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An accessible or inclusive building design does not disable any user; it should enable the independent and equal use of a facility by all. With the introduction of the Disability Discrimination Act 1995 (DDA), the consideration of issues such as access and inclusive design become even more important. Space analysis is an important aspect of the current accessibility assessment. Existing space analysis techniques, such as space syntax, have tackled the local and global accessibility of a building layout using graph theory. However, there are difficulties in the automatic transfer of design information from architectural drawings into a space analysis tool. With the recent development of the building information model and Industry Foundation Classes (IFCs), it is now possible to automate the transfer process. This paper demonstrates the automation process and how it can be used in accessibility analysis.

Prostate cancer is the second most diagnosed cancer in men, but there is considerable debate over whether or not to screen for the condition. The issues in the debate surrounding screening are clarified in this paper. One of the recommendations of the guidelines for urology from the National Institute for Clinical Excellence (NICE, 2002) is that patients receive balanced information about management options for their condition.The NICE guidelines also suggest that ‘major improvements' are required in information and support services for patients and carers, and that nurse specialists in the urology cancer team will play a key role in these services. The options for management and treatment are discussed in the light of these recommendations and the relative merits of each are considered.

The vast amount of information and research available in dentistry engenders an immense challenge for dentists to manage patients. The future of dental practice rests on the ability of professionals to learn essential strategies for reliably accessing and evaluating the most current and valid research development for the benefit of each individual patient. Evidence-based research in dentistry emerged as a systematic process of critically assessing the published evidence to determine the best treatment for any given patient. The process consists of 5 steps: 1) defining the research question; 2) searching for the pertinent published literature; 3) evaluating the research reports systematically; 4) forming a consensus statement of the best available evidence; and 5) evaluating its clinical relevance. Evidence-based dentistry relies on standard methodology and instruments for searching the available evidence, for analyzing the quality of research reports (ie, internal and external validity), and for evaluating the implications of the best available evidence for the dental community of professionals, patients, insurance carriers, and funding agencies. This article describes the principal tools and methods now available for evidence-based research in dentistry. We also propose avenues of future evolution for this emerging field of research in dental practice.

Most of us in the field of journalism are familiar with the view that print newspapers are nearing their death at an alarming pace, and that the future of journalism rests on digital technologies. ...

Background: In chronic obstructive pulmonary disease (COPD), the degree of circadian variation in forced expiratory volume in 1 second (FEV1) and the influence of anticholinergic blockade is not known. Tiotropium is a long acting inhaled anticholinergic bronchodilator that increases daytime FEV1 in COPD. We hypothesised that tiotropium would modify the overnight change in FEV1, and this would be unaffected by the timing of drug administration. Methods: A double blind, randomised, placebo controlled trial was conducted with tiotropium 18 mg once daily in the morning (09.00 hours), evening (21.00 hours), or an identical placebo. Patients with stable COPD (n=121, FEV1=41% predicted) underwent spirometric tests every 3 hours for 24 hours at baseline and after 6 weeks of treatment. Results: There were no significant differences at baseline between the groups. Tiotropium improved mean (SE) FEV1 (over 24 hours) in the morning (1.11 (0.03) l) and evening (1.06 (0.03) l) groups compared with placebo (0.90 (0.03) l), and nocturnal FEV1 (mean of 03.00 and 06.00 hours) in the morning (1.03 (0.03) l) and evening (1.04 (0.03) l) groups compared with placebo (0.82 (0.03) l) at the 6 week visit (p

Exposure of Pseudomonas aeruginosa to aminoglycosides frequently selects for recalcitrant subpopulations exhibiting an unstable, “adaptive” resistance to these antibiotics. In this study, we investigated the implication in the phenomenon of MexXY-OprM, an active efflux system known to export aminoglycosides in P. aeruginosa . Immunoblotting experiments demonstrated that the transporter MexY, but not the outer membrane pore OprM, was overproduced during the post-drug exposure adaptation period in wild-type strain PAO1. Furthermore, MexY production was dependent upon the degree of bacterial exposure to gentamicin (drug concentration). In contrast to parental strain PAO1, mutants defective in MexXY or in OprM were unable to develop adaptive resistance. Altogether, these results indicate that the resistance process requires the rapid production of MexXY and the interaction of these proteins with the constitutively produced component OprM.

A substantial body of research has found that spinal cord injury (SCI) patients have relatively high degrees of energy, impulsivity, and risk-taking (W. Fordyce, 1964; G. P. Taylor, 1970; B. Woodbury, 1978). The present study endeavors to extend our knowledge to the personality disorder (PD) domain. Forty SCI participants and 40 matched controls were given a semistructured diagnostic interview and a self-report personality disorder instrument. Findings indicated that 27.5% of SCI patients, and a similar number of controls, have PDs. Unexpectedly, impulsive/externalizing disorders (histrionic, narcissistic, antisocial, and borderline) were not unusually high in SCI patients, and were not higher than controls. Avoidant and depressive disorders were unexpectedly high.

Aging is characterized by declines in all physiological processes and concomitant changes in body composition. Age-related changes in metabolism, body composition and gastrointestinal function were investigated in naked mole-rats (Heterocephalus glaber), rodents that exhibit extended longevity. Maximum lifespan of these 40 g rodents (>27 year) is approximately 9 times greater than predicted allometrically. We investigated changes in basal metabolic rate (BMR), body composition and intestinal glucose transport in 1, 5, 10 and 20-year-old male individuals. Body composition was measured using dual X-ray absorptiometry and activity of sodium glucose co-transporters (SGLT1) determined using everted gut sleeves. One-year-olds had lower body mass than other age cohorts, as they had not attained full adult form. Among the 5, 10, and 20-year-olds, no age-related changes in body mass, BMR, percentage body fat, fat-free mass or bone mineral density were found. SGLT1 activity declined moderately (

Background: Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD. Methods: A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 g once daily via dry-powder inhaler, compared with salmeterol, 50 g bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George’s Respiratory Questionnaire (SGRQ). Results: A total of 623 patients participated (tiotropium, n 209; salmeterol, n 213; and placebo, n 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV1 (mean, 1.08 0.37 L; percent predicted, 40 12% [ SD]). Compared with placebo treatment, the mean predose morning FEV1 following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV1 (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, 5.14 U (p < 0.05 vs placebo); salmeterol, 3.54 U (p 0.4 vs placebo); and placebo, 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001). Conclusions: Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD. (CHEST 2002; 122:47–55)

e18057 Background: Gastric cancer is the third leading cause of cancer death worldwide. In Rwanda and East Africs in general, gastric cancer is common in young men and women to the point where the region is known as the "stomach cancer region." Previously reported molecular profiling of Rwandan gastric cancer specimens indicate a lower mutation burden than expected based on historic western-based data; the corresponding database of endoscopy results suggests lsrge differences in access to care. This study compares a US endoscopy database to one from the University of Rwanda, to highlight the disparities of care in low and middle income countries (LMIC’s) compared to higher income countries. Methods: Retrospective pathology, demographic and radiographic data was collected from 164 Rwandan patients who presented for endoscopy at the Kigali University Teaching Hospital and compared with a matching cohort of patients at Dartmouth-Hitchcock Medical Center , Lebanon, NH (DHMC). Results: Approximately 85% of the Rwandan endoscopy cohort presented with gastric cancer, whereas none was seen in the DHMC cohort; the latter group was older than the Rwandan cohort (62.3 vs. 58.6 years). The most common indication for endoscopy among the DHMC cohort was gastroesophageal reflux disease (GERD) or anemia (72%) while the Rwandan cohort most commonly presented with pain or vomiting (68%). A matched US gastric cancer cohort revealed that 63% of US cases of gastric cancer receive treatment with curative intent compared to 7.4% of Rwandan cases. Conclusions: The Rwandan cohort presented with more severe symptoms and was more likely to be diagnosed with gastric cancer than the DHMC patients yet less likely to receive treatment with curative intent. These results highlight the disparities of care in LMIC’s and the need for improving access to early detection and curative treatments.

Synapses are intrinsically ‘noisy’ in that neurotransmitter is occasionally released in the absence of an action potential. At inhibitory synapses, the frequency of action potential-independent release is orders of magnitude higher than that at excitatory synapses raising speculations that it may serve a function. Here we report that the frequency of action potential-independent inhibitory synaptic ‘noise’ (i.e. miniature inhibitory postsynaptic currents, mIPSCs) is highly regulated by sensory experience in visual cortex. Importantly, regulation of mIPSC frequency is so far the predominant form of functional plasticity at inhibitory synapses in adults during the refractory period for plasticity and is a locus of rapid non-genomic actions of oestrogen. Models predict that regulating the frequency of mIPSCs, together with the previously characterized synaptic scaling of miniature excitatory PSCs, allows homeostatic maintenance of both the mean and variance of inputs to a neuron, a necessary feature of probabilistic population codes. Furthermore, mIPSC frequency regulation allows preservation of the temporal profile of neural responses while homeostatically regulating the overall firing rate. Our results suggest that the control of inhibitory ‘noise’ allows adaptive maintenance of adult cortical function in tune with the sensory environment. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

This paper is built upon prior research on enterprise knowledge sharing. Our objective is to explore the role of affect among knowledge workers on adoption of knowledge sharing tools (KST). We examine two different constructs: positive affect and negative affect and their relationships. These affective constructs will be added into TAM (Technology Adoption Model) developed by Davis. Positive affect like joy, happiness, contentment, interest and enthusiasm have been largely neglected in both basic and applied disciplines that deal with affect. A lot of researchers pay attention to study on negative affect; this is because positive affect poses more difficulties in information systems research. Hence a lot of models on affect that were developed neglected the role of positive affect in these studies. As more research works focus on different states of affect by Information Systems researchers, this provides us with strong basis to justify and rationalize the need to consider states of affect in our research works. This study uses survey to conduct an empirical investigation. Our instruments are designed based on the Technology Affect Scale developed by Perlusz [23]. The data collected will be analyzed to ensure internal consistency and reliability of variables is achieved. This research study was among the first to use Technology Acceptance model embedding the role of affect in the context of enterprise knowledge sharing using knowledge tools.

The proposed 6-Hop P2P (6-Hop) is an improved overlay network topology that intends to enhance the current P2P that houses a file sharing and media broadcasting (FSMB) application. A P2P system provides a serverless platform for the current FSMB application. It allows media files in each peer to be located by other peers in the network using any word in the file name. The current FSMB application is a closed system where only registered peers can join the overlay network. However, the current broadcasting system has shown some aspects of inefficiency. Two principle weaknesses identified are as follow: query messages flood the overlay network which taking up the bandwidth of the network; and, the search service is not reliable. When a new peer joins the P2P-based FSMB system, registered peers will randomly join clusters in the network. When a peer queries a specific or part of a file name, the current P2P examine all the peers and all the files in each peer. This has resulted in low recall rate and heavy query messages in the overlay network. The proposed 6-Hop P2P is an overlay network that adopts small-world characteristics attempting to improve the recall rate and to reduce the amount of query messages. The proposed P2P is designed using the "similarity interest" value to reduce unnecessary routing and to cut down the number of hops required by the search. It also rewires peers base on recall-rate learning algorithm to form clusters relying on the `interest' bit value of QRP table. This paper presents the proposed 6-Hop model and the work-in-progress results with a short discussion on its prototype.

This paper looked at an IT company by implementing a social networking system, Yammer, to implement an enterprise microblogging system as a alternate knowledge sharing tool for better knowledge sharing practices among employees. This paper highlighted that survey responses and interview followed with focus group study showed that Yammer, an enterprise microblogging system, is a possible future knowledge sharing tool to be used to replace the current knowledge system. It allowed better connection among employees, status update and monitoring of progress on projects. Important findings such as prior training or experience on social networking systems see higher usage among employees. The constraints of the project are short implementation period and small number of participating knowledge workers. The paper concludes by drawing the significant findings of the project and looking at some possible future research works to be conducted.

During the course of rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are chronically exposed to an inflammatory milieu. The purpose of this study was to test the hypothesis that prolonged exposure of FLS to tumor necrosis factor α (TNFα) augments inflammatory responses to secondary stimuli (priming effect).FLS obtained from RA patients were exposed to TNFα for 3 days and were then stimulated with interferons (IFNs). Expression of IFN target genes was measured by real-time quantitative reverse transcription-polymerase chain reaction analysis and enzyme-linked immunosorbent assay. Total STAT-1 protein and IFN-mediated STAT-1 activation were evaluated by Western blotting. Total histone levels, histone acetylation, and NF-κB p65 and RNA polymerase II (Pol II) recruitment were measured at the CXCL10 promoter (encodes IFNγ-inducible 10-kd protein [IP-10]) by chromatin immunoprecipitation assays.Prolonged pre-exposure of FLS to TNFα enhanced the magnitude and extended the kinetics of CXCL10/IP-10, CXCL9, and CXCL11 production upon subsequent IFN stimulation. This phenotype was retained over a period of days, even after the removal of TNFα. Prolonged TNFα exposure decreased histone levels, increased acetylation of the remaining histones, and heightened recruitment of NF-κB p65 and Pol II to the CXCL10 promoter. In parallel, an increase in intracellular STAT-1 led to amplification of IFN-induced STAT-1 activation.Our study reveals a novel pathogenic function of TNFα, namely, prolonged and gene-specific priming of FLS for enhanced transcription of inflammatory chemokine genes due to the priming of chromatin, the sustained activation of NF-κB, and the amplification of STAT-1 activation downstream of IFNs. These data also suggest that FLS gain an "inflammatory memory" upon prolonged exposure to TNFα.

Microbes can respond quickly to environmental disturbances through adaptation. However, processes determining the constraints on this adaptation are not well understood. One process that could affect the rate of adaptation to environmental perturbations is genetic robustness, the ability to maintain phenotype despite mutation. Genetic robustness has been theoretically linked to evolvability but rarely tested empirically using evolving populations. We used populations of the RNA bacteriophage ϕ6 previously characterized as differing in robustness, and passaged them through a repeated environmental disturbance: periodic 45°C heat shock. The robust populations evolved faster to withstand the disturbance, relative to the less robust (brittle) populations. The robust populations also achieved relatively greater thermotolerance by the end of the experimental evolution. Sequencing revealed that thermotolerance occurred via a key mutation in gene P5 (viral lysis protein), previously shown to be associated with heat shock survival in the virus. Whereas this identical mutation fixed in all of the independently evolving robust populations, it was absent in some brittle populations, which instead fixed a less beneficial mutation. We concluded that robust populations adapted faster to the environmental change, and more easily accessed mutations of large benefit. Our study shows that genetic robustness can play a role in determining the relative ability for microbes to adapt to changing environments.

Antagonism of aminoglycosides by divalent cations is well documented for Pseudomonas aeruginosa and is regarded as one of the problems in aminoglycoside therapy. It is generally considered that divalent cations interfere with uptake of aminoglycosides at both the outer and inner membranes. It has been demonstrated recently that aminoglycosides can be removed from cells of P. aeruginosa by the three-component multidrug resistance efflux pump MexXY-OprM. We sought to investigate the interplay between efflux and uptake in resistance to aminoglycosides in P. aeruginosa . To do so, we studied the effects of the divalent cations Mg 2+ and Ca 2+ on susceptibility to aminoglycosides in a wild-type strain of P. aeruginosa and in mutants either overexpressing or lacking the MexXY-OprM efflux pump. MICs of gentamicin, streptomycin, amikacin, apramycin, netilmicin, and arbekacin were determined in Mueller-Hinton broth in the presence of cations added at concentrations that varied from 0.125 to 8 mM. We found, unexpectedly, that while both Mg 2+ and Ca 2+ antagonized aminoglycosides (up to a 64-fold decrease in susceptibility at 8 mM), antagonism was seen only in the strains of P. aeruginosa that contained the functional MexXY-OprM efflux pump. Our results indicate that inhibition of the MexXY-OprM efflux pump should abolish the antagonism of aminoglycosides by divalent cations, regardless of its precise mechanism. This may significantly increase the therapeutic index of aminoglycosides and improve the clinical utility of this important class of antibiotics.

Whole-cell assays were implemented to search for efflux pump inhibitors (EPIs) of the three multidrug resistance efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN) that contribute to fluoroquinolone resistance in clinical isolates of Pseudomonas aeruginosa . Secondary assays were developed to identify lead compounds with exquisite activities as inhibitors. A broad-spectrum EPI which is active against all three known Mex efflux pumps from P. aeruginosa and their close Escherichia coli efflux pump homolog (AcrAB-TolC) was discovered. When this compound, MC-207,110, was used, the intrinsic resistance of P. aeruginosa to fluoroquinolones was decreased significantly (eightfold for levofloxacin). Acquired resistance due to the overexpression of efflux pumps was also decreased (32- to 64-fold reduction in the MIC of levofloxacin). Similarly, 32- to 64-fold reductions in MICs in the presence of MC-207,110 were observed for strains with overexpressed efflux pumps and various target mutations that confer resistance to levofloxacin (e.g., gyrA and parC ). We also compared the frequencies of emergence of levofloxacin-resistant variants in the wild-type strain at four times the MIC of levofloxacin (1 μg/ml) when it was used either alone or in combination with EPI. In the case of levofloxacin alone, the frequency was ∼10 −7 CFU/ml. In contrast, with an EPI, the frequency was below the level of detection (−11 ). In summary, we have demonstrated that inhibition of efflux pumps (i) decreased the level of intrinsic resistance significantly, (ii) reversed acquired resistance, and (iii) resulted in a decreased frequency of emergence of P. aeruginosa strains that are highly resistant to fluoroquinolones.

Computational cardiac physiology has great potential to improve the management of cardiovascular diseases. One of the main bottlenecks in this field is the customization of the computational model to the anatomical and physiological status of the patient. We present a fully automatic service for the geometrical personalization of cardiac ventricular meshes with high-order interpolation from segmented images. The method is versatile (able to work with different species and disease conditions) and robust (fully automatic results fulfilling accuracy and quality requirements in 87% of 255 cases). Results also illustrate the capability to minimize the impact of segmentation errors, to overcome the sparse resolution of dynamic studies and to remove the sometimes unnecessary anatomical detail of papillary and trabecular structures. The smooth meshes produced can be used to simulate cardiac function, and in particular mechanics, or can be used as diagnostic descriptors of anatomical shape by cardiologists. This fully automatic service is deployed in a cloud infrastructure, and has been made available and accessible to the scientific community.

Summary As a land-grant research university without a geography or cartography department, Washington State University Libraries present a unique organizational context for the adoption of GIS services. The authors consider the implementation of GIS services at the Washington State University Libraries, particularly at the Holland/New Library, which originated from an ARL/GIS Literacy Grant in 1992. The authors cover the following topics in the development of the service: Historical Background, System Architecture, Project Issues and Service Provision, Reference Services Policies, Current Implementation and Related Campus-Wide Issues, and Future Agenda. The services offered were essentially at a minimum level, that is, only providing limited access to government and commercial geospatial data using Arc View and Landview software. The approach to GIS in reference work has been to view it as a specialized service within a standard reference framework very similar to the computer-mediated searching programs ...

The term n dimensional modeling nD is gaining increased usage in the field of information communication technologies ICTs in construction; the concept is heightened by the £0.5-millionfunded three-dimensional 3D to nD modeling project at the University of Salford in the United Kingdom. nD modeling is an evolution of the four-dimensional modeling concept and aims to integrate an nth number of design dimensions into a holistic model that enables users to portray and visually project a building design over its complete life cycle. nD modeling is an extension of the building information model BIM , a concept first introduced in the 1970s that has been the basis of considerable research in construction IT ever since. The idea evolved with the introduction of object-oriented computer-aided design CAD ; the “objects” in these CAD systems e.g., doors, walls, windows, roofs can also store nongraphical data about the building in a logical structure. We therefore define an nD model as an extension of BIM by incorporating all the design information required at each stage of the life cycle of a building facility. However, implementing BIM on real-life projects has presented significant challenges, which range from interoperability to integrating knowledge from multiple-domain points of view. In recent years, leading CAD vendors have promoted BIM heavily with their own solutions. However, because these solutions are based on different, noncompatible standards, an open and neutral data format is required to ensure data interoperability across the different applications. In fact, the construction industry has been facing this problem for many years. Research into the development of standard data models has recently been quite substantial. From as early as the late 1970s, the IGES and PDDI efforts in the United States, the VDA-FS effort in Germany, and Standard for the Exchange of Product Model Data STEP have so far produced two international standards: the Building Elements Using Explicit Shape Representation Part 225 of STEP , which deals with the exchange of 3D

Web 2.0 has changed the landscape of collaborative and broadcast communications among users in organizations. Enterprise 2.0 and KM 2.0 are derivations of Web 2.0. The deployments of Web 2.0 have created lot of impacts on enterprise KM sharing and reuse. Web 2.0 is used as platforms to improve ties in social networks as well as knowledge sharing and reuse activities in organizations. Many studies have shown that adoption of technologies in organizations is not the only success factor for enterprises knowledge creation and sharing among employees. Other factors such as organizational culture, man power, benefit schemes, budget and policy [33] in organizations are equally important. They should be considered to ensure the implementation of knowledge creation and sharing in organization is a successful one. This research intends to propose a Web 2.0 Affectivity model that focuses on the role of a Affect which may be able to improve the acceptance of Web 2.0 as tools for organizational knowledge sharing and reuse. The ultimate goal of the study is to improve on the enterprise knowledge creation, sharing and reuse in the organizations. The proposed model is supported by theories and many past research works on the use of affection construct in areas such as commitment toward organizations, knowledge sharing, decision making and adoption of enterprise systems. The paper presents the proposed model, discusses the research framework and research subjects, and presents on the justifications of the proposed model.

Cortisol responses are typically more pronounced under low controllability conditions, yet little is known about the role of individual differences. This study examined whether cortisol response to a situation with low controllability differs as a function of preexisting control beliefs and age. We manipulated level of controllability using a driving simulator. Control beliefs were assessed prior to the lab session. Salivary cortisol was measured before and after the driving simulation. Participants were 152 adults aged 22–84 from a Boston area sample. In comparison to the normal controllability condition, those in the low controllability condition reported less perceived control over driving, supporting the effectiveness of the manipulation. In the low controllability condition those with higher control beliefs showed a greater cortisol response than those with low control beliefs. Older adults showed a greater cortisol response than younger adults during the challenge. Implications of acute cortisol responses for performance outcomes are discussed.

Several scholars have emphasized moral domain as a critical component of school leadership. Fullan (2003) addressed principalship as a moral enterprise and school leadership as following moral imperatives. Sergiovanni (1992) stressed three dimensions of leadership called “head”, “heart” and “hand”, which are connected and interactive.

The human ZFX, human ZFY, and mouse Zfx genes have CpG islands near their 5′ ends. These islands are typical in that they span about 1.5 kb, contain transcription initiation sites, and encompass some 5′ untranslated exons and introns. However, comparative nucleotide sequencing of these human and mouse islands provided evidence of evolutionary conservation to a degree unprecedented among mammalian 5′ CpG islands. In one stretch of 165 nucleotides containing 19 CpGs, mouse Zfx and human ZFX are identical to each other and differ from human ZFY at only 9 nucleotides. In contrast, we found no evidence of homologous CpG islands in the mouse Zfy genes, whose transcription is more circumscribed than that of human ZFX, human ZFY, and mouse Zfx. Using the isoschizomers Hpa II and Msp I to examine a highly conserved segment of the ZFX CpG island, we detected methylation on inactive mouse X chromosomes but not on inactive human X chromosomes. These observations parallel the previous findings that mouse Zfx undergoes X inactivation while human ZFX escapes it.

The convergence between a leader’s assessment of his/her leadership behaviors and assessments from the leader’s subordinates, peers, and superiors-also known as “leader insight”- is linked to impor...

We describe a mathematical/computational model for thrombin concentration gradients generated by procoagulant circulating tumor cells (CTCs) in flow. We examine how CTCs enhance blood coagulation as they diffuse tissue factor (TF)-dependent coagulation enzymes in a flow environment with vessel walls. Concentration fields of various enzymes, such as prothrombin and thrombin, diffuse to and from CTCs, respectively, as they propagate through the bloodstream. The diffusion-dependent generation of these enzymes sets up complex time-dependent concentration fields. The CTCs are modeled as diffusing point particles in an incompressible fluid, and we exploit exact analytical solutions based on three-dimensional Green’s functions for unbounded domains with one wall for high-resolution numerical simulations. Time-dependent gradient trackers are used to highlight that concentration fields build up (i) near boundaries (vessel walls), (ii) in regions surrounding the diffusing particles, and (iii) in complex time-dependent regions of the flow where fields associated with different particles overlap. Two flow conditions are modeled: no flow, and unidirectional constant flow. Our results indicate that the CTC-generated thrombin diffuses to and persists at the blood vessel wall, and that the spatial distribution of CTCs in flow determines local thrombin concentration. The magnitude of the diffusion gradient and local thrombin concentration is dependent upon bulk solution concentrations of coagulation factors within normal reported concentration ranges. Therefore, our model highlights the potential to determine patient-specific risks for CTC-induced hypercoagulability as a function of CTC number and individual patient concentration of coagulation factors.

This paper assesses the effects of personality traits on economic preparation for retirement, wealth accumulation, and consumption, among persons 66 to 69 years of age. Among the five chief personality traits of neuroticism, extroversion, agreeableness, conscientiousness, and openness, we focus most on conscientiousness. We find levels of adequate economic preparation for retirement ranging from 29 percent to 90 percent and that conscientiousness positively affects the proportion of persons adequately prepared for retirement, while neuroticism negatively affects it. Both consumption and wealth increase with conscientiousness but wealth increases faster, indicating that more conscientious persons save more out of retirement resources.

A low-dimensional parametric deformation model of a cancer cell under shear flow is developed. The model is built around an experiment in which MDA-MB-231 adherent cells are subjected to flow with increasing shear. The cell surface deformation is imaged using differential interference contrast microscopy imaging techniques until the cell releases into the flow. We post-process the time sequence of images using an active shape model from which we obtain the principal components of deformation. These principal components are then used to obtain the parameters in an empirical constitutive equation determining the cell deformations as a function of the fluid normal and shear forces imparted. The cell surface is modeled as a 2D Gaussian interface which can be deformed with three active parameters: H (height), σ(x) (x-width), and σ(y) (y-width). Fluid forces are calculated on the cell surface by discretizing the surface with regularized Stokeslets, and the flow is driven by a stochastically fluctuating pressure gradient. The Stokeslet strengths are obtained so that viscous boundary conditions are enforced on the surface of the cell and the surrounding plate. We show that the low-dimensional model is able to capture the principal deformations of the cell reasonably well and argue that active shape models can be exploited further as a useful tool to bridge the gap between experiments, models, and numerical simulations in this biological setting.

Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety-one non-demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater-administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep-wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non-motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non-motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep-wakefulness, and incipient cognitive decline in PD.

The nonresolving character of synovial inflammation in rheumatoid arthritis (RA) is a conundrum. To identify the contribution of fibroblast-like synoviocytes (FLS) to the perpetuation of synovitis, we investigated the molecular mechanisms that govern the tumor necrosis factor α (TNFα)-driven inflammatory program in human FLS.FLS obtained from the synovial tissues of patients with RA or osteoarthritis were stimulated with TNFα and assayed for gene expression and cytokine production by real-time quantitative reverse transcription-polymerase chain reaction analysis and enzyme-linked immunosorbent assay. NF-κB signaling was evaluated by Western blotting. Histone acetylation, chromatin accessibility, and NF-κB p65 and RNA polymerase II (Pol II) occupancy at the interleukin-6 (IL-6) promoter were measured by chromatin immunoprecipitation and restriction enzyme accessibility assays.In FLS, TNFα induced prolonged transcription of messenger RNA (mRNA) for IL-6 and progressive accumulation of IL-6 protein over 4 days. Similarly, induction of mRNA for CXCL8/IL-8, CCL5/RANTES, matrix metalloproteinase 1 (MMP-1), and MMP-3 after TNFα stimulation was sustained for several days. This contrasted with the macrophage response to TNFα, which characteristically involved a transient increase in the expression of proinflammatory genes. In FLS, TNFα induced prolonged activation of NF-κB signaling and sustained transcriptional activity, as indicated by increased histone acetylation, chromatin accessibility, and p65 and Pol II occupancy at the IL-6 promoter. Furthermore, FLS expressed low levels of the feedback inhibitors A20-binding inhibitor of NF-κB activation 3 (ABIN-3), IL-1 receptor-associated kinase M (IRAK-M), suppressor of cytokine signaling 3 (SOCS-3), and activating transcription factor 3 (ATF-3), which terminate inflammatory responses in macrophages.TNFα signaling is not effectively terminated in FLS, which leads to an uncontrolled inflammatory response. The results suggest that prolonged and sustained inflammatory responses by FLS in response to synovial TNFα contribute to the persistence of synovial inflammation in RA.

Text data understanding on social networking systems has become an important source of data for companies to understand their stakeholders better. The shift from pattern mining of structured database to non-structured text data has alerted companies to have a stronger presence in the new social media world. This research uses text miner module in the Statistical Analysis System (SAS) to analyze conversational data compiled from Yammer enterprise microblogging system. These inputs are used to study the topics discussed among employees. It is also used to examine the knowledge sharing activity among employees in the case company. This can be accomplished by analyzing the topics maps produced SAS software system. One is able to analyze the topic of discussion and the frequency of each topic on microblogging system platforms to observe the knowledge sharing and knowledge creation activity among employees. The case study company in this research project is a knowledge centric organization involves in knowledge sharing activity using a server-based Knowledge Management System (KMS). This research chooses employees that are involved in an active project. They will use Yammer instead of the current KMS system. The topic and text analysis diagrams are used to identify the patterns of discussion and the topics exchanged between employees. SAS (Statistical Analysis System) text mining tool is used to carry out the text mining analysis works where a number of visual representation graph were developed to study the communication patterns among employees. The results of this research had shown that text mining is able to surface employees' frequency of communication and topics of conversation through posting activities using Yammer in this research.

The concept of "Small-World" paradigm has been used by many peer-to-peer (P2P) systems to achieve high clustering and low number of hops to arrive to its desired target. This approach intends to improve performance of P2P systems. The Small world concept requires that the architecture of a P2P system to achieve high cluster coefficient and low average hop between any two randomly chosen peers. In this research, we propose an enhanced hierarchical overlay network by incorporating the concept of Small world into the base hierarchical architecture. This research adopts the Query Routing Protocol (QRP) data structure of a hierarchical P2P network by storing the interest information of files in the leaf peers in the network. The QRP in the leaf peers will be aggregated and propagated to the Super Peer so that interest information could be used to form short-range, medium-range and long-range links with other Super Peers to achieve low average hop. As peers join and leave the network, a proposed rewiring protocol is used to ensure peers are clustered by interest to form high clustering coefficient so that search activities are yielding higher relevance results in a more predictable fashion. We simulated the porposed small world P2P using test scenarios to evaluate recall rate of the small world P2P system. Our simulated results evaluate and benchmark our proposed Small-World Bee (SWB) overlay network with iCluster [3], Firework Query Model [5] and Lime wire [1] to assess performance obtained and goals achieved in the research work so that future research directions could be planned.

The use of knowledge management systems to support knowledge creation and sharing activities has become the priority of organizations to stay competitive in the global market. This is a case study that focuses on how IT Shared Services Company adopted knowledge management system as an automated IT tool and there action of the employees with respect to the organization when the system is implemented using few strategies to cultivate knowledge creation and sharing environment and culture in the organization. Due to many unknown variables and factors, the research undertaken and presented in this paper is an exploratory study with objectives to analyse and investigate the outcomes from the implementation of knowledge management system in the organization. The results revealed that the use of knowledge management system in the organization depends on the employees "taskgroup" classifications which had been categorized based on their daily job activities, whereas for the types of incentives [6, 8] provided to the employees as a motivating factor to employees varies among staff who have served the organization for a number of years. The findings of this study is able to help both practitioners and researcher to build a fundamental understanding of how knowledge management system is being used by employees from different types of job category who are more likely to use knowledge management system in an IT Shared Services company.

PurposeThere has been considerable interest in the “two‐week rule” referral pathway efficacy for patients with suspected colorectal cancer. This study aims to explore the psychological impact on these patients.Design/methodology/approachConsecutive patients referred for urgent investigations under the “two‐week rule” were invited to take part in semi‐structured interviews using interpretative phenomenological analysis (IPA). Interviews were audio‐taped, transcribed verbatim and analysed using investigator triangulation to enhance data trustworthiness.FindingsTen out of 23 (43.5 per cent) patients consented to interviews; none were diagnosed with cancer. Four super‐ordinate themes were explored, referring to the “making sense of the threat to health”, impact on self, impact on others, reflections on the “two‐week rule” referral, and its investigative process. Participants reported their anxiety, fear, vulnerability and coping mechanisms, but also raised concerns about the communication received during the “two‐week rule” referral process. Female participants preferred a female endoscopist.Originality/valueThis study is the first of its kind exploring the psychological effects of the “two‐week rule” process for colorectal cancer, highlighting potential areas for improvement in patient information, and satisfaction with the referral process.

Construction organisations (SMEs in particular) are now taking a responsible attitude, going beyond the minimum legal requirements. In line with the UK Government’s innovation objectives under The Strategy for Sustainable Construction, organisations are looking to develop and implement management systems to address the corporate responsibility (CR) aspects of the business. This paper investigates the initiation, development and practice of CR in construction organisations, and presents a case for possible adoption for construction SMEs. By combining key indicators of CR and achieving business success and competitive advantage, the pervasiveness of CR for construction SMEs is determined.

Variance in academic performance that persists when situational variables are held constant suggests that whether students fail or thrive depends not only on circumstance, but also on relatively stable individual differences in how children respond to circumstance. More academically talented children generally outperform their less able peers, but much less is known about how traits unrelated to general intelligence influence academic outcomes. This paper addresses several related questions: What insights can be gleaned from historical interest in the role of temperament in the classroom? What does recent empirical research say about the specific dimensions of temperament most important to successful academic performance? In particular, which aspects of temperament most strongly influence school readiness, academic achievement, and educational attainment? What factors mediate and moderate associations between temperament and academic outcomes? What progress has been made in deliberately cultivating aspects of temperament that matter most to success in school? And, finally, for researchers keenly interested in better understanding how and why temperament influences academic success, in which direction does future progress lie?

A temperature-sensitive mutation (act1-1) in the essential actin gene of Saccharomyces cerevisiae can be suppressed by mutations in the SAC2 gene. A cloned genomic DNA fragment that complements the cold-sensitive growth phenotype associated with such a suppressor mutation (sac2-1) was sequenced. The fragment contained an open reading frame that encodes a 641 amino acid predicted hydrophilic protein with a molecular weight of 74 445. No sequences with significant similarity to SAC2 were found in the GenBank and EMBL databases. A SAC2 disruption mutation was constructed which had phenotypes similar to the sac2-1 point mutation. A haploid SAC2 disruption strain failed to grow at low temperature and the disruption allele suppressed the temperature-sensitive act1-1 growth defect. The suppression phenotype was dependent on the strain background. The SAC2 sequence has been submitted to the EMBL data library (Accession Number Z29988).