bluuebunny/crossref_metadata_2025 huggingface dataset:
Bus Dwell Time Modeling Using Gene Expression Programming
Authors: Rashidi Soroush , Ranjitkar Prakash
Published: April 2015

This article proposes a gene expression programming (GEP)‐based approach to model and estimate bus dwell time (BDT) as an alternative to the more commonly used multiple linear regression (MLR) model. The proposed model is calibrated and validated using the data collected from 22 bus stops in Auckland and compared against the MLR model based on five different performance measures namely: mean error, mean absolute error, root mean square error, mean absolute percentage error, and R2 value. The proposed GEP‐based approach shows prospects to estimate BDT more accurately and overcome some of the issues associated with the MLR method, including the restrictions to stick with a predefined model form and the need to satisfy assumptions made on multicollinearity, homoscedasticity, and the normality of random error, which are often difficult to satisfy in real world applications.
Stationary‐phase induction of vvpS expression by three transcription factors: repression by LeuO and activation by SmcR and CRP
Authors: Kim Jeong‐A. , Park Jin Hwan , Lee Mi‐Ae , Lee Hyun‐Jung , Park Soon‐Jung , Kim Kun‐Soo , Choi Sang‐Ho , Lee Kyu‐Ho
Published: April 2015

An exoprotease of Vibrio vulnificus, VvpS, exhibits an autolytic function during the stationary phase. To understand how vvpS expression is controlled, the regulators involved in vvpS transcription and their regulatory mechanisms were investigated. LeuO was isolated in a ligand‐fishing experiment, and experiments using a leuO‐deletion mutant revealed that LeuO represses vvpS transcription. LeuO bound the extended region including LeuO‐binding site (LBS)‐I and LBS‐II. Further screening of additional regulators revealed that SmcR and cyclic adenosine monophosphate‐receptor protein (CRP) play activating roles in vvpS transcription. SmcR and CRP bound the regions overlapping LBS‐I and ‐II, respectively. In addition, the LeuO occupancy of LBS‐I and LBS‐II was competitively exchanged by SmcR and CRP, respectively. To examine the mechanism of stationary‐phase induction of vvpS expression, in vivo levels of three transcription factors were monitored. Cellular level of LeuO was maximal at exponential phase, while those of SmcR and CRP were maximal at stationary phase and relatively constant after the early‐exponential phase, respectively. Thus, vvpS transcription was not induced during the exponential phase by high cellular content of LeuO. When entering the stationary phase, however, LeuO content was significantly reduced and repression by LeuO was relieved through simultaneous binding of SmcR and CRP to LBS‐I and ‐II, respectively.
Density‐dependent, central‐place foraging in a grazing herbivore: competition and tradeoffs in time allocation near water
Authors: Rozen‐Rechels David , van Beest Floris M. , Richard Emmanuelle , Uzal Antonio , Medill Sarah A. , McLoughlin Philip D.
Published: April 2015

Optimal foraging theory addresses one of the core challenges of ecology: predicting the distribution and abundance of species. Tests of hypotheses of optimal foraging, however, often focus on a single conceptual model rather than drawing upon the collective body of theory, precluding generalization. Here we demonstrate links between two established theoretical frameworks predicting animal movements and resource use: central‐place foraging and density‐dependent habitat selection. Our goal is to better understand how the nature of critical, centrally placed resources like water (or minerals, breathing holes, breeding sites, etc.) might govern selection for food (energy) resources obtained elsewhere – a common situation for animals living in natural conditions. We empirically test our predictions using movement data from a large herbivore distributed along a gradient of water availability (feral horses, Sable Island, Canada, 2008–2013). Horses occupying western Sable Island obtain freshwater at ponds while in the east horses must drink at self‐excavated wells (holes). We studied the implications of differential access to water (time needed for a horse to obtain water) on selection for vegetation associations. Consistent with predictions of density‐dependent habitat selection, horses were reduced to using poorer‐quality habitat (heathland) more than expected close to water (where densities were relatively high), but were free to select for higher‐quality grasslands farther from water. Importantly, central‐place foraging was clearly influenced by the type of water‐source used (ponds vs. holes, the latter with greater time constraints on access). Horses with more freedom to travel (those using ponds) selected for grasslands at greater distances and continued to select grasslands at higher densities, whereas horses using water holes showed very strong density‐dependence in how habitat could be selected. Knowledge of more than one theoretical framework may be required to explain observed variation in foraging behavior of animals where multiple constraints simultaneously influence resource selection.
Performativities in Brief einer Unbekannten
Authors: Zheng Aili
Published: April 2015

Stefan Zweig's novella Brief einer Unbekannten continues to draw critical and popular interest for its intriguing contents. The article explores the performativities relating to social status and then discusses its culturally and cinematically distinct representations in the Hollywood adaptation by Max Ophüls (1948) and the film by Chinese director Xu Jinglei (2004). This approach suggests that the novella consists of two interwoven narrative threads, one devoted to the theme of unrequited love and the other to the development of Aladdin's “rags to riches” motif linked to the performativities of social status. The challenge for a film adaptation is the creation of a visual representation that will retain the impassioned voice speaking from the written text. Ophüls shifts the narrative and performativities toward a melodramatic romance with an ending that plays into the practical expectations of Hollywood. Xu is concerned not with the relief from an emotional condition but with feudal mentalities.
Indoor total volatile organic compounds exposure at 6 months followed by atopic dermatitis at 3 years in children
Authors: Kwon Jung Hyun , Kim Eunjeong , Chang Moon‐Hee , Park Eun Ae , Hong Yun‐Chul , Ha Mina , Park Hyesook , Kim Yangho , Park Choonghee , Ha Eun‐Hee
Published: April 2015

Background

Exposure to indoor air pollutants is thought to cause allergic inflammation. Volatile organic compounds (VOCs) are one of the aggravating factors of asthma and other allergic diseases. However, the influence of VOCs on development of atopic dermatitis is ambiguous in the clinical field. We therefore investigated the associations of indoor total volatile organic compounds (TVOCs) and development of atopic dermatitis in young Korean children.

Methods

From the birth cohort of a MOthers and Children's Environmental Health (MOCEH) study, 257 infants, whose parents agreed with the environmental measurement, were enrolled. Total VOCs were measured in infant's bedrooms at the age of 6 month. A total of 105 parents answered a questionnaire at 36 month. Concentrations of TVOCs were divided into two groups by third quartile (75th). Associations between the high VOCs exposure group and development of atopic dermatitis at the age of 36 months were estimated by multivariate logistic regression.

Results

The average concentration of TVOCs was 174.7 ± 115.1 ㎍/m3. We defined the high TVOCs exposure group by those with more than 75 percentile of the distribution (242.1 ㎍/m3). An increased risk of atopic dermatitis was observed in the high TVOCs exposure group, after adjustment for parents history of allergy, household income, breast‐feeding longer than 6 month (OR = 3.116, 95% Cl 1.041–9.323). Risk of atopic dermatitis was increased when the family bought new furniture within 1 yr.

Conclusion

Our results showed that exposure to high concentration of VOCs during infancy, an indoor pollutant, increased the risk of atopic dermatitis at 36 months.
Development of acute pancreatitis after Nissen fundoplication
Authors: Inoue Mikihiro , Uchida Keiichi , Otake Kohei , Okigami Masato , Maji Tomoaki , Kusunoki Masato
Published: April 2015

Acute pancreatitis subsequent to Nissen fundoplication for gastroesophageal reflux disease (GERD) is an extremely rare adverse event. We describe a pediatric case of acute pancreatitis resulting from superior mesenteric artery syndrome (SMAS) and gas bloat after fundoplication. Gas bloat is one of the known postoperative complications after Nissen fundoplication. Poor nutrition status, which is often associated with severe pediatric GERD, is a risk factor for SMAS. In this case, development of gas bloat and SMAS led to the formation of a closed loop and increased intraluminal pressure of the duodenum and pancreatic duct. Many pediatric patients who need anti‐reflux surgery face the risk of developing this entity. Preventive measures, such as treatment with prokinetics and frequent small‐volume meals, should be considered until improvement of nutritional status after fundoplication.
Opacity, Transparency, and the Paradox of the Accessibility Requirement
Authors: Fontaine Julie
Published: April 2015

Key issues in epistemology for the most part have to do with epistemic values such as justification, truth, and knowledge—that is, values related to the epistemic status of our propositional attitudes, mental events, and states. However, another important issue that is worth examining is the extent to which a subject is in a position to evaluate the strength of her epistemic position. In this paper, I wish to emphasize two properties of our mental states that play a decisive part in that respect: their opacity and transparency. In the following, I will assume that a mental state is opaque whenever it presents itself with no underlying reason, whereas states that are supported by apparent reasons are transparent.

One main argument that I will defend is that even when the opacity and transparency of our mental states are not reliable cues, still they remain highly informative. Notably, I draw some implications relative to the externalist/internalist debate in epistemology. I examine the claim that only mental states that are justified are well grounded or justification conferring and the idea that often stands behind, that is, that only states whose reasons are accessible are justified—namely, the Accessibility Requirement. I also examine the source of a recent debate in epistemology: the epistemic status of our intuitive states, as these are perfect instances of opaque mental states. I conclude that intuitive states in some respect are less misleading than states that are supported by apparent reasons.
Looking beyond the induction of Th2 responses to explain immunomodulation by helminths
Authors: Nutman T. B.
Published: April 2015

Although helminth infections are characteristically associated with Th2‐mediated responses that include the production of the prototypical cytokines IL‐4, IL‐5 and IL‐13 by CD4+ cells, the production of IgE, peripheral blood eosinophilia and mucus production in localized sites, these responses are largely attenuated when helminth infections become less acute. This modulation of the immune response that occurs with chronic helminth infection is often induced by molecules secreted by helminth parasites, by non‐Th2 regulatory CD4+ cells, and by nonclassical B cells, macrophages and dendritic cells. This review will focus on those parasite‐ and host‐mediated mechanisms underlying the modulated T‐cell response that occurs as the default in chronic helminth infections.
Clinical concepts for regenerative therapy in intrabony defects
Authors: Cortellini Pierpaolo , Tonetti Maurizio S.
Published: April 2015

Evidence indicates that periodontal regeneration is an efficacious and predictable procedure for the treatment of isolated and multiple intrabony defects. Meta‐analyses from systematic reviews indicate an added benefit, in terms of clinical attachment level gain, when demineralized freeze‐dried bone allograft, barrier membranes and active biologic products/compounds are applied in addition to open flap debridement. On the other hand, a consistent amount of variability of the outcomes is evident among different studies and within the experimental population of each study. This variability is explained, at least in part, by different patient and defect characteristics. Patient‐related factors include smoking habit, compliance with home oral hygiene and residual inflammation after cause‐related therapy. Defect‐associated factors include defect depth and radiographic angle, the number of residual bony walls, pocket depth and the degree of hypermobility. In addition, surgical‐related variables, such as surgical skill, clinical experience and knowledge, and application of the different regenerative materials, have a significant impact on clinical outcomes. This paper presents a strategy to optimize the clinical outcomes of periodontal regeneration. The surgical design of the flap, the use of different regenerative materials and the application of appropriate passive sutures are discussed in this review along with the scientific foundations.
Temporal sequence of hard and soft tissue healing around titanium dental implants
Authors: Salvi Giovanni E. , Bosshardt Dieter D. , Lang Niklaus P. , Abrahamsson Ingemar , Berglundh Tord , Lindhe Jan , Ivanovski Saso , Donos Nikos
Published: April 2015

The objective of the present review was to summarize the evidence available on the temporal sequence of hard and soft tissue healing around titanium dental implants in animal models and in humans. A search was undertaken to find animal and human studies reporting on the temporal dynamics of hard and soft tissue integration of titanium dental implants. Moreover, the influence of implant surface roughness and chemistry on the molecular mechanisms associated with osseointegration was also investigated. The findings indicated that the integration of titanium dental implants into hard and soft tissue represents the result of a complex cascade of biological events initiated by the surgical intervention. Implant placement into alveolar bone induces a cascade of healing events starting with clot formation and continuing with the maturation of bone in contact with the implant surface. From a genetic point of view, osseointegration is associated with a decrease in inflammation and an increase in osteogenesis‐, angiogenesis‐ and neurogenesis‐associated gene expression during the early stages of wound healing. The attachment and maturation of the soft tissue complex (i.e. epithelium and connective tissue) to implants becomes established 6–8 weeks following surgery. Based on the findings of the present review it can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.
Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair
Authors: Chiquet Matthias , Katsaros Christos , Kletsas Dimitris
Published: April 2015

Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal‐like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound‐healing processes of the individual patient.
Experimental models for guided bone regeneration in healthy and medically compromised conditions
Authors: Donos Nikolaos , Dereka Xanthippi , Mardas Nikos
Published: April 2015

The increased use of dental implants and related bone‐augmentation procedures creates a need for reliable proof‐of‐principle preclinical models for evaluating different bone‐regenerative techniques. The simulation of clinical scenarios by such models is of importance when the experiments are designed in order for the outcomes to provide basic points of clinical relevance. At the same time, the increased proportion of the population with different chronic diseases of ageing necessitates the need to reproduce these conditions in the same proof‐of‐principle preclinical models to allow evaluation of the effect of the relevant chronic disease on the bone‐healing process. This review presents a number of ‘proof‐of‐principle’ preclinical models in health and in chronic systemic conditions in which the guided bone regeneration principle was evaluated.
Clinical concepts for regenerative therapy in furcations
Authors: Sanz Mariano , Jepsen Karin , Eickholz Peter , Jepsen Søren
Published: April 2015

Furcation involvements present one of the greatest challenges in periodontal therapy because furcation‐involved molar teeth respond less favorably to conventional periodontal therapy compared with noninvolved molar or nonmolar teeth. Various regenerative procedures have been proposed and applied with the aim of eliminating the furcation defect or reducing the furcation depth. An abundance of studies and several systematic reviews have established the effectiveness of membrane therapy (guided tissue regeneration) for buccal Class II furcation involvement of mandibular and maxillary molars compared with open flap surgery. Bone grafts/substitutes may enhance the results of guided tissue regeneration. However, complete furcation closure is not a predictable outcome. Limited data and no meta‐analyses are available on the effects of enamel matrix proteins for furcation regeneration. Enamel matrix protein therapy has demonstrated clinical improvements in the treatment of buccal Class II furcation defects in mandibular molars; however, complete closure of the furcation lesion is achieved only in a minority of cases. Neither guided tissue regeneration nor enamel matrix protein therapy have demonstrated predictable results for approximal Class II and for Class III furcations. Promising preclinical data from furcation regeneration studies in experimental animals is available for growth factor‐ and differentiation factor‐based technologies, but very limited data are available from human clinical studies. Although cell‐based therapies have received considerable attention in regenerative medicine, their experimental evaluation in the treatment of periodontal furcation lesions is at a very early stage of development. In summary, the indications and the limitations for currently available treatment modalities for furcation defects are well established. New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects.
Influence of soil properties on coastal sandplain grassland establishment on former agricultural fields
Authors: Neill Christopher , Wheeler Megan M. , Loucks Elizabeth , Weiler Annalisa , Von Holle Betsy , Pelikan Matthew , Chase Tom
Published: April 2015

The decline in species‐rich grasslands across the United States has increased the importance of conservation and restoration efforts to preserve the biodiversity supported by these habitats. Abandoned agricultural fields often provide practical locations for the reestablishment of species‐rich grasslands. However, these fields often retain legacies of agriculture both in their soils, which may have higher pH and nitrogen (N) contents than soils that were never farmed, and in their plant communities, which are dominated by non‐native species and poor in native seed stock. We considered methods of reversing these legacies to create native‐species‐rich grassland on former agricultural land. We tested seeding and tilling combined with additions of sulfur (S), carbon (C), N or water to establish diverse sandplain grassland vegetation on an old field on Martha's Vineyard, Massachusetts. We measured soil pH, extractable nitrate and ammonium, and total and native species richness and native species cover for 5 years after treatment. S additions lowered pH to values typical of never‐tilled sandplain ecosystems and increased native species cover, but had no effect on species richness. C, N, and water additions had no significant effects on the soil or vegetation. Seeding and tilling were more effective at restoring native species richness than any soil amendments and indicated a greater importance of biotic factors compared with soil conditions in promoting sandplain vegetation establishment. S amendment accelerated establishment of native species cover for several years but the effect of S additions compared with seeding and tilling alone declined over time.
Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks
Authors: Todd Weaver J. , Malladi Sasidhar , Spackman Erica , Swayne David E.
Published: April 2015

Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a zone under permit. Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be permitted, considering inactivation of HPAI virus via pasteurization. Active surveillance testing at the flock level, using targeted matrix gene real‐time reversed transcriptase‐polymerase chain reaction testing (RRT‐PCR) has been incorporated into HPAI emergency response plans as the primary on‐farm diagnostic test procedure to detect HPAI in poultry and is considered to be a key risk mitigation measure. To inform decisions regarding the potential movement of NPLE to a pasteurization facility, average HPAI virus concentrations in NPLE produced from a HPAI virus infected, but undetected, commercial table‐egg‐layer flock were estimated for three HPAI virus strains using quantitative simulation models. Pasteurization under newly proposed international design standards (5 log10 reduction) is predicted to inactivate HPAI virus in NPLE to a very low concentration of less than 1 embryo infectious dose (EID)50/mL, considering the predicted virus titers in NPLE from a table‐egg flock under active surveillance. Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in a 40,000 lb tanker‐truck load of NPLE containing eggs from disease‐free flocks was also considered. Risk assessment can be useful in the evaluation of commodity‐specific risk mitigation measures to facilitate safe trade in animal products from countries experiencing outbreaks of highly transmissible animal diseases.
Hemolytic events after the administration of lyophilized versus liquid immune globulin: an analysis of a single manufacturer's safety database
Authors: Berg Roger , Jacob Dalia , Fuellenhals Elisabeth
Published: April 2015

BACKGROUND

Recent publications have raised concerns that liquid immune globulins (IGs) may be associated with either a higher or a lower frequency of hemolytic events compared to lyophilized IGs, among other reasons due to the differences of their isohemagglutinin content. The aim of this study was to evaluate the relationship of hemolytic events to product presentation (liquid versus lyophilized) and to examine the relationship between total IG doses administered and the individual isohemagglutinin titers of IG lots infused.

STUDY DESIGN AND METHODS

The reporting rate as well as the proportional reporting rate (PRR) of hemolytic events for liquid (Gammagard liquid [GGL]) and lyophilized IG (Gammagard S/D [GGSD]) received spontaneously from the United States was calculated. For all hemolytic events received spontaneously from global sources, total IG doses (g/kg body weight) and the loading dose of isohemagglutinins (total IG dose infused × isohemagglutinin titers of infused lots) were determined.

RESULTS

With 0.27 and 0.33 cases per 1 million grams distributed, the reporting rates for GGL and GGSD are comparable, further confirmed by a PRR of 1.0 (95% confidence interval, 0.4‐2.7). Hemolytic events for GGL and GGSD were observed with low loading doses of isohemagglutinins, and lots with high isohemagglutinin titers did not contribute to the development of hemolytic events in a higher proportion than lots with low titers

CONCLUSIONS

Hemolysis associated with GGL or GGSD can occur even with low loading doses of isohemagglutinins. Data presented do not indicate that high isohemagglutinin titers of IG products play a major role in the development of these events.
First record of autochthonous canine ehrlichiosis caused byEhrlichia canisin Romania
Authors: Morar Doru , Dărăbuş Gheorghe , Imre Mirela , Ilie Marius Stelian , Imre Kálmán
Published: April 2015

This case study describes the first genetically confirmed and clinically manifested autochthonousEhrlichia canisinfection in a 9‐year‐old female mixed‐breed dog from Romania. Health screening of the dog included clinical examination, evaluation of stained peripheral blood smear and hematologic variables, as well as serologic testing and molecular analysis. Clinical signs included fever, apathy, dehydration, pale mucous membranes, and weakness. The microscopic examination of the blood smear and immunologic assays forBorrelia burgdorferi, Anaplasma phagocytophilum, andE canisantibodies, and forDirofilaria immitisantigen yielded negative results. Hematologic abnormalities included moderate nonregenerative anemia, leucopenia with neutropenia, and moderate thrombocytopenia. The biochemical abnormalities identified were hypoalbuminemia, and mildly increased serum enzyme activities ofASTandALT. In addition, increased urea and creatinine levels associated with low urine specific gravity and proteinuria were also present. NestedPCRamplification of the partialE canis16SrRNAgene demonstrated the presence of this rickettsial pathogen in the dog's blood, which subsequently was confirmed through sequencing based on the 100% homology with GenBank depositedE canisisolates. After specific treatment with doxycycline (10 mg/kg, orally,SID) for one month, the proteinuria, and hematologic and serum biochemical abnormalities with the exception of mild azotemia resolved. This report supports the geographical expansion of canine ehrlichiosis caused byE canisin nonendemic regions of Europe.
Red blood cell transfusion‐induced inflammation: myth or reality
Authors: Hod E. A.
Published: April 2015

Red blood cells (RBCs) destined for transfusion can be refrigerator‐stored for up to 42 days prior to transfusion. Our studies in mice and dogs suggest that transfusion of older, stored RBCs, but not fresh RBCs, produce acute elevations in circulating pro‐inflammatory cytokine levels. Although our study in healthy adult human volunteers failed to demonstrate a pro‐inflammatory cytokine response following transfusion of RBCs stored for 40–42 days, a recent study in preterm infants suggests that RBC transfusions are associated with a pro‐inflammatory response. Thus, whether RBC transfusions, particularly of older, stored RBCs, result in a pro‐inflammatory cytokine response, is still an unresolved issue. Animal studies suggest this to be true, yet human studies have yet to demonstrate definitively that such an inflammatory response occurs. Potential explanations for this include differences between human and animal biology, the dose of RBCs transfused and baseline differences in levels of inflammation. This review will summarize the currently available evidence and approaches to resolving whether transfusions of older, stored RBCs are associated with inflammation in recipients.
Transfusion of fresh vs. older red blood cells in the context of infection
Authors: Klein H. , Natanson C. , Flegel W.
Published: April 2015

The red blood cell (RBC) storage interval has been extended from less than a week to the current storage interval of 6–8 weeks. Regulatory criteria for extending storage rely upon a minimal degree of hemolysis and acceptable in vivo 24‐h post transfusion recovery. Clinical studies of safety and efficacy have never been required. Concerns have arisen that RBC toward the end of storage develop a ‘storage lesion’ with previously unrecognized toxicity. Of the several mechanisms proposed, the bolus of iron delivered to macrophages as a result of hemolysis of stored RBC might pose a particular risk to patients with existing infections. We developed a canine model of pneumonia to compare the toxicity of stored RBC transfusion. We described increased mortality after transfusion of old RBC. We found that transfused older RBC increased mortality, in vivo hemolysis, circulating cell‐free hemoglobin that scavenges nitric oxide, and elevations of non‐transferrin bound and plasma labile iron. Disappearance of circulating iron correlated with increased mortality, worsening pulmonary function, and bacterial proliferation. Washing decreased the mortality associated with transfusing older RBC, but had the opposite effect on fresher blood. With low doses of bacteria, survival was unaffected by the age of blood, whereas high bacteria doses masked any effect of RBC age on mortality. Older RBC may have adverse effects, but the patient's clinical status, the age, volume and method of preparation of the RBC may be critical variables. Several mechanisms may account for this toxicity, but in the presence of bacterial infection, availability of iron likely plays a major role.
Models used to predict the impact of having less stringent deferral policies for men who had sex with men: can we validate these predictions?
Authors: Germain M. , Delage G.
Published: April 2015

Many jurisdictions still do not accept blood donations from men who had sex with men (MSM). Those who defend the status quo argue that a less stringent policy would unduly increase the risk to recipients. In an effort to address this dilemma, investigators have tried to project the impact of having less stringent deferral policies on HIV transmission risk, using mathematical models that rely on empirical data. Under certain assumptions, these models predicted very small but definite increases in risk if MSM were allowed to donate after a temporary deferral period. However, the predicted increase in the number of transfusion‐transmitted infections would be so small as to remain imperceptible in reality. Models also predict a sizeable increase in the number of HIV‐positive donors who would present to donate, an outcome that should be more readily observable. When applied to the Australian experience, where a one‐year deferral policy for MSM was implemented, most models would have predicted significant increases in the prevalence of HIV in male donors. The actual rate of HIV among Australian male donors remained very low and unchanged, suggesting that these models were overly pessimistic. It will be interesting to validate this finding in other countries that implemented a time‐based deferral. The Australian experience, if confirmed in other countries, would suggest that a time‐based deferral for MSM poses an even lower risk than what the models predict.
How to approach an apheresis consultation using the American Society for Apheresis guidelines for therapeutic apheresis procedures
Authors: Pham Huy P. , Schwartz Joseph
Published: April 2015

Therapeutic apheresis (TA) is a treatment modality currently being used in many disease conditions. However, the decision to treat a patient with TA depends on many factors, including but not limited to the most likely diagnosis the patient has and whether there is a rationale for TA to be used as a treatment modality, the risk versus benefit ratio of the treatment and the technical aspects of the procedure if apheresis is performed. The guidelines on the use of therapeutic apheresis in clinical practice – evidence‐based approach from the writing committee of the American Society for Apheresis (ASFA) are update every 3 years and are based on the review of the most up to date medical literature addressing the rationale as well as technical aspect of apheresis. The guidelines are meant to help with clinical decision‐making in apheresis consultations and to encourage research on the use of apheresis for novel indications. The format used for the different disease conditions is one‐page fact sheet. In this article, the development and application of these fact sheets in those guidelines are discussed along with an example for each of ASFA's four categories.
Assessing infectious threats – trick or threat?
Authors: Kiely P. , Seed C. R.
Published: April 2015

Background

Effective surveillance for, and response to, emerging infectious disease (EID) agents is a pivotal component of blood safety risk management policy. The rate of emergence of new potential agents is increasing which demands a robust risk management strategy for rapidly assessing and ranking potential threats. This review discusses the general principles of threat assessment for EID agents.

Methods

Various schema for the management of the risk posed by EID agents have been proposed. Examples are the AABB ‘toolkit’ for EIDs which includes a framework for recognition, assessment and management of EID agents, and the Australian Red Cross Blood Service's EID management strategy. Both systems incorporate EID agent ‘templates’ to assist with ranking the threat level and formulating an appropriate response.

Results

Threats are primarily assessed based on three main criteria: prevalence in donor population, transmissibility by blood and the severity of clinical disease in recipients. Where the threat is deemed significant, quantitative risk assessment and cost‐effectiveness analysis for potential interventions can assist in defining the most appropriate mitigation strategy. Hepatitis E virus (HEV) is an excellent contemporary case study with transfusion–transmissibility now proven, but further studies required to define the extent of clinically significant disease in immunocompetent recipients.

Conclusions

The emergence of vCJD and subsequently West Nile virus underscored the importance of an effective EID risk management framework. However, not all EIDs necessarily pose a significant threat to blood safety, and therefore, an effective ranking system is required which we suggest should primarily assess prevalence, transmissibility and recipient disease outcome.
Plasmodium knowlesi – an emerging pathogen
Authors: Ahmed M. A. , Cox‐Singh J.
Published: April 2015

Ten years have passed since the publication of a large focus of Plasmodium knowlesi infections in the human population. The discovery was made during a molecular investigation of atypical P. malariae cases in the Kapit Health Division, Sarawak, Malaysian Borneo. Patients were more symptomatic with higher parasite counts than expected in P. malariae infections. The investigation found only P. knowlesi DNA present in patient blood samples. Morphological similarity had allowed P. knowlesi to masquerade as P. malariae during routine diagnostic microscopy for malaria. P. knowlesi, a malaria parasite of macaque monkeys, had entered the human population. The subsequent development of P. knowlesi species‐specific PCR assays soon demonstrated that the entry was not confined to the Kapit Division but extended across island and mainland Southeast Asia. Relevant clinical descriptions and guidelines for the treatment and management of patents with P. knowlesi malaria were not available. Nor was it clear whether P. knowlesi had undergone a host switch event into the human population or if infections were zoonotic. The outputs of studies on P. knowlesi malaria during the past 10 years will be summarized, highlighting major findings within the context of pathophysiology, virulence, host switch events, treatment, control and importantly malaria elimination.
Iron depletion and routine ferritin measurement in blood donors
Authors: Goldman M.
Published: April 2015

Iron is an essential nutrient, and blood donation leads to significant iron loss. Iron stores can be estimated by measurement of ferritin levels. Several studies of donor ferritin levels have provided data on the frequency and risk factors for iron deficiency in various countries. Iron deficiency is common, particularly in female donors, and donation frequency is an important risk factor for iron deficiency in both males and females. The significance of iron deficiency alone on donor health, and the optimal strategy to integrate ferritin testing into routine operations in large blood centres remain to be determined.
Determining the clinical significance of alloantibodies
Authors: Meny G.
Published: April 2015

The detection and identification of red cell alloantibodies are important processes familiar to all laboratory professionals. A term frequently utilized to describe an alloantibody likely to cause an adverse event is ‘clinically significant’. The laboratory usually assesses the clinical significance of alloantibodies based upon specificity, serologic phases of reactivity and cross‐match results and make transfusion recommendations accordingly. However, using specificity, reactivity patterns and cross‐match results alone cannot always distinguish between clinically significant and nonsignificant alloantibodies. Searches for ‘compatible’ blood can occur when alloantibodies are identified and ‘incompatible’ cross‐matches occur, leading to inappropriate delays in transfusion and potentially causing patient harm. Cellular assays, such as the monocyte monolayer assay, can be used as an adjunct to predict transfusion outcome. Current routine serology assays will not predict with absolute certainty whether ‘incompatible’ red cells transfused to a recipient with an alloantibody will be destroyed or whether that recipient will suffer the devastating clinical consequences of a hemolytic transfusion reaction. The monocyte monolayer assay can be of particular assistance when the antibody specificity is of ‘variable’ clinical significance or the antibody specificity is to a high incidence antigen and rare blood is requested. Finally, it is important to remember that laboratory professionals will be called upon for advice and information by clinicians and patients regarding transfusion recommendations. We are all partners working together to determine the optimal transfusion option. And we must reaffirm to all that transfusion should never be withheld from a patient whose life depends on urgent transfusion.
Organizing a national blood service with limited resources – developments in the South African National Blood Service
Authors: Mpuntsha L. , Reddy R.
Published: April 2015

Background

South Africa has a population of 52 million people and is classified as a Middle Human Development Index (HDI) Country. Up until 1994, the majority Black population lived under discriminatory apartheid laws with resulting in significant socio‐economic disparities between the various population groups. The health system is two tier with Government funding health care in the public sector and medical insurance schemes funding health care in the private sector for those who can afford it. Fiscal allocation for health care in the public sector has been averaging at about 8·5% of the country's gross domestic product (GDP) and is utilized by 84% of the population as the majority of the population cannot afford medical insurance. There is inadequate value contribution due to high disease burden, increasing demand for services from previously disadvantaged groups and inefficiencies in service delivery. The blood services operate on a fee‐for‐service basis supplying about 60% of blood to public sector hospitals and about 40% to private health facilities. The South African National blood service (SANBS) supplies blood and blood products to 88% of the population in eight of the nine provinces and the Western Province Blood Transfusion Service (WPBTS) which operates independently in the Western Cape Province supplies the remaining 12%. Both blood services operate on a ‘vein to vein’ basis managing blood collections from 100% voluntary non‐remunerated donors, processing whole blood into various components, testing for viral markers and cross matching and issuing blood products to doctors on request. SANBS was formed as a National Blood Service in 2001 as a result of the amalgamation of 6 regional blood service organizations. The mission of SANBS is ‘to provide all patients with sufficient, safe, quality blood products and related medical services in a sustainable manner’. Blood safety and sufficiency are the most critical objectives of both blood establishments (BEs).

Aim

To present historical developments and achievements of SANBS in pursuit of its mandate over the last 12 years. The objective is to share outcomes of various strategies that enabled and strengthened delivery in the South African resource‐constrained environment and challenging socio‐economic context.

Methods

A review of the strategic plans, governance framework, operational service delivery and efficiency, human resource management, financial efficiency and stakeholder management was performed to highlight the strategy, challenges and successes of organizing a national blood service.

Results

Despite significant socio‐economic challenges and limited resources SANBS has managed to effectively provide a low risk and sustainable blood supply to the patients that it serves.
The sorting of blood group‐active proteins during enucleation
Authors: Satchwell T. J. , Bell A. J. , Toye A. M.
Published: April 2015

Enucleation represents the critical stage during red blood cell development when the nucleus is extruded from an orthochromatic erythroblast in order to generate a nascent immature reticulocyte. Extrusion of the nucleus results in loss of a proportion of the erythroblast plasma membrane, which surrounds the nucleus, the bulk of the endoplasmic reticulum and a small region of cytoplasm. For this reason, enucleation provides an important point in erythroblast differentiation at which proteins not required for the function of the erythrocyte can be lost, whilst those that are important for the structure‐function properties of the mature erythrocyte must be efficiently retained in the reticulocyte plasma membrane. Disturbances in protein distribution during enucleation are envisaged to occur during human diseases such as hereditary spherocytosis. This article will discuss our current understanding of erythroblast enucleation in the context of retention and loss of proteins that display antigenic blood group sites, that are known to exist within multiprotein complexes within the erythrocyte membrane.
What to do about transfusion‐related acute lung injury?
Authors: Eder A. F.
Published: April 2015

Background

In recent years, blood centres in several countries have taken measures to effectively reduce the risk of transfusion‐related acute lung injury (TRALI) from plasma transfusion but challenges remain.

Methods

This article reviews recently published studies and data on TRALI from the American Red Cross haemovigilance programme.

Results

Since 2008, over 95% of the approximately 1·6 million plasma components distributed annually for transfusion by the American Red Cross is from male donors. With this approach, the rate of TRALI after plasma transfusion decreased by about 80%. However, the risk associated with group AB plasma compared to other blood groups did not change, because female donors were still needed for almost half of the group AB plasma to meet demand. Between 2006 and 2011, the use of group AB plasma in the United States steadily increased by over 30%, while plasma use overall decreased by about 3%. To meet the new standard for plasma safety, US blood centres and transfusion services took additional measures to ensure an adequate supply of group AB plasma and appropriate utilization of a limited resource.

The switch to a male‐donor predominant plasma strategy resulted in a sustained and significant reduction in the risk of TRALI. The collaborative effort of blood centres and transfusion services to further advance evidence‐based haemotherapy practices will likely have a broader effect on transfusion safety than in preventing TRALI alone.
Red cell antigen testing
Authors: Scharberg E. A. , Richter E. , Bugert P.
Published: April 2015

The testing of red cell antigens in blood donors and blood recipients is the basic and most important part of the pretransfusion diagnostics. Depending on the national guidelines, the testing includes different mandatory typing ranging from ABO only up to ABO, RhD, RhCcEe, K and the RhD genotyping of serologically RhD‐negative donors. Testing of additional blood group antigens in blood donors and recipients is needed to provide compatible blood products for patients with clinically significant red cell antibodies. The red cell antigen testing is performed by a variety of serological methods mostly using haemagglutination test. For typing of ABO, RhD, RhCcEe, K and some further antigens, monoclonal IgM sera have become standard reagents. However, for extended antigen testing, polyclonal sera remained the most frequently used reagents. For some antigens, no certified commercial sera are available. The testing of the antigens has different significance in blood donors and recipients. Because of possible false‐negative reactions with weak or partial antigens, the typing of blood donors requires more sensitive techniques and reagents. In the last 10 years, molecular DNA typing of blood group alleles has become available for the routine. Providing genotypes, it gives essential information predicting the phenotype of red cell antigens when serological testing is not possible because of reagent limitations or in pretransfused patients.