides easy access to data and analysis tools on top of the database.

The transient receptor potential channel TRPV1 is a polymodal nociceptor. It is primarily expressed in dorsal root ganglia and peripheral sensory nerve endings, and to a much lesser extent, in the central nervous system. It has also been implicated in the functional properties of e.g. urinary and bronchial epithelia. TRPV1 has long been under intensive investigation by the pharmaceutical industry as a candidate drug target especially for pain conditions. This review summarizes the current knowledge of the molecular determinants of TRPV1 channel activation by heat, protons and capsaicin. Newly discovered heat and proton activation sites within the pore domain are discussed as well as potential consequences for drug discovery. Polymodal TRPV1 antagonists were found to cause hyperthermia in a species-dependent manner in-vivo, hence the discovery of euthermic compounds with an appropriate modality selectivity profile will be crucial for TRPV1's future as a drug target.

The Candida albicans gene PGA26 encodes a small cell wall protein and is upregulated during de novo wall synthesis in protoplasts. Disruption of PGA26 caused hypersensitivity to cell wall-perturbing compounds (Calcofluor white and Congo red) and to zymolyase, which degrades the cell wall β-1,3-glucan network. However, susceptibility to caspofungin, an inhibitor of β-1,3-glucan synthesis, was decreased. In addition, pga26Δ mutants show increased susceptibility to antifungals (fluconazol, posaconazol or amphotericin B) that target the plasma membrane and have altered sensitivities to environmental (heat, osmotic and oxidative) stresses. Except for a threefold increase in β-1,6-glucan and a slightly widened outer mannoprotein layer, the cell wall composition and structure was largely unaltered. Therefore, Pga26 is important for proper cell wall integrity, but does not seem to be directly involved in the synthesis of cell wall components. Deletion of PGA26 further leads to hyperfilamentation, increased biofilm formation and reduced virulence in a mouse model of disseminated candidiasis. We propose that deletion of PGA26 may cause an imbalance in the morphological switching ability of Candida, leading to attenuated dissemination and infection.

Research on ethnolinguistic heterogeneity has so far mostly focused on domestic measures, while little attention has been paid to ethnolinguistic relations between nations. In this paper, I propose a way of measuring ethnolinguistic affinity between nations. This index measures the degree of similarity two randomly drawn individuals from two different populations are expected to display. I show that this measure has several attractive theoretical characteristics, which make it particularly useful. Subsequently, I construct the measure for all countries in Africa and use it to show that civil conflict in Africa is likely to spill over between contiguous ethnolinguistically similar countries.

Purpose: It is desirable to identify a potential organ donor (POD) as early as possible to achieve a donor conversion rate (DCR) as high as possible which is defined as the actual number of organ donors divided by the number of patients who are regarded as a potential organ donor. The DCR is calculated with different assessment tools to identify a POD. Obviously, with different assessment tools, one may calculate different DCRs, which make comparison difficult. Our aim was to determine which assessment tool can be used for a realistic estimation of a POD pool and how they compare to each other with regard to DCR. Methods: Retrospective chart review of patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage. We applied three different assessment tools on this cohort of patients. Results: We identified a cohort of 564 patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage of whom 179/564 (31.7%) died. After applying the three different assessment tools the number of patients, before exclusion of medical reasons or age, was 76 for the IBD-FOUR definition, 104 patients for the IBD-GCS definition and 107 patients based on the OPTN definition of imminent neurological death. We noted the highest DCR (36.5%) in the IBD-FOUR definition. Conclusion: The definition of imminent brain death based on the FOUR-score is the most practical tool to identify patients with a realistic chance to become brain dead and therefore to identify the patients most likely to become POD.

The brain dead patient is the ideal multiorgan donor. Conversely, brain death (BD) is an undesirable outcome of critical care medicine. Conditions that can lead to the state of BD are limited. An analysis showed that a (aneurysmal) subarachnoid hemorrhage, traumatic brain injury, or intracerebral hemorrhage in 83% precede the state of BD. Because of better prevention and treatment options, we should anticipate on an inescapable and desirable decline of BD. In this article, we offer arguments for this statement and discuss alternatives to maintain a necessary level of donor organs for transplantation.

Posterior circulation stroke, which includes basilar artery occlusion (BAO), accounts for approximately 20% of all ischemic strokes. Much is unclear concerning the early historical descriptions of basilar artery occlusion, and some modern authors cite the historical sources incorrectly and incompletely. The case described by the Scottish physician John Abercrombie in 1828 is probably the first description of this form of stroke. The progressive bulbar signs that Abercrombie described in his case were striking, i.e., dysphagia and speech difficulties. Many authors in the 19th century described a waxing and waning clinical course for several days before profound coma and death. They also noticed signs and symptoms such as hemiplegia without loss of sensitivity and bulbar symptoms such as swallowing and speech impairment, vertigo, and altered consciousness. After Virchow's epoch-making work on embolism and thrombosis, all authors correctly described BAO as resulting from emboli and thrombosis based on arteriosclerosis instead of ossification of the arterial walls or inflammation. Around 1880, the clinical symptoms of BAO were obviously well-known to the experienced clinician. In this article we offer a chronological description of historical sources. Neurology (R) 2011;76:1520-1523

The mucosal layers colonized by the pathogenic fungus Candida albicans differ widely in ambient pH. Because the properties and functions of wall proteins are probably pH dependent, we hypothesized that C. albicans adapts its wall proteome to the external pH. We developed an in vitro system that mimics colonization of mucosal surfaces by growing biomats at pH 7 and 4 on semi-solid agarose containing mucin as the sole nitrogen source. The biomats expanded radially for at least 8 days at a rate of ∼30 μm h−1. At pH 7, hyphal growth predominated and growth was invasive, whereas at pH 4 only yeast and pseudohyphal cells were present and growth was noninvasive. Both qualitative mass spectrometric analysis of the wall proteome by tandem mass spectrometry and relative quantification of individual wall proteins (pH 7/pH 4), using Fourier transform mass spectrometry (FT-MS) and a reference mixture of 15N-labelled yeast and hyphal walls, identified similar sets of >20 covalently linked wall proteins. The adhesion proteins Als1 and Als3, Hyr1, the transglucosidase Phr1, the detoxification enzyme Sod5 and the mammalian transglutaminase substrate Hwp1 (immunological detection) were only present at pH 7, whereas at pH 4 the level of the transglucosidase Phr2 was >35-fold higher than at pH 7. Sixteen out of the 22 proteins identified by FT-MS showed a greater than twofold change. These results demonstrate that ambient pH strongly affects the wall proteome of C. albicans, show that our quantitative approach can give detailed insights into the dynamics of the wall proteome, and point to potential vaccine targets.

The cell wall of the human-pathogenic fungus Candida albicans is a robust but also dynamic structure which mediates adaptation to changing environmental conditions during infection. Sap9 and Sap10 are cell surface-associated proteases which function in C. albicans cell wall integrity and interaction with human epithelial cells and neutrophils. In this study, we have analyzed the enzymatic properties of Sap9 and Sap10 and investigated whether these proteases cleave proteins on the fungal cell surface. We show that Sap9 and Sap10, in contrast to other aspartic proteases, exhibit a near-neutral pH optimum of proteolytic activity and prefer the processing of peptides containing basic or dibasic residues. However, both proteases also cleaved at nonbasic sites, and not all tested peptides with dibasic residues were processed. By digesting isolated cell walls with Sap9 or Sap10, we identified the covalently linked cell wall proteins (CWPs) Cht2, Ywp1, Als2, Rhd3, Rbt5, Ecm33, and Pga4 as in vitro protease substrates. Proteolytic cleavage of the chitinase Cht2 and the glucan-cross-linking protein Pir1 by Sap9 was verified using hemagglutinin (HA) epitope-tagged versions of both proteins. Deletion of the SAP9 and SAP10 genes resulted in a reduction of cell-associated chitinase activity similar to that upon deletion of CHT2 , suggesting a direct influence of Sap9 and Sap10 on Cht2 function. In contrast, cell surface changes elicited by SAP9 and SAP10 deletion had no major impact on the phagocytosis and killing of C. albicans by human macrophages. We propose that Sap9 and Sap10 influence distinct cell wall functions by proteolytic cleavage of covalently linked cell wall proteins.

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at root s = 900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (vertical bar eta vertical bar (INEL) = 0.483 +/- 0.001 (stat.) +/- 0.007 (syst.) GeV/c and (NSD) = 0.489 +/- 0.001 (stat.) +/- 0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET. (C) 2010 Published by Elsevier B.V.

The relationship between conflict and education has been studied before. However, previous authors have always focused strongly on the supply-side effects, whereas this article examines the influence of conflict on the demand for education. It is theoretically shown that, under relatively general conditions, individuals living in a conflict area have an incentive to increase their level of education and that this effect depends on the individual’s skill level. This hypothesis is tested using the conflict in the Basque Region as a case study, which is an example of a conflict in which one would not expect strong supply-side effects. Using other Spanish regions, an artificial region is created in which the population has a similar educational distribution as in the Basque Region. When comparing the true and artificial regions, individuals with a medium education level clearly show an increase in education during the conflict, as predicted by the theoretical model.

One of the main questions for politicians is how to introduce more flexibility in the labour market while still providing employees with ample social security. The concept of flexicurity has sprung to attention through its success in Denmark. This paper explores whether the Danish model can also be successful in other European countries. A simultaneous equations model is constructed and estimated using regional data, which is an extension of the Blanchard-Katz model developed in 1992. It is found that a European country such as the Netherlands can permanently lower its unemployment rate and increase its participation and employment growth rates at the regional level, by 1.47, 2.08 and 1.05 percentage points respectively, if it copies the Danish model.

The glycosylphosphatidylinositol-modified protein Rhd3/Pga29 of the human pathogen Candida albicans belongs to a family of cell wall proteins that are widespread among Candida species but are not found in other fungi. Pga29 is covalently linked to the beta-1,3-glucan framework of the cell wall via beta-1,6-glucan. It is a small and abundant O-glycosylated protein and requires the protein-O-mannosyl transferase Pmt1 for glycosylation. Furthermore, Pga29 is strongly expressed in yeast cells but is downregulated in hyphae. Removal of the PGA29 gene in C. albicans leads to a significant reduction of cell wall mannan; however, Pga29 does not seem to have a major role in maintaining cell wall integrity. In addition, adhesion capacity and hyphae formation appear normal in pga29 deletion mutants. Importantly, the pga29 deletion mutant is less virulent, and infection of reconstituted human epithelium with the pga29 mutant results in a diminished induction of proinflammatory cytokines, such as GM-CSF, TNF, IL-6 and IL-8. We propose that the reduced virulence of the pga29 mutant is a consequence of altered surface properties, resulting in altered fungal recognition.

Context: Development of Graves' disease (GD) is related to HLA-DRB1*0301 (DR3),and more specifically to arginine at position 74 of the DRB1 molecule. The extracellular domain (ECD) of human TSH receptor (hTSH-R) contains the target antigen. Objective and Design: We analyzed the relation between hTSH-R-ECD peptides and DR molecules to determine whether aspartic acid (D) or glutamic acid (E) at position four in the binding motif influenced selection of functional epitopes. Results: Peptide epitopes from TSH-R-ECD with D or E in position four (D/E+) had higher affinity for binding to DR3 than peptides without D/E (D/E−) (IC50 29.3 vs. 61.4, P = 0.0024). HLA-DR7, negatively correlated with GD, and DRB1*0302 (HLA-DR18), not associated with GD, had different profiles of epitope binding. Toxic GD patients who are DR3+ had higher responses to D/E+ peptides than D/E− peptides (stimulation index 1.42 vs. 1.22, P = 0.028). All DR3+ GD patients (toxic + euthyroid) had higher responses, with borderline significance (Sl; 1.32 vs. 1.18, P = 0.051). Splenocytes of DR3 transgenic mice immunized to TSH-R-ECD responded to D/E+ peptides more than D/E− peptides (stimulation index 1.95 vs. 1.69, P = 0.036). Seven of nine hTSH-R-ECD peptide epitopes reported to be reactive with GD patients' peripheral blood mononuclear cells contain binding motifs with D/E at position four. Conclusions: TSH-R-ECD epitopes with D/E in position four of the binding motif bind more strongly to DRB1*0301 than epitopes that are D/E− and are more stimulatory to GD patients' peripheral blood mononuclear cells and to splenocytes from mice immunized to hTSH-R. These epitopes appear important in immunogenicity to TSH-R due to their favored binding to HLA-DR3, thus increasing presentation to T cells.

The range 3.0 K to 24.5561 K of the International Temperature Scale of 1990 (ITS-90) was realized at VSL with a 4He interpolating constant-volume gas thermometer (ICVGT). The standard uncertainty of the generated scale ranged from 0.32 mK at 3.3 K to 0.38 mK at 24.5561 K. The ICVGT scale was compared with the classical absolute gas thermometer scales of the National Physical Laboratory (NPL-75, 1975) and the Kamerlingh Onnes Laboratory (KOL, 1986) and was found to deviate from them by a maximum of 1.5 mK. The non-uniqueness of the generated scale was investigated by comparing it with alternative ICVGT scales (but having equal status because still satisfying all the requirements of the ITS-90) obtained from different choices of the lowest calibration temperature and interpolation function. The size of correction effects such as thermo-molecular pressure, aerostatic head pressure and dead volume was calculated and the effectiveness of the ICVGT calibration procedure in compensating for such correction effects was evaluated.

In this article, the influence of conflict on the economies of neighbouring countries is discussed. The results from previous papers show a strong negative effect for an entire area around a country suffering from conflict, but this paper reaches a different conclusion, by using more recent data and adjusting the methodology previously employed. Additionally, a new type of contiguity matrix is constructed and used in the actual analysis. The final analysis consists of a large number of regressions and concludes that conflict actually has two opposing effects. First, like conflict countries themselves, directly contiguous countries actually suffer from the negative effects of proximate conflict. Secondly, however, there is also a positive spillover of conflict, which affects non‐contiguous countries and this effect is larger for countries that are closer to the conflict country. The results from the paper predominantly hold for the most violent kind of conflict.

DC magnetization and AC susceptibility measurements on LuFe 2 O 4 single crystals reveal a ferrimagnetic transition at 240 K followed by additional magnetic transitions at 225 K and 170 K, separating cluster glass phases, and a kinetically arrested state below 55 K. The origin of giant magnetic coercivity is attributed to the collective freezing of ferrimagnetic clusters and enhanced domain wall pinning associated with a structural transition at 170 K. Magnetocaloric effect measurements provide additional vital information about the multiple magnetic transitions and the glassy states. Our results lead to the emergence of a complex magnetic phase diagram in LuFe 2 O 4 .

If patients on the intensive care unit (ICU) are awake and life-sustaining treatment is suspended because of the patients' request, because of recovering from the disease, or because independence from organ function supportive or replacement therapy outside the ICU can no longer be achieved, these patients can suffer before they inevitably die. In The Netherlands, two scenarios are possible for these patients: (1) deep palliative (terminal) sedation through ongoing administration of barbiturates or benzodiazepines before withdrawal of treatment, or (2) deliberate termination of life (euthanasia) before termination of treatment. In this article we describe two awake patients who asked for withdrawal of life-sustaining measures, but who were dependent on mechanical ventilation. We discuss the doctrine of double effect in relation to palliative sedation on the ICU. Administration of sedatives and analgesics before withdrawal of treatment is seen as normal palliative care. We conclude that the doctrine of the double effect is not applicable in this situation, and mentioning it criminalised the practice unnecessarily and wrongfully.

The covalently linked wall proteins of Saccharomyces cerevisiae and Candida albicans and to a lesser extent of Candida glabrata have been extensively studied. Here we describe some of their main structural features and discuss their conservation in other ascomycetous fungi. We also discuss the hybrid nature of many wall proteins and the frequent occurrence of families of wall proteins with a common multi-domain structure. Finally, some quantitative data regarding wall proteins are presented.

A number of different methodologies are developed for examining the sensitivities of an index. These methodologies are applied to examine the characteristics of the Canadian Fire Weather Index (FWI) and the McArthur Forest Fire Danger Index (FFDI) using 8 years of gridded data throughout Australia. Percentile changes in input conditions show that the indices are similar to each other in that they are both most sensitive to wind speed, then secondly to relative humidity and thirdly to temperature. On a finer scale, a combination of the relationship between the indices and their partial derivatives shows that the FFDI is relatively less sensitive to wind speed and rainfall, and more sensitive to temperature and relative humidity, than the FWI. A method based on equilibrium values of the indices shows that the FFDI has a temperature threshold set by recent rainfall above which its sensitivity increases, resulting in some non-linearity in its relationship with the FWI. The sensitivity differences between the indices mean that the indices are complementary in that they each respond to a somewhat different set of conditions, as is shown by examining a number of recent fire events. The fire events also reveal that index values associated with dangerous fire behaviour can vary greatly between different regions. Methods to reduce the consequences of this variation are examined, including the use of index percentiles. Copyright © 2009 Royal Meteorological Society

The cell wall of Candida albicans consists of an internal skeletal layer and an external protein coat. This coat has a mosaic-like nature, containing c. 20 different protein species covalently linked to the skeletal layer. Most of them are GPI proteins. Coat proteins vary widely in function. Many of them are involved in the primary interactions between C. albicans and the host and mediate adhesive steps or invasion of host cells. Others are involved in biofilm formation and cell-cell aggregation. They further include iron acquisition proteins, superoxide dismutases, and yapsin-like aspartic proteases. In addition, several covalently linked carbohydrate-active enzymes are present, whose precise functions remain hitherto largely elusive. The expression levels of the genes that encode covalently linked cell wall proteins (CWPs) can vary enormously. They depend on the mode of growth and the combined inputs of several signaling pathways that sense environmental conditions. This is reflected in the unusually long intergenic regions of most of these genes. Finally, the precise location of several covalently linked CWPs is temporally and spatially regulated. We conclude that covalently linked CWPs of C. albicans play a crucial role in fitness and virulence and that their expression is tightly controlled.