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Aim Design Methods Results Conclusions No Patient or Public Contribution What Is Already Known What This Paper Adds Develop evidence‐based recommendations for managers to support primary healthcare nurses to thrive at work.A mixed‐methods sequential explanatory design.National data were collected in 2020 via an e‐survey based on a meta‐analysis of antecedents of thriving from 213 primary healthcare nurses across New Zealand. Structural equation modelling analysis identified the key factors supporting primary healthcare nurses to thrive. This informed a second open‐ended e‐survey in 2022 of 19 nurses from one primary healthcare organization. The thematic analysis provided recommendations for improving management strategies to support thriving primary healthcare nurses.The vitality component of thriving significantly reduced burnout and intention to leave organization and profession. In contrast, the learning component of thriving had a significant positive effect on burnout. The key factors that support thriving at work are empowering leadership and perceived organizational supports (decreases burnout and intention to leave organization and profession through enhanced vitality). Recommendations for improving thriving were made in eight key areas: communication, effective management, professional development, scope of practice, autonomy, effective orientation, reward and work–life balance.Vitality is important in reducing burnout and turnover intentions. While learning was identified as increasing burnout, professional development and training for managers were identified as essential. Hence, the vitality dimension of the thriving at work construct should be studied at the dimension level, but more research is needed into the impact of learning on thriving over time. Primary healthcare nurses have identified that empowering leadership and perceived organizational support are critical factors in supporting them to thrive, and they provide specific recommendations for managers to improve these factors in the clinical setting.This study collected data from Registered Nurses only. A plethora of existing research focuses on resilience in nurses rather than thriving at work. Enabling employees to thrive at work contributes to improved well‐being and sustainable organizational performance. Empowering leadership and perceived organizational support are the key factors that support primary healthcare nurses to thrive at work. The vitality dimension of the thriving at work construct should be studied at the dimension level, and further research is needed into the impact of learning on thriving over time. Primary healthcare nurses recommend that managers focus on improving communication, management efficiency, professional development, scope of practice, autonomy, orientation, reward and work–life balance. [ABSTRACT FROM AUTHOR]

Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and colonization is a common source of infection. Staphylococcal infections of animals not only are of major importance for animal well-being but have considerable economic consequences, such as in the case of staphylococcal mastitis, which costs billions of dollars annually. Furthermore, pet animals can be temporary carriers of strains infectious to humans. Moreover, antimicrobial resistance is a great concern in livestock infections, as there is considerable antibiotic overuse, and resistant strains can be transferred to humans. With the number of working antibiotics continuously becoming smaller due to the concomitant spread of resistant strains, alternative approaches, such as anti-virulence, are increasingly being investigated to treat staphylococcal infections. For this, understanding the virulence mechanisms of animal staphylococcal pathogens is crucial. While many virulence factors have similar functions in humans as animals, there are increasingly frequent reports of host-specific virulence factors and mechanisms. Furthermore, we are only beginning to understand virulence mechanisms in animal-specific staphylococcal pathogens. This review gives an overview of animal infections caused by staphylococci and our knowledge about the virulence mechanisms involved. [ABSTRACT FROM AUTHOR]

"Facing China: The Prospect for War and Peace" by Jean-Pierre Cabestan is a translated book that provides a clear and readable overview of Chinese politics and international relations. The book covers topics such as Sino-US relations, China-India contention, and regional affairs like the South China Seas disputes and the Senkaku Islands conflict. The author argues that while a hot war between China and the US is unlikely, there are ongoing "gray zone" conflicts and trade and tech wars. The book is supported by extensive research and is recommended for policymakers, researchers, and academics studying Chinese foreign policy and international relations. [Extracted from the article]

Most organizational researchers understand the detrimental effects of measurement errors in testing relationships among latent variables and hence adopt structural equation modeling (SEM) to control for measurement errors. Nonetheless, many of them revert to regression-based approaches, such as moderated multiple regression (MMR), when testing for moderating and other nonlinear effects. The predominance of MMR is likely due to the limited evidence showing the superiority of latent interaction approaches over regression-based approaches combined with the previous complicated procedures for testing latent interactions. In this teaching note, we first briefly explain the latent moderated structural equations (LMS) approach, which estimates latent interaction effects while controlling for measurement errors. Then we explain the reliability-corrected single-indicator LMS (RCSLMS) approach to testing latent interactions with summated scales and correcting for measurement errors, yielding results which approximate those from LMS. Next, we report simulation results illustrating that LMS and RCSLMS outperform MMR in terms of accuracy of point estimates and confidence intervals for interaction effects under various conditions. Then, we show how LMS and RCSLMS can be implemented with Mplus, providing an example-based tutorial to demonstrate a 4-step procedure for testing a range of latent interactions, as well as the decisions at each step. Finally, we conclude with answers to some frequently asked questions when testing latent interactions. As supplementary files to support researchers, we provide a narrated PowerPoint presentation, all Mplus syntax and output files, data sets for numerical examples, and Excel files for conducting the loglikelihood values difference test and plotting the latent interaction effects. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. This pathogen can cause a wide variety of diseases, ranging from moderately severe skin infections to fatal pneumonia and sepsis. Treatment of S. aureus infections is complicated by antibiotic resistance and a working vaccine is not available. There has been ongoing and increasing interest in the extraordinarily high number of toxins and other virulence determinants that S. aureus produces and how they impact disease. In this review, we will give an overview of how S. aureus initiates and maintains infection and discuss the main determinants involved. A more in-depth understanding of the function and contribution of S. aureus virulence determinants to S. aureus infection will enable us to develop anti-virulence strategies to counteract the lack of an anti-S. aureus vaccine and the ever-increasing shortage of working antibiotics against this important pathogen. [ABSTRACT FROM AUTHOR]

Bacterial sepsis is a major global cause of death. However, the pathophysiology of sepsis has remained poorly understood. In industrialized nations, Staphylococcus aureus represents the pathogen most commonly associated with mortality due to sepsis. Because of the alarming spread of antibiotic resistance, anti-virulence strategies are often proposed to treat staphylococcal sepsis. However, we do not yet completely understand if and how bacterial virulence contributes to sepsis, which is vital for a thorough assessment of such strategies. We here examined the role of virulence and quorum-sensing regulation in mouse and rabbit models of sepsis caused by methicillin-resistant S. aureus (MRSA). We determined that leukopenia was a predictor of disease outcome during an early critical stage of sepsis. Furthermore, in device-associated infection as the most frequent type of staphylococcal blood infection, quorum-sensing deficiency resulted in significantly higher mortality. Our findings give important guidance regarding anti-virulence drug development strategies for the treatment of staphylococcal sepsis. Moreover, they considerably add to our understanding of how bacterial sepsis develops by revealing a critical early stage of infection during which the battle between bacteria and leukocytes determines sepsis outcome. While sepsis has traditionally been attributed mainly to host factors, our study highlights a key role of the invading pathogen and its virulence mechanisms. Author summary: Bacterial infections often develop sepsis as a complication. Sepsis is a severe blood infection and one of the main reasons for death, especially in hospitals of the developed world. Sepsis is believed to be due to an overshooting immune reaction to structures that most bacteria share. However, this model fails to explain why some bacteria cause more frequent and severe sepsis than others. In our study, which we performed with the main sepsis-causing bacteria, Staphylococcus aureus, we show that the outcome of sepsis depends on the battle between bacteria and white blood cells that happens early during infection. Many of the weapons that bacteria use for that battle are controlled by a quorum-sensing regulator, which implies that so-called anti-virulence strategies directed at that regulator may work to treat sepsis. However, we also show that targeting quorum-sensing is counterproductive when sepsis originates from biofilms on implanted catheters, which it often does. Our study shows that bacterial weaponry plays a key role in sepsis and gives important advice on how to use this finding for alternative drug development. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. This pathogen can cause a wide variety of diseases, ranging from moderately severe skin infections to fatal pneumonia and sepsis. Treatment of S. aureus infections is complicated by antibiotic resistance and a working vaccine is not available. There has been ongoing and increasing interest in the extraordinarily high number of toxins and other virulence determinants that S. aureus produces and how they impact disease. In this review, we will give an overview of how S. aureus initiates and maintains infection and discuss the main determinants involved. A more in-depth understanding of the function and contribution of S. aureus virulence determinants to S. aureus infection will enable us to develop anti-virulence strategies to counteract the lack of an anti-S. aureus vaccine and the ever-increasing shortage of working antibiotics against this important pathogen. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection. Here we show that the Staphylococcus aureus Pmt ABC transporter defends the bacteria from killing by important human AMPs and elimination by human neutrophils. By showing that Pmt contributes to virulence during skin infection in an AMP-dependent manner, we provide evidence that AMP resistance plays a key role in bacterial infection. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen success during infection have not yet been described. Here we show that the clonal complex (CC) 30 lineage, a major cause of hospital-associated sepsis and hematogenous complications, expresses an allelic variant of the PSMα3 peptide. We found that this variant, PSMα3N22Y, is characteristic of CC30 strains and has significantly reduced cytolytic and pro-inflammatory potential. Notably, CC30 strains showed reduced cytolytic and chemotactic potential toward human neutrophils, and increased hematogenous seeding in a bacteremia model, compared to strains in which the genome was altered to express non-CC30 PSMα3. Our findings describe a molecular mechanism contributing to attenuated pro-inflammatory potential in a main MRSA lineage. They suggest that reduced pathogen recognition via PSMs allows the bacteria to evade elimination by innate host defenses during bloodstream infections. Furthermore, they underscore the role of point mutations in key S. aureus toxin genes in that adaptation and the pivotal importance PSMs have in defining key S. aureus immune evasion and virulence mechanisms. [ABSTRACT FROM AUTHOR]

Phenol-soluble modulins (PSMs) are a recently discovered family of amphipathic, alpha-helical peptides that have multiple roles in staphylococcal pathogenesis and contribute to a large extent to the pathogenic success of virulent staphylococci, such as Staphylococcus aureus. PSMs may cause lysis of many human cell types including leukocytes and erythrocytes, stimulate inflammatory responses, and contribute to biofilm development. PSMs appear to have an original role in the commensal lifestyle of staphylococci, where they facilitate growth and spreading on epithelial surfaces. Aggressive, cytolytic PSMs seem to have evolved from that original role and are mainly expressed in highly virulent S. aureus. Here, we will review the biochemistry, genetics, and role of PSMs in the commensal and pathogenic lifestyles of staphylococci, discuss how diversification of PSMs defines the aggressiveness of staphylococcal species, and evaluate potential avenues to target PSMs for drug development against staphylococcal infections. [ABSTRACT FROM AUTHOR]

Abstract: Phenol-soluble modulins are secreted staphylococcal peptides with an amphipathic α-helical structure. Some PSMs are strongly cytolytic toward human neutrophils and represent major virulence determinants during Staphylococcus aureus skin and blood infection. However, capacities of PSMs to lyse human erythrocytes have not been investigated. Here, we demonstrate that many S. aureus and Staphylococcus epidermidis PSMs lyse human erythrocytes. Furthermore, synergism with S. aureus β-toxin considerably increased the hemolytic capacities of several PSMs. This synergism may be of key importance in PSM and β-toxin-producing S. aureus or in mixed-strain or -species infections with PSM and β-toxin producers. Of specific interest, several PSMs, in particular PSMα peptides, contributed to a considerable extent to synergistic hemolysis with β-toxin or when using the β-toxin-producing strain RN4220 in CAMP assays. Thus, CAMP-type assays should not be used to detect or quantify S. aureus δ-toxin production, but may be used for an overall assessment of Agr functionality. Our study suggests an additional role of PSMs in staphylococcal pathogenesis and demonstrates that the repertoire of staphylococcal hemolysins is not limited to S. aureus and is much larger and diverse than previously thought. [Copyright &y& Elsevier]

Chinese foreign policy has multiple sources, and the incentives that are driving its behaviour have grown from the domestic/international, as well as from regional, economic, normative, multilateral, and cultural levels. Foreign policy-making in China is becoming increasingly complex and sophisticated. This special issue is drawn from some edited papers presented in the joint workshop between Fudan and Durham Universities on Chinese foreign policy on 29-30 March 2010. By assessing the economic, domestic, regional, global and cultural sources of Chinese foreign policy, we aim to illustrate the various sources and to locate possible ways to consolidate the transitional process, and to spur future endeavour facing China's foreign policy. [ABSTRACT FROM AUTHOR]

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are causing an ongoing pandemic of mostly skin and soft tissue infections. The success of CA-MRSA as pathogens is due to a combination of antibiotic resistance with high virulence. In addition, it has been speculated that CA-MRSA strains such as the epidemic U.S. clone USA300 have increased capacity to colonize human epithelia, owing to bacteriocin-based bacterial interference. We here analyzed the molecular basis of antimicrobial activity detected in S. aureus strains, including those of the USA300 lineage. In contrast to a previous hypothesis, we found that this activity is not due to expression of a lantibiotic-type bacteriocin, but proteolytically processed derivatives of the phenol-soluble modulin (PSM) peptides PSMα1 and PSMα2. Notably, processed PSMα1 and PSMα2 exhibited considerable activity against Streptococcus pyogenes, indicating a role of PSMs in the interference of S. aureus strains with the competing colonizing pathogen. Furthermore, by offering a competitive advantage during colonization of the human body, the characteristically high production of PSMs in USA300 and other CA-MRSA strains may thus contribute not only to virulence but also the exceptional capacity of those strains to sustainably spread in the population, which so far has remained poorly understood. [ABSTRACT FROM AUTHOR]

The current pandemic of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections is caused by several genetically unrelated clones. Here, we analyzed virulence of globally occurring CA-MRSA strains in a rabbit skin infection model. We used rabbits because neutrophils from this animal species have relatively high sensitivity to Panton-Valentine leukocidin (PVL), a toxin epidemiologically correlated with many CA-MRSA infections. Virulence in the rabbit model correlated with in vitro neutrophil lysis and transcript levels of phenol-soluble modulin a and a-toxin, but not PVL genes. Furthermore, abscesses caused by USA300 and its PVL-negative progenitor USA500 were comparatively large and similar in size, suggesting that PVL has played a limited role in the evolution of USA300 virulence in the context of skin infections. Our study indicates a major but not exclusive impact of virulence on the epidemiological success of USA300 and other CA-MRSA strains and emphasizes the importance of core genome-encoded toxins in CA-MRSA skin infections. [ABSTRACT FROM AUTHOR]

The global financial crisis of 2008-2009 tested the U.S. financial leadership, while at the same time it sent a beam of hope to many emerging countries in finding ways to shoulder the global financial leadership. The major idea behind this article is to demonstrate and critically assess the possibility of emerging economies reshaping the future financial system. I use Shanghai and Dubai to discern the meaning of a government-supported international financial center project. This article first assesses the challenge of the current financial turmoil in relation to financial globalization. Second, I illustrate the efforts of Shanghai and Dubai-both before and after the financial crisis-in the establishment of an international financial center with a view of the challenges facing the current financial system. Finally, I endeavor to draw some parallels/differences of the responses or measures taken by the countries that were affected by the financial crisis in Asia in 1997 to examine the possibility and shortcomings of government-backed financial policy in connection with the global financial architecture. [ABSTRACT FROM AUTHOR]

Chinese family enterprises in the United Kingdom have penetrated many different sectors of the economy, including restaurants, wholesaling, retailing, trading, manufacturing, property development, computer services and investment holding. Among the companies in these sectors, those involved in different segments of the food industry, as manufacturers, retailers and wholesalers, reputedly feature characteristics of Chinese culture. A majority of these enterprises, for example, function as family firms. This study explores the assertion that, among companies owned by ethnic minorities, culture strongly influences form of business development. This argument will be assessed through a focus on Chinese food-based enterprises in the UK. Two family-controlled companies, Seven Seas (Frozen Food) Ltd and Dayat Foods Packaging Ltd, were selected as case studies as they are involved in key business components of the Chinese food chain industry. Through an in-depth comparative study of the history and development of these two firms, we consider the argument that Chinese businesses have evolved well because of family ties and their inclusion in mutually-beneficial ethnically-constructed networks. Through these case studies, we provide an alternative perspective to diasporic Chinese business development which brings into question the extensive use of the concept of ethnic enterprise. [ABSTRACT FROM AUTHOR]

Abstract: A comparison was made of the cytotoxic activity and secondary structural features of four recombinant forms of adenylate cyclase toxin (CyaA). These forms were fully functional CyaA, CyaA lacking adenylate cyclase enzymatic activity (CyaA*), and non-acylated forms of these toxins, proCyaA and proCyaA*. At a toxin concentration >1μg/ml, CyaA* was as cytotoxic towards J774.2 cells as CyaA and mediated cell killing at a faster rate than CyaA. At concentrations <0.5μg/ml, CyaA* was less cytotoxic than CyaA and, at <0.1μg/ml of CyaA*, no activity was detected. CyaA, but not CyaA*, was able to induce caspase 3/7 activity, a measure of apoptosis. ProCyaA and proCyaA* had no detectable cytotoxic or apoptotic activity. CyaA caused 50% inhibition of the zymosan-stimulated oxidative burst at 0.003μg/ml, whereas a ∼500-fold greater toxin concentration of CyaA* or proCyaA was needed for 50% inhibition. ProCyaA* was inactive. CyaA is a calcium-binding protein and far UV circular dichroism (CD), near UV CD and fluorescence spectra analyses showed that all the forms of CyaA had similar overall structures at different calcium concentrations up to 5.0mM. At 7.5mM CaCl2, the far UV spectrum of CyaA altered significantly, indicating a change in secondary structure associated with high β-sheet content or a β-aggregated state, whereas the spectrum of CyaA* showed only a slight alteration at this calcium concentration. Near UV CD and fluorescence studies were consistent with a rearrangement of secondary structural elements in the presence of CaCl2 for all CyaA forms. There was a marked dependence on protein concentration of the far UV spectra of these CyaA forms, implying an interaction between individual molecules at higher protein concentrations. [Copyright &y& Elsevier]

The interaction between two perspectives—China as a world factory and Chinese business knowledge—has been complicated by the ever greater tensions generated from the national—China—and the transnational actors—Chinese—in understanding the economic driving force behind the real meanings of the rise of China. The construction process of the rise of Chinese economic power puts the state in direct contact with regional and global economic/political changes. On the one hand, Chinese business knowledge, identities, economic and political interactions also give rise to the notion of network building and sub-regional development, which help transcend country-specific relations. On the other hand, the notion of the rise of China is still being re-constructed through the interplay between regional and global political economy. [ABSTRACT FROM AUTHOR]

The composition of Greater China among the PRC, Hong Kong and Taiwan entails an emerging form of micro governance where an ecological evolution of sub-group interaction and crossover of economic and social activities has been generating a dynamic of change within the East Asian region. The constitution of Greater China by social, economic, political, business and even daily commuting creates some soul searching questions about the possible outcomes of their intense interaction. To what extent has integration been made within Greater China through these interactions? Is China the economic linchpin or does China need to cooperate in one way or another to facilitate the modes of economic development? What are the attitudes and strategies used by Hong Kong or Taiwan when confronted with such an economic cum social entity? More importantly, where, and, under what conditions, will the interactions among the PRC, Taiwan and Hong Kong lead to? In this paper, I am going to use a conceptual model which includes four interactions: integration, interdependence, identity and independence (Four Is) to capture the catalyst of change that collectively entails these intermingled economic, social and cultural elements. People who live in the vast context of this geographical region experience the change. Through daily interaction, they help write the context of change through business activities, investment, migration, trade, culture, academic exchange, political and social development along the Four Is. [ABSTRACT FROM AUTHOR]

Abstract: Three different recombinant forms of CyaA were used to investigate transcriptional responses of murine bone marrow-derived macrophages (BMMs) using Affymetrix Mouse Genome GeneChips®. These forms were enzymically active, invasive CyaA, non-enzymically active, invasive CyaA (CyaA*) and non-enzymically active, non-invasive CyaA (proCyaA*). BMMs, treated with 20ng/ml of CyaA for 24h, showed over 1000 significant changes in gene transcription compared with control cells. CyaA caused an increase in transcription of many inflammatory genes and genes associated with various signalling cascades such as those involved in cyclic AMP-dependent protein kinase A signalling. Most strikingly, CyaA caused down-regulation of numerous genes involved in cell proliferation. CyaA* at 20ng/ml significantly up-regulated the transcription of only twelve genes after 24h whereas proCyaA* at this concentration significantly increased the transcription of only two genes. [Copyright &y& Elsevier]

Purpose: Percutaneous vertebroplasty (PVP) is a minimally invasive outpatient procedure whereby vertebral compression fractures are stabilized by the injection of bone cement, or polymethyl methacrylate (PMMA). Rapid partial or complete pain relief can usually be achieved through this procedure. We prospectively evaluate the efficacy of PVP in the relief of pain and improvement in quality of life of patients with intractable pain from osteoporotic and metastatic fractures. Materials and Methods: Patients with intractable pain from vertebral metastases (many resistant to palliative radiation therapy) and patients with intractable painful osteoporotic fractures were treated with parapedicular or transpedicular injection of PMMA. Plane X-rays, computed tomography (CT) scan, and magnetic resonance imaging (MRI) scan were performed on all patients. With a reflex hammer, percussion pain was correlated to the imaging abnormalities. The preplanning CT scan was used to calculate the exact entry point and angle of the bone-biopsy needle. All patients were assessed before and after the procedure for quality of life and amount of pain. The following measures were used: 1) the Edmonton Symptom Assessment System (ESAS), for global pain, nausea, tiredness, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath; 2) a site-specific pain score (SSPS); 3) the amount of analgesic intake in morphine equivalents in the last 24 hours; and 4) the Townsend Functional Assessment Scale (TFAS), ascertaining mobility. A postprocedural CT scan was performed the same day on all patients. Follow-up assessment consisted of a phone call at Days 1, 2, and 4 and Weeks 1, 2, 4, 8, and 12. Patients with recurrent back pain or complications were followed in the bone metastases clinic. Results: Thirty patients (19 women, 11 men) were evaluated. Their median age was 68 years (range 31 to 87 years). Thirty procedures (n = 30) at 45 vertebral levels were performed; 13 were for pathologic fractures, and 17 were for osteoporotic fractures. SSPS showed a decrease of 2 or more levels in 88.5% of patients at 12-week follow-up. The mean SSPS with movement was 8.7 preprocedure and 1.8 postprocedure (P < 0.0001). Also, there was significant improvement in all 9 ESAS domains (P < 0.0004). The ingestion of analgesics in morphine equivalents showed a trend toward reduction post-PVP (P < 0.0599). When the patients with pathologic fractures were separated out, the reduction in ingestion of analgesics was significant (P < 0.0008). The TFAS demonstrated significant improvement in patient mobility and function. Extravertebral extravasation of cement was noted in 55.6% of the levels. We used a general linear mixed-model repeated-measures analysis of variance to analyze the data. Conclusions: PVP in osteoporotic and metastatic fractures significantly improved many patients' global quality-of-life scores and function by markedly decreasing their back pain and reducing their intake of pain medications. The procedure is safe, with no serious complications noted in our study. [ABSTRACT FROM AUTHOR]

Along the contemporary migration history of the overseas Chinese in Southeast Asia, three distinctive images have been constructed through the interaction between the overseas Chinese and Mainland China. First, the image of involuntary migrant, formulated by their migration activity and the continuous remittance they sent back to their hometowns, closely linked to the political and social-economic disturbances in the early years of the twentieth century. Second, the image of the overseas Chinese as political revolutionary was heavily politicised by the revolutionary policies of Mainland China in the 1950s and 1960s. Third, through the operational means of foreign direct investment, the overseas Chinese image of economic energiser was re-focused and mirror-imaged with the imperative of the economic reform of Mainland China in the 1970s and 1980s. On the one hand, the images of involuntary migrant, political revolutionary and economic energiser of the Southeast Asian overseas Chinese describe their situational status. On the other hand, these images also reflect the contemporary historical development of Mainland China. [ABSTRACT FROM AUTHOR]

This paper attempts to analyse how and in what ways the Chinese diaspora interacts with globalisation in Southeast Asia through their economic and social capital. It explores the theories of globalisation and contrasts them with the thematic changes of Southeast Asia studies, and it conceptualises the economic power, the geographical dispersal nature and the social networking of Chinese diaspora in order to understand how a virtual nation is being constructed. It then examines empirical studies of that economic power using the specific case of Indonesia; comparative studies of Chinese companies in Southeast Asian countries; and foreign direct investment in China from the Association of Southeast Asian Nations. Finally, it surveys the building of the virtual community through ethnicity, languages, associations and Confucianism, from which social capital has been generated among the Chinese diaspora in Southeast Asia. [ABSTRACT FROM AUTHOR]

Introduces several articles featured in the 2004 issue of "East Asia: An International Quarterly," including the regionalism in China and its economic diplomacy with Singapore.

Measurement invariance is usually tested using Multigroup Confirmatory Factor Analysis, which examines the change in the goodness-of-fit index (GFI) when cross-group constraints are imposed on a measurement model. Although many studies have examined the properties of GFI as indicators of overall model fit for single-group data, there have been none to date that examine how GFIs change when between-group constraints are added to a measurement model. The lack of a consensus about what constitutes significant GFI differences places limits on measurement invariance testing. We examine 20 GFIs based on the minimum fit function. A simulation under the two-group situation was used to examine changes in the GFIs (ΔGFIs) when invariance constraints were added. Based on the results, we recommend using Δcomparative fit index, ΔGamma hat, and ΔMcDonald's Noncentrality Index to evaluate measurement invariance. These three ΔGFIs are independent of both model complexity and sample size, and are not correlated with the overall fit measures. We propose critical values of these ΔGFIs that indicate measurement invariance. [ABSTRACT FROM AUTHOR]

Deals with a study on the methodologies used in the cross-cultural consumer studies between 1991 and 1996. Research objectives; Methodology; Results; Conclusion.

Describes a procedure for addressing the problem concerning multigroup research. Question of factorial invariance raised by comparing different groups using survey-type instruments; Structured approach for testing large models; Development of two computer programs designed to make the recommended procedures less laborious; Testing for factorial invariance; Factor-ratio test.

Argues that non-invariant items in cross-cultural studies may represent important sources of data relating to between-group differences. Conditions they may be legitimately included in cross-cultural comparisons; Proposal of a procedure that permits calculation of their contributions to observed cross-cultural differences; How groups may differ; Ways the proposed method offer to assess differences.

Analyses the 1993 Chinese Taxation Reform. Indication that the 1993 taxation reform was a product of the previous immature reforms; Identification of the four periods which the taxation reforms after 1978 could be broadly divided into; Feature of China's taxation system.

The article discusses a research study by N. T. Pauli and colleagues on the role of protein A of Staphylococcus aureus in the immune response. Topics noted include the suppression of reactivity toward important determinants of virulence of the bacteria, ways on how the human immune system prevent bacterial infections, antigen specificity of plasmablasts, and inclusion of protein A-specific components in the development of Staphylococcus aureus vaccines.

Presents information on "East Asia: An International Quarterly." Description of the two phases of the journal; Scope and academic coverage; Information on the editorial team of the journal.

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia. [ABSTRACT FROM AUTHOR]

Dowager's hump is described as excessive kyphotic curvature in the thoracic spine with a Cobb angle of more than 40 degrees. This case report presents a 61 years old female office clerk who experienced headaches and neck pain for 3 years that extended into her right shoulder and upper chest. She consulted her primary care physician two months before seeing the chiropractor when the neck pain worsened. A diagnosis of cervicalgia related to osteoarthritis was made based on cervical and thoracic X-ray findings. The patient received non-steroid anti-inflammatory drugs (celecoxib and etoricoxib) and stretching exercises at home. At the onset of chiropractic care, radiographs showed loss of cervical lordosis, narrowing at the C4-5, C5-C6, and C6-7 intervertebral disc space with marginal osteophytes. Based on these findings, a working diagnosis of cervicogenic headache was established. After treatment for 9 months, the patient showed improvement in symptoms and function from cervical curve radiographic change and dextro-convexity of the thoracic spine. Avoiding forward head flexion and maintaining correct posture in daily activities will be key mechanisms to prevent the reoccurrence of Dowager's hump. The improvement of symptoms following chiropractic therapy has been shown to correlate with radiographic markers of spinal realignment. [ABSTRACT FROM AUTHOR]

Many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. Intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. In this article, we demonstrate that activator of G-protein signaling 3 (AGS3), an LPS-inducible protein in macrophages, affects both lysosomal biogenesis and activity. AGS3 binds the Gi family of G proteins via its G-protein regulatory (GoLoco) motif, stabilizing the Got subunit in its GDP-bound conformation. Elevated AGS3 levels in macrophages limited the activity of the mammalian target of rapamycin pathway, a sensor of cellular nutritional status. This triggered the nuclear translocation of transcription factor EB, a known activator of lysosomal gene transcription. In contrast, AGS3-deficient macrophages had increased mammalian target of rapamycin activity, reduced transcription factor EB activity, and a lower lysosomal mass. High levels of AGS3 in macrophages enhanced their resistance to infection by Burkholderia cenocepacia J2315, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus, whereas AGS3-deficient macrophages were more susceptible. We conclude that LPS priming increases AGS3 levels, which enhances lysosomal function and increases the capacity of macrophages to eliminate intracellular pathogens. [ABSTRACT FROM AUTHOR]

Community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) are on a global rise. However, analysis of virulence characteristics has been limited almost exclusively to the US endemic strain USA300. CA-MRSA strains that do not produce Panton-Valentine leukocidin (PVL) have not been investigated on a molecular level. Therefore, we analyzed virulence determinants in a PVL-negative CA-MRSA strain, ST72, from Korea. Genome-wide analysis identified 3 loci that are unique to that strain, but did not affect virulence. In contrast, phenol-soluble modulins (PSMs) and the global virulence regulator Agr strongly affected lysis of neutrophils and erythrocytes, while α-toxin and Agr had a major impact on in vivo virulence. Our findings substantiate the general key roles these factors play in CA-MRSA virulence. However, our analyses also showed noticeable differences to strain USA300, inasmuch as α-toxin emerged as a much more important factor than PSMs in experimental skin infection caused by ST72. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an "off-switch" by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule. [ABSTRACT FROM AUTHOR]

Biofilms are surface-attached agglomerations of microorganisms embedded in an extracellular matrix. Biofilm-associated infections are difficult to eradicate and represent a significant reservoir for disseminating and recurring serious infections. Infections involving biofilms frequently develop on indwelling medical devices in hospitalized patients, and Staphylococcus epidermidis is the leading cause of infection in this setting. However, the molecular determinants of biofilm dissemination are unknown. Here we have demonstrated that specific secreted, surfactant-like S. epidermidis peptides--the β subclass of phenol-soluble modulins (PSMs)--promote S. epidermidis biofilm structuring and detachment in vitro and dissemination from colonized catheters in a mouse model of device-related infection. Our study establishes in vivo significance of biofilm detachment mechanisms for the systemic spread of biofilm-associated infection and identifies the effectors of biofilm maturation and detachment in a premier biofilm-forming pathogen. Furthermore, by demonstrating that antibodies against PSMβ peptides inhibited bacterial spread from indwelling medical devices, we have provided proof of principle that interfering with biofilm detachment mechanisms may prevent dissemination of biofilm-associated infection. [ABSTRACT FROM AUTHOR]

Fluorescent proteins have wide applications in biology. However, not all of these proteins are properly expressed in bacteria, especially if the codon usage and genomic GC content of the host organism are not ideal for high expression. In this study, we analyzed the DNA sequences of multiple fluorescent protein genes with respect to codons and GC content and compared them to a low-GC gram-positive bacterium, Bacillus anthracis. We found high discrepancies for cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), and the photoactivatable green fluorescent protein (PAGFP), but not GFP, with regard to GC content and codon usage. Concomitantly, when the proteins were expressed in B. anthracis, CFP- and YFP-derived fluorescence was undetectable microscopically, a phenomenon caused not by lack of gene transcription or degradation of the proteins but by lack of protein expression. To improve expression in bacteria with low genomic GC contents, we synthesized a codon-optimized gfp, and constructed optimized photoactivatable pagfp, cfp, and yfp, which were in contrast to nonoptimized genes highly expressed in B. anthracis and in another low-GC gram-positive bacterium, Staphylococcus aureus. Using optimized GFP as a reporter, we were able to monitor the activity of the protective antigen promoter of B. anthracis and confirm its dependence on bicarbonate and regulators present on virulence plasmid pXO1. [ABSTRACT FROM AUTHOR]

Two-level data sets are frequently encountered in social and behavioral science research. They arise when observations are drawn from a known hierarchical structure, as when individuals are randomly drawn from groups that are randomly drawn from a target population. When the covariance structures in the group level and the individual level are the same, standard structural equation modeling software such as LISREL can be used easily to analyze 2-level data sets. However, if the data set consists of variables that have group-level characteristics, LISREL cannot be used in a straightforward manner to implement the analysis of structural equation models that have different structures at the group and individual level. This article illustrates how 2-level structural equation models with additional group-level variables, and hence different structures at the group and individual levels, can be analyzed by LISREL with appropriate settings. A small-scale simulation study was conducted to examine the performance of the proposed method. The results indicate that the proposed method can produce reliable parameter estimates, standard errors, and goodness-of-fit test statistics. The proposed procedure was also used to analyze real data from a study on leadership effectiveness, which examines the correlation between self-ratings and ratings from multiple subordinates. [ABSTRACT FROM AUTHOR]

Discusses the methodologies used in cross-cultural advertising studies. Treatment and selection of culture; Selection of cultural unit; Establishment of conceptual and metric equivalence.

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB to S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains. Many isolates of the predominant Asian community-associated methicillin-resistant S. aureus lineage sequence type (ST) 59 harbor seb, implying a significant role of SEB in the observed hypervirulence of this lineage. We created an isogenic seb mutant in a representative ST59 isolate and assessed its virulence potential in mouse infection models. We detected a significant contribution of seb to systemic ST59 infection that was associated with a cytokine storm. Our results directly demonstrate that seb contributes to S. aureus pathogenesis, suggesting the value of including SEB as a target in multipronged antistaphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of community-associated methicillin-resistant S. aureus infection. [ABSTRACT FROM AUTHOR]

Phenol-soluble modulins (PSMs) are amphipathic peptides produced by staphylococci that have multiple functions in pathogenesis. For example, they may function as cytotoxins and pro-inflammatory agents. Additionally, in a recent study we demonstrated that Staphylococcus aureus PSMs structure biofilms and cause dissemination during biofilm infection. Based on those results suggesting a surfactant-like mechanism by which PSMs work, we here propose that all PSM functions in pathogenesis arose from an original role in non-pathogenic surface colonization. This original role may have included overcoming surface tension in environments of strongly varying hydrophobicity and emulsification of hydrophobic molecules for use as food sources. [ABSTRACT FROM AUTHOR]

Phenol-soluble modulins (PSMs) are amphipathic, alpha-helical peptides that are secreted by staphylococci in high amounts in a quorum-sensing-controlled fashion. Studies performed predominantly in Staphylococcus aureus showed that PSMs structure biofilms, which results in reduced biofilm mass, while it has also been reported that S. aureus PSMs stabilize biofilms due to amyloid formation. We here analyzed the roles of PSMs in in vitro and in vivo biofilms of Staphylococcus epidermidis , the leading cause of indwelling device-associated biofilm infection. We produced isogenic deletion mutants for every S. epidermidis psm locus and a sequential deletion mutant in which production of all PSMs was abolished. In vitro analysis substantiated the role of all PSMs in biofilm structuring. PSM-dependent biofilm expansion was not observed, in accordance with our finding that no S. epidermidis PSM produced amyloids. In a mouse model of indwelling device-associated infection, the total psm deletion mutant had a significant defect in dissemination. Notably, the total psm mutant produced a significantly more substantial biofilm on the implanted catheter than the wild-type strain. Our study, which for the first time directly quantified the impact of PSMs on biofilm expansion on an implanted device, shows that the in vivo biofilm infection phenotype in S. epidermidis is in accordance with the PSM biofilm structuring and detachment model, which has important implications for the potential therapeutic application of quorum-sensing blockers. Unlabelled Image [ABSTRACT FROM AUTHOR]

Aims: To develop a comprehensive model of nursing turnover intention by examining the effects of job demands, job resources, personal demands and personal resources on burnout and work engagement and subsequently on the intention to leave the organization and profession. Background: The ageing population and a growing prevalence of multimorbidity are placing increasing strain on an ageing nursing workforce. Solutions that address the anticipated nursing shortage should focus on reducing burnout and enhancing the engagement of Registered Nurses (RNs) to improve retention. Design: A cross-sectional survey design. Method: Data were collected in 2014-2015 via an e-survey from 2,876 RNs working in New Zealand. Data were analysed with structural equation modelling. Results: Higher engagement results in lower intention to leave the organization and profession. Burnout has significant effects on intentions to leave through lower engagement. While most of the demands and resources' variables (except professional development) have effects on intentions to leave, greater workload and greater work-life interference result in higher burnout and are the strongest predictors of intentions to leave. Greater emotional demands (challenges) and greater selfefficacy also have strong effects in lowering intentions to leave through higher engagement. Conclusions: Employee burnout and work engagement play an important role in transmitting the impacts of job demands, job resources, personal demands and personal resources into RN intention to leave the organization and profession. Work-life interference and high workloads are major threats to nursing retention while challenge demands and higher levels of self-efficacy support better retention. [ABSTRACT FROM AUTHOR]

Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally “unintended” interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches. [ABSTRACT FROM AUTHOR]

Novel cell therapies derived from human T lymphocytes are exhibiting enormous potential in early-phase clinical trials in patients with hematologic malignancies. Ex vivo modification o fT cells is currently limited to a small number of centers with the required infrastructure and expertise. The process requires isolation, activation, transduction, expansion and cryopreservation steps. To simplify procedures and widen applicability for clinical therapies, automation of these procedures is being developed. The CliniMACS Prodigy (Miltenyi Biotec) has recently been adapted for lentiviral transduction ofT cells and here we analyse the feasibility of a clinically compliant T-cell engineering process for the manufacture ofT cells encoding chimeric antigen receptors (CAR) for CD 19 (CAR19), a widely targeted antigen in B-cell malignancies. Using a closed, single-use tubing set we processed mononuclear cells from fresh or frozen leukapheresis harvests collected from healthy volunteer donors. Cells were phenotyped and subjected to automated processing and activation using TransAct, a polymeric nanomatrix activation reagent incorporating CD3/CD28-specific antibodies. Cells were then transduced and expanded in the CentriCult-Unit of the tubing set, under stabilized culture conditions with automated feeding and media exchange. The process was continuously monitored to determine kinetics of expansion, transduction efficiency and phenotype of the engineered cells in comparison with small-scale transductions run in parallel. We found that transduction efficiencies, phenotype and function of CAR19T cells were comparable with existing procedures and overall T-cell yields sufficient for anticipated therapeutic dosing. The automation of closed-system T-cell engineering should improve dissemination of emerging immunotherapies and greatly widen applicability. [ABSTRACT FROM AUTHOR]

Study Design: This was a case-control study.Objective: This study aimed to investigate the body composition and its correlation with leptin and soluble leptin receptor (sOB-R) levels in girls with adolescent idiopathic scoliosis (AIS) and compared with healthy controls.Summary Of Background Data: Patients with AIS are associated with lower body weight, taller stature, lower body mass index (BMI), and deranged bone quality. Despite the widely reported lower BMI and body weight in girls with AIS, the body composition of these patients was not thoroughly studied with sufficient sample size. Leptin is an important factor in regulating energy and bone metabolism, and has been postulated as one of the etiologic factors of AIS.Methods: One hundred forty-eight AIS and 116 control girls aged 12 to 14 were recruited. Body composition was measured with bioelectrical impedance analysis. Caloric intake and physical activity level were assessed by food frequency and Baecke questionnaires respectively. Serum total leptin and sOB-R levels were measured with enzyme-linked immunosorbent assay, and free leptin index was calculated.Results: AIS girls had lower body weight and BMI, other anthropometric and sexual maturity parameters were comparable with controls. There were no difference in caloric intake and physical activity levels. After adjustment for physical activity level, AIS girls had lower skeletal muscle mass, lower body fat, and %body fat. Higher sOB-R and lower free leptin index were found in AIS girls after adjusted for age and body weight. Weaker correlations between serum total leptin, FLI, and body composition parameters were observed in AIS girls.Conclusion: Results suggested that the lower body weight in AIS girls was contributed by both lower skeletal muscle mass and lower body fat. Altered leptin bioavailability also exists in AIS girls and could lead to lower body weight, lower BMI, and abnormal body composition that were manifested in AIS simultaneously.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Adoptive immunotherapy using autologous T cells endowed with chimeric antigen receptors (CAR) has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T cells must be generated on a custom-made basis. Here we show that electroporation of transcription activator--like effector nuclease (TALEN) mRNA allows highly efficient multiplex gene editing in primary human T cells. We use this TALEN-mediated editing approach to develop a process for the large-scale manufacturing of T cells deficient in expression of both their αβ T-cell receptor (TCR) and CD52, a protein targeted by alemtuzumab, a chemotherapeutic agent. Functionally, T cells manufactured with this process do not mediate graft-versus-host reactions and are rendered resistant to destruction by alemtuzumab. These characteristics enable the administration of alemtuzumab concurrently or prior to engineered T cells, supporting their engraftment. Furthermore, endowing the TALEN-engineered cells with aCD19CARled to efficient destruction ofCD19+ tumor targets even in the presence of the chemotherapeutic agent. These results demonstrate the applicability of TALEN-mediated genome editing to a scalable process, which enables the manufacturing of third-party CAR T-cell immunotherapies against arbitrary targets. As such, CAR T-cell immunotherapies can therefore be used in an "off-the-shelf" manner akin to other biologic immunopharmaceuticals. [ABSTRACT FROM AUTHOR]

Neutrophils form the first line of host defense against bacterial pathogens. They are rapidly mobilized to sites of infection where they help marshal host defenses and remove bacteria by phagocytosis. While splenic neutrophils promote marginal zone B cell antibody production in response to administered T cell independent antigens, whether neutrophils shape humoral immunity in other lymphoid organs is controversial. Here we investigate the neutrophil influx following the local injection of Staphylococcus aureus adjacent to the inguinal lymph node and determine neutrophil impact on the lymph node humoral response. Using intravital microscopy we show that local immunization or infection recruits neutrophils from the blood to lymph nodes in waves. The second wave occurs temporally with neutrophils mobilized from the bone marrow. Within lymph nodes neutrophils infiltrate the medulla and interfollicular areas, but avoid crossing follicle borders. In vivo neutrophils form transient and long-lived interactions with B cells and plasma cells, and their depletion augments production of antigen-specific IgG and IgM in the lymph node. In vitro activated neutrophils establish synapse- and nanotube-like interactions with B cells and reduce B cell IgM production in a TGF- β1 dependent manner. Our data reveal that neutrophils mobilized from the bone marrow in response to a local bacterial challenge dampen the early humoral response in the lymph node. [ABSTRACT FROM AUTHOR]