BACKGROUND
The normal human intravenous endotoxin model has been used for more than 50 years. It was once considered a possible model of sepsis, but, because no infection is present, it is better described as a model of systemic inflammation. We demonstrate herein that at least three of four systemic inflammatory response syndrome (SIRS) criteria are achieved with the model.

METHODS
Otherwise healthy human volunteers were given Escherichia coli endotoxin 2 ng/kg intravenously. Vital signs were monitored, and blood samples were collected over time for assessment of white blood cells (WBCs), cytokines, counter-regulatory hormones, and monocyte receptors.

RESULTS
The means of three variables (core temperature, heart rate, WBC) met the SIRS criteria. Compared with baseline, cytokines were elevated acutely, with tumor necrosis factor-alpha (TNFα) exhibiting temporal primacy over the other cytokines. Counter-regulatory hormones (cortisol, epinephrine) also were elevated acutely. Finally, the monocyte cell-surface receptors cluster of differentiation molecule (CD) 11b and TNF receptor-II were elevated and decreased, respectively.

CONCLUSIONS
The experimental human endotoxin model satisfies SIRS criteria and probably is best described as a model of Toll-like receptor 4 agonist-induced systemic inflammation.


Objective—Intimal thickening is considered to result from the dedifferentiation of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype, and their subsequent migration and proliferation. It is unknown whether nectin-like molecule (Necl)-5, which is overexpressed in cancer cells, is involved in intimal thickening. Approach and Results—Necl-5 was upregulated in mouse carotid artery after ligation. Compared with wild-type mice, intimal thickening after carotid artery ligation was milder in Necl-5 knockout mice. In vitro, the expression levels of SMC differentiation markers were higher, whereas the expression level of an SMC dedifferentiation marker was lower, in Necl-5 knockout mouse aortic SMCs (MASMCs) compared with wild-type MASMCs. The migration, proliferation, and extracellular signal–regulated kinase activity in response to serum were decreased in Necl-5 knockout MASMCs compared with wild-type MASMCs. In wild-type MASMCs, inhibition of extracellular signal–regulated kinase acti...


Background: Regular performance of multiple health behaviors additively benefits well-being (Loef & Walach, 2012); however, little is known about the psychological pathways by which the performance of one health behavior affects the subsequent performance of a second health behavior. A theoretical model was developed to examine select psychological constructs that might mediate this effect and is tested using exercise and eating behaviors.

Methods: In a naturalistic study, participants completed measures assessing the psychological constructs before and after an acute exercise session. They were then given the choice of a healthy or an unhealthy snack.

Findings: If the variables of health self-efficacy, health identity strength, and commitment to health goals increase after the exercise session and are related to an increased likelihood of selecting the healthy snack, it will support the hypothesis that a completed exercise session may lead to healthier eating (i.e., a promotion spillover).

Discussion: Theoretically, understanding the changes in an individual's psyche after the performance of a health behavior (e.g., an acute exercise session) and how those changes affect the performance of a subsequent, different health behavior (e.g., snack choice) provides information about how to expand current behavior change models to delineate how people manage multiple health behaviors over time. Practically, elucidating these pathways can be used to design more effective interventions that increase the performance of multiple health behaviors that ultimately would improve overall health.


Social connections are known to be helpful for modeling users' potential preferences and improving the performance of recommender systems. However, in social-aware recommendations, there are two issues which in uence the inference of users' preferences, and haven't been well-studied in most existing methods: First, the preferences of a user may only partially match that of his friends in certain aspects, especially when considering a user with diverse interests. Second, for an individual, the in uence strength of his friends might be di erent, as not all friends are equally helpful for modeling his preferences in the system. To address the above issues, in this paper, we propose a novel Social Attentional Memory Network (SAMN) for social-aware recommendation. Speci cally, we rst design an attention-based memory module to learn userfriend relation vectors, which can capture the varying aspect attentions that a user share with his di erent friends. Then we build a friend-level attention component to adaptively select informative friends for user modeling. The two components are fused together to mutually enhance each other and lead to a ner extended model. Experimental results on three publicly available datasets show that the proposed SAMN model consistently and signi cantly outperforms the state-of-the-art recommendation methods. Furthermore, qualitative studies have been made to explore what the proposed attention-based memory module and friend-level attention have learnt, which provide insights into the model's learning process.


Generally the information system development is designing the systems with the use of visual design tools and takes the target modelling artefact as a basis to manually define the software application code. The process of mapping business requirements to the application code involves several parts that make the whole development process again very sensitive to errors. In this paper, we present a model-driven approach to overcome the gap between business requirements on one hand and service oriented architecture on the other. For this, we focus on the development of service oriented information system (SOIS) and a set of model transformation rules. Different ways of transforming a model into another exist. The choice of a target model differs according to quality criteria and is determined on the basis of specific requirements. The development process proposed is based on a BPMN meta-model, SOAML meta-model and a component meta-model. The approach leading elements are: the meta-modelling and automated mapping rules. Finally, we illustrate our proposal with a case study.


Under pressures related to economic growth and environmental protection, China is facing an increasingly severe "environment–health–poverty" trap risk. Fuel taxation is generally considered an effective policy to counter such a risk. Since 2009 China has raised the fuel tax rate many times to enhance tax reform. However, the effects of this policy remain unknown. Therefore, it is vitally important to estimate the impacts of China's current fuel taxation policy on environment, public health and the national economy. As the first attempt in existing literature on China, this paper builds a general equilibrium framework with the feedback effect of public health on economy. We find that that the fuel tax policy benefits the adjustment of the economic structure and improves human health; however, it is detrimental to economic growth, public welfare and price stability. In this sense, it plays a limited role in reducing the trap risk and might not be sustainable in the long term.


Step‐stress accelerated life testing is a design strategy where the stress is modified several times during the test. In this work we address the problem of designing such a test. We focus on temperature accelerated life testing and we address the problems of setting the step duration and the stress levels. Assuming an Arrhenius model, maximum likelihood estimates of the parameters are computed. Relying on the properties of these estimators we compare different criteria for assessing the optimality of the plans produced. Some tables are presented to illustrate the method. For a fixed number of steps and a set of temperatures, a table of optimal length steps can be computed. For fixed step lengths, sets of temperatures leading to optimal plans are also available. Thus, this work provides useful tools to help engineers make decisions in testing strategy. Copyright © 2007 John Wiley & Sons, Ltd.


Fuel cells are static energy conversion devices that convert the chemical energy of fuel into electrical energy directly. Compared with conventional power generation systems, they have many advantages, such as high efficiency, zero or low emission (of pollutant gases), and flexible modular structure. Fuel cells are expected to play an important role in future distributed generation (DG) applications. Fuel cell DGs (FCDGs) can either be connected to a utility grid for network reinforcement or installed in a remote area to supply stand-alone power. In this article, a load transient mitigation controller is described for hybrid PEMFC-battery power generation systems. The hybrid FCDG is controlled in a way that during a load transient, the fuel cell provides the steady-state part of the load, and the battery will supply the transient part of the load. The proposed technique can be especially useful in fuel cell vehicles (motor starting and accelerating) as well as in stationary applications, where load transients are unavoidable. The load transient mitigation controller is applicable to other types of FCDGs


Temporomandibular joint (TMJ) is one of the structures of the stomatognathic system. Temporomandibular joint is a ginglymoarthrodial joint composed of synovial cavity, articular cartilage and a capsule that covers the same joint. Temporomandibular joint disorder (TMD) has multifactorial etiology, and the commonly reported ones are emotional tension, occlusal interference, teeth loss, postural deviation, masticatory muscular dysfunction, internal and external changes in Temporomandibular structures. Removal of the third molars has been propounded as a factor with the potential to damage TMJ. Trauma resulting from the surgery of third molars has been reported to be a predisposing factor in the progression of TMD symptoms. The aim of this study was to assess the prevalence of TMJ disorders in patients with impacted teeth. A prospective study was conducted in the department of oral and maxillofacial surgery in Saveetha Dental College and Hospital from October 2019-December 2019. The study population included 28 patients with impacted teeth and 28 patients without impacted teeth. Thus, the sample size included a total of 56 patients who were evaluated for the presence of clinical findings of TMD. Data was collected and statistical analysis was performed. Microsoft Excel 2016 (Microsoft office 10) data spreadsheet was used to collect data and later exported to SPSS IBM (version 23.0). Descriptive statistics and chi square test were employed with a level of significance set at p<0.05. In the current study out of 56 patients, it was seen that the symptoms of Temporomandibular joint disorders were more prevalent in female patients (58.06%). Clicking sound of TMJ was more prevalent in patients without impaction (56.52%) when compared to patients with impaction (43.48%). Association between clinical findings of TMD and impacted teeth was statistically not significant. p value=0.273. Within the limits of the study, temporomandibular joint disorders were present both in patients with and without impacted teeth, and impacted teeth had no significant influence on the development of temporomandibular Joint disorders.


Background: Multiple myeloma (MM), the second most hematological malignancy, the molecular mechanism and pathogenesis of the relapse of MM is poorly understood. This study aimed to identify novel prognostic model for MM and explore potential mechanism of relapse. Methods: Gene expression data,clinical data(GSE24080) and HTseq-Counts files were downloaded from Gene Expression Omnibus (GEO) and TCGA database. Co-expression modules of genes were built by Weighted Correlation Network Analysis (WGCNA).KEGG and GO enrichment analysis were performed in each module. TATFs (tumor-associated transcription factors) were retrieved from the Cistrome. Twenty-two immune cell compositions was calculated by CIBERSORT algorithm.Univariate and multivariate Cox congression were performed and a predictive model by prognostic genes was constructed,the predictive power of the model was evaluated by Kaplan–Meier curve and time-dependent receiver operating characteristic (ROC) curves. Results: A total of 940 DEGs were identified,and in WGCNA analysis, yellow, brown and sky-blue modules were most associated with clinic traits.The yellow module related with the cell cycle and the brown and sky-blue modules correlated with cytokine and its receptors, where the M2 macrophage fraction is positively correlated with CCL18, CCL2, CCL8, CXCL12 and CCl23 were positively correlated with plasma cells by Cibersort analysis.Prognostic genes were identified and two genes (TPX2,PRAM1) were finally identified to construct a risk model for predicting EFS.


Niosomes - vesicular systems made of non-ionic surfactants - have several advantages over conventional non-vesicle formulations. In recent years, niosomes have become the vesicles of choice in drug delivery. Niosome vesicles are found to be of value in immunology, membrane biology and diagnostic techniques. The focus of this review was to bring out different aspects related to niosome preparation, characterization, entrapment efficiency, invitro drug release, and applications.


Background The combination of a radioisotope with a chemotherapeutic agent in a liposomal carrier (ie, Indium-111-labeled polyethylene glycol pegylated liposomal vinorelbine, [111In-VNB-liposome]) has been reported to show better therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this therapeutic effect is attributable to the combination of a radioisotope with chemotherapeutics. The goal of this study was to investigate the pharmacokinetics, biodistribution, and correlation of Indium-111 radioactivity and vinorelbine concentration in the 111In-VNB-liposome. Methods The VNB-liposome and 111In-VNB-liposome were administered to rats. Blood, liver, and spleen tissue were collected to determine the distribution profile of the 111In-VNB-liposome. A liquid chromatography tandem mass spectrometry system and gamma counter were used to analyze the concentration of vinorelbine and radioactivity of Indium-111. Results High uptake of the 111In-VNB-liposome in the liver and spleen demonstrated the properties of a nanosized drug delivery system. Linear regression showed a good correlation (r = 0.97) between Indium-111 radioactivity and vinorelbine concentration in the plasma of rats administered the 111In-VNB-liposome. Conclusion A significant positive correlation between the pharmacokinetics and biodistribution of 111Indium radioactivity and vinorelbine in blood, spleen, and liver was found following administration of the 111In-VNB-liposome. The liposome efficiently encapsulated both vinorelbine and Indium-111, and showed a similar concentration-radioactivity time profile, indicating the correlation between chemotherapy and radiotherapy could be identical in the liposomal formulation.


ABSTRACT Automation is not new, but the possibilities for automation have been significantly expanded in recent years through advancements in artificial intelligence. Such technologies may drive some improvements, although they are not without risk and we lack a solid evidence base to suggest the implications of these changes. Framing AI supported automation as 'technological outsourcing', we draw on the well-established outsourcing literature to derive lessons about the possible implications of public sector automation and outline some principles that agencies can use to assist in their decision-making about whether to invest in automation of particular processes.


1. Papaverine is converted to its 4'-, 6- and 7-desmethyl metabolites when incubated with hepatic microsomal preparations from phenobarbital-induced rats. The 7-desmethyl compound was predominantly formed in these studes. When incubated with guinea-pig microsomal preparations, papaverine was converted to its 6- and 4'-desmethyl metabolites in approximately equal amounts. 2. The O-demethylation of papaverine was studied with sixty micro-organisms. Ten organisms (including Aspergillus Cunninghamella and Streptomyces species) were found to actively metabolize this drug in a manner similar to that of mammals. 3. A strain of Aspergillus alliaceus was used to produce gram quantitites of the mammalian metabolite, 6-desmethylpapaverine. Preparative amounts of 4'-desmethylpapaverine, a major mammalian metabolite of papaverine in vivo, was produced with a strain of Cunninghamella echinulata.


We present an innovative approach to distributed estimation, featuring selective update of parameter estimates. In distributed parameter estimation, sensor nodes consume energy not only in processing data, but most costly, in communicating and diffusing updated parameter estimates. Reducing the number of parameters to be updated and reducing the frequency of updates are thus effective ways to save in energy consumption. The approach presented in this paper features advantages of set-membership adaptive filtering (SMAF) and those of partial updates in adaptive filtering. Simulation results show that the proposed algorithm offers substantial reduction in energy consumption without much, if any, performance degradation.


Kay Adshead's 2001 play The Bogus Woman explores how asylum narratives are traumatised by a legal process that seeks coercively to uncover an accurate and acceptable version of events. Echoing Spivak's sense of the representational challenge that subaltern subjectivities pose, I argue that Adshead's play critiques the mediation through which the asylum seeker emerges into public discourse and vividly foregrounds the intricacies of narrativised experience which cannot be easily phrased in received representation. The play's polyvocal performance strategy destabilises the pursuit of a definitive, documentary and originary story, distinguishing it from recent documentary theatre of asylum which too swiftly privileges narrative credibility. Adshead's critique of authenticity extends to conceiving of the body as another document, which is read through its wounds and scars. Ultimately, I consider how far theatrical representation, in its negotiation of narrative at the intersection of text, performer and audience, might present new and more complex ways of perceiving the experience of seeking asylum.


This study compared personality characteristics of children with cleft lip and palate to another group of children with different observable physical impairment (orthopedic disability) and speech difficulties. It was hypothesized that different types of observable physical stigmata may result in different personality adaptations. Forty-five children from each of two groups (25 males and 20 females) were matched for sex, age, and intelligence. They were compared using the Missouri Children's Picture Series, a non-verbal personality test, on the following dimensions: Conformity, Masculinity/Femininity, Maturity, Agression, Inhibition, Activity Level Sleep Disturbance and Somatization. The results indicate that males with cleft lip and palate are significantly higher on Maturity and Inhibition while Orthopedically Disabled males are higher on Agression, Activity Level, and Somatization. Cleft lip and palate females are significantly higher on Maturity and Inhibition while Orthopedically Disabled females are higher on Masculinity. The results indicate differential personality adaptations in the two different types of observable physical impairments. Results are discussed in terms of their relationship to selected psychosocial variables.


Background

Evidence-based programs are slow to disseminate to create public health impact. Mexican Americans have low uptake of the modifiable healthy behaviors of fruit and vegetable (FV) consumption and physical activity (PA). This study analyzed the dissemination and implementation of an evidence-based community-wide campaign (CWC), Tu Salud ¡Si Cuenta! (TSSC), in augmenting these behaviors among Mexican Americans living along the U.S.-Mexico Border.
Methods

We examined reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of the program. For effectiveness, participants were classified into "low exposure" and "high exposure" groups based on home visits by a community health worker (CHW). A dietary questionnaire and the Godin-Shepherd Exercise Questionnaire were used to quantify mean FV consumption and weekly PA level, respectively. Mean differences in change from baseline to follow-up was compared between the groups based on multivariable linear regression analysis, adjusting for age, gender, insurance and poverty status, and program components received. Odds of newly meeting FV and PA guidelines at follow-up were estimated with multivariable logistic regression analysis. All analyses were repeated for each location separately.
Results

Low-income Mexican-Americans (N = 8225) across twelve locations along the U.S.-Mexico border were analyzed. The program reached 2.2% of the total population of the lower Rio Grande Valley region (Cameron and Hidalgo Counties, Texas). The high exposure group had significantly greater FV intake (adjusted mean difference = + 0.65 FV servings, 95% CI: 0.53–0.77) and PA (adjusted mean difference = + 185.6 MET-minutes, 95% CI: 105.9-265.4) than the low exposure group. The high exposure group was significantly more likely to meet FV guidelines (adjusted odds ratio (AOR) = 2.03, 95% CI: 1.65–2.47) and PA guidelines (AOR = 1.36, 95% CI: 1.10–1.68) at follow-up. In location-specific analysis, the association of increasing program exposure to degree of improvement in FV consumption and PA was replicated. 92.3% (12/13) of locations offered the program adopted it. 58.3% (7/12) of program locations implemented with fidelity, and 91.7% (11/12) maintained the program.
Conclusions

The results indicate this CWC intervention shows promise for improving health outcomes among low-income Mexican Americans in a scaled-up implementation effort. The adoption and maintenance of the program was strong, but staff capacity and turnover adversely impacted implementation fidelity.
Trial registration:
 NCT03199365. Date: June 26, 2017


Model-Driven Engineering (MDE) is a software engineering paradigm that uses models as main assets in all development phases. While many languages for model manipulation exist (e.g., for model transformation or code generation), there is a lack of frameworks to define and apply model mutations. A model mutant is a variation of an original model, created by specific model mutation operations. Model mutation has many applications, for instance, in the areas of model transformation testing, model-based testing or education. In this paper, we present a domain-specific language, called Wodel, for the specification and generation of model mutants. Wodel is domain-independent, as it can be used to generate mutants of models conforming to arbitrary metamodels. Its development environment is extensible, permitting the incorporation of post-processors for different applications. As an example, we show an application consisting on the automated generation of exercises for particular domains (automata, class diagrams, electronic circuits, etc.).


The ability of gelatin-based hydrogels of incorporating and releasing under controlled conditions 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a melanin-related metabolite endowed with marked antioxidant properties was investigated. The methyl ester of DHICA, MeDHICA, was also tested in view of its higher stability, and different solubility profile. Three types of gelatin-based hydrogels were prepared: pristine porcine skin type A gelatin (HGel-A), a pristine gelatin cross-linked by amide coupling of lysines and glutamic/aspartic acids (HGel-B), and a gelatin/chitosan blend (HGel-C). HGel-B and HGel-C differed in the swelling behavior, showed satisfactorily high mechanical strength at physiological temperatures and well-defined morphology. The extent of incorporation into all the gelatins tested using a 10% w/w indole to gelatin ratio was very satisfactory ranging from 60 to 90% for either indoles. The kinetics of indole release under conditions of physiological relevance was evaluated up to 72 h. The highest values were obtained with HGel-B and HGel-C for MeDHICA (90% after 6 h), and an appreciable release was observed for DHICA reaching 30% and 40% at 6 h for HGel-B and HGel-C, respectively. At 72 h, DHICA and MeDHICA were released at around 30% from HGel-A at pH 7.4, with an increase up to 40% at pH 5.5 in the case of DHICA. DHICA incorporated into HGel-B proved fairly stable over 6 h whereas the free compound at the same concentration was almost completely oxidized. The antioxidant power of the indole loaded gelatins was monitored by chemical assays and proved unaltered even after prolonged storage in air, suggesting that the materials could be prepared in advance with respect to their use without alteration of their efficacy.


In recent years, scholars have contested conventional narratives such as that the League of Nations was a complete 'failure' or that the United Nations was a novelty in comparison with the League. Scholars now offer more nuanced and archive-based analyses. However, while traditional research has emphasised the establishment of the first formally independent international civil service and the corresponding secretariat as one of the League's few big achievements, the subject has not substantially benefitted from these new historical studies. This article helps to shed some light on the secretariat's nature and how international the staff really was. After examining the prevailing image of the international civil service at the League, the data will be supplemented by an analysis of the archive material with regard to recruitment and selected personnel files. This article argues that the secretariat was international in a European understanding of the notion. The administration further built on an understanding of international affairs that implied a separation in European 'high politics' and non-European regional affairs.


The increase of malware that are exploiting the Internet daily has become a serious threat. The manual heuristic inspection of malware analysis is no longer considered effective and efficient compared against the high spreading rate of malware. Hence, automated behavior-based malware detection using machine learning techniques is considered a profound solution. The behavior of each malware on an emulated (sandbox) environment will be automatically analyzed and will generate behavior reports. These reports will be preprocessed into sparse vector models for further machine learning (classification). The classifiers used in this research are k-Nearest Neighbors (kNN), Naïve Bayes, J48 Decision Tree, Support Vector Machine (SVM), and Multilayer Perceptron Neural Network (MlP). Based on the analysis of the tests and experimental results of all the 5 classifiers, the overall best performance was achieved by J48 decision tree with a recall of 95.9%, a false positive rate of 2.4%, a precision of 97.3%, and an accuracy of 96.8%. In summary, it can be concluded that a proof-of-concept based on automatic behavior-based malware analysis and the use of machine learning techniques could detect malware quite effectively and efficiently.


In chronic renal failure, inorganic phosphate (Pi) retention speeds up the progression to end-stage renal disease. The current therapy for hyperphosphatemia in patients with chronic renal failure consists of dietary Pi restriction combined with administration of Pi binders, but each therapy has practical problems. Thus, the discovery of foods or nutrients that inhibit Pi absorption may be useful for the treatment of hyperphosphatemia. In the present study, we investigated whether wakame (Undaria pinnatifida) is a useful food for the prevention of hyperphosphatemia in a rat model of renal failure. Feeding a diet containing 5% wakame significantly decreased plasma and urinary Pi levels and increased the amount of fecal Pi. In addition, wakame significantly reduced plasma blood urea nitrogen and plasma Pi levels in 5/6 nephrectomized rats fed a high-Pi diet. Biochemical analyses showed that the reduction of intestinal Pi absorption is the main reason for the decrease in plasma Pi levels in rats fed a diet containing wakame. In addition, feeding alginic acid and fucoidan, major components of wakame fiber, was effective in reducing plasma Pi levels in normal rats. Finally, we concluded that wakame may be a useful food for the prevention of hyperphosphatemia in rodents.


Persistent wheezing in very young children is associated with lower respiratory inflammation. Am J Respir Crit Care Med 2001;163:1338–43. 22 Marguet C, Jouen-Boedes F, Dean TP, et al. Bronchoalveolar cell profiles in children with asthma, infantile wheeze, chronic cough, or cystic fibrosis. Am J Respir Crit Care Med 1999;159:1533–40. 23 Najafi N, Demanet C, Dab I, et al. Differential cytology of bronchoalveolar lavage fluid in asthmatic children. Pediatr Pulmonol 2003;35:302–8. 24 Stevenson EC, Turner G, Heaney LG, et al. Bronchoalveolar lavage findings suggest two different forms of childhood asthma. Clin Exp Allergy 1997;27:1027–35. 25 Ennis M, Turner G, Schock BC, et al. Inflammatory mediators in bronchoalveolar lavage samples from children with and without asthma. Clin Exp Allergy 1999;29:362–6. 26 Le Bourgeois M, Goncalves M, Le Clainche L, et al. Bronchoalveolar cells in children ,3 years old with severe recurrent wheezing. Chest 2002;122:791–7. 27 Cai Y, Carty K, Henry RL, et al. Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children. Eur Respir J 1998;11:848–53. 28 Azevedo I, de Blic J, Dumarey CH, et al. Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants. Eur Respir J 1997;10:1767–73. 29 Gibson PG, Norzila MZ, Fakes K, et al. Pattern of airway inflammation and its determinants in children with acute severe asthma. Pediatr Pulmonol 1999;28:261–70. 30 Norzila MZ, Fakes K, Henry RL, et al. Interleukin8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma. Am J Respir Crit Care Med 2000;161:769–74. 31 Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol 1995;154:4719–25. 32 Meagher LC, Cousin JM, Seckl JR, et al. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 1996;156:4422–8. 33 O'Donnell RA, Frew AJ. Is there more than one inflammatory phenotype in asthma? Thorax 2002;57:566–8. 34 Stick SM, Holt PG. The airway epithelium as immune modulator: the LARC ascending. Am J Respir Cell Mol Biol 2003;28:641–4. 35 Knight DA, Holgate ST. The airway epithelium: structural and functional properties in health and disease. Respirology 2003;8:432–46. 36 Chung KF, Barnes PJ. Cytokines in asthma. Thorax 1999;54:825–57. 37 Kamath AV, Pavord ID, Ruparelia PR, et al. Is the neutrophil the key effector cell in severe asthma? Thorax 2005;60:529–30. 38 Mikami M, Llewellyn-Jones CG, Bayley D, et al. The chemotactic activity of sputum from patients with bronchiectasis. Am J Respir Crit Care Med 1998;157:723–8. 39 Colotta F, Re F, Polentarutti N, et al. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 1992;80:2012–20. 40 Lee A, Whyte MK, Haslett C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 1993;54:283–8. 41 Matute-Bello G, Liles WC, Radella F, et al. Neutrophil apoptosis in the acute respiratory distress syndrome. Am J Respir Crit Care Med 1997;156:1969–77. 42 Kotecha S, Mildner RJ, Prince LR, et al. The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants. Thorax 2003;58:961–7. 43 Martin TR. Neutrophils and lung injury: getting it right. J Clin Invest 2002;110:1603–5. 44 Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 1997;89:3503–21. 45 Hiemstra PS, van Wetering S, Stolk J. Neutrophil serine proteinases and defensins in chronic obstructive pulmonary disease: effects on pulmonary epithelium. Eur Respir J 1998;12:1200–8. 46 Liu H, Lazarus SC, Caughey GH, et al. Neutrophil elastase and elastase-rich cystic fibrosis sputum degranulate human eosinophils in vitro. Am J Physiol 1999;276:L28–34. 47 Nadel JA, Takeyama K, Agusti C. Role of neutrophil elastase in hypersecretion in asthma. Eur Respir J 1999;13:190–6. 48 Persson CG. Role of plasma exudation in asthmatic airways. Lancet 1986;2:1126–9. 49 Anticevich SZ, Hughes JM, Black JL, et al. Induction of hyperresponsiveness in human airway tissue by neutrophils: mechanism of action. Clin Exp Allergy 1996;26:549–56.


Procollagen C-proteinase enhancers (PCPE-1 and -2) are extracellular glycoproteins that can stimulate the C-terminal processing of fibrillar procollagens by tolloid proteinases such as bone morphogenetic protein-1. They consist of two CUB domains (CUB1 and -2) that alone account for PCPE-enhancing activity and one C-terminal NTR domain. CUB domains are found in several extracellular and plasma membrane-associated proteins, many of which are proteases. We have modeled the structure of the CUB1 domain of PCPE-1 based on known three-dimensional structures of CUB-containing proteins. Sequence alignment shows conserved amino acids, notably two acidic residues (Asp-68 and Asp-109) involved in a putative surface-located calcium binding site, as well as a conserved tyrosine residue (Tyr-67). In addition, three residues (Glu-26, Thr-89, and Phe-90) are found only in PCPE CUB1 domains, in putative surface-exposed loops. Among the conserved residues, it was found that mutations of Asp-68 and Asp-109 to alanine almost completely abolished PCPE-1 stimulating activity, whereas mutation of Tyr-67 led to a smaller reduction of activity. Among residues specific to PCPEs, mutation of Glu-26 and Thr-89 had little effect, whereas mutation of Phe-90 dramatically decreased the activity. Changes in activity were paralleled by changes in binding of different PCPE-1 mutants to a mini-procollagen III substrate, as shown by surface plasmon resonance. We conclude that PCPE-stimulating activity requires a calcium binding motif in the CUB1 domain that is highly conserved among CUB-containing proteins but also that PCPEs contain specific sites that could become targets for the development of novel anti-fibrotic therapies.


Death certificate information was used to examine seasonal variations in infant deaths attributable to diarrheal and respiratory diseases during a 5-year period (1974-78) in the Brazilian state of Rio Grande do Sol. The state has a subtropical climate with 4 marked seasons in which the temperature ranges from 14 degrees Centigrade to 24 degrees Centigrade. Rainfall is fairly evenly distributed througout the year but varies from year to year. Death registration is relatively high in the area, and deaths are coded according to the 8th revision of the International Classification of Diseases. In this study all diseases classified as 000-009 were considered to be diarrheal deaths, and all those classified as 460-519 were considered to be respiratory deaths. A total of 40,219 infants deaths were recorded during the 5-year period. Monthly mortality rates were computed. The denominator for all monthly rates was the number of infants alive at the midpoint of the 5-year period as estimated from census materials. The same denominator could be used since there was little change in the birth rate during the 5-year period and little seasonal variation in birth rates. 16.2% of the infant deaths occurring during 1974-78 were attributable to diarrheal diseases, and 19.8% were attributable to respiratory diseases. About 1/2 of all the respiratory and diarrheal deaths occurred during the 1st 4 months of life. For example, the diarrheal death rate at months 0-3 was 120/100,000 infants, and by the 12th month the rate declined to 7.5/100,000 infants. 30.5% of the deaths attributed to respiratory diseases occurred during the 1st month of life, and then the rate declined sharply. There were marked and statistically significant seasonal variations in deaths due to both causes. The incidence of diarrheal deaths was almost 4 times higher during the summer months (January-February) than during the winter months (July-October). This correlation was significant at the 0.0008 level. The pattern was reversed for respiratory deaths. The respiratory death rate was twice as high during the winter months June-July as during the summer months of December-Februray. This correlation was significant at the 0.0002 level. There was no significant relationship between rainfall and deaths due to respiratory and diarrheal diseases. Multiple linear regression analysis revealed that temperature explained 68.9% of the variation in diarrheal deaths and 85.9% of the variation in respiratory deaths. Infants born in October through December (the months just preceding the summer months) had a higher risk of diarrheal death than infants born during other months. In contrast, infants born in March through July had a higher risk of death from respiratory disease than infants born during other months. The overall rate of infant deaths due to respiratory disease was 860.4/100,000 infants. The overall rate of infant deaths due to diaarheal diseases was 70.4/100,000 infants. Some caution should be used in interpreting the results of the study. The overall rate for diarrheal deaths appears to be relatively low for the region and may indicate an underreporting of deaths. Furthermore, the cause of death noted on the death certificate was accepted without further checking. Data on the major causes of all infant deaths in also provided.


This paper sets out the challenges facing the English NHS now and in the future and identifies the reforms we believe are needed to meet these challenges. It has been written as a contribution to the listening exercise initiated by the coalition government following the announcement at the beginning of April of a pause in the parliamentary passage of the Health and Social Care Bill. It builds on The King's Fund's response to the health White Paper published in July 2010 (Dixon and Ham 2010), our briefing for the second reading debate on the Bill in the House of Commons (The King's Fund 2011a), and our extensive programme of policy analysis and research.


Summary form only given. With rapid growth of networking, in particular the Internet, a large variety of information could be accessed by different users all over the world through a number of software systems. However, the development of corresponding security mechanisms does not parallel with the development of the networks and software systems. Many attacks occur and cause big losses. According to ZDNet Security News dated January 2004, "computer virus attacks cost global businesses an estimated $55 billion in damages in 2003, a sum that is expected to increase this year." In this talk, the author discusses different types of attacks and countermeasures in software system security. The author also presents some research result on secure mobile agent model and intrusion detection system


Part of the legal aid treaties between Ukraine and other states contains rules concerning conflict of laws. Where those that determine the law applicable to contractual obligations, family, and hereditary relations are not in line with current approaches to determining the law applicable to the specified groups of relations. The purpose of the paper is to uncover the differences between the regulation of conflict of laws in private relations in the legal aid treaties between Ukraine and some EU countries and the modern approaches to the regulation of conflict of laws in such relations, contained in other sources of private international law; an explanation of how to solve conflicts between legal aid treaties and other international treaties; outlining the main areas of improvement of rules concerning conflict of laws in legal aid treaties. The methods of the study were comparative, dialectical, and Aristotelian, which allowed to identify the problems of regulation of conflict of law in legal aid treaties and to draw conclusions for their elimination. Application of these methods allowed to find out that lex loci contractus is most often used to regulate contractual obligations in the absence of an agreement of the parties on the choice of applicable law. The agreement between Ukraine and Romania does not provide for the choice of the law for contractual obligations. Legal aid treaties imperatively determine the law applicable to the property relations of the spouses. They apply a dualistic approach to determining the right to inherit. It has been established that competition between the rules of this Convention and the rules of legal aid treaties between Ukraine and Poland and Ukraine and Estonia should be decided in favour of the Hague Convention. It is proposed to amend the legal aid treaties concluded between Ukraine and the EU Member States: the rules concerning conflict of laws, which define the law applicable to contractual, family, and hereditary relations should be revised using the relevant EU regulations as a model.


There is increased interest in the contribution of secreted phospholipase A2 (sPLA2) enzymes to neurodegenerative diseases. Systemic treatment with the nonapeptide CHEC-9, a broad spectrum uncompetitive inhibitor of sPLA2, has been shown previously to inhibit neuron death and aspects of the inflammatory response in several models of neurodegeneration. A persistent question in studies of sPLA2 inhibitors, as for several other anti-inflammatory and neuroprotective compounds, is whether the cell protection is direct or due to slowing of the toxic aspects of the inflammatory response. To further explore this issue, we developed assays using SY5Y (neuronal cells) and HL-60 (monocytes) cell lines and examined the effects of sPLA2 inhibition on these homogeneous cell types in vitro. We found that the peptide inhibited sPLA2 enzyme activity in both SY5Y and HL-60 cultures. This inhibition provided direct protection to SY5Y neuronal cells and their processes in response to several forms of stress including exposure to conditioned medium from HL-60 cells. In cultures of HL-60 cells, sPLA2 inhibition had no effect on survival of the cells but attenuated their differentiation into macrophages, with regard to process development, phagocytic ability, and the expression of differentiation marker CD36, as well as the secretion of proinflammatory cytokines TNF-α and IL-6. These results suggest that sPLA2 enzyme activity organizes a cascade of changes comprising both cell degeneration and inflammation, processes that could theoretically operate independently during neurodegenerative conditions. The effectiveness of sPLA2 inhibitor CHEC-9 may be due to its ability to affect both processes in isolation. Testing potential anti-inflammatory/neuroprotective compounds with these human cell lines and their conditioned media may provide a useful screening tool prior to in vivo therapeutic applications.


Deciding what to do with the dog during working hours is a problem that many dog owners are faced with. One possible solution is to bring the dog to work, for example the office. It is, however, not known how this environment and the everyday events and situations there affect the welfare of the dogs. The aim of this project was to study how the dog is affected by commonly occurring situations when at the owner at work in an office environment. The subjects were 12 privately owned dogs which routinely accompanied their owners to the office at the University of Agricultural Sciences. Dogs and owners were filmed in the office during four different treatments. Behaviours were analyzed separately, but some were also grouped in physically active (in motion), mentally active (in motion, or not moving but focused) and behaviours often suggested to indicate arousal (yawn, lick, shake and stretch). Numbers of transitions between different states (how often the dog switched body position and/or switched between different activities) were recorded. The four 30 minute treatments were: I) Control; dog and owner together, telephone rings II) Separation and Return; owner leaves dog and returns for short visits repeatedly III) Alone; the dog is alone for 20 minutes with disturbances: an unfamiliar dog passes the doorway, and a sudden noise is heard IV) Visitors; two minute visits from two unfamiliar persons, one enthusiastic and contact seeking (E), and one neutral which ignores the dog (N).

Results of this study show that even though there were individual differences, dogs' reactions in the different situations were mild. Overall mean values show that dogs on average spent 89.5% of the time lying down. Very little barking occurred. During Control treatment dogs were least active. The Visitor treatment caused an increased mental activity (P<0.05), which in large part could be explained by physically dynamic behaviour such as the dog moving around to interact with visitors. This treatment also elicited high frequencies of indicators of arousal (P<0.05) and caused an increased number of posture changes (P<0.05). Also in Separation and Return, mental activity increased (P<0.05), but the average dog was to a larger proportion physically stationary during their mental behaviour, i e the dog was not as much in motion but focused on the environment, such as the owner and doorway. Variation in mental activity was large in the treatment Alone, indicating that dogs coped with being left for 20 minutes in different ways. Some were physically active; others were static but still mentally active, while some showed little reaction. There was a tendency (P=0.055) for dogs to be located near the door to a greater extent when the owner was absent (15.2% time) compared to present (4.5%). As expected, the enthusiastic visitor elicited much stronger reactions than the neutral. Out of 12 dogs, 11 interacted with visitor E, but only 3 with visitor N. Although both visitors caused reactions initially, visitor E had both a significantly larger (P<0.05) and more long-lasting effect even after the visit. It is unclear if these effects could have a negative impact on the dog, or if they can function as a stimulating enrichment. An unfamiliar dog passing caused increased intensities of restlessness (P<0.05) and mental activity (P<0.01), while the only reaction to the noise was that HR increased initially (P<0.01) probably indicating that there was an element of surprise, from which the dog quickly recovered. Results do not show any clear indications that bringing the dog to the office would affect the welfare of the dog. To consider the character of and the effects on the individual dog is a crucial key when determining whether to bring the dog to the office or not.


CBSE School The Board witnessed rapid growth and expansion at the level of Secondary education resulting in improved quality and standard of education in institutions. But with the advent of State Universities and State Boards in various parts of the country the jurisdiction of the Board was confined only to Ajmer, Bhopal and Vindhya Pradesh later. As a result of this, in 1952, the constitution of the Board was amended wherein its jurisdiction was extended to part-C and Part-D territories and the Board was given its present name 'Central Board of Secondary Education'. It was in the year 1962 finally that the Board was reconstituted. The main objectives were to serve the educational institutions more effectively, to be responsive to the educational needs of those students whose parents were employed in the Central Government and had frequently transferable jobs.


Striated muscle has a highly ordered structure in which specialized domains of the cell membrane involved in force transmission (costameres) and excitation-contraction coupling (T tubules) as well as the internal membranes of the sarcoplasmic reticulum are organized over specific regions of the sarcomere. Optimal muscle function is dependent on this high level of organization but how it established and maintained is not well understood. Due to its ex utero development and transparency, the zebrafish embryo is an excellent vertebrate model for the study of dynamic relationships both within and between cells during development. Transgenic models have allowed the delineation of cellular migration and complex morphogenic rearrangements during the differentiation of skeletal myocytes and the assembly and organization of new myofibrils. Molecular targeting of genes and transcripts has allowed the identification of key requirements for myofibril assembly and organization. With the recent advances in gene editing approaches, the zebrafish will become an increasingly important model for the study of human myopathies and muscular dystrophies. Its high fecundity and small size make it well suited to high-throughput screenings to identify novel pharmacologic and molecular therapies for the treatment of a broad range of neuromuscular conditions. In this review, we examine the lessons learned from the zebrafish model regarding the complex interactions between the sarcomere and the sarcolemma that pattern the developing myocyte and discuss the potential for zebrafish as a model system to examine the pathophysiology of, and identify new treatments for, human myopathies and muscular dystrophies.


Contemporary problems in philosophy From Mr Jeremy T Wright Department of Obstetrics & Gynaecology West Middlesex University Hospital Sir, I very much enjoyed Professor Ayer's scholarly monograph in the May issue of the Journal (p 344), but am surprised that he did not mention the seminal works of Karl Popper, which are in my view fundamental to the induction of new thought in medicine. Professor Ayer as a positivist dispenses with 'refutation' in a single sentence on page 349 when he says, 'Some philosophers take this "holism" further to the point of saying that every accredited observation puts the whole corpus of our beliefs at risk, but this is surely an exaggeration'. Surely not, Professor Ayer; it is just this refutation that moves medical science along, often against the wishes of its elders. Popper's view is to take a problem (which is usually a rebuff to existing theory or expectation), to propose a new solution or a new theory and then deduce testable propositions from this new theory and test these by, amongst other things, experiments and observations and then to establish a preference between the two theories. Absolute truth will not be established, one theory will be rebuffed or refuted, to be replaced by another in time, but it is unlikely that anything will be finally true. This is particularly so of statistics in relation to medicine. Statistical theory enables one to calculate how likely it is that the results of an investigation could have arisen as a matter of chance when in truth there is no difference a type I error. It is also possible to conclude wrongly that there is no difference when in fact there is a type II error. In any medical investigation there is only a balance of probabilities, whose strength or power one can measure, not truth. In 'Conjectures and Refutations' (Routledge & Kegan Paul, London, 1963), Popper discusses this in relation to Adlerian and Freudian psychology, in which many cases are used to verify a theory, being interpreted in the light of that theory. Thus observations are each in turn interpreted in the light of previous experience and at the same time counted as additional confirmation. They in fact confirm nothing other than that they can be interpreted in the light of a particular theory. This means little other than that any case can be interpreted in the light of either Freud's or Adler's theory. Knowledge is increased only by a series of refutations as theories are exploded and replaced by others. Professor Ayer, in his field, is as reactionary to new theory as we sadly are in our own. Yours faithfully


Objective: To explore the surgical effect and experience of endoscope-assisted excision for congenital nasal dermoid and sinus cyst (NDSC) in children. Methods: Fifty-three patients with congenital NDSC treated in Beijing Children's Hospital from January 2007 to December 2018 were retrospectively reviewed, including 30 boys and 23 girls, with the age ranging from 9 to 145 months (mean age 35.6 months). The ultra-low-dose CT scan and MRI of the paranasal sinuses were performed for all patients. Excisions of NDSC under general anesthesia were performed for all patients, and surgical approaches were dependent on location and extent of the lesions according to radiographic workups. All intra-osseous patients and complicated superficial cases underwent surgical excision of NDSC and nasal reconstruction with the assistance of endoscope. Initial presentation, medical history, imaging workups, surgical approaches, complications, rates of recurrence and cosmetic outcomes were evaluated. Descriptive statistics was used for the results analysis. Results: Among 53 cases, the most common presentation included a nasal-glabella mass (n=21, 39.6%), a dorsal punctum (n=13, 24.5%) and a dorsal mass (n=9, 17.0%). The sites of NDSC included nasal glabella (n=22, 41.5%), nasal bridge (n=27, 50.9%) and nasal tip (n=4, 7.5%). Of all patients, 24 cases (45.3%) had superficial lesions, 19 cases (35.8%) had intraosseous extension into the frontonasal bones, 10 cases (18.9%) extended intracranially but remained extradural. Surgical approaches included transverse incision (n=22, 41.5%), minimal midline vertical incision (n=27, 50.9%) and external rhinoplasty (n=4, 7.5%). All NDSC were successfully excised and no nasal reconstruction needed. All cases were followed up from 9 to 151 months with a mean of 67.3 months. Five patients (9.4%) with recurrence were observed and were managed successfully with reoperation. During the follow-up, no nasal deformity was noted, and cosmetic outcome was favorable for all patients. Conclusion: Endoscope-assisted excision has the advantage of clear vision, small trama and low recurrence rate for children with NDSC.


Diabetes remains the seventh leading cause of death in the United States and is associated with many complications, including both microvascular and macrovascular comorbidities (1). In 2013, average medical expenditures among people diagnosed with diabetes were 2.3 times higher than among those without diabetes. According to the 2014 National Diabetes Statistics Report, 1.4 million Americans are diagnosed with diabetes annually (1). Although diabetes affects people from different races and ethnic backgrounds, the rates of diagnosed diabetes continue to be higher in ethnic minority groups such as non-Hispanic blacks, Hispanics, and Asian Americans, among others (1,2).

The U.K. Prospective Diabetes Study demonstrated that maintaining diabetes control with an A1C of ∼7% during the first 10 years after diagnosis decreases the risk of microvascular complications for people with type 2 diabetes (3). Among the treatment options available for diabetes, insulin is the mainstay of therapy for type 1 diabetes and is also recommended in newly diagnosed type 2 diabetes (4,5).

Despite its effectiveness and guideline recommendations for its use, insulin remains underutilized among adults with diagnosed diabetes in the United States (3,6,7). Between 1997 and 2011, the percentage of adults who reported taking only insulin to treat their diabetes decreased from 26 to 17.8% (1). In contrast, the percentage of people taking only oral medications for diabetes increased from 42.1 to 50.3%. Even with the addition of new insulin analogs for the treatment of diabetes, the usage rate of oral diabetes medications among adults with type 2 diabetes has remained almost three times higher than that of insulin (50.3 vs. 17.8%) (1). The usage rates of any diabetes medications by Hispanics, non-Hispanic blacks, and whites are similar; however, the usage rate of insulin among ethnic minority populations continues to be lower than …


Two diimine-bridged Ru(II),Mn(I) complexes with a [(bpy)2Ru(BL)Mn(CO)3Br]2+ architecture, where bpy = 2,2'-bipyridine and BL = 2,3-bis(2-pyridyl)pyrazine (dpp; Ru(dpp)Mn) or 2,2'-bipyrimidine (bpm; Ru(bpm)Mn), were designed to both dissociate multiple equivalents of CO and produce 1O2 when irradiated with visible light. Analysis of the complexes by Fourier transform infrared (FTIR) spectroscopy and cyclic voltammetry suggest a stronger π-accepting ability for bpm compared to that of dpp. Both complexes absorb light throughout the UV and visible regions with lowest energy absorption bands comprising overlapping Ru(dπ)→BL(π*) and Mn(dπ)→BL(π*) singlet metal-to-ligand charge transfer (1MLCT) and Br(p)→dpp(π*) singlet halide-to-ligand charge transfer (1XLCT) transitions. This lowest energy band is centered at 510 nm (ε = 12 000 M-1cm-1) for Ru(dpp)Mn and 553 nm (ε = 3240 M-1cm-1) for Ru(bpm)Mn, and the absorption band extends to nearly 700 nm in each case. Irradiation with visible light (both 470 and 627 nm) releases all three CO ligands, as observed by a combination of UV-vis, FTIR, and gas chromatography. The exchange of the first CO ligand with a solvent molecule occurs more efficiently for Ru(dpp)Mn (Φ470 = 0.22 ± 0.03 in H2O; 0.37 ± 0.06 in CH3CN) than for Ru(bpm)Mn (Φ470 = 0.049 ± 0.008 in H2O and 0.16 ± 0.03 in CH3CN), and the CO dissociation efficiency is unaffected by irradiation wavelength. The differences between Ru(dpp)Mn and Ru(bpm)Mn are proposed to result from the variation in electron density distribution across each formally reduced BL in the Mn(dπ)→BL(π*) 1MLCT excited state based on the nature of BL. Exhaustive photolysis causes the decomplexation of oxidized Mn(II), and the resulting [(bpy)2Ru(BL)]2+ complexes produce 1O2 with quantum yields (ΦΔ) of 0.37 ± 0.03 and 0.16 ± 0.01 for Ru(dpp) and Ru(bpm), respectively, with 460 nm irradiation. This bimetallic architecture presents the opportunity to use visible light to codeliver both CO and 1O2, both of which have biological relevance in photoactivated therapeutics, with spatiotemporal control.


Languages usually switch within a multilingual speech signal, especially in a bilingual society. This phenomenon is referred to as code-switching (CS), making automatic speech recognition (ASR) challenging under a multilingual scenario. We propose to improve CS-ASR by biasing the hybrid CTC/attention ASR model with multi-level language information comprising frame- and token-level language posteriors. The interaction between various resolutions of language biases is subsequently explored in this work. We conducted experiments on datasets from the ASRU 2019 code-switching challenge. Compared to the baseline, the proposed interactive language biases (ILB) method achieves higher performance and ablation studies highlight the effects of different language biases and their interactions. In addition, the results presented indicate that language bias implicitly enhances internal language modeling, leading to performance degradation after employing an external language model.


A 3D pursuit-evasion situation where a highly manoeuvrable evader is engaged by a faster bank-to-turn pursuer is considered in this paper. The differential game (DG) is solved as a 'game of kind' (GOK), establishing barrier strategies and capture criteria in terms of the game parameters. Some of these strategies and the associated optimal pursuit-evasion manoeuvres have been presented in two earlier papers for the 'classical' type of barrier surface, i.e. with a tangential termination on the target set. This paper covers a larger region in the game parameter space, introducing a new type of game termination.


In recent years, Gaza City is exposed to a large amount of land use and land cover changes, as aresult of lack of planning and monitoring programs. This leads to complex serious problems such as: lack of storm water infiltration, impact of global warming, potential agricultural failures, soil erosion, etc. Due to increasing changes of land use, mainly by human activities, detection of such changes, assessment of their trends and environmental effects are necessary for future planning and resource management. This study aims to detect changes occurred in Gaza City for land use and land cover during the interval between 1999 and 2007using GIS techniques. It shows that within the period from 1999 to 2007, the built up areas have been reached the highest increase (8.06%). On the other hand, both of green and dry lands have been decreased. Certainty, the green lands is transformed from 41.79% in 1999 to 38.80% and the dry lands become 18.80% in 2007 while it is 24.16% in 1999. For the wet lands, the area of this category has been increased with a percent of 0.96% as a total in 2007. Depending on those numbers, the study expects that the built up areas will be the dominance at the expense of other categories as a result of the continuous population growth and in accordance to the proposed master plan of 2025 of Gaza City. The study strongly recommends giving real opportunity for the local community in sharing in the awareness campaigns to introduce the scope of this study for all community sectors to be aware about LULC for upcoming generations.


This paper focuses on the risks associated with "negative emission" techniques for drawing carbon dioxide from the atmosphere through photosynthesis and storing it in land-based sinks or underground. It examines what these risks may imply for near-term actions to limit warming to 1.5°C or 2°C above pre-industrial levels. Negative emission techniques increasingly appear – explicitly or implicitly – in discussions of options for meeting climate goals, such as those of the Paris Agreement. Negative emissions could allow society to "undo" earlier emissions, enabling us to stay within a given carbon budget in the long run, even if we exceed it early in the century. We identify three types of risks in counting on negative emissions: (i) that negative emission options will not ultimately prove feasible; (ii) that their large-scale deployment involves unacceptable ecological and social impacts; and, (iii) that negative emissions activities prove less effective than hoped, either because they are subsequently reversed by human or natural forces, or because climate change impacts prove irreversible. We examine four main land-based negative emissions options in light of those risks: ecosystem restoration, mosaic-landscape restoration, reforestation, and bioenergy with carbon capture and sequestration (BECCS). Many mitigation pathways aiming to keep warming below 1.5°C or 2°C assume negative emissions as high as 1,000 Gt CO2. We find that negative emission options cannot be safely relied upon to fill such a large gap. Embarking on such pathways could lead societies to do too little to decarbonize, and greatly exceed their carbon budgets without a way to undo the damage. Pathways that rely on much smaller amounts of negative emissions, however, could prove viable, with ecosystem restoration and reforestation providing close to the required volume of negative emissions. This avoids the need to rely on other options (BECCS, in particular) that pose higher risks of technical infeasibility and unacceptable ecological and social impacts. RISKS OF RELYING ON TOMORROW'S 'NEGATIVE EMISSIONS' TO GUIDE TODAY'S MITIGATION ACTION SEI-WP-2016-08


ABSTRACT Sixty-eight drug-resistant Mycobacterium tuberculosis isolates (44.2% of all resistant cases) were analyzed by IS6110 restriction fragment length polymorphism fingerprinting and spoligotyping to provide a deeper insight into the status of drug-resistant tuberculosis in Hungary. A total of 54.4% of the drug-resistant cases and 75% of the multidrug-resistant cases could be clustered. Analysis of the spoligotyping patterns of the strains revealed a high rate (66.2%) of infection by the Haarlem genotype, while none of the patients were infected by the Beijing genotype. The magnitude and the dynamics of drug-resistant tuberculosis are underestimated in Hungary.


The main motivation in using intensity attributes to analyze and compare the technologies of mammography images acquisition is that such images are intrinsically of low contrast, which hinders the lesions detection and interpretation. Considering the viewing conditions, the study is under development to validate the influence of the contrast variation of many types of equipment on the radiologist's diagnosis. However, for the image processing, the contrast variation can be considered a problem affecting the detection of important structures. A large-intensity variation in a digitized image can be manipulated by image-processing techniques and aid in lesion detection. However, low-intensity variation, as observed in the images of full-field digital mammography systems, can impede the detection of some lesions types, as masses are structures of low contrast. Therefore, the new technologies should be tested and validated for an adequate calibration according to the procedures adjacent to the image acquisition itself.


The positron lifetimes of some compounds with NaCl-type crystal structure are calculated with the method of atomic superposition approximation (ATSUP) based on the theories of local-density-approximation (LDA) and general-gradient-approximation (GGA). The systematical results are fitted to a curve as a function of lattice constants. The positron bulk lifetimes of some other compounds with NaCl-type crystal structure, which are deduced from the systematical results, are in agreement with the experimental results given in other literature.


Of the approaches toward bone repair, bone tissue engineering elicits some of the more complex ethical questions, owing to the incorporation of living, considerably altered cells in the product. We discuss three areas where ethical issues occur: cell sourcing, clinical trials and therapy. cells are key components of all bone tissue engineered products. Embryonic stem cells may be used in the future, but this remains ethically controversial. Non-embryonic cells are not controversial but cell donation and the informed consent procedure accompanying it raises questions: both the cells' material value and their informational value for the donor need to be examined when deciding on the conditions of cell donation for tissue engineering purposes. Regeneration through the creation and implantation of metabolically active constructs is a new medical approach which requires a profound analysis of the implications of the new approach for the design of clinical trials and of therapy to protect the safety and autonomy of vulnerable persons. This includes assessments of efficacy, risks and safety. It also requires an evaluation of informed consent procedures. This may not only benefit bone tissue engineering, but other bone repair interventions as well. A third issue is safeguarding the access of patients. The economic thresholds for this therapy will be considerable. However, the presence of living cells may also create a biological threshold owing to immunological requirements. Tissue engineered products may be unavailable for some persons, unless biological diversity is taken into account from the design of bone tissue engineered products and through accurate cell sourcing strategies.


We demonstrate a compact optical fiber microwire current sensor based on the Faraday effect with gigahertz frequency of current sensing capabilities.


This study evaluates two approaches for partitioning eddy covariance fluxes into principle components (NPP and Soil respiration for carbon, and Transpiration and soil respiration for water). Both of the approaches (SK10 and TH08) rely on information contained in the raw, high frequency flux data, interpreted with assumptions about how the deviations in wind and gas concentrations should be correlated/coordinated for air parcels emerging from the canopy versus subcanopy. The developers of these approaches (Scanlon, Thomas) appear as co-authors on the paper, and the literature describing the approaches has been described elsewhere. Thus, while neither SK10 or TH08 is a perfect partitioning approach, I will focus my comments specifically on this effort to compare them (as opposed to comments about the underlying assumptions of


Although cutaneous leishmaniasis lesions usually heal spontaneously they cause unsightly scarring. This study evaluated a possible new therapy in 38 patients, with 70 lesions, randomly assigned to intralesional injection of ciprofloxacin (0.2%) or intralesional sodium chloride hypertonic solution (7%). After excluding patients who defaulted on treatment, lesions assigned to sodium chloride treatment (n = 21) were completely healed (with or without scarring) in 76.2% of cases, and, when a scar remained, the scar size was reduced 66.0% compared with the original lesion. Lesions assigned to ciprofloxacin (n = 27) showed an 81.5% healing rate with an average scar size reduction of 68.6%. Intralesional 0.2% ciprofloxacin was as effective as hypertonic saline in the treatment of cutaneous leishmaniasis infection.


IN A MATTER OF A FEW MONTHS, WE HAVE WITNESSED FAR-REACHING CHANGES IN American global doctrines, the domestic economy and politics of government, and national security and criminal justice. Our focus in this essay is on shifts in the cultural politics of nationalism. During the flush years of an exuberant dot-com economy, being an American meant little more than the freedom to consume or visit Disneyland. But since the September 11 attacks, a resurgent patriotism is omnipresent and nowhere is it more on display than in our schools. (1) In October2001, the Bush administration launched a series of initiatives aimed at prescribing patriotism among the nation's 52 million schoolchildren. Government officials urged students to take part in a mass recitation of the Pledge of Allegiance, and called upon veterans to teach "Lessons for Liberty" (Milbank, 2001: A2). The House of Representatives voted 444-0 for the display of signs proclaiming "God Bless America" in the public schools. At the local level, the New York City Board of Education unanimously passed a resolution requiring all public schools to lead a daily pledge in the morning and at all school assemblies. "It's a small way to thank the heroes of 9/11," explained the Board's president (Wyatt, 2001: A20). In Madison, Wisconsin, the School Board reversed its previous position and voted to allow schools to recite a daily Pledge of Allegiance and sing "The Star-Spangled Banner" (Associated Press, 2001: A12). Nebraska dusted off a 1949 state law requiring schools to devise curricula aimed at in stilling a "love of liberty, justice, democracy and America...in the hearts and minds of the youth." And after years of futile attempts, a conservative, fringe organization in Orange County -- Celebration USA Inc. -- succeeded in synchronizing a nationwide recitation of the pledge at 2:00 p.m. eastern time on October 12th (Sack, 2001: B1). In the aftermath of September 11, people are hungry for social rituals and eager to communicate a deeper sense of national belonging. Yet this new wave of orchestrated patriotism is aimed at closing down debate and dissent through the imposition of a prescribed allegiance. Rituals of patriotism were first institutionalized in the United States between the Civil War and World War I. At the end of the bloodiest civil war of the 19th century, the combatants left the battlefields for political, economic, and cultural arenas, where the struggle to make a nation continued with renewed intensity. In fact, many of the patriotic symbols and rituals that we now take for granted or think of as timeless were created during this period and emerged not from a harmonious, national consensus, but out of fiercely contested debates, even over the wording of the Pledge. Confronted by the dilemma that Americans are made, not born, educators and organizations, such as the Grand Army of the Republic, Women's Relief Corps, and Daughters of the American Republic, campaigned to transform schools, in George Balch's words, into a "mighty engine for the inculcation of patriotism." Balch, a New York City teacher and Civil War veteran, wrote what is thought to be the first pledge to the flag in which students promised to "give our heads and our hearts to God and our Country! One nation! One language! One flag!" Balch intended the pledge to teach discipline and loyalty to the "human scum, cast on our shores by the tidal wave of a vast migration." In 1890, Balch published a primer for educators on Methods for Teaching Patriotism in the Public Schools, which called for the use of devotional rites of patriotism modeled along the lines of a catechism. "There is nothing which more impresses the youthful mind and excites its emotions," noted the West Point graduate, than the "observance of form." To commemorate the first celebration of Columbus Day in 1892 and in preparation for the grand opening of the Columbian Exposition in Chicago, the Youth's Companion magazine charged Francis Bellamy with writing a new pledge. …


The OECD recently recognised that the Human Resources for Science and Technology (HRST) stock of any given country is sharply affected by migration flows of qualified people. We have thus undertaken a study of highly-qualified immigrants in Rome.... The conclusion is that the resident foreign population in Rome has a high mean level of instruction by no means lower than the mean level of Romans at least up until the 1991 census. It also emerges however that among graduates differences in level of instruction vary according to geographical areas and above all the level of industrialisation of the country of origin. (EXCERPT) (SUMMARY IN ENG AND FRE)


This study examined the clinical performance of the scalloped NobelPerfect implant in a one-stage procedure (immediate provisionalization in the esthetic zone). In 20 patients, immediate prosthetic restorations were placed on 31 NobelPerfect implants and followed for up to 27 months. Outcome variables were success rates, marginal bone levels, and Pink Esthetic Score (PES) assessed per implant. One implant failed (success rate: 96.8%). Marginal bone levels averaged 1.7 mm above the first thread and remained stable during the observation period. Mean PES ratings were 11.3 (range, 8 to 14). Survival rates, marginal bone levels, and esthetic results suggest proof of principle for the preservation of the interproximal bony lamella with a scalloped implant design.


Introduction Adenoma detection rate (ADR) is the recommended surrogate marker for a thorough colonoscopic examination. Collecting histology makes its calculation arduous so polyp detection rate (PDR) is often used instead. It has been proposed that the ADR:PDR ratio can be used as a "conversion factor" to accurately estimate ADR. Work from the Bowel Cancer Screening Programme (BCSP) has shown that adenomas are more prevalent in this population suggesting the ratio may be different. We aimed to assess the feasibility of using a "conversion factor" to estimate ADR from PDR in different UK populations. Methods Colonoscopy performance data from the symptomatic services were collected over a 3-month period from 12 units in the northern region of England. Data from all procedures performed by BCSP accredited colonoscopists were excluded from this group. National colonoscopy performance data were extracted from the BCSP database from a 12-month period. Colonoscopists detecting polyps in ≥10 patients were included. Data collected included colonoscopist, PDR and ADR. The conversion factor was calculated separately for each group. The ADR:PDR ratio was calculated at the level of the colonoscopist and the group mean used as the conversion factor. The estimated ADR was calculated using: PDR × conversion factor. The relationship between the actual and estimated ADR was evaluated using Pearson's correlation coefficient. Results In the symptomatic services 3219 colonoscopies were performed by 55 colonoscopists. In the BCSP 31 017 procedures were performed by 147 colonoscopists. The PDR and ADR respectively for the symptomatic group were 30.7%, IQR 24.8–40.0 and 18.0%, IQR 14.0–24.0, and for the BCSP group were 59.3%, IQR 53.8–65.0 and 46.0%, IQR 43.0–51.3. The ADR:PDR ratio in the symptomatic and BCSP groups were 0.59 (IQR 0.47–0.69) and 0.78 (IQR 0.74–0.81). The correlation between the estimated and actual ADR was 0.68 (p<0.001) and 0.83 (p<0.001) for the symptomatic and BCSP groups respectively. Conclusion We demonstrate using estimated ADR, when calculation of ADR is not feasible, may be an acceptable marker of quality in colonoscopy. The difference in the conversion factors between the groups studied here is likely to be due to the selected population colonoscoped within the BCSP but suggests it will need to be adjusted for different patient populations. Studies to further validate this concept and ensure that conversion factors remain consistent over time are ongoing. Competing interests None declared.


We model the problem of assigning referees to matches of volleyball championships as a combinatorial optimization problem. To solve it, we adapt three local search heuristics and study their behavior as a funtion of their parameters. We show the limitations of these algorithms and that the use of refined initialization algorithms and an "endgame" strategy can significantly enhance their efficiency.


Single-sludge biological treatment systems for nitrification-denitrification and phosphorus removal have become widely accepted process options due to the increasingly greater demand for effluent nutrient control. The Soreq Biological Treatment Plant is a regional facility for municipal wastewater treatment and effluent reclamation for irrigation purposes, with a current average capacity of 220,000 m 3 /day. The performance data presented for one full year of operation (1989-1990) under automatic process control indicate consistently high rates of carbon oxidation, nitrification-denitrification and enhanced phosphorus removal.


A pure-strategy, simplified poker (PSP) game is proposed, where two players draw from a small and discrete number of hands. Equilibrium strategies of the game are described and an experiment is conducted where 120 subjects played the PSP against a computer, which was programmed to play either the equilibrium solution or a fictitious play (FP) learning algorithm designed to take advantage of poor play. The results show that players did not adopt the cutoff-type strategies predicted by the equilibrium solution; rather they made considerable "errors" by: Betting when they should have checked, checking when they should have bet, and calling when they should have folded. There is no evidence that aggregate performance improved over time in either condition although considerable individual differences were observed among subjects. Behavioral learning theory (BLT) cannot easily explain these individual differences and cognitive learning theory (CLT) is introduced to explain the apparent anomalies. Copyright © 2009 John Wiley & Sons, Ltd.


Acoustic Doppler current profilers (ADCPs) are commonly used to measure streamflow and water velocities in rivers and streams. This paper presents laboratory, field, and numerical model evidence of errors in ADCP measurements caused by flow disturbance. A state-of-the-art three-dimensional computational fluid dynamic model is validated with and used to complement field and laboratory observations of flow disturbance and its effect on measured velocities. Results show that near the instrument, flow velocities measured by the ADCP are neither the undisturbed stream velocity nor the velocity of the flow field around the ADCP. The velocities measured by the ADCP are biased low due to the downward flow near the upstream face of the ADCP and upward recovering flow in the path of downstream transducer, which violate the flow homogeneity assumption used to transform beam velocities into Cartesian velocity components. The magnitude of the bias is dependent on the deployment configuration, the diameter of the instrument, and the approach velocity, and was observed to range from more than 25% at 5 cm from the transducers to less than 1% at about 50 cm from the transducers for the scenarios simulated.


Conventional power plant performance metrics are designed for dispatchable generation. These can be difficult to apply to variable generators such as wind and solar power. This article describes additional metrics that can be applied to photovoltaic (PV ) power plants and illustrates these metrics using measured data collected from a 1-MW PV plant in Tennessee over a one-year period. The article persuades that new metrics will be needed to measure and effectively employ PV for duty in a traditional generation fleet.


Hepatic and renal electron microscopic investigations were carried out in 10 chickens that had experimental intraduodenal infection with Clostridium perfringens Type A. Fourteen days postinfection, there were ultrastructural changes in hepatocytes and renal tubular epithelial cells; these included mitochondrial lesions (swelling, cristolysis, rarefication of the matrix, myelin figures), glycogen loss, and capillary endothelial cell swelling in both organs, as well as thickening of glomerular basement membrane. The findings are discussed with particular reference to the pathogenesis of Clostridium perfringens Type A enterotoxemia.


Global integrated biochemostratigraphic studies of Silurian conodont biostratigraphy and carbon isotope chemostratigraphy typically focus on the biogeochemical events of the Wenlock through Pridoli epochs (Ireviken, Mulde, Lau, and Klonk events). The global change events that took place during the Llandovery Epoch (early Aeronian, late Aeronian, and Valgu events) are poorly understood in comparison. One major contributing factor is the fact that Llandovery strata are often shale-dominated or replete with unconformities in carbonate-dominated successions. As a result, only a handful of stratigraphically complete carbon isotopic and conodont biostratigraphic data sets are presently available from this interval worldwide. The Knapp Creek Core, Johnson County, east-central Iowa, preserves 228 feet (69.5 m) of dolomitic Silurian strata from the East-Central Iowa Basin and contains the Blanding, Hopkinton, Scotch Grove, and Gower formations. Integrated high-resolution carbon isotope chemostratigraphy and conodont biostratigraphy produced here demonstrate the presence of the late Aeronian, early Telychian ʻValgu', and early Sheinwoodian ʻIreviken' positive carbon isotope excursions in the core. Biostratigraphically significant conodonts recovered from the core include Pseudolonchodina (formerly Aspelundia) fluegeli, Distomodus staurognathoides, Aulacognathus kuehni, Aulacognathus bullatus, Wurmiella? polinclinata polinclinata, Pterospathodus eopennatus, Pterospathodus amorphognathoides angulatus, Pterospathodus amorphognathoides amorphognathoides, and Kockelella ranuliformis. Biochemostratigraphic data from the core indicate that the late Aeronian to early Sheinwoodian interval is well represented in the Iowa stratigraphic succession, help to validate recent and ongoing revisions to the Welsh Basin and base Telychian GSSP, and demonstrate that the East-Central Iowa Basin is an important region that provides the opportunity to study Llandovery biogeochemical events in an expanded carbonate setting.


Context: There is still a dearth of knowledge regarding the types of dermatoses occurring in postmenopausal women. The common disorders occurring in postmenopausal women and the probable effects of hormonal fluctuations on the skin have to be considered while treating postmenopausal women. Aims: To study clinical patterns of dermatosis in menopausal women. Settings and Design: It was a cross-sectional study conducted in the dermatology department from May 2017 to June 2018 after approval from ethical committee. Materials and Methods: All postmenopausal patients having dermatoses were included in the study after taking their written consent in vernacular language. Statistical Analysis Used: All findings were analyzed using STATA (14.2). Results: The study included 150 postmenopausal women. Most of the patients belonged to the age group of 61–70 years (38.67%) with a mean age of 61.52 years. The age of menopause was most commonly achieved between 40 and 50 years (57.33%). The genital dermatoses were found in 90 (60%) subjects and included atrophic vaginitis (21, 33.33%), lichen sclerosus et atrophicus (14, 15.55%), lichen simplex chronicus (14,15.55%) and tinea cruris (10,11.11%) among others. The extragenital dermatoses were found in 96 (64%) cases and common ones were dermatophytosis (16, 16.33%), lichen planus (11, 11.22%), psoriasis (9, 9.18%) and eczema (8,8.16%). Conclusion: This study is useful in understanding the various clinical patterns of postmenopausal dermatoses and thereby help the physician, dermatologist, and gynecologist to effectively manage the conditions.


Interferon (IFN) helps cells fight viral infections by further inducing the expression of many downstream IFN-stimulated genes (ISGs). Human interferon-inducible transmembrane proteins (IFITM) are one of these ISGs. The antiviral function of human IFITM1, IFITM2, and IFITM3 are well known. In this study, we report that IFITM can significantly inhibit EMCV infectivity in HEK293 cells. Overexpression of IFITM proteins could promote IFN-β production. Meanwhile, IFITMs facilitated type I IFN signaling pathway adaptor MDA5 expression. We detected the binding of IFITM2 to MDA5 in a co-immunoprecipitation assay. It was also found that the ability of IFITM2 to activate IFN-β was significantly inhibited after interfering with MDA5 expression, suggesting that MDA5 may play an important role in the activation of the IFN-β signaling pathway by IFITM2. Moreover, the N-terminal domain plays an active role in the antiviral activity and the activation of IFN-β by IFITM2. These findings suggest that IFITM2 plays a vital role in antiviral signaling transduction. In addition, a positive feed-forward loop between IFITM2 and type I IFN establishes a key role for IFITM2 in enforcing innate immune responses.


This study evaluated eight high performing public motor bus transit agencies of different sizes and operating characteristics to identify the common factors underlying their performance. The study was specifically concerned with the use of strategic management within high performing systems. High performance was defined in terms of efficiency (hourly operating cost and utilization of labor, vehicle, and maintenance resources). Study agencies were selected from among the more than 300 federally-assisted bus systems, utilizing the Irvine Performance Evaluation Method (IPEM) and Section 15 data for 1980 to 1983. Site visits were conducted at the eight agencies and case reports were written of the findings. Major findings of the study were that none of the high performing systems were supported by dedicated local operating assistance, which created a strong incentive to control costs; that a majority were contract-managed; and that all but one had generally operated under multi-year labor agreements, which managers had sought in an effort to control labor expenses. One group of systems continued to be operated in a manner similar to their operation under private ownership, in which service decisions were based on maintaining high farebox recovery. As public systems they had avoided marketing unprofitable services which would have caused operating costs to escalate. In a second group of systems, managers had implemented short-range planning or strategic management in an effort to maintain performance. Inability to forecast funds had complicated the strategic management efforts in all agencies. Results from the research provide case examples of the use of the Irvine Performance Evaluation Method to analyze the management of transit systems. The report describes the principles and characteristics of the IPEM procedure thoroughly. Transit managers interested in implementing a performance evaluation system in their agencies may find the report particularly useful for this purpose.


We report the case of an adult female chamois Rupicapra rupicapra within the Gran Paradiso National Park (Italy), showing an abnormal horn-like growth hanging from the skin of the region between the right shoulder and the neck. Similar cases have previously been reported in both domestic and wild animals, including Alpine chamois. The singu- larity of this case lies in the remarkable size of the structure, normally much shorter and thinner. Based on macroscopic appearance of the mass, we hypothesise the occurrence of a cutaneous horn. In the absence of proper biopsy, however, we have no indications as for the origin of this abnormal growth.


The purpose of this study was to determine if there was a relationship between tennis serve speed and isometric mid-thigh pull (IMTP) kinetic variables; countermovement jump height (CMJ Height), shoulder internal and external rotation strength and anthropometric measures in elite adolescent tennis players. Twenty-one elite junior tennis players from the Tennis Australia National Academy were recruited for this study (male, n = 12, female, n = 9). Correlations between the performance variables and peak tennis serve speed were calculated using a Pearson's product-moment correlation coefficient. A significant positive correlation was found between peak serve speed and body height (r = 0.80, p < 0.01), IMTP peak force (r = 0.87, p < 0.01), CMJ Height (r = 0.77, p = < 0.01) and impulse at 300ms (r = 0.71, p = < 0.01). A significant, strong correlation was found between peak serve speed and impulse at 100ms (r = 0.58, p = < 0.01), impulse at 200ms (r = 0.64, p = < 0.01), internal rotation <90 (r = 0.63, p = < 0.01) and external rotation <90 (r = 0.63, p = < 0.01). Due to the significant positive correlations between IMTP variables, CMJ Height and peak serve speed, strength and conditioning coaches with access to a force plate should consider using the isometric mid-thigh pull in order to athletically profile athletes in regards to their strength, power and injury risk.


The ceramide metabolite sphingosine 1-phosphate (S1P) is an important modulator of a wide variety of physiologic functions via its action as a second messenger in intracellular signaling pathways and its extracellular interaction with specific G protein-coupled receptors on the cell surface. In the immune system, interaction of S1P with one of its receptors, S1P1, leads to inhibition of lymphocyte egress from primary and secondary lymphoid tissues resulting in peripheral lymphopenia, a mechanism with demonstrated effects in recent human clinical studies using the S1P1 receptor agonist, FTY720. S1P lyase (S1PL), which catalyzes the only irreversible step in sphingosine metabolism, the degradation of S1P to hexadecenal and ethanolamine phosphate, has recently been suggested to be a target of 2-acetyl-4-tetrahydroxybutylimidazole (THI), a compound known to increase tissue S1P levels and alter lymphocyte trafficking. In the current study, genetic inactivation of S1PL in knockout (KO) mice resulted in severe depletion of lymphocytes in the peripheral blood accompanied by accumulation of mature T cells in the thymus. This abnormal pattern of lymphocyte distribution suggests that results previously seen in THI treated mice were indeed due to THI's inhibition of S1PL rather than another unknown activity. S1PL KO mice also demonstrated significantly reduced viability, perhaps due to increased numbers of myeloid cells which infiltrated the lungs. In a S1PL humanized allele, in which the human S1PL has been introduced into S1PL KO mice and restores ∼17% of wild type S1PL activity, the reduced viability trait is rescued while peripheral lymphopenia is maintained. Since the phenotypes are genetically separable by an allele that reduces S1PL activity, the lack of observed toxicity at doses of THI resulting in lymphopenia is likely due to its partial inhibition of S1PL activity at those doses, perhaps due to differences in S1P or S1P receptor expression or metabolism in different cell types. The potential for separation of lymphopenia and myeloid cell lung pathology effects by chemical inhibition was confirmed by chronic treatment of mice with the oral, small molecule S1PL inhibitor, LX2931, for 47 days during which no effects on viability were observed while the altered profile of lymphocyte migration seen in the partially inhibited humanized S1PL allele was maintained. Rats and monkeys treated with LX2931 also exhibited peripheral lymphopenia suggesting that the S1PL signaling pathway is conserved across mammalian species. Both S1PL KO and LX2931 treated mice were protected in the oxazolone challenge assay of delayed type hypersensitivity and the collagen induced model of rheumatoid arthritis, demonstrating that the reduction of peripheral lymphocytes previously observed with S1PL inhibition can beneficially affect the development of autoimmune disease.


UNLABELLED
Thyroid autoimmunity is a frequent comorbid condition subjects with in type 1 diabetes mellitus (DM1). We evaluated the prevalence of antithyroid autoantibodies (antimicrosomal, antithyroglobulin and antithyroid peroxidase), in addition to clinical (gender, age, DM duration) and laboratory (TSH, HbA1) characteristics of 101 patients (mean age 20 +/- 9.6 years; 62 female) followed at the HC/UEL.

RESULTS
Autoantibodies were found in 31 subjects (30.7%). In the age group <12 years, 15% had thyroid antibodies; from 12 to 18 years, 32%, and >18 years, 35.7% (p= 0.22). Among the patients with positive antibodies, 40% had some thyroid dysfunction vs only 4.4% of those without antibodies (p<0.001). The average TSH was higher in the positive than in negative group (3.75 and 2.32microU/mL, respectively; p= 0.01).

CONCLUSIONS
The prevalence of thyroid antibodies was 30.7%, in accordance to the literature.


The growth kinetics of Mucor plumbeus and Mortierella ramanniana colonies was studied during cultivation of these two soil fungi on solid media with glucose as a limiting substrate. Within the whole studied range of glucose concentrations (s), the radial growth rate of colonies (Kr) can be satisfactorily described with the following equation that takes substrate inhibition into consideration: (Formula: see text) The values of kinetic parameters for M. plumbeus and Mort. ramanniana, respectively, are: the maximal radial growth rate Kr(max), 0.434 and 0.075 mm/hr; the saturation constant Ks, 6.5 and 5.6 mg/l; the substrate inhibition constant, Ks(i), 3315 and 98.6 mg/l. The mechanism of substrate inhibition is manifested in a decrease in the width (volume) of the peripheral zone of the colonial growth at high substrate concentrations, and is not related to a decrease in the specific growth rate of the fungi. Regardless of the drastic differences in the Kr of the two cultures, their specific growth rates are similar and depend on the substrate concentration according to in the same pattern.


Long-term results of surgical treatment of lumbar discopathy in 29 patients with 5 years follow-up (14 girls, 15 boys) operated at the age of 13-18 years in Neurosurgery Department, Medical University in Białystok between 1970 and 1993. Ten years follow-up was available in 26 patients (14 girls, 12 boys) operated between 1970 and 1988. Over period of 10 years 64.3% girls and 16.7% boys preserved recommended diet, 92.8% and 8.3% boys continued muscle strengthening exercises. Cigarette smoking abandoned 100% girls and none of the boys. Ten years after surgical treatment for lumbar discopathy excellent results were found in 85.7% females and 50% males.


The COVID19 pandemic which came unprecedentedly has brought forward a lot of confusion and unrest in the world. There are a lot of changes with regard to the global landscape in multiple ways. SARS-CoV-2 is the primary virus, which is the root contributor to the COVID19 outbreak, which started in Wuhan, Hubei Province, China, in December 2019. It did not take much time to spread across the world. This pandemic has resulted in a universal health crisis, along with a major decline in the global economy. One of the major reasons for the fluctuation in the stock price is supply and demand. When the number of people who want to sell their stocks outnumbers those who want to purchase it, the stock price drops. Due to the result in the gap, the financial markets will suffer in the short duration, but in the long run, markets will correct themselves and would increase again. There is a sharp decline in the stock price because of the pandemic. The current scenario has resulted in a world health crisis which has contributed to global and economic crises. Almost all financial markets across the world have been affected by the recent health crisis, with stock and bond values falling gradually and severely. In the United States, the Dow Jones and S& P 500 indices have fallen by more than 20%. The Shanghai Stock Exchange and the New York Dow Jones Stock Exchange both indicate that they had a significant impact on China's and the United States' financial markets. The primary purpose of this paper is to determine the impact of COVID19 on stock markets. The rapid spread of the virus has left a major impact on the global financial markets. There is a link between the pandemic and the stock market, and this has been studied in this paper. Along with it, an attempt is taken to compare stock price returns in pre-COVID19 and post-COVID19 scenarios. The stock market in India faced uncertainty during the pandemic, according to the findings.