bluuebunny/crossref_metadata_2025 huggingface dataset:
Nursing staff connect libraries with improving patient care but not with achieving organisational objectives: a grounded theory approach
Authors: Chamberlain David , Brook Richard
Published: April 2014

Background

Health organisations are often driven by specific targets defined by mission statements, aims and objectives to improve patient care. Health libraries need to demonstrate that they contribute to organisational objectives, but it is not clear how nurses view that contribution.

Objectives

To investigate ward nursing staff motivations, their awareness of ward and organisational objectives; and their attitudes towards the contribution of health library services to improving patient care.

Method

Qualitative research using focus group data was combined with content analysis of literature evidence and library statistics (quantitative data). Data were analysed using thematic coding, divided into five group themes: understanding of Trust, Ward and Personal objectives, use of Library, use of other information sources, quality and Issues. Four basic social‐psychological processes were then developed.

Results

Behaviour indicates low awareness of organisational objectives despite patient‐centric motivation. High awareness of library services is shown with some connection made by ward staff between improved knowledge and improved patient care.

Conclusion

There was a two‐tiered understanding of ward objectives and library services, based on level of seniority. However, evidence‐based culture needs to be intrinsic in the organisation before all staff benefit. Libraries can actively engage in this at ward and board level and improve patient care by supporting organisational objectives.
A checklist to assess database‐hosting platforms for designing and running searches for systematic reviews
Authors: Bethel Alison , Rogers Morwenna
Published: April 2014

Background

Systematic reviews require literature searches that are precise, sensitive and often complex. Database‐hosting platforms need to facilitate this type of searching in order to minimise errors and the risk of bias in the results.

Objectives

The main objective of the study was to create a generic checklist of criteria to assess the ability of host platforms to cope with complex searching, for example, for systematic reviews, and to test the checklist against three host platforms (EBSCOhost, OvidSP and ProQuest).

Method

The checklist was developed as usual review work was carried out and through discussion between the two authors. Attributes on the checklist were designated as ‘desirable’ or ‘essential’. The authors tested the checklist independently against three host platforms and graded their performance from 1 (insufficient) to 3 (performs well).

Results

Fifty‐five desirable or essential attributes were identified for the checklist. None of the platforms performed well for all of the attributes on the checklist.

Conclusions

Not all database‐hosting platforms are designed for complex searching. Librarians and other decision‐makers who work in health research settings need to be aware of the different limitations of host platforms for complex searching when they are making purchasing decisions or training others.
Outreach services in healthcare libraries: perceptions and impacts
Authors: Dorset Rebecca
Published: April 2014

Outreach services are becoming more prevalent throughout the health library sector both in the UK and abroad, and they have the potential to impact on information support for evidence‐based medicine. This article reports on a study which explored the perceptions of UK health library staff about the term ‘outreach’ and demonstrated that a variety of services are being offered under this umbrella term. Whilst practitioners are also divided over the impact of outreach services, many of them see this as key to future service developments. The study was completed by Rebecca Dorsett as part of her MSc in Information and Library Management at Northumbria University. She was supervised by Sue Childs and graduated in 2012 with a Distinction. Rebecca is now due to commence a new role as Information Support Officer for the Ministry of Defence.

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Research trends in teens’ health information behaviour: a review of the literature
Authors: Kim Sung Un , Syn Sue Yeon
Published: April 2014

Objective

This study aims to examine trends in studies of teens’ health information behaviour.

Methods

Eighty‐two articles published between 2000 and 2012 were selected and analysed in various aspects: health topics by year, information sources, data collection methods, use of theories and models, collaborative and interdisciplinary efforts and published journals.

Results

Fifty‐seven per cent of the studies focused on specific health topics, such as sexual health, while the rest covered general health topics. Almost half of the studies examined how teens search for and use health information on the Internet. Surveys were the most popular data collection technique. Only 12.2% were based on a theory or model. About 42% were conducted collaboratively by authors from multiple disciplines.

Discussion and Conclusions

With the increasing attention to specific health topics and online resources, the health information behaviour of teens has been examined more frequently since the mid‐2000s. Its interdisciplinary nature was evidently shown from various disciplines that the authors were affiliated with and the journals of the published studies represented. This study suggests that there should be efforts to reflect new technology tools, apply mixed methods and increase the engagement level of collaboration to evolve this research domain.
Influence of pH, concentration of sodium lactate as an additive and ultrasonic treatment on synthesis of zinc phosphate white pigments
Authors: Onoda H. , Haruki M. , Toyama T.
Published: April 2014

Zinc oxide that has the photocatalytic activity is used as a white pigment for cosmetics. A certain degree of sebum on the skin is decomposed by the ultraviolet radiation in sunlight. In this work, zinc phosphates were prepared from zinc nitrate and phosphoric acid at pH 5 and 7 with and without the addition of sodium lactate and ultrasonic treatment as a novel white pigment for use in cosmetics. The chemical composition, powder properties, photocatalytic activity, colour phase, moisture retention and smoothness of the zinc phosphates were studied. The obtained materials had a Zn/P ratio of about 1.5, which corresponds to zinc orthophosphate Zn3(PO4)2. Samples prepared with ultrasonic treatment indicated the high ratios of large particles in scanning electron microscopy images and particle‐size distributions. The photocatalytic activity of these zinc phosphate particles was too less to protect the sebum on the skin. The materials obtained and their thermal products at 100°C showed a high reflectance within the range of visible light. The slipping resistance and roughness of the powder were enough low for use in cosmetics.
Evaluation of the content – containing interaction in cosmetic products using gas chromatography–mass spectrometry
Authors: Thomas C. , Siong D. , Pirnay S.
Published: April 2014

Synopsis

Objective

Since the publication of the Regulation (EC) No 1223/2009 on cosmetic products, the content‐containing interaction between the packaging and the product must be considered for the safety assessment of the product. Indeed, some compounds are able to migrate from packaging to the product and may be harmful to the consumer health. The developed and validated method of investigation was applied on 79 cosmetic products.

Methods

Packaging materials and products at risk were determined by studying data of cosmetic product information files assessed by EXPERTOX. To evaluate the content‐containing interaction, a gas chromatography–mass spectrometry method was developed and validated. Liquid–liquid extraction was used to extract contaminants (some of phthalates, volatile organic compounds and substance of very high concern) from migration simulants and products.

Results

Analysis of product information files showed that HDPE and PE are the most widely used plastics for cosmetic product packaging. Calibration curves showed good linearity regression from 50 to 500 ng mL−1, and detection and quantification limits were 25 and 50 ng mL−1, respectively. The accuracy, precision, repeatability of the analytical method and extraction yields were acceptable. The frequency at which the DEHP was found in products is 90% for 11 stick deodorants and 83% for 12 perfumes.

Conclusion

Plastic is the most material used in cosmetic due to the diversity of form and colour. The gas chromatography–mass spectrometry method was validated and can be used for the evaluation of the content‐containing interaction of cosmetic products. For all tests performed on 79 products in contact with six kind of packaging, the DEHP was found at 90% for stick deodorants and 83% for perfumes. No other contaminant was found.
Aqueous dispersions of organogel nanoparticles – potential systems for cosmetic and dermo‐cosmetic applications
Authors: Kirilov P. , Rum S. , Gilbert E. , Roussel L. , Salmon D. , Abdayem R. , Serre C. , Villa C. , Haftek M. , Falson F. , Pirot F.
Published: April 2014

Synopsis

Objective

The preparation and physicochemical characterization of organogel nanoparticles dispersed in water have been developed. These systems could be employed as nanocarrier for cosmetic applications or as hydrophobic reservoirs for drug delivery.

Methods

Gelled particles of organic liquid and 12‐hydroxystearic acid (organogelator) were obtained by hot emulsification (T>Tgel), with a surfactant (acetylated glycol stearate) and polymers (sodium hyaluronate and polyvinyl alcohol) as stabilizing agents, and cooling at room temperature (T<Tgel). An organic UVB sunscreen molecule, obtained by microwave activation, was used as a hydrophobic model molecule. The physicochemical properties of the starting organogel (gelation tests; rheological study) and the dispersed gelled particles (rheological study; particle mean size, size distribution, zeta‐potential measurements; physical stability evaluation; UVB absorption and water resistance ability) were studied. The synthesis of sunscreen compound using microwave activation was also described.

Results

According to the gelation test results, organogels were obtained with various organic liquids. Vaseline and almond oils were selected as organic medium for the gelled nanoparticle preparation. A preliminary formulation study was carried out in order to determine the optimal experimental conditions to obtain stable nanoparticle dispersions. Gelled nanoparticles contained the sunscreen model molecule, with mean size of 450 nm, polydispersity index of 0.18 and zeta‐potential value above −30 mV, were obtained by ultrasound probe homogenization method. A comparative study of their dispersion ageing showed a greatly enhanced stability after gelation. According to the UVB absorption evaluation, gelled particles improved the photoprotective ability and the photostability of immobilized UVB blocker. They showed a high water resistance (~83%) even after 40 min of immersion.

Conclusion

The obtained results demonstrate the interest of these gelled nanoparticles and their aqueous dispersion for the preparation of new formulations for cosmetic and dermo‐cosmetic applications.
Understanding the dandruff scalp before and after treatment: an in vivo Raman spectroscopic study
Authors: Bonnist E. Y. M. , Pudney P. D. A. , Weddell L. A. , Campbell J. , Baines F. L. , Paterson S. E. , Matheson J. R.
Published: April 2014

Synopsis

Objectives

To study and characterize the stratum corneum (SC) of dandruff scalp using in vivo Raman spectroscopy, to study how it compares with the non‐dandruff scalp and to see the effect of treatment with a zinc pyrithione (ZnPTO)‐based anti‐dandruff shampoo.

Methods

The scalp skin was measured using a recently developed in vivo Raman probe. This method allows the inherent molecular components of the SC to be measured in vivo and confocally with depth, in particular the levels of natural moisturizing factors (NMF), lipids, lactic acid, urea and water.

Results

Depth‐profile data for the skin components in dandruff SC in vivo are shown for the first time. The dandruff SC has lower NMF than the non‐dandruff SC (0.16 compared with 0.39 a.u.), lower hydration, elevated levels of urea and lower levels of lactic acid. Treatment with an anti‐dandruff shampoo containing 1% ZnPTO substantially restores the levels of each of these components close to the non‐dandruff levels. Further to this, it is shown that sebum penetrates deeper into dandruff SC and at higher levels compared with non‐dandruff SC. The levels of sebum localized within the SC are also brought closer to those of the non‐dandruff condition after ZnPTO treatment.

Conclusion

The in vivo Raman probe has allowed the direct measurement of dandruff‐affected skin in situ for the first time. It has been shown that the dandruff SC is different from that of the non‐dandruff scalp and that it is changed by treatment with shampoo containing ZnPTO and brought towards the characteristics of non‐dandruff scalp. It offers novel insights into how the nature of a healthy scalp should be defined.
Short‐term clinical of peel‐off facial mask moisturizers
Authors: Velasco M. V. R. , Vieira R. P. , Fernandes A. R. , Dario M. F. , Pinto C. A. S. O. , Pedriali C. A. , Kaneko T. M. , Baby A. R.
Published: April 2014

Synopsis

Objective

This study aimed to compare the efficacy of a peel‐off facial mask based on polyvinyl alcohol (PVA) with an oil‐in‐water (o/w) emulsion and the effect of a soybean extract fermented by Bifidobacterium animale incorporated in those formulations (5% w/w).

Methods

The formulations were submitted to randomized clinical studies in volunteers to evaluate the measurement effects as (a) tensor by Cutometer®, (b) moisturizing by Corneometer® and transepidermal water loss (TEWL) by Tewameter®. These effects were determined in a short‐term study (3 h) in a controlled‐temperature room.

Results

The tensor effect and TEWL values indicated no significant difference between the use of facial mask and emulsion. On the other hand, the moisturizing effect of the facial mask on the stratum corneum was more significant than that of the emulsion according to Corneometer® measurements. Biometric cutaneous evaluation of peel‐off facial masks (short‐term study) showed that the masks promoted moisturizing effect of the stratum corneum more effectively than the oil‐in‐water emulsions. Thus, the facial masks were more efficient than emulsions in relation to moisturizing effects, but this efficiency is not related to the presence of fermented soybean extract.

Conclusion

The results indicated that peel‐off facial masks increase skin hydration in a process related to the occlusive effect.
Yashada bhasma (Zinc calx) and Tankana (Borax) inhibit Propionibacterium acne and suppresses acne induced inflammation in vitro
Authors: Sandeep Varma R. , Shamsia S. , Thiyagarajan O. S. , Vidyashankar S. , Patki P. S.
Published: April 2014

Objective

Yashada bhasma (YB) and Tankana (TA) are well characterized minerals used in traditional medicine for the treatment of various skin ailments. Yashada bhasma and TA are a unique preparation of zinc and borax, respectively. The study was conducted to evaluate the in vitro inhibitory effect of YB, TA and its combination (YBTA) on Propionibacterium acne growth and P. acne‐induced inflammation.

Methods

The minerals were tested for anti‐P. acne activity by disc diffusion and broth microdilution methods. The effect of these minerals on P. acne induced TNF‐α and IL‐8 production and gene expression were studied in THP‐1 cells. In vitro toxicity was tested on human keratinocytes (HaCaT) and mouse embryonic fibroblasts (NIH3T3) using MTT assay.

Results

The minimum inhibitory concentrations (MIC values) for YB, TA and YBTA against P. acne were 0.1 ± 0.2, 1.9 ± 0.5 and 0.3 ± 0.5 mg mL−1, respectively. YB, TA and YBTA inhibited TNFα by 57.57%, 59.09% and 68.93% and IL‐8 production by 48.76%, 47.92% and 51.13% in P. acne‐stimulated THP‐1 cells, respectively. The CTC50 values on HaCaT and NIH3T3 was 17.44 ± 0.5 and 16.37 ± 0.2 μg mL−1 for YB, 1023.03 ± 4.0 and 1286.17 ± 4.4 μg mL−1 for TA and 89.12 ± 2.3 and 111.58 ± 3.5 μg mL−1 for YBTA, respectively.

Conclusion

The present study revealed the inhibitory effect of YB, TA and YBTA on P. acne growth and inflammation. Clinical studies have suggested the anti‐acne benefits of formulations containing YB and TA. The findings obtained from the present in vitro studies provide evidence to support the mechanism of anti‐acne properties of YB and TA.
Frequency and significance of IgG4 immunohistochemical staining in liver explants from patients with primary sclerosing cholangitis
Authors: Fischer Sandra , Trivedi Palak J. , Ward Stephen , Greig Paul D. , Therapondos George , Hirschfield Gideon M.
Published: April 2014

Dense tissue infiltrates of IgG4+ plasma cells >50/high‐powered field (HPF) are purportedly highly specific for IgG4‐related disease. However, the frequency and significance of liver‐infiltrating IgG4+ plasma cells in primary sclerosing cholangitis (PSC) applying these cut‐offs has not been determined. We sought to determine the incidence of intrahepatic IgG4‐positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4+ staining was found to be mild (10–29 IgG4+ cells/HPF) in 23.0%, moderate (30–50/HPF) in 9.0% and marked (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4+ staining (P < 0.001). No patient had marked peripheral IgG4+ staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4+ staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post‐transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4+ staining, whereas mild staining was seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4+ lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4+, this does not seemingly associate with clinical disease course.
Acquired hemophilia: a case report and review of the literature
Authors: Mulliez S. M. N. , Vantilborgh A. , Devreese K. M. J.
Published: April 2014

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). FVIII autoantibody is characterized as polyclonal immunoglobulin G directed against the FVIII procoagulant activity. This disease occurs most commonly in the elderly population and with preponderance of men in nonpregnancy‐related AHA. There are well‐established clinical associations with AHA such as malignancy, other autoimmune diseases and pregnancy. However, up to 50% of reported cases remain idiopathic. The clinical manifestation of AHA includes mostly spontaneous hemorrhages into skin, muscles and soft tissues, or mucous membranes. AHA should be suspected when a patient with no previous history of bleeding presents with bleeding and an unexplained prolonged activated partial thromboplastin time. The diagnosis is confirmed in the laboratory by the subsequent identification of reduced FVIII levels and FVIII inhibitor titration. There is a high mortality, making prompt diagnosis and treatment vitally important. The principles of treatment consist in controlling the bleeding and eradicating the inhibitor. Because of the overall high relapse rate (15–33%), it is also recommended to follow up these patients. The review summarizes what is currently known about the epidemiology, pathogenesis, clinical features, diagnosis, treatment and prognosis of AHA and starts with a case report.
How should we test for nonsevere heritable platelet function disorders?
Authors: Norman J. E. , Westbury S. K. , Jones M. L. , Mumford A. D.
Published: April 2014

Heritable platelet function disorders (HPFD) are a heterogeneous group of bleeding disorders with diverse clinical and laboratory characteristics. In contrast to the severe phenotype disorders, Glanzmann thrombasthenia and Bernard–Soulier syndrome, most nonsevere HPFD are incompletely characterized. This is a consequence of the poor standardization of diagnostic tests and of the lack of consensus about diagnostic criteria for the different subgroups of nonsevere HPFD. Distinguishing patients who have a nonsevere HPFD from those who do not is an essential first step in diagnosis which may be aided by bleeding assessment tools and screening tests such as the Platelet Function Analyser‐100. However, high diagnostic accuracy can only be achieved with both light transmission aggregation (LTA) and secretion tests, for which streamlined agonist panels may be of similar utility to extended panels. Standardization of the methodology of these tests and quality assurance are essential for robust diagnosis. Identification of which platelet pathway is defective in patients with nonsevere HPFD is also usually possible with LTA and secretion tests. This strategy also sometimes enables exact diagnosis by implicating a single candidate protein and gene. Next‐generation sequencing may offer a rapid approach to diagnosis of nonsevere HPFD, although rigorous strategies must be adopted to distinguish causative gene defects from bystander variations.
Leukocytosis
Authors: Chabot‐Richards D. S. , George T. I.
Published: April 2014

An increased white blood cell count, or leukocytosis, is a common laboratory finding. Appropriate specimen evaluation depends on which lineages are increased and the morphologic findings on peripheral blood smear review to guide further testing. The presence of blasts is concerning for acute leukemia and may require bone marrow biopsy. Lymphocytosis may be morphologically divided into polymorphic and monomorphic populations. Polymorphic lymphocytosis is most consistent with a reactive process, while monomorphic populations are concerning for lymphoproliferative neoplasm. The differential can be further narrowed based on morphologic findings. Myeloid leukocytosis can occur in a number of reactive conditions as well as myeloid malignancies. The types of cells present and morphology can help to guide additional workup. This study provides guidance for the appropriate evaluation and further workup of leukocytosis.
Update on the causes of platelet disorders and functional consequences
Authors: Freson K. , Wijgaerts A. , van Geet C.
Published: April 2014

Platelets are derived from megakaryocytes in the bone marrow that create the cellular machinery the platelet needs to participate in the different processes of primary hemostasis including adhesion, activation and clot formation at the site of injury. Defects related to megakaryocyte differentiation, platelet formation, and/or platelet function can result in bleeding. Patients with thrombopathies can present with mucous membrane bleeding but may also present with bleeding following trauma or surgery. In this review, we have classified inherited platelet bleeding disorders (IPD) according to their underlying defective pathway: transcription regulation, TPO signaling, cytoskeletal organization, apoptosis, granule trafficking, and receptor signaling. Platelet function testing has provided insights into the underlying molecular defects that can result in bleeding. A major step forward was made during the last 3 years using new‐generation genetic approaches that resulted in the discovery of novel genes such as NBEAL2, RBM8A, ACTN1, and GFI1B for the well‐known IPD that cause gray platelet syndrome, thrombocytopenia‐absent radius syndrome, and autosomal dominant thrombocytopenias, respectively. In the near future, it is expected that a similar approach will identify many novel genes that cause IPD of unknown etiology, which are common. The future challenge will be to use a functional, systems biology approach to study the genes mutated in IPD and determine their roles in megakaryocyte and platelet biology and pathology.
Thrombocytopenia: an update
Authors: Smock K. J. , Perkins S. L.
Published: April 2014

Thrombocytopenia is a common clinical problem with numerous potential causes including decreased bone marrow platelet production, increased peripheral platelet destruction, increased splenic sequestration, and dilution. Investigation of the etiology of thrombocytopenia requires careful consideration of clinical history and laboratory features. A complete blood count and peripheral smear review are essential components of the diagnostic work‐up, and physicians should be knowledgeable about appropriate selection and interpretation of more specialized tests, including bone marrow examination, to assist with diagnosis. This review article aims to summarize and address appropriate work‐up of the major and/or life‐threatening causes of thrombocytopenia and some of the better‐characterized congenital thrombocytopenias.
Evaluation of an automated method for measuring von Willebrand factor activity in clinical samples without ristocetin
Authors: Graf L. , Moffat K. A. , Carlino S. A. , Chan A. K. C. , Iorio A. , Giulivi A. , Hayward C. P. M.
Published: April 2014

Introduction

The development of an automated, von Willebrand factor (VWF) activity assay, Innovance® VWF Ac (VWF:Ac), which measures VWF binding to the platelet receptor glycoprotein Ibα without ristocetin, led us to evaluate the assay for diagnosing von Willebrand disease (VWD) and monitoring therapy.

Methods

After validating that the assay could be performed on an instrument from a different manufacturer, we compared VWF:Ac to VWF ristocetin cofactor activity (VWF:RCo) findings, including ratios of activity/antigen, for 100 healthy controls and 262 consecutive clinical samples from 217 patients (197 adults, 64 children, n = 1 age unknown) referred for VWF testing.

Results

There was excellent correlation (R2 = 0.96) between VWF:Ac results run at two different sites on two different instruments. VWF:Ac had greater precision and sensitivity to low levels of VWF than the VWF:RCo method. Although there was good correlation between VWF:Ac and VWF:RCo results among healthy controls and patient subjects, VWF:Ac results were undetectable and/or significantly lower than VWF:RCo among patients who had types 2A, 2B, or 2M VWD. Additionally, a higher proportion of patient samples were classified as showing qualitative defects using the VWF:Ac compared with VWF:RCo method. While most samples drawn on VWD therapy had similar VWF levels by VWF:Ac and VWF:RCo, a type 2B VWD subject on replacement had much lower activity estimated by VWF:Ac.

Conclusion

We conclude that Innovance® VWF Ac is suitable for the diagnosis, classification, and monitoring of VWD, and that it has a number of advantages over VWF:RCo method.
Laboratory testing issues for protein C, protein S, and antithrombin
Authors: Marlar R. A. , Gausman J. N.
Published: April 2014

Thrombophilia is a complex disease process, which clinically expresses as venous thrombosis. The presence of a genetic defect in one of the major contributing components (protein C [PC], protein S [PS], and antithrombin [AT]) to thrombophilia can be determined by clinical laboratory assays. However, understanding the limitations and problems associated with assays is paramount to an accurate analysis of the genetic status. This review will discuss the major analytical issues and provide recommendations for assaying PC, PS, and AT in plasma. Recommendations are also made about pre‐analytical and postanalytical issues clinically affecting these assays.
Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges
Authors: Hayward C. P. M. , Moffat K. A. , Graf L.
Published: April 2014

Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF‐collagen‐binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme‐linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end‐point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin‐dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain‐of‐function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain‐of‐function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays.
Diagnosis and treatment of disseminated intravascular coagulation
Authors: Levi M.
Published: April 2014

Disseminated intravascular coagulation (DIC) is a condition in which systemic activation of coagulation without a specific localization occurs, resulting in extensive formation of intravascular fibrin, particularly in small and midsize vessels. Disseminated intravascular coagulation may lead to several altered coagulation parameters, including a low platelet count, abnormal global clotting assays, low levels of physiological anticoagulant proteases, or increased fibrin degradation products. Also, more complex assays for activation of coagulation factors or pathways may indicate involvement of these molecules in DIC. None of these tests alone, however, can accurately ascertain or rebuff a diagnosis of DIC. Nonetheless, a combination of readily available routine assays may be instrumental in establishing a diagnosis of DIC and can also be useful to point to a subset of patients with DIC that may need definite, often costly, interventions in the hemostatic system. Current insights on relevant etiological pathways that may contribute to the occurrence of DIC have led to innovative therapeutic and adjunctive approaches to patient with DIC. Management options directed at the amelioration of hemostatic activation may tentatively be indicated and were found to be advantageous in experimental and clinical investigations. These treatments encompass elimination of tissue factor‐mediated thrombin generation or restitution of normal anticoagulant function.
Tracking down contact activation – from coagulation in vitro to inflammation in vivo
Authors: de Maat S. , Tersteeg C. , Herczenik E. , Maas C.
Published: April 2014

The contact system is a volatile and versatile enzyme system in blood plasma that responds to the presence of nonphysiological surface materials by spontaneous generation of enzymatic activity. In subsequent steps, it can trigger blood coagulation and is responsible for the generation of the proinflammatory peptide bradykinin. The physiological role of the contact system is presently unknown, but it is commonly used to trigger coagulation in a diagnostic setting. In this three‐part review, we will first describe the molecular mechanisms that drive contact activation on nonphysiological materials. Next, we will summarize and compare a number of bioassays, which are commonly used to investigate the contact system in health and disease. Finally, we will discuss recent findings from both fundamental and clinical studies on the contributions of contact system to cardiovascular, infectious, and inflammatory disease.
Rare hereditary red blood cell enzymopathies associated with hemolytic anemia – pathophysiology, clinical aspects, and laboratory diagnosis
Authors: Koralkova P. , van Solinge W. W. , van Wijk R.
Published: April 2014

Hereditary red blood cell enzymopathies are genetic disorders affecting genes encoding red blood cell enzymes. They cause a specific type of anemia designated hereditary nonspherocytic hemolytic anemia (HNSHA). Enzymopathies affect cellular metabolism, which, in the red cell, mainly consists of anaerobic glycolysis, the hexose monophosphate shunt, glutathione metabolism, and nucleotide metabolism. Enzymopathies are commonly associated with normocytic normochromic hemolytic anemia. In contrast to other hereditary red cell disorders such as membrane disorders or hemoglobinopathies, the morphology of the red blood cell shows no specific abnormalities. Diagnosis is based on detection of reduced specific enzyme activity and molecular characterization of the defect on the DNA level. The most common enzyme disorders are deficiencies of glucose‐6‐phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). However, there are a number of other enzyme disorders, often much less known, causing HNSHA. These disorders are rare and often underdiagnosed, and the purpose of this review. In this brief review, we provide an overview of clinically relevant enzymes, their function in red cell metabolism, and key aspects of laboratory diagnosis.
Aplastic anemia: possible associations with lymphoproliferative neoplasms
Authors: Tzankov A. , Medinger M.
Published: April 2014

Aplastic anemia (AA) may precede, co‐occur, or follow a lymphoproliferative neoplasm. The best molecularly clarified scenario is that of concurrent AA and unsuspected (occult) T‐cell large granular lymphocyte leukemia. Several reported cases of AA and concurrent small B‐cell lymphomas/leukemias and Hodgkin lymphomas suggest also a possible link to simultaneous or preceding AA that might be sought in an antineoplastic immunological attempt to ‘eradicate’ the underlying malignant clone. The ‘immuno‐deregulatory’ potential and the direct cytotoxicity of regimens used for lymphoma therapy might be able to trigger AA in cases evolving after lymphoma treatment too. Alternative explanations of AA associated with lymphoproliferative disorders might be particular (immuno‐)genetic patient backgrounds predisposing to both AA and lymphoid neoplasms or exposures to environmental factors, increasing the risk for both diseases. Finally, the most common causal relationship of AA and lymphoma is that of immunosuppression‐ or allogeneous hematopoietic stem cell transplantation‐associated posttransplantational lymphoproliferative disorders in AA patients, who are treated in the respective manner. As all above scenarios are differently (specifically) therapeutically approachable and accompanied by diverse outcomes, they should be actively sought for and diagnosed as precisely as possible. This review summarizes the current knowledge on associations between AA and lymphoproliferative neoplasms.
Commonalities and contrasts in recent guidelines for lupus anticoagulant detection
Authors: Moore G. W.
Published: April 2014

Updates to guidelines covering lupus anticoagulant (LA) detection have recently been published by the International Society on Haemostasis and Thrombosis (ISTH) and British Committee for Standards in Haematology (BCSH), in 2009 and 2012, respectively. The Clinical and Laboratory Standards Institute (CLSI) published its first LA guideline in 2014. Cross‐panel agreement exists on sample manipulation, use of dRVVT analysis, conversion of clotting times to ratios, calculations to demonstrate phospholipid dependence, mixing test interpretation and provision of interpretive reporting. Whilst ISTH restricts assay choice to just dRVVT and activated partial thromboplastin time, BCSH and CLSI consider the case for additional tests. All panels acknowledge the potential for false‐negative mixing tests, yet they remain mandated by ISTH and BCSH, the latter, however, indicating that a negative mixing test need not exclude a LA if testing on undiluted plasma is unequivocal. CLSI reprioritizes test order to screen‐confirm‐mix to reduce false‐negative reporting when antibodies are diluted to undetectable levels in mixing tests. Recommendations differ on how to derive cut‐off levels, particularly in view of the realities of relatively low donor numbers. Each guideline considers testing of anticoagulated patients, BCSH and CLSI endorsing Taipan snake venom time as a useful supplementary assay in patients on vitamin K antagonists. Although full consensus is not apparent, these publications represent significant moves towards engendering common practices.
Flow cytometric pattern recognition of lymph node biopsies with lymphomas that lack lineage characteristics
Authors: Hebeda K. , Preijers F.
Published: April 2014

Although immunophenotyping (IPT) using flow cytometry is a routine technique that is applied in many laboratories as a diagnostic tool for lymphadenopathy, some diagnostic challenges persist. In this review, we will discuss pitfalls in the daily practice of lymph node diagnostics with the focus on general characteristics as lymphoid scatter patterns and lineage specific antigens that are used to define lymphoid populations. The absence of these characteristics on proliferating lymphoid cells can potentially lead to a wrong diagnosis. At the same time, this provides evidence for malignant transformation. Sporadic examples of reactive lymphoid proliferations with similar phenotypes are also discussed, illustrating the need for correlating IPT with morphology and clinical features.
ICSH: on board for new projects
Authors: Zini G. , Kern W. , Brereton M. , Stephens A. D.
Published: April 2014

The International Council for Standardization in Hematology (ICSH) is a not‐for‐profit organization aimed at improving global quality and harmonization of analytical methods, and achieving reliable and reproducible results in diagnostic hematology. ICSH co‐ordinates Working Groups of experts to examine laboratory methods and instruments for hematological analyses, and co‐operates with different international organizations which have similar scientific goals. Among seven ongoing approved projects, three ICSH projects have been selected and will be presented in the ICSH session at the XXVIIth ISLH International Symposium on Technological Innovations in Laboratory Hematology in The Hague, on May 2014. The project on ‘Guideline for flow cytometric evaluation of patients with suspected acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)’ covers different aspects of the application of immunophenotyping by multiparameter flow cytometry (MFC) in the diagnosis of AML and MDS including integration into multimodal diagnostic workflow, quality control, antibody selection, interpretation of findings, reporting, and personnel. Data from the pilot study of the project for ‘International Standardization of Hematology Reporting Units’ suggest that there is a wide variation in reporting units for the routine blood cell count and highlights the areas of nomenclature and units of measurement where standardization is necessary and feasible, such as units for cell counts, white cell differentials, and hemoglobin concentration. The project on ‘Standardization of HbA2 measurement and its implications for clinical practice’ starts from the observation that different instruments give different results for hemoglobin A2; it is aimed at producing recommendations as to how instrument manufacturers and laboratories should assess their equipment before using it to analyze patient samples. These projects are examples of how the ICSH represents a great opportunity for scientists involved in hematology laboratory to participate in a process of expert collaboration and discussion all around the world.
Red blood cell: from its mechanics to its motion in shear flow
Authors: Viallat A. , Abkarian M.
Published: April 2014

There is a number of publications on red blood cell deformability, that is, on the remarkable cell ability to change its shape in response to an external force and to pass through the narrowest blood capillaries and splenic sinuses. Cell deformability is postulated to be a major determinant of impaired perfusion, increase of blood viscosity, and occlusion in microvessels. Current deformability tests like ektacytometry measure global parameters, related to shape changes at the whole cell scale. Despite strong advances in our understanding of the molecular organization of red blood cells, the relationships between the rheology of each element of the cell composite structure, the global deformability tests, and the cell behavior in microflows are still not elucidated. This review describes recent advances in the description of the dynamics of red blood cells in shear flow and in the mechanistic understanding of this dynamics at the scale of the constitutive rheological and structural elements of the cell. These developments could open up new horizons for the determination of red blood cell mechanical parameters by analyzing their motion under low shear flows.
Antiphospholipid antibody testing and standardization
Authors: Devreese K. M. J.
Published: April 2014

The laboratory criteria that define patients with antiphospholipid syndrome (APS) include lupus anticoagulant (LAC), anticardiolipin antibodies and anti‐β2 glycoprotein I antibodies (aβ2GPI). All assays show methodological shortcomings and the combination of the three tests, each with different sensitivity and specificity, and hence, differences in clinical utility make the laboratory diagnosis of APS challenging. Consensus guidelines and proposals for antiphospholipid antibodies (aPL) testing have been published in the last 20 years and have led to a substantial improvement. Despite efforts so far, standardization is not reached yet, but progress has been made. On‐going efforts to reduce the interlaboratory/interassay variations remain important; even an absolute standardization cannot be feasibly achieved. Taking into account the methodological shortcomings of the means we have available, more detailed guidelines may help in adequate performance of aPL testing. This review will focus on the efforts and achievements in standardization and on the weaknesses and strengths of the current available laboratory methods.
Interpretation of coagulation test results under direct oral anticoagulants
Authors: Mani H.
Published: April 2014

Diagnostic of global coagulation parameters is part of the daily clinical routine practice in conservative as well in operative disciplines. The correct interpretation of in vitro test results in context to the ex vivo influence of anticoagulant drugs and the in vivo hemostatic system of the individual patient is dependent on the doctors clinical and laboratory experience. This article shortly reviews the laboratory interference of oral anticoagulants including the target‐specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation parameters and discusses the potential of several methods for measuring the anticoagulant effect of the direct oral anticoagulants.
Current insights into the laboratory diagnosis of HIT
Authors: Bakchoul T. , Zöllner H. , Greinacher A.
Published: April 2014

Heparin‐induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross‐linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune‐mediated disorders, the currently available laboratory tests for anti‐PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations.
Toward routine detection of extracellular vesicles in clinical samples
Authors: van der Meel R. , Krawczyk‐Durka M. , van Solinge W. W. , Schiffelers R. M.
Published: April 2014

The majority, if not all, of human cell types secrete extracellular vesicles (EVs) into their environment, at least partly as a means of intercellular communication. These secreted vesicles can be detected in most bodily fluids including blood, urine, and saliva. The number of secreted vesicles and their composition is altered in various pathological conditions, raising opportunities to exploit EVs as diagnostic and/or prognostic biomarkers. For this to become a reality, it is important to reach consensus regarding the standardization of protocols for sample collection, EV isolation, handling, and storage for valid comparison and interpretation of measurements. Depending on the information required, there are several detection options including EV number and size distribution, molecular surface markers, procoagulation activity, and RNA content. For these purposes, different techniques are currently utilized or under development. This review discusses the techniques that have the potential to become standard EV detection methods in a clinical diagnostic setting. In addition to the accuracy of the detection technique, other factors such as high‐throughput, cost‐effectiveness, time consumption, and required operator skill are important to consider. A combination of increasing fundamental knowledge, technological progress, standardization of sample collection, and processing protocols is required for EVs to become reliable predictors of altered physiology or development of disease suitable for routine clinical diagnostics. Cancer and (cardio)vascular disorders are examples of pathologies where EV detection may be applied in the near future for diagnosis and/or prognosis.
Intergenerational Mobility of the Mexican-Origin Population in California and Texas Relative to a Changing Regional Mainstream
Authors: Park Julie , Myers Dowell , Jiménez Tomás R.
Published: April 2014

We combine two approaches to gauge the achievements of the Mexican-origin second generation: one the intergenerational progress between immigrant parents and children, the other the gap between the second generation and non-Latino whites. We measure advancement of the Mexican-origin second generation using a suite of census-derived outcomes applied to immigrant parents in 1980 and grown children in 2005, as observed in California and Texas. Patterns of second-generation upward mobility are similar in the two states, with important differences across outcome indicators. Assessments are less favorable for men than women, especially in Texas. We compare Mexican-Americans to a non-Latino white reference group, as do most assimilation studies. However, we separate the reference group into those born in the same state as the second generation and those who have migrated in. We find that selective in-migration of more highly-educated whites has raised the bar on some, not all, measures of attainment. This poses a challenge to studies of assimilation that do not compare grown-children to their fellow natives of a state. Our model of greater temporal and regional specificity has broad applicability to studies guided by all theories of immigrant assimilation, integration and advancement.