bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon‐like peptide‐1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study
Authors: Ahern T. , Tobin A.‐M. , Corrigan M. , Hogan A. , Sweeney C. , Kirby B. , O’Shea D.
Published: June 2012

Background  Diabetes and obesity are more prevalent amongst psoriasis patients as is disturbance of the innate immune system. GLP‐1 analogue therapy considerably improves weight and glycaemic control in people with type 2 diabetes and its receptor is present on innate immune cells.

Objective  We aimed to determine the effect of liraglutide, a GLP‐1 analogue, on psoriasis severity.

Methods  Before and after 10 weeks of liraglutide therapy (1.2 mg subcutaneously daily) we determined the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) in seven people with both psoriasis and diabetes (median age 48 years, median body mass index 48.2 kg/m2). We also evaluated the immunomodulatory properties of liraglutide by measuring circulating lymphocyte subset numbers and monocyte cytokine production.

Results  Liraglutide therapy decreased the median PASI from 4.8 to 3.0 (P = 0.03) and the median DLQI from 6.0 to 2.0 (P = 0.03). Weight and glycaemic control improved significantly. Circulating invariant natural killer T (iNKT) cells increased from 0.13% of T lymphocytes to 0.40% (P = 0.03). Liraglutide therapy also effected a non‐significant 54% decrease in the proportion of circulating monocytes that produced tumour necrosis factor alpha (P = 0.07).

Conclusion  GLP‐1 analogue therapy improves psoriasis severity, increases circulating iNKT cell number and modulates monocyte cytokine secretion. These effects may result from improvements in weight and glycaemic control as well as from direct immune effects of GLP‐1 receptor activation. Prospective controlled trials of GLP‐1 therapies are warranted, across all weight groups, in psoriasis patients with and without type 2 diabetes.
Microbial diversity and dynamics of Pecorino di Filiano PDO, a traditional cheese of Basilicata region (Southern Italy)
Authors: BONOMO MARIA G , SALZANO GIOVANNI
Published: June 2012

The evolution of microbial populations of ‘Pecorino di Filiano’ (PF) cheese was investigated during ripening in natural cave and storeroom. 62.5% of isolates grow at 45 and 15 °C and 77.7% showed high salt concentrations tolerance. Brevibacterium linens was dominant in surface samples. Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus paracasei subsp. paracasei were more frequently isolated both surface and core samples, while Leuconostoc lactis and Leuconostoc mesenteroides subsp. mesenteroides prevailed among Leuconostoc isolates. Our results suggest the importance of the ripening environment of cheeses and how a biological ecosystem affects and produces the typical features of artisanal products.
New Zealand nurses perceptions of caring for patients with influenza A (H1N1)
Authors: Honey Michelle , Wang Wendy YQ
Published: June 2012

Aim: This study aimed to explore the perceptions of the highly specialized nurses who provided extracorporeal membrane oxygenation therapy for the mostly young and critically ill patients during the 2009 H1N1 pandemic.

Background: The 2009 influenza A (H1N1) virus caused a global pandemic and also affected New Zealand during that winter. Nine H1N1‐infected adult patients with severe acute respiratory distress syndrome were admitted into an intensive care unit of a large urban hospital for rescue extracorporeal membrane oxygenation therapy.

Design: The study used a two‐phase mix methods study design.

Methods: Phase 1 of the study involved five nurses attending a focus group interview to collect their views of the challenges and issues of caring for these patients. The results of the focus group were used to formulate the phase 2 survey. In total, 25 eligible nurses were invited to complete an anonymous survey; 18 completed and returned surveys giving a 72% response rate.

Results: The survey identified issues including the acuity and high mortality rate of those affected, nurses working in an isolated environment because of infection control requirements, limited support and being asked to work extra shifts.

Conclusion: Despite these challenges, the nurses felt positive about their experience of caring for the H1N1 patients, and felt the experience advanced their skills and improved job satisfaction.

Relevance to Clinical Practice: For future pandemics, this study identified the need for all staff to have a basic understanding of extracorporeal membrane oxygenation; strengthen inter‐professional collaboration and communication; provision for more support and recognition of these highly specialized nurses, along with providing regular pandemic updates and offering counselling services.
Optimal Security Investments and Extreme Risk
Authors: Mohtadi Hamid , Agiwal Swati
Published: June 2012

In the aftermath of 9/11, concern over security increased dramatically in both the public and the private sector. Yet, no clear algorithm exists to inform firms on the amount and the timing of security investments to mitigate the impact of catastrophic risks. The goal of this article is to devise an optimum investment strategy for firms to mitigate exposure to catastrophic risks, focusing on how much to invest and when to invest. The latter question addresses the issue of whether postponing a risk mitigating decision is an optimal strategy or not. Accordingly, we develop and estimate both a one‐period model and a multiperiod model within the framework of extreme value theory (EVT). We calibrate these models using probability measures for catastrophic terrorism risks associated with attacks on the food sector. We then compare our findings with the purchase of catastrophic risk insurance.
A Manager's Perspective on Virtual Customer Integration for New Product Development
Authors: Bartl Michael , Füller Johann , Mühlbacher Hans , Ernst Holger
Published: June 2012

Despite the high potential of virtual customer integration (VCI) methods for new product development (NPD) mentioned in the literature, practical use is still limited. This paper aims to provide a deeper understanding of managers’ perspectives on VCI and their intentions to use these methods for NPD. The theory of planned behavior (TPB) served as basis for developing a research model, which considers managers’ cognition, attitude, subjective norms, and perceived behavioral control as important factors affecting their intention to apply VCI. Because more recent literature has expressed doubts about the explanatory potential of the rather simple TPB model, a more complex alternative model was proposed for comparison. The alternative model included the market orientation of the company, the hierarchical position of the innovation manager as well as the manager's level of innovativeness as additional explanatory variables. An empirical online study was conducted in the field of consumer goods and services. Based on a sample of 216 German‐speaking innovation managers, the results show that the model derived from the TPB explains 68% of the variance in the managers’ intention to apply VCI compared with 69% of variance explained by the model containing additional explanatory variables. An extension of the model does not significantly improve its explanatory power. Managers show high interest in virtually integrating customers in NPD processes. Managers consider identification of future customer needs, a broader decision basis, increased efficiency in gathering and use of customer information, and increased customer retention as major advantages of VCI. Disadvantages considered by managers in making their overall judgment are the lack of secrecy and only incremental innovations. The perceived potential contribution of VCI to NPD, the assessment of its general acceptance within the company, and the perceived ability of innovation managers to successfully implement VCI mainly influence the adoption decision. Managers’ attitudes toward VCI have no significant influence on their intention to use VCI. The results suggest that strong promotion of VCI through senior management would enforce the positive effect of subjective norms on applying VCI. Measures such as including VCI on innovation managers’ personal scorecard, trainings offered, and cross‐functional meetings could help speed up VCI in NPD processes by increasing innovation managers’ perceived behavioral control toward VCI.
Narrative Transportation in Concept Tests for Really New Products: The Moderating Effect of Reader–Protagonist Similarity
Authors: van den Hende Ellis A. , Dahl Darren W. , Schoormans Jan P. L. , Snelders Dirk
Published: June 2012

The authors investigate the benefits of using a narrative (i.e., a storyline featuring a protagonist) to convey product information in the evaluation of really new product concepts by consumers. In the context of early product evaluation, the imagination of consumers can be guided by a narrative about a protagonist who uses the new product in a series of actions and events. In this way, a narrative can present information about the new product concept in a way that is evocative and relevant.

The authors build on narratives research and study the implications of different protagonist focal characters. Further, the role of a protagonist focal character in facilitating consumer evaluations is examined, and evaluation formats (narrative versus attribute/benefit listings) are compared. Utilizing three empirical studies, this research looks at the potential effects of protagonist (dis)similarity with the reader on transportation and new product evaluation both in narrative and bulleted list evaluation formats. Study 1 shows an interactive effect of reader–protagonist similarity and evaluation format on transportation and product evaluation. The results from this study show that reader–protagonist similarity is needed for a narrative to be effective.

Studies 2 and 3 provide further understanding of the effects of reader–protagonist (dis)similarity. Study 2 shows that the negative impact of a dissimilar protagonist can be mitigated by explicitly instructing the readers to imagine themselves as the protagonist, thus enabling them to fully experience the storyline. Study 3 decomposes the reader–protagonist dissimilarity and shows that not all protagonists dissimilar to the reader deliver a negative outcome. A dissimilar protagonist that is not from a dissociative out‐group for the reader effectuates a positive result. Finally, the underlying process for the observed effects is demonstrated: narrative transportation is shown to mediate the observed effects in all three studies.

With these studies, the authors advance narrative transportation and social identity theory. Furthermore, the research provides practical guidelines for how narratives should be constructed and utilized to obtain consumer evaluations of product concepts in the new product development process.
The Interplay of Customer and Product Innovation Dynamics: An Exploratory Study
Authors: Bohlmann Jonathan D. , Spanjol Jelena , Qualls William J. , Rosa José A.
Published: June 2012

The challenges of successfully developing radical or really new products have received considerable attention from a variety of marketing, strategic, and organizational perspectives. Previous research has stressed the importance of a market‐driven customer orientation, the resolution of market and technological uncertainty, and organizational processes such as cross‐functional teams and organizational learning. However, several fundamental issues have not been addressed. From a customer's perspective, a more innovative product tends to have uncertain benefits and requires customers to learn new behaviors. Customer preferences can, therefore, change as product experience and learning increase. From a firm's perspective, it is unclear how to be customer‐oriented under such dynamic preferences, and product strategies using evolving technologies will tend to interact with how customers learn about an innovation. This research focuses on identifying unresolved issues about these customer and product innovation dynamics. A conceptual framework and series of propositions are presented that relate both changing technology and customer learning to a firm's strategic decisions in developing and launching really new products. The framework is based on in‐depth interviews with high‐tech product managers across several sectors, focusing on the business‐to‐business context. The propositions resulting from the framework highlight the need to consider relevant customer dynamics as integral to a firm's product innovation process. Successful innovation strategies and future research challenges are discussed, and applications to better understanding customer needs and theories of disruptive innovation are examined. Several key insights for innovation success hinge on a broad, downstream orientation to customer needs and product innovation dynamics. To be effective innovators, firms must know their customers' customers and competitors as well as or better than their immediate customers do. Market research must extend downstream for a comprehensive understanding of customer needs dynamics. In the context of disruptive innovation, new dimensions of customer needs may become more valuable based on perceived downstream customer trends. Firms may also innovate on secondary needs because mainstream customers do not always give firms the design freedom to radically innovate on primary features. Understanding customer commitments and how they develop under evolving needs can help firms focus resources on innovative efforts more likely to be accepted by customers.
High Thermoelectric Performance of Nanostructured In2O3‐Based Ceramics
Authors: Lan Jinle , Lin Yuan‐Hua , Liu Yong , Xu Shaoliang , Nan Ce‐Wen
Published: June 2012

Nanostructured Zn and Ce co‐doped In2O3‐based ceramics were fabricated using co‐precipitation and Spark plasma sintering. It is shown that the nanograins in Zn and Ce co‐doped In2O3‐based ceramics can lead to 50% reduction in the thermal conductivity of the sample with a 50 nm grain size and meanwhile keep good electric conductivity. As a result, a reported high ZT value of 0.4 at 1050 K was achieved for n‐type oxide thermoelectrics. It is expected that the ZT value could reach 0.7 when the grain size is smaller than 20 nm. Our results indicate that nanosized grain is highly desired for reducing thermal conductivity and hence a higher ZT value in oxide thermoelectrics.
Comparative evaluation of the role of the adhesion molecule CD177 in neutrophil interactions with platelets and endothelium
Authors: Pliyev Boris K. , Menshikov Mikhail
Published: June 2012

Neutrophil‐specific glycoprotein CD177 is expressed on a subset of human neutrophils and has been shown to be a counter‐receptor for platelet endothelial cell adhesion molecule‐1 (PECAM‐1, CD31). Previous studies have demonstrated that the interaction of CD177 with endothelial PECAM‐1 supports neutrophil transendothelial migration resulting in preferential transmigration of the CD177‐expressing neutrophil subset. As PECAM‐1 is also abundantly expressed on platelets, we addressed a follow‐up suggestion that CD177/PECAM‐1 adhesive interaction may mediate platelet–neutrophil interactions and CD177‐positive neutrophils may have a competitive advantage over CD177‐negative neutrophils in binding platelets. Here, we report that CD177‐positive and CD177‐negative neutrophils do not differ significantly in their capacity to form platelet–neutrophil conjugates as assayed in whole blood and in mixed preparations of isolated platelets and neutrophils. Under flow conditions, neither platelet nor neutrophil activation resulted in preferential binding of platelets to CD177‐expressing neutrophils. Furthermore, no significant difference was found in the ability of both neutrophil subsets to adhere to and migrate across surface‐adherent activated platelets, whereas predominantly CD177‐positive neutrophils migrated across HUVEC monolayers. In addition, we demonstrated that S536N dimorphism of PECAM‐1, which affects CD177/PECAM‐1 interaction, did not influence the equal capacity of the two neutrophil subsets to interact with platelets but influenced significantly the transendothelial migration of CD177‐expressing neutrophils. Thus, CD177/PECAM‐1 adhesive interaction, while contributing to neutrophil‐endothelial cell interaction in neutrophil transendothelial migration, does not contribute to or is redundant in platelet–neutrophil interactions.
Assessing facial wrinkles: automatic detection and quantification
Authors: Cula G. O. , Bargo P. R. , Nkengne A. , Kollias N.
Published: June 2012

Background

As people mature, their skin gradually presents lines, wrinkles, and folds that become more pronounced with time. Skin wrinkles are perceived as important cues in communicating information about the age of the person. Nowadays, documenting the facial appearance through imaging is prevalent in skin research, therefore detection and quantitative assessment of the degree of facial wrinkling can be a useful tool for establishing an objective baseline and for assessing benefits to facial appearance due to various dermatological treatments. However, few image‐based algorithms for computationally assessing facial wrinkles are present in the literature, and those that exist have limited reliability.

Methods

In this work, an algorithm for automatic detection of facial wrinkles is developed, based on estimating the orientation and the frequency of elongated spatial features, captured via digital image filtering.

Results

The algorithm is tested against one set of clinically validated 11‐point wrinkle scales present on the face. The algorithm is employed for assessing the presence of forehead furrows on a set of 100 clinically graded facial images. The proposed computational assessment correlates well with the corresponding clinical scores.

Conclusion

We find that the results are in better agreement with clinical scoring when the wrinkle depth information, approximated via filter responses, is combined with the wrinkle length information as opposed to the case when the two measures are considered separately.
Human–carnivore conflict in China: a review of current approaches with recommendations for improved management
Authors: PETTIGREW Melissa , XIE Yan , KANG Aili , RAO Madhu , GOODRICH John , LIU Tong , BERGER Joshua
Published: June 2012

Human–wildlife conflict (HWC) is a conservation concern that increasingly threatens the continued existence of some of the world's most endangered species. With an increase in human population, urban sprawl and subsequent encroachment on wild land, human and wildlife interaction has become inevitable. In the majority of cases, this interaction results in a negative outcome for humans, wildlife or both. In China, these key elements, along with a decrease in wild prey species, have resulted in the expansion of HWC encounters, and the need for alleviating this conflict has become a conservation priority. Loss of human life, livestock and/or crops is most often the catalysts that fuel HWC. Techniques to alleviate conflict around the world have included preventative measures and mitigation techniques, such as financial compensation and other incentive programs. Both types of measures have had variable success. We review the current status of human–carnivore conflict management in China, and, drawing lessons from around the globe, we make recommendations for improving conservation management in China. For example, an increase in law enforcement in nature reserves is vital to reducing human disturbance in prime carnivore habitat, thereby reducing conflict encounters. Also, modifications to current wildlife compensation programs, so that they are linked with preventative measures, will ensure that moral hazards are avoided. Furthermore, investigating the potential for a community self‐financed insurance scheme to fund compensation and increasing efforts to restore wild prey populations will improve the outcome for wildlife conservation. Ultimately, HWC management in China will greatly benefit from an integrative approach.
Life management and quality of life issues for those with urinary incontinence
Authors: Nichols Thomas R. , Layton Matthew
Published: June 2012

The phrase urinary incontinence conjures up many images, none of which can be said to be positive. Incontinence is often a hidden condition, secreted by many and often feared as it can result in a loss of independence and quality of life. However, not all who suffer from incontinence seek treatment, and many who have, have found the results to be less than satisfying and have turned to other non‐clinical resources for support. This study presents insight into the life management and quality of life of those responding to an invitation to participate in a Continence Comprehensive Health and Life Assessment survey. Seventy‐three percent currently do not undergo treatment for bladder problems, and 28% state they have never sought treatment. The respondents report a variety of problems that affect everyday living, and ordinary activities. Although urinary incontinence may affect life activities, this should not be interpreted as a complete lack of bladder management. Of those surveyed, only 29% stated they cannot manage their bladder problems to maintain the activity level they would like.
Prevalence of urinary incontinence in older Korean women
Authors: So Aeyoung , De Gagné Jennie C , Palmer Mary H
Published: June 2012

Worldwide prevalence of any type urinary incontinence (UI) in women 20 years and over is estimated to be over 275 million in 2013 and the 4th International Consultation on Incontinence expects it to increase to over 300 million in 2018. While UI in women is considered to be an aging and public health issue with global implications, most research cited in the UI literature comes from English language sources. The absence of information from many Asian and other countries may be due to reliance on scientific reports written in English by editorial policies, authors of systematic literature reviews and other researchers. Moreover, the financial costs and time constraints associated with translation and dissemination of findings into English language journals could act as dissemination barriers. Therefore, the purpose of this study was to describe the current state of knowledge about prevalence and correlates of UI in Korean older women from non‐English language sources. Twelve research articles, two research monographs and one master's thesis, and data on UI abstracted from South Korea's 2008 National Health Insurance Cooperation Reports were reviewed in full. The prevalence of UI in women 60 years and older ranged from 11·2% to 76·3%. Personal, physical and psychological factors were found to be associated with UI including age, income and educational level, presence of comorbidities, body mass index, depression, anxiety and cognitive impairment. There was little difference between rural and urban dwelling older women in help‐seeking behavior: 93.8% rural and 90.5% urban dwelling older women sought no help for their incontinence. Inclusion of reports from non‐English sources is considered as an important contribution to better understanding of the worldwide epidemiology of UI in older women.
Mechanisms behind adhesive erythrocytes in sickle‐cell disease
Authors: Telen M. J.
Published: June 2012

Erythrocytes containing primarily hemoglobin S (SS RBCs) are abnormally adherent to a number of ligands, including normal constituents of the extracellular matrix as well as those present on the surfaces of other blood cells and endothelial cells. However, SS RBCs are not really very different from normal (AA) RBCs, except that they are younger. In general, they express the same range of adhesion receptors, and the levels of expression of these receptors, although increased in some cases, are not sufficient to explain the difference between the adhesivity of SS and AA RBCs. However, SS RBCs have activated adhesion receptors, and the signaling pathways responsible for this activation are also upregulated in SS RBCs. In addition, SS RBCs convey different extracellular signals, which are also likely to affect their adhesion to other blood cells and endothelial cells. Together, SS RBCs induce cell–cell interactions mediated by the B‐CAM/LU, ICAM4 (LW), CD44 (In), CD47, α4β1 integrin, and CD36 adhesion molecules on SS RBCs with target ligands on leukocytes and endothelial cells. Other, as yet unidentified cell surface moieties on SS RBCs are probably also responsible for SS RBC interactions with P‐selectin. Interestingly, at least some of these RBC adhesion receptors may also mediate adhesion and adverse physiologic events in the setting of transfusion of stored normal RBCs. Therefore, understanding the mechanisms behind SS RBC adhesion may offer opportunities for improving both therapy of sickle‐cell disease as well as transfusion practices.
A primer on evidence‐based plasma therapy
Authors: Yazer M. H.
Published: June 2012

Background and Objectives  Although traditionally fresh‐frozen plasma (FFP) has been the product of choice for reversing a significant coagulopathy, the modern blood bank will have several different plasma preparations for use in reversing a significant coagulopathy or arresting coagulopathic bleeding. These products include the aforementioned FFP which is frozen within 8 h of collection, plasma frozen within 24 h after phlebotomy (FP24), and thawed plasma (TP) prepared from either FFP or FP24. Based on their factor levels, these products should all be equally efficacious in reversing a significant coagulopathy although a head‐to‐head comparison between these products has not been performed. Evidence from two systematic literature reviews and numerous observational studies suggest that for a stable patient with a mild coagulopathy, transfusing plasma for an INR ≤ 1·5 does not confer a hemostatic benefit. This lack of benefit is due to the exponential relationship that exists between factor levels and a mildly elevated INR, that is, a large quantity of plasma would be required to produce a reduction in the INR when its pre‐transfusion value is <1·6. By contrast, the relationship becomes more linear when the INR is more significantly prolonged. Thus, even if a reduction in a mildly elevated INR could be achieved with plasma transfusion, the clinical significance of the decrease is dubious and the transfusion itself exposes the recipient to a variety of adverse events such as allergic reactions and transfusion‐related acute lung injury (TRALI). Furthermore, emerging evidence indicates that transfusion‐associated circulatory overload (TACO) following plasma transfusion is an important and under reported adverse event. This review will discuss the various plasma products that are available, describe why the commonly used markers of hemostasis (such as the PT/INR) are not effective markers of perioperative hemostasis, and present some of the current literature on the clinical uses of plasma. Strategies to reduce non‐evidence‐based plasma transfusion, ranging from automated interventions at the time plasma is ordered to more labour‐intensive manual attempts to dissuade providers from ordering plasma unnecessarily, will also be addressed.
Management of acutely bleeding patients who refuse blood transfusion
Authors: Brooks J. P.
Published: June 2012

Patients who refuse blood transfusions yet require them for continued health present difficulties to physicians. In the elective setting, physicians and patients can calmly discuss benefits, risks, alternatives and referral to special centers that have a niche practice in bloodless medicine. Care of the acutely bleeding patient who objects to transfusion presents a uniquely challenging situation. Patients may refuse based upon general health considerations or deeply held religious beliefs. In the exsanguinating patient, lengthy conversations are not options nor are referrals to specialized centers. Management of the acutely bleeding transfusion objector is presented and highlights the medical, moral, ethical and legal issues physicians will find themselves confronted with. Surgical and pharmacological interventions that may be of benefit will also be discussed.
Can we improve safety for young blood donors?
Authors: Eder A. F.
Published: June 2012

Young volunteers between the ages of 16–18 years contribute substantially to the blood supply in the United States, accounting for about 14% of the allogeneic whole blood collected by the American Red Cross in 2011. Donating blood, while quite safe, has some attendant risk, and reactions are most likely to occur in the youngest donors. Typically, reactions are minor, “vasovagal‐type” symptoms such as lightheadedness or dizziness that usually resolve promptly but are still unpleasant for the donor. Less commonly, syncope occurs after blood donation, and falls may result in injuries, such as concussions, lacerations or dental trauma. The risk of syncopal reactions is largely influenced by young age, estimated blood loss (>15% total blood volume), and inexperience with whole blood donation. This review describes the recent initiative to improve safety for young donors and the ongoing surveillance of reactions after whole blood donation in the American Red Cross.
Extracorporeal lessons from sheep
Authors: Fung Y. L. , Diab S. , Dunster K. , Foley S. R. , McDonald C. I. , Passmore M. , Platts D. , Simonova G. , Shekar K. , Stewart D. , Fraser J. F.
Published: June 2012

Background  Extracorporeal circulation (ECC), the diversion of blood flow through a circuit located outside of the body, has been one of the major advances in modern medicine. Cardio‐pulmonary bypass (CPB), renal dialysis, apheresis and extracorporeal membrane oxygenation (ECMO) are all different forms of ECC. Despite its major benefits, when blood comes into contact with foreign material, both the coagulation and inflammation cascades are activated simultaneously. Short periods of exposure to ECC e.g. CPB (∼2 h duration), are known to be associated with haemolysis, coagulopathies, bleeding and inflammation which demand blood product support. Therefore, it is not unexpected that these complications would be exaggerated with prolonged periods of ECC such as in ECMO (days to weeks duration). The variability and complexities of the underlying pathologies of patients requiring ECC makes it difficult to study the cause and effect of these complications. To overcome this problem we developed an ovine (sheep) model of ECC.

Method  Healthy female sheep (1–3 y.o.) weighing 40–50 kg were fasted overnight, anaesthetised, intubated and ventilated [1]. Half the group received smoke induced acute lung injury (S‐ALI group) (n = 8) and the other half did not (healthy group) (n = 8). Sheep were subsequently cannulated (Medtronic Inc, Minneapolis, MN, USA) and veno‐venous ECMO commenced using PLS ECMO circuit and Quadrox D oxygenator (Maquet Cardiopulmonary AG, Hechinger Straße, Germany). There was continuous physiological monitoring and blood was collected at specified time intervals for full blood counts, platelet function analysis (by Multiplate®), routine coagulation and assessment of clot formation and lysis (by ROTEM®).

Preliminary results  Full blood counts and routine coagulation results from normal healthy sheep were comparable to those of normal human adults. Within 15 min of initiating of ECMO, PT, PTT and EXTEM clot formation time increased, whilst EXTEM maximum clot firmness decreased in both cohorts.

Discussion & Conclusions  Preliminary results of sheep from both 2 h ECMO cohorts showed that the anatomy, haematology and coagulation parameters of an adult sheep are comparable to that a human adult. Experiments are currently underway with healthy (n = 8) and S‐ALI (n = 8) sheep on ECMO for 24 h. In addition to characterising how ECMO alters haematology and coagulation parameters, we hope that it will also define which blood components will be most effective to correct bleeding or clotting complications during ECMO support.
Modeling transfusion reactions with kodecytes and enabling ABO‐incompatible transfusion with function‐spacer‐lipid constructs
Authors: Henry S. M. , Barr K. L. , Oliver C. A.
Published: June 2012

Background  KODE technology uses Function‐Spacer‐Lipid (FSL) constructs for artificial attachment of blood group antigens onto live cells (kodecytes) and visualisation, thus making it potentially suitable to model both transfusion reactions and determine in vivo cell survival. Additionally, as some FSL constructs are glycolipid‐like, the possibility exists that they may also neutralise circulating antibodies, in the same way Lewis glycolipids were historically used to allow Lewis incompatible transfusions.

Aims  To determine if kodecytes can be used to both mimic and monitor transfusion reactions in an animal model, and also to determine if FSL construct infusions can neutralise circulating antibodies and allow for an incompatible transfusion.

Methods  Naïve, anti‐A positive (immunised), and anti‐A positive/FSL‐A neutralised mice were given transfusions of murine kodecytes created with FSL‐biotin and FSL‐A. Levels of surviving kodecytes were determined at multiple time‐points via their biotin label. Analysis for anti‐A was performed with inkjet printed FSL‐A constructs in a micro immunoassay.

Results  Normal kodecyte survival was observed in control animals. Mice with anti‐A predominantly cleared their incompatible A‐kodecyte transfusions within 6 min. Mice with anti‐A that had been neutralised with an FSL‐A infusion had normal survival of their incompatible A‐kodecyte transfusions. Re‐challenge transfusions of A‐kodecytes into mice previously given FSL‐A (once the FSL‐A had cleared from their circulation) gave two different results. One group cleared the incompatible A‐kodecytes within minutes while the other had normal survival, suggesting potential induction of tolerance.

Conclusions  Kodecytes can be used to model blood group A incompatible transfusions in animals. FSL‐A can neutralise anti‐A and allow for incompatible A‐kodecyte transfusion. The potential exists to extend these research observations into clinical use to allow for transfusion and transplantation across the ABO barrier, or at least mitigate the consequences of accidental ABO incompatibilities.
Pregnancy immunology and maternal alloimmune responses
Authors: Kumpel B. M.
Published: June 2012

Pregnancy is an “immunological Paradox”. This is because pregnant women are tolerant of their semi‐allogeneic fetus but are not immunosuppressed and indeed make strong antibody responses. The immunological changes required are driven mainly by the placenta, an organ derived from cells of the blastocyst surrounding the embryo. Trophoblast cells on the surface of the placenta form the interface between the fetus and maternal tissues and blood. They differentiate into (a) villous syncytiotrophoblast (ST) that are in contact with maternal blood and transfer gases and nutrients between maternal and fetal blood and (b) extravillous trophoblast cells that invade into the maternal decidua lining the uterus. Trophoblast cells escape allorecognition because they lack classical HLA class I and II molecules. Local immunoregulation, or tolerance, in the decidua is mediated mainly by HLA‐G+ extravillous trophoblasts that prevent killing of fetal and placental cells by maternal natural killer cells, cytotoxic T cells and macrophages, thus ensuring the fetus is not rejected. Placental hormones orchestrate the composition and regulatory function of maternal immune cells in the decidua. ST at the surface of chorionic villi, together with ST debris that is shed into maternal blood, maintain a state of mild maternal systemic inflammation by enhancing innate immunity and skewing the immune response towards humoral (antibody) immunity. This enables a healthy immune system to be maintained in pregnant women, with robust protective antibody responses to pathogens whilst enabling survival of the fetus. However, this immunological skewing ensures that pregnant women readily form alloantibodies to incompatible fetal alloantigens. If fetomaternal haemorrhage (FMH) occurs, they can make antibodies to fetal red cells, platelets and leucocytes that are in her blood. The alloantibodies are initially of low affinity but after re‐immunisation of the woman with further FMH (most commonly at delivery), they become functionally effective, high titre IgG. Maternal IgG is transferred by the ST to the fetus, to give the baby protective immunity to survive infancy. This has the unfortunate consequence that alloantibodies to blood cells are also transported, leading to haemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). Both HDFN and FNAIT may result in death or serious neurological damage to the baby. HDFN due to anti‐D can be prevented by administration of prophylactic anti‐D to the mother, destroying or clearing D‐positive fetal red cells in FMH from her circulation before they can become immunogenic.
The case for universal access to tranexamic acid
Authors: Roberts I. , Ker K. , Jairath V. , Shakur H.
Published: June 2012

Tranexamic acid safely reduces mortality in bleeding trauma patients and reduces exposure to allogenic blood transfusion in surgical patients. Considering the growing burden of trauma and the risk of transfusion transmitted viral infections in many parts of the world, a strong case can be made for ensuring universal access to this inexpensive treatment. Indeed, efforts to ensure universal access to safe blood without taking steps to reduce the need for blood transfusion seem inappropriate.
Gastrointestinal bleeding
Authors: Jairath V. , Stanworth S. J.
Published: June 2012

Gastrointestinal bleeding is the commonest medical emergency with major bleeding and a leading indication for transfusion of blood components. It can be considered to arise from an upper gastrointestinal source (non‐variceal or variceal)or a lower gastrointestinal source, although the principles of management are broadly similar. In this article we focus specifically upon the use of red blood cells, highlighting areas of uncertainty in practice where there is a need for a randomised trial, prevalence and management of coagulopathy and discuss the potential that anti‐fibrinolytic agents may have as adjunctive therapy to existing treatments.
Hemovigilance in Honduras
Authors: Vinelli E.
Published: June 2012

Abstract:  The Honduras Red Cross Blood Program has worked actively to implement a hemovigilance process which gathers information regarding the donors and the donation process as well as serious untoward effects in transfusion recipients. This review will go over the different epidemiological and statistical indicators that are used routinely to follow trends in donor complications and to anticipate any risks to the blood supply (both in terms of new/reemerging infectious diseases or factors that might affect donor availability).
EndoS, a “drug from a bug” as a novel treatment for autoimmunity of the blood
Authors: Collin M.
Published: June 2012

Pathogens have through co‐evolution become the true experts of our immune system and have during this process developed a multitude of strategies to manipulate the immune response. This is fundamental for the pathogens to persist and cause disease, but we can also exploit this nature’s own high throughput screening system as a source for novel biologicals to treat disease. We have identified several immunomodulating molecules from pathogens (PADIMMs) and here we present one example, the immunoglobulin glycan hydrolyzing enzyme EndoS from the human pathogen Streptococcus pyogenes. EndoS hydrolysis of IgG completely alters the effector functions of IgG, with reduced complement activation and altered binding to Fc‐receptors on white blood cells. When taken out of its infectious context, EndoS can be administered as an experimental drug in animal models of antibody‐mediated autoimmunity. We have been able to show that EndoS has a dramatic positive effects in several animal models of autoimmunity, including rheumatoid arthritis, systemic lupus erythematosus (SLE), and of particular interest for this forum, autoimmune hemolytic anemia (AIHA), and immune thrombocytopenic purpura (ITP). The hope is, by telling this story, to stimulate other researchers to join the “Drugs from Bugs” movement in the hunt for the immunomodulating biologicals of tomorrow.
A new approach to identify human red blood cell receptors for Plasmodium parasites
Authors: Wright G. J. , Rayner J. C.
Published: June 2012

Malaria is one of the most significant public health burdens facing the developing world. While there are several Plasmodium species that can cause malaria in humans, the overwhelming majority of malaria mortality is caused by Plasmodium falciparum parasites. The P. falciparum life cycle is complex, but red blood cell invasion is essential for Plasmodium falciparum survival and pathogenesis, and is therefore a topic of particular interest for the development of novel control and intervention strategies. Invasion involves multiple interactions between parasite ligands and their receptors on human red blood cells, and most of these interactions are thought to have overlapping and redundant roles. However, although multiple P. falciparum invasion ligands are known, in very few cases have their red blood cell receptors been identified. This is in part due to the genetic inaccessibility of the erythrocyte, but also in part because cell surface protein‐protein interactions are often of very low affinity, making them hard to identify using standard biochemical approaches. To overcome this, we have used AVEXIS, a systematic protein interaction screening approach designed to detect low affinity extracellular interactions to identify novel red blood cell‐parasite interactions. As a first test of this approach, we produced a library of more than 40 recombinant red blood cell surface protein ectodomains, and screened them against the P. falciparum invasion ligand PfRH5. AVEXIS identified basigin/CD147 as the receptor for PfRH5. Basigin (the Oka blood group antigen) has not previously been implicated as playing a role during P. falciparum invasion. Critically, we showed that basigin was essential for parasite entry in every P. falciparum strain tested to date, as invasion in vitro is potently blocked in all parasite strains tested by soluble basigin receptor ectodomains and by receptor‐specific monoclonal antibodies. The PfRH5‐basigin interaction therefore appears to be an essential and universal entry route for P. falciparum parasites, and is therefore a high priority target for vaccine development. While this work focuses on pathogen‐red blood cell interactions, the AVEXIS approach could equally be applied to identify novel extracellular interactions between other cell types within the human blood system.
Blood supply system in Mexico
Authors: Rojo‐Medina J.
Published: June 2012

Mexico with a population of 112 million in 32 federal states, has made  great progresses in the lasts years in regulation, access and security of blood and components; actually the challenge is to reverse the reposition to voluntary blood donation system. The blood system counts with 555 blood banks and 4,342 transfusion services. 25% of the blood banks belong to the Ministry of Health, 15% to the Mexican Social Security Institute (IMSS) and 10% to the Institute of Security and Social Services for State Workers (ISSSTE), the blood banks of the Ministry of Defense, Navy and “Petroleos Mexicanos” constitute only 3% and more than 40% are private. Only 31 of them collect more than 10,000 units/year, 64 have an annually average collection between 10,000 and 5,000 and 101 collect over 2,000 and less than 5,000; 70% of the blood banks participated in the external quality control program. In 2011 the total country collection was 1,698,124 blood units, with an average increase of 50,000/year. PAHO’s rate of blood donors for every 10,000 inhabitants in Mexico is 148, indicating self‐sufficiency, but only 2·38% is obtained from voluntary blood donors. The IMSS collects more than 40% of the blood in country; but 99·7% is obtained by replacement donors. The frequency of transfusion transmission infectious diseases in blood donors was for HIV 0·31%, HBV 0·20%, HCV 0·60%, syphilis 0·47%, Chagas’s disease 0·46% and brucellosis 0·39%. The analyzed results highlight the need to promote voluntary blood donation, regionalization of blood services and to increase the participation in external quality programs in order to reduce the risks associated to blood transfusions in Mexico. The Ministry of Health promotes voluntary blood donations through external collects in universities, enterprises and embassies obtaining good responds. The “National Policy of Use of Blood and Blood Components” from 1993, was reviewed and updated including a mandatory establishment of a quality system based in GMP′s, participation in external quality programs, voluntary blood donation promotion, evaluation of the performance services information and hemovigilance reports.
Trends in Hypertension Prevalence, Awareness, Treatment, and Control Rates in Shandong Province of China
Authors: Zhao Yong , Lu Fanghong , Sun Hui , Liu Zhendong , Zhao Yingxin , Sun Shangwen , Wang Shujian , Diao Yutao , Zhang Hua
Published: June 2012

J Clin Hypertens (Greenwich). 2012; 14:637–643. © 2012 Wiley Periodicals, Inc.

The authors retrospectively examined data from 3 surveys on hypertension according to the 2010 Chinese Guidelines for the Management of Hypertension. These surveys were conducted in 1991, 1999, and 2007, and included 85,371 individuals 18 years and older who were living in Shandong Province, China. Age‐standardized prevalent hypertension increased from 15.6% in 1991 to 17.3% in 1999 and 32.7% in 2007 (both P<.0001). The ascending prevalence can be partially explained by increasing body weight. Among individuals with hypertension, awareness increased significantly from 27.8% in 1991 to 39.1% in 1999 and 49.2% in 2007. The proportion of pharmacologic treatment also considerably improved, with the estimate of 12.9%, 28.1%, and 43.3% in the 3 surveys, respectively. Hypertension control increased from 3.0% to 4.4% to 7.1% in the past 20 years. The upward trend in blood pressure control was mostly attributable to a rise among men and persons at middle age. This study suggests that the prevalence of hypertension increased in the Shandong population from 1991 to 2007. Although substantially improved, control rates were still unacceptably low. Comprehensive strategies are urgently required to put into practice for the management of hypertension in Shandong Province, China.
Hypertension and the Risk of Incident Gout in a Population‐Based Study: The Atherosclerosis Risk in Communities Cohort
Authors: McAdams‐DeMarco Mara A. , Maynard Janet W. , Baer Alan N. , Coresh Josef
Published: June 2012

J Clin Hypertens (Greenwich). 2012; 14:675–679. ©2012 Wiley Periodicals, Inc.

The authors quantified the impact of hypertension on gout incidence in middle‐aged white and African American men and women. The Atherosclerosis Risk in Communities Study (ARIC) was a prospective population‐based cohort that recruited patients between 1987 and 1989 from 4 US communities. Using a time‐dependent Cox proportional hazards model, the authors estimated the adjusted hazard ratio (HR) of incident gout by time‐varying hypertension and tested for mediation by serum urate level. There were 10,872 participants among whom 45% had hypertension during follow‐up; 43% were men and 21% were African American. Over 9 years, 274 (2.5%) participants developed gout (1.8% of women and 3.5% of men). The unadjusted HR of incident gout was approximately 3 times (HR, 2.87; 95% confidence interval [CI], 2.24–3.78) greater for those with hypertension. Adjusting for confounders resulted in an attenuated but still significant association between hypertension and gout (HR, 2.00; 95% CI, 1.54–2.61). Adjustment for serum urate level further attenuated but did not abrogate the association (HR, 1.36, 95% CI, 1.04–1.79). There was no evidence of effect modification by sex (P=.35), race (P=.99), or obesity at baseline (P=.82). Hypertension was independently associated with increased gout risk in middle‐aged African American and white adults. Serum urate level may be a partial intermediate on the pathway between hypertension and gout.