Search

A survey investigated UK companies which had invested in Poland and the Czech Republic to establish reasons for investment, the methods of investment, and to highlight any problems. The survey revealed that the economic climate and the market size were significant factors in the choice to invest in these countries. Most companies find the high level of bureaucracy to be a problem and, whilst companies expressed satisfaction with local labour, the lack of marketing and management skills is a significant difficulty.

Metformin reduces the incidence of placental-mediated disease (PMD) in pregnancies with and without diabetes, but the mechanism through which it exerts these effects is not yet fully understood. We performed a systematic review and meta-analysis to examine the effect of metformin on biomarkers implicated in the pathogenesis of PMD. We searched Medline, Embase and the Cochrane Library for studies of metformin and biomarkers of PMD in pregnancy. Meta-analysis was undertaken where comparable data were obtained from two or more studies. 12 studies were included in the final review. Meta-analysis of 2 studies including 323 pregnant women showed significantly reduced CRP levels following treatment with metformin compared to placebo [mean difference = -1.72, 95% CI (-2.97; -0.48); p = 0.007]. Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFα, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women. Metformin significantly decreased the release of anti-angiogenic factors sFlt-1 and sEng from ex-vivo placental and umbilical vein tissue, and increased maternal serum levels of non-phosphorylated IGFBP-1. Overall, our findings show that metformin mediates several molecular pathways implicated in the pathogenesis of pre-eclampsia and intrauterine growth retardation. Metformin therefore has exciting potential as a therapeutic, as well as preventative, agent in the treatment of PMD, which warrants further investigation. [ABSTRACT FROM AUTHOR]

To assess the validity of Spanish versions of the Survey of Well-being of Young Children (SWYC) Milestones and the Ages & Stages Questionnaire, Third Edition (ASQ-3), and to document the rates of developmental delays in an urban cohort of children with Hispanic parents. Spanish-speaking families with a child 9 to 60 months of age (N = 991) were initially screened using Spanish translations of the SWYC Milestones and the ASQ-3. A stratified random sample of 494 of these children subsequently received standardized clinical assessment to confirm the presence of developmental delays. Reverse weighting corrected for the selection bias inherent in the stratification scheme. Fifty-five percent of toddlers (9 to 41 months of age) and 34.8% of preschoolers (42 to 60 months of age) scored in the moderately to severely delayed range, most frequently in language. Sensitivity and specificity for toddlers with severe delays associated with the SWYC were 0.69 and 0.64, respectively, and 0.55 and 0.75 for the ASQ-3. Sensitivity and specificity for preschoolers with severe delays associated with the SWYC were 0.87 and 0.58, respectively, and 0.71 and 0.86 for the ASQ-3. Although psychometric properties of the Spanish translated versions are not as strong as the English versions, the findings suggest that both the SWYC Milestones and ASQ-3 represent promising tools for identifying Hispanic children with developmental delays. The rate of delays were consistent with other studies showing a high percentage of Hispanic children with developmental delays, most frequently in language skills. [ABSTRACT FROM AUTHOR]

Tourism relates to many other industries, such as hospitality, transport, and agriculture. In practice, a tourism destination or place has often been promoted together with local products, especially agrifood products. The co-marketing practice between tourism and agrifood products has faced challenges and one of them is consumer acceptance. Although the importance of local agrifood products in promoting a tourism place has been acknowledged in prior literature, little research has empirically examined the establishment of a strong product-place relationship. Using experimental designs, this study empirically investigated how image transfer and self-congruity influence tourists' evaluations of a co-marketing initiative between the tourism (place) and the agrifood (products) sectors. The study collected a sample of 662 potential tourists from China and data was analysed using Structural Equation Modelling. Results showed that an agrifood product's symbolic images can be directly transferred to a tourism place and subsequently generate stronger tourist desire to visit the place than any other product images. Functional images of an agrifood product can also be transferred to a place, but only indirectly through the process of self-congruity. Experiential images were unable to be transferred in a product-place context. Both theoretical and practical implications are discussed with limitations and future research outlined. • examined the product-place relationship from a co-marketing perspective. • Investigated the role of products in tourism marketing. • examined image transfer through three types of benefit transfers. • examined self-congruity in consumer acceptance of a co-marketing initiative. • discussed implications of effective co-marketing practices. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering.Aim: The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure.Design: This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40weeks of treatment with spironolactone 25mg once daily to chlorthalidone 25mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40weeks of randomly allocated drug therapy and at 46weeks after discontinuation of the study drug. [ABSTRACT FROM AUTHOR]

Credit rationing does not mean that lending is above full-information levels as is shown by a model with implications for lending policy which includes an assessment of the risk of overinvestment.

A previously studied immunosuppressive cytokine, Soluble Immune Response Suppressor (SIRS), may have relevance to current studies of immune suppression in a variety of human disease states. Despite extensive efforts using experimental models, mainly in mice, much remains to be discovered as to how autoimmune cells in mice and humans escape normal regulation and, conversely, how tumor cells evade evoking an immune response. It is the contention of this commentary that the literature pre-2000 contain results that might inform current studies. The broadly immunosuppressive protein, SIRS, was studied extensively from the 1970s to 1990s and culminated in the determination of the n-terminal 21mer sequence of this 15 kDa protein which had high homology to the short neurotoxins from sea snakes, that are canonical members of the three finger neurotoxin superfamily (3FTx). It was not until 2007 that the prophylactic administration of the synthetic N-terminal peptide of the SIRS 21mer, identical to the published sequence, was reported to inhibit or delay the development of two autoimmune diseases in mice: experimental allergic encephalomyelitis (EAE) and type I diabetes (T1D). These findings were consistent with other studies of the 3FTx superfamily as important probes in the study of mammalian pharmacology. It is the perspective of this commentary that SIRS, SIRS peptide and the anti-peptide mAb, represent useful, pharmacologically-active probes for the study of the immune response as well as in the potential treatment of autoimmune, inflammatory diseases and cancer. [ABSTRACT FROM AUTHOR]

Performance-based building requirements have become more prevalent because it gives freedom in building design while still maintaining or exceeding the energy performance required by prescriptive-based requirements. In order to determine if building designs reach target energy efficiency improvements, it is necessary to estimate the energy performance of a building using predictive models and different weather conditions. Physics-based whole building energy simulation modeling is the most common approach. However, these physics-based models include underlying assumptions and require significant amounts of information in order to specify the input parameter values. An alternative approach to test the performance of a building is to develop a statistically derived predictive regression model using post-occupancy data that can accurately predict energy consumption and production based on a few common weather-based factors, thus requiring less information than simulation models. A regression model based on measured data should be able to predict energy performance of a building for a given day as long as the weather conditions are similar to those during the data collection time frame. This article uses data from the National Institute of Standards and Technology (NIST) Net-Zero Energy Residential Test Facility (NZERTF) to develop and validate a regression model to predict the energy performance of the NZERTF using two weather variables aggregated to the daily level, applies the model to estimate the energy performance of hypothetical NZERTFs located in different cities in the Mixed-Humid Climate Zone, and compares these estimates to the results from already existing EnergyPlus whole building energy simulations. This regression model exhibits agreement with EnergyPlus predictive trends in energy production and net consumption, but differs greatly in energy consumption. The model can be used as a framework for alternative and more complex models based on the experimental data collected from the NZERTF. [ABSTRACT FROM AUTHOR]

Purpose Patient-centered health care recognizes that adolescents and parents are stakeholders in adolescent health. We investigate adolescent and parent interest in receiving information about health topics and parent-teen communication from clinicians. Methods Ninety-one parent-adolescent dyads in one practice completed individual interviews. Items assessed levels of interest in receiving health and health communication information from the adolescent's doctor about 18 topics, including routine, mental health, sexual health, substance use, and injury prevention issues. Analyses tested differences between parents and adolescents, within-dyad correlations, and associations with adolescent gender and age. Results Most parents were female (84%). Adolescents were evenly divided by gender; 36 were aged 12–13 years, 35 were aged 14–15 years, and 20 were aged 16–17 years. Adolescent race reflected the practice population (60% black; 35% white). The vast majority of parents and adolescents reported moderate or high levels of interest in receiving information about all 18 health issues and information to increase parent-teen communication about these topics. Parents' interest in receiving information varied by adolescent age when the expected salience of topics varied by age (e.g., acne, driving safety), whereas adolescents reported similar interest regardless of age. Adolescent gender influenced parent and adolescent interest. Level of interest in receiving information from doctors within adolescent-parent pairs was not significantly correlated for one-half of topics. Conclusions Parents and adolescents want health care professionals to help them learn and talk about a wide range of adolescent health topics. Feasible primary care interventions that effectively improve parent-teen health communication, and specific adolescent health outcomes are needed. [ABSTRACT FROM AUTHOR]

Typical cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are morphologically dissimilar. It is well known, however, that poorly differentiated SCC may assume a basaloid phenotype, complicating the histologic distinction between these 2 neoplasms. Selected immunohistochemical stains have been used in the past to aid in that differential diagnosis. In the current study, additional markers were evaluated to determine whether they would be helpful in that regard. Twenty-nine cases of metatypical (squamoid) BCC (MBCC) and 25 examples of basaloid SCC (BSCC) were studied using the antibodies Ber-EP4 and MOC-31 as well as a plant lectin preparation from Ulex europaeus I ( UEA-1 ). The resulting immunostains were interpreted independently by 3 pathologists, and the results showed that MBCCs demonstrated strong and diffuse staining for Ber-EP4 (25/29) and MOC-31 (29/29). In contrast, BSCCs tended to be only sporadically reactive for both markers (4/25 and 1/25 cases, respectively). Labeling for UEA-1 was observed in almost all BSCCs (24/25), but only 6 of 29 cases of MBCC showed limited, focal staining with that lectin. These data suggest that MOC-31 is a useful marker in the specified differential diagnosis, especially when used together with UEA-1. [ABSTRACT FROM AUTHOR]

Summary The incidence and prevalence of chronic kidney disease (CKD) is increasing. Despite current therapies, many patients with CKD have suboptimal blood pressure, ongoing proteinuria, and develop progressive renal dysfunction. Further therapeutic options therefore are required. Over the past 20 years the endothelin (ET) system has become a prime target. Experimental models have shown that ET-1, acting primarily via the endothelin-A receptor, plays an important role in the development of proteinuria, glomerular injury, fibrosis, and inflammation. Subsequent animal and early clinical studies using ET-receptor antagonists have suggested that theses therapies may slow renal disease progression primarily through blood pressure and proteinuria reduction. This review examines the current literature regarding the ET system in nondiabetic CKD. [ABSTRACT FROM AUTHOR]

Abstract: Animals have been used as models to study inflammation and autoimmunity for more than 80 years. During that time it has been understood that although the use of such models is an important and necessary part of understanding human disease, they inevitably display significant differences from the human disease state. Since our understanding of human inflammation and autoimmunity is necessarily incomplete, it may be concluded that the animal models will also be reflective of the state of knowledge regarding such diseases. Nevertheless, animal models of rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis have been successfully used to enhance the understanding of the human disease and have made significant contributions to the development of powerful new therapies. However, there are exceptions. One of the most persistent has been the study of sepsis where the animal models have been woefully inadequate in uncovering targets for drug discovery and have led to repeated clinical failures. As will be explained, only by using newly developed genomics tools has it been possible to uncover the differences between sepsis in mice and sepsis in man. It is concluded that approaches using the newer genomic and proteomic data derived from human tissues, will make possible the development of animal models with more predictive power as aids to drug discovery. [Copyright &y& Elsevier]

Purpose: Human papillomavirus (HPV) is of etiologic significance in the development of oral squamous carcinoma and is noted to result in p16 overexpression. Identification of HPV is clinically important because the presence of HPV has prognostic and epidemiologic associations. Detection of HPV by polymerase chain reaction (PCR) is expensive and not widely accessible. The authors examined p16 immunohistochemistry (IHC) as a surrogate marker for high-risk HPV and its use as an alternative test to PCR. Patients and Methods: A retrospective cohort of patients with oral squamous cell carcinoma underwent surgery and then analysis with p16 IHC and HPV PCR. The p16 IHC staining intensity was graded from 0 to 3+, and these results were compared with PCR. Descriptive and frequency statistics were performed by comparing HPV PCR results with p16 IHC, patient age, gender, and outcome. Results: Eighty-one cases were included in the study. Forty-four study patients were men and 37 were women (mean age, 63.9 yr). Forty-five cases (55.6%) had 0 staining, 22 cases (27.2%) had 1+ staining, and 7 cases (8.6%) had 2+ staining. Seven cases (8.6%) had 3+ staining, all of which were positive for HPV serotype 16 by PCR. Three of 7 HPV PCR-positive cases had keratinization typical of an oral cavity location and not the basaloid growth of HPV oropharyngeal tumors. There was a statistical correlation (P < .001) among HPV PCR positivity, 3+ staining, and younger age. Conclusion: p16 3+ staining correlates with HPV PCR positivity. p16 IHC is a technically simple and widely available test, and this study establishes the use of p16 IHC as an alternative test to HPV PCR. Given the clinical significance of HPV in oral squamous carcinoma, p16 IHC should be performed in all cases and included in the pathology report. [Copyright &y& Elsevier]

Abstract: Monoclonal antibodies (mAbs) have been used for decades as tools to probe the biology and pharmacology of receptors in cells and tissues. They are also increasingly being developed for clinical purposes against a broad range of targets, albeit to a lesser extent for G-protein-coupled receptors (GPCRs) relative to other therapeutic targets. Recent pharmacological, structural and biophysical data have provided a great deal of new insight into the molecular details, complexity and regulation of GPCR function. Whereas GPCRs used to be viewed as having either “on” or “off” conformational states, it is now recognized that their structures may be finely tuned by ligands and other interacting proteins, leading to the selective activation of specific signaling pathways. This information coupled with new technologies for the selection of mAbs targeting GPCRs will be increasingly deployed for the development of highly selective mAbs that recognize conformational determinants leading to novel therapeutics. [Copyright &y& Elsevier]

Objectives: Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non–heart-beating donor lungs. Methods: Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia–reperfusion injury. Results: The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. Conclusions: Uncontrolled non–heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs. [Copyright &y& Elsevier]

Objective: Adenosine A2A receptor activation after lung transplantation attenuates ischemia–reperfusion injury by reducing inflammation. However, the effect of adenosine A2A receptor activation in donor lungs before transplant remains ill defined. This study compares the efficacy of 3 different treatment strategies for adenosine A2A receptor agonist in a clinically relevant porcine lung transplantation model. Methods: Mature porcine lungs underwent 6 hours of cold ischemia before allotransplantation and 4 hours of reperfusion. Five groups (n = 6/group) were evaluated on the basis of treatment with ATL-1223, a selective adenosine A2A receptor agonist: thoracotomy alone (sham), transplant alone (ischemia–reperfusion), donor pretreatment via ATL-1223 bolus (ATL-D), recipient treatment via ATL-1223 infusion (ATL-R), and a combination of both ATL-1223 treatments (ATL-D/R). Lung function and injury were compared. Results: Blood oxygenation was significantly higher among ATL-D, ATL-R, and ATL-D/R groups versus ischemia–reperfusion (392.0 ± 52.5, 428.9 ± 25.5, and 509.4 ± 25.1 vs 77.2 ± 17.0 mm Hg, respectively, P < .001). ATL-1223–treated groups had lower pulmonary artery pressures (ATL-D = 30.5 ± 1.8, ATL-R = 30.2 ± 3.3, and ATL-D/R = 29.3 ± 4.5 vs IR = 45.2 ± 2.1 mm Hg, P < .001) and lower mean airway pressures versus ischemia–reperfusion (ATL-D = 9.1 ± 0.8, ATL-R = 9.1 ± 2.6, and ATL-D/R = 9.6 ± 1.3 vs IR = 21.1 mm Hg, P < .001). Likewise, ATL-1223–treated groups had significantly lower lung wet/dry weight, proinflammatory cytokine expression, and lung injury scores by histology compared with ischemia–reperfusion. All parameters of lung function and injury in ATL-1223–treated groups were similar to sham (all P > .05). Conclusions: Pretreatment of donor lungs with ATL-1223 was as efficacious as other treatment strategies in protecting against ischemia–reperfusion injury. If necessary, supplemental treatment of recipients with ATL-1223 may provide additional protection. These results support the development of pharmacologic A2AR agonists for use in human clinical trials for lung transplantation. [Copyright &y& Elsevier]