bluuebunny/crossref_metadata_2025 huggingface dataset:
Mountain barriers and river conduits: phylogeographical structure in a large, mobile lizard (Varanidae: Varanus varius) from eastern Australia
Authors: Smissen Peter J. , Melville Jane , Sumner Joanna , Jessop Tim S.
Published: May 2013

Aim

Across eastern Australia, mountain ranges (the Great Dividing Range) and river catchments (the Murray–Darling Basin) are likely to have shaped the phylogeographical structure of many species. We address how such processes have influenced the phylogeography of the lace monitor, Varanus varius, a large mobile lizard.

Location

Eastern and south‐eastern Australia.

Methods

Phylogeographical hypotheses were tested using up to 90 museum and field‐collected samples from across the entire species' range; a 671‐bp region of the mtDNA gene ND4 was sequenced and all individuals were genotyped (eight microsatellite loci).

Results

Maximum‐likelihood analysis of sequence data revealed three geographically separate clades, with divergences estimated to have occurred during the Pleistocene. The south‐eastern clade showed an expansion pattern from northern refugia and dispersal appears to have occurred along the Murray–Darling river system. Microsatellite analyses support mtDNA clades but indicate secondary contact in the Hunter Valley, New South Wales.

Main conclusions

Our results indicate that phylogeographical structure and contemporary gene flow in Varanus varius is shaped by dispersal capacity, geographical barriers and the presence of ancient river corridors. Indeed, only the most significant geological (McPherson Range) and habitat barriers (Burdekin Gap) appear to limit gene flow in this species. The expansion of the clade on the western side of the Great Dividing Range suggests that ancient riparian corridors have facilitated extensive gene flow. Our study highlights the importance of understanding a species' ecological dynamics when examining broad‐scale evolutionary patterns.
Microalbuminuria and Hypertension in Pregnancy: Role of Aldosterone and Inflammation
Authors: Armanini Decio , Ambrosini Guido , Sabbadin Chiara , Donà Gabriella , Clari Giulio , Bordin Luciana
Published: May 2013

Women with a history of hypertension in pregnancy are at increased risk of microalbuminuria later in life. Microalbuminuria is a marker of kidney dysfunction frequently related to an inflammatory event. Pregnancy is a dynamic process characterized by immune tolerance, angiogenesis, and hormonal regulation. Menstruation and pregnancy are associated with a physiological inflammation, which is altered in preeclampsia and probably in other hypertensive situations of pregnancy. An imbalance between pro‐oxidant factors and the ability to scavenge these factors produces oxidative stress, which has been evaluated in many cells, but leukocytes are the main source of inflammatory cytokines and experimental and clinical evidence support a possible role of aldosterone as a mediator of placental and renal damage mediated by growth factors, reactive oxygen species, and cytokines. Angiotensin‐converting enzyme inhibitors and aldosterone receptor blockers are frequently effective in reducing the risk of progression of cardiovascular and renal disease.
Role of propagule pressure in colonization success: disentangling the relative importance of demographic, genetic and habitat effects
Authors: Hufbauer R. A. , Rutschmann A. , Serrate B. , Vermeil de Conchard H. , Facon B.
Published: May 2013

High propagule pressure is arguably the only consistent predictor of colonization success. More individuals enhance colonization success because they aid in overcoming demographic consequences of small population size (e.g. stochasticity and Allee effects). The number of founders can also have direct genetic effects: with fewer individuals, more inbreeding and thus inbreeding depression will occur, whereas more individuals typically harbour greater genetic variation. Thus, the demographic and genetic components of propagule pressure are interrelated, making it difficult to understand which mechanisms are most important in determining colonization success. We experimentally disentangled the demographic and genetic components of propagule pressure by manipulating the number of founders (fewer or more), and genetic background (inbred or outbred) of individuals released in a series of three complementary experiments. We used Bemisia whiteflies and released them onto either their natal host (benign) or a novel host (challenging). Our experiments revealed that having more founding individuals and those individuals being outbred both increased the number of adults produced, but that only genetic background consistently shaped net reproductive rate of experimental populations. Environment was also important and interacted with propagule size to determine the number of adults produced. Quality of the environment interacted also with genetic background to determine establishment success, with a more pronounced effect of inbreeding depression in harsh environments. This interaction did not hold for the net reproductive rate. These data show that the positive effect of propagule pressure on founding success can be driven as much by underlying genetic processes as by demographics. Genetic effects can be immediate and have sizable effects on fitness.
Effects of a large northern European no‐take zone on flatfish populationsa
Authors: Florin A.‐B. , Bergström U. , Ustups D. , Lundström K. , Jonsson P. R.
Published: May 2013

In March 2006, a 360 km2no‐take zone (NTZ) was established north of Gotland in the central Baltic Sea, with the purpose to scientifically evaluate the effects of a fishing ban on flatfish populations. A monitoring programme was set up to study the populations in the NTZ and in a reference area east of Gotland where the fishing pressure was high. The programme included fishing with multimesh survey nets, modelling of potential larval export and estimation of fish consumption by large marine predators. Overall, the results showed a clear positive effect of the NTZ on turbotScophthalmus maximus, with higher densities in the closed area compared with the fished area and also higher densities after closure compared with before. The NTZ also had older individuals and a more even sex ratio. This, in combination with a high potential for larval export from the NTZ to Gotland, shows that the marine reserve may be important for maintaining a viableS. maximusstock at Gotland. Also, for flounderPlatichthys flesus, the densities were higher in the NTZ compared to the reference area and there was a net larval export to the fished area. For both species, density‐dependent growth was evident, with a lower length at age in the closed area. Potential predation by grey sealHalichoerus grypusand great cormorantPhalacrocorax carbo sinesison flatfishes, that could hamper the evaluation of the marine reserve, was also addressed. Taken together, the results show that there are clear benefits of the fishing ban for both flatfish species within the NTZ, while the net effects on fisheries are difficult to quantify.
Plaque control improves the painful symptoms of oral lichen planus gingival lesions. A short‐term study
Authors: Salgado Daniela S. , Jeremias Fabiano , Capela Marisa V. , Onofre Mirian A. , Massucato Elaine Maria S. , Orrico Silvana R. P.
Published: May 2013

Background

Lichen planus is a mucocutaneous disease with manifestation in the oral mucosa, the gingiva being one of the most affected regions. In some cases, the lesion may be painful and lead to fragility of the tissues, so that precise diagnosis and adequate treatment are indispensible factors for improving the clinical condition. The aim of this study was to evaluate the effectiveness of plaque control in the improvement of clinical features and painful symptoms of oral lichen planus with gingival involvement.

Methods

Twenty patients diagnosed with gingival lichen planus confirmed by histopathological examination were selected. The patients were evaluated by a trained examiner, with regard to the clinical features of the lesions [Index of Escudier et al. (Br J Dermatol, 157, 2007, 765)]; painful symptoms (Visual Analog Scale); and periodontally, as regards the visible plaque and gingival bleeding indices. Periodontal treatment consisted of supragingival scaling and oral hygiene instruction, with professional plaque removal afterward for a period of 4 weeks. The entire sample was evaluated at the baseline and at the conclusion of treatment, and the results were analyzed by the Wilcoxon nonparametric test.

Results

The data demonstrated that the majority of patients were women (90%), with a mean age of 55.9 years. Periodontal treatment resulted in statistically significant reduction (P < 0.05) in the periodontal indices, with consequent improvement in the clinical features and painful symptoms of the lesions.

Conclusions

It was demonstrated that plaque control was effective in improving the clinical features and painful symptoms of oral lichen planus with gingival involvement.
Gingival crevicular fluid and interleukin‐23 concentration in systemically healthy subjects: their relationship in periodontal health and disease
Authors: Himani G. S. , Prabhuji M. L. V. , Karthikeyan B. V.
Published: May 2013

Background and Objective

There is a substantial magnitude of data implicating the role of interleukin‐23 (IL‐23) in the initiation and progression of periodontal disease. The main aim of this study was to evaluate the levels of IL‐23 in the gingival crevicular fluid of systemically healthy subjects in periodontal health and disease. In addition, we explored the effectiveness of periodontal interventional therapy on the levels of IL‐23 in subjects with chronic periodontitis to obtain a deeper insight into the possible role of IL‐23 in three separate periodontal conditions in three different populations.

Material and Methods

In this study, 54 individuals, satisfying the study inclusion and exclusion criteria, were recruited. They were categorically divided, on the basis of gingival index, probing pocket depth and relative attachment loss, into three groups: Group 1 (patients with a clinically healthy periodontium, n = 18); Group 2 (patients with gingivitis, n = 18); and Group 3a (patients with chronic periodontitis, n = 18). Samples taken from all 18 subjects of Group 3a, 3 mo after the initial therapy, constituted Group 3b. All clinical parameters were recorded at baseline and 3 mo after scaling and root planing. Gingival crevicular fluid samples were obtained in which the IL‐23 concentration was measured using ELISA.

Results

The highest mean IL‐23 concentration in gingival crevicular fluid was found for Group 3a (16448.69 pg/mL) and the lowest for Group 1 (2565.28 pg/mL). The mean IL‐23 concentrations in Group 2 (5425 pg/mL) and Group 3b (6272.22 pg/mL) lay between the maximum and minimum values. This implies a positive correlation between the gingival crevicular fluid IL‐23 concentration and relative attachment loss (p < 0.05).

Conclusion

A noteworthy increase in the gingival crevicular fluid IL‐23 concentration was seen that was proportional to the amount of periodontal tissue damage. As the IL‐23 concentration in gingival crevicular fluid is directly proportional to the severity of the periodontal affliction, it can be speculated that IL‐23 has a possible role in the pathogenesis of periodontal disease.
The impact of non‐surgical periodontal treatment on serum levels of long chain–polyunsaturated fatty acids: a pilot randomized clinical trial
Authors: Martinez G. L. , Koury J. C. , Brito F. , Fischer R. G. , Gustafsson A. , Figueredo C. M.
Published: May 2013

Background and Objective

Our group recently found higher levels of serum long chain–polyunsaturated fatty acids (LC‐PUFAs) in patients with chronic periodontitis compared to controls. However, the effect of periodontal treatment on LC‐PUFA serum levels has not been investigated. The primary aim of the present study was to investigate the impact of periodontal treatment on LC‐PUFA serum levels. A secondary aim was to assess the effect of dietary ω‐3 supplementation on clinical outcome.

Material and Methods

The test group was composed of 10 patients with generalized chronic periodontitis (mean age 44 ± 6.4 years) treated with scaling and root planing associated with 4 mo of ω‐3 supplementation eicosapetaenoic acid (EPA) plus docosahexaenoic acid (DHA), 3 g/d. The placebo group was composed of 11 patients (47.9 ± 10.5 years) that received scaling and root planing plus placebo. The periodontal examination included probing depth, clinical attachment level, bleeding on probing and visible plaque index. Docosapentaenoic acid (DPA), EPA, DHA and arachidonic acid (AA) were detected using gas chromatograph.

Results

In the placebo group, all LC‐PUFAs levels reduced significantly (DHA, DPA and AA, p = 0.004; EPA, p = 0.008). In the test group, only DPA and AA showed a significant reduction (p = 0.005). Moreover, a significant decrease in the ratios AA/EPA and AA/DHA (p = 0.005) was observed in the test group.

Conclusion

Non‐surgical periodontal treatment reduced significantly the serum levels of all analyzed LC‐PUFAs except those presented in the supplementation. The ω‐3 dietary supplementation had no effect on clinical outcome of treatment.
The Short‐term Effectiveness of a Remedial Mathematics Course: Evidence from a UK University
Authors: Di Pietro Giorgio
Published: May 2013

While there is growing debate in the USA about the effectiveness of remedial university courses, there have been fewer questions raised in the UK. Using a sharp regression discontinuity approach and data from a large School within a post‐1992 UK university, we estimate the effect of remediation on student outcomes. We find no evidence that taking a math remedial course improves student performance in the first year. This finding is consistent and complements that of a recent study by Lagerlöf and Seltzer (2009, Journal of Economic Education, Vol. 40, pp. 115–136), which is based on data from a pre‐1992 UK university.
The fire blight pathogen Erwinia amylovora requires the rpoN gene for pathogenicity in apple
Authors: Ramos Laura S. , Lehman Brian L. , Sinn Judith P. , Pfeufer Emily E. , Halbrendt Noemi O. , McNellis Timothy W.
Published: May 2013

RpoN is a σ54 factor regulating essential virulence gene expression in several plant pathogenic bacteria, including Pseudomonas syringae and Pectobacterium carotovorum. In this study, we found that mutation of rpoN in the fire blight pathogen Erwinia amylovora caused a nonpathogenic phenotype. The E. amylovora rpoN Tn5 transposon mutant rpoN1250::Tn5 did not cause fire blight disease symptoms on shoots of mature apple trees. In detached immature apple fruits, the rpoN1250::Tn5 mutant failed to cause fire blight disease symptoms and grew to population levels 12 orders of magnitude lower than the wild‐type. In addition, the rpoN1250::Tn5 mutant failed to elicit a hypersensitive response when infiltrated into nonhost tobacco plant leaves, and rpoN1250::Tn5 cells failed to express HrpN protein when grown in hrp (hypersensitive response and pathogenicity)‐inducing liquid medium. A plasmid‐borne copy of the wild‐type rpoN gene complemented all the rpoN1250::Tn5 mutant phenotypes tested. The rpoN1250::Tn5 mutant was prototrophic on minimal solid and liquid media, indicating that the rpoN1250::Tn5 nonpathogenic phenotype was not caused by a defect in basic metabolism or growth. This study provides clear genetic evidence that rpoN is an essential virulence gene of E. amylovora, suggesting that rpoN has the same function in E. amylovora as in P. syringae and Pe. carotovorum.
Natural variation of C‐repeat‐binding factor (CBFs) genes is a major cause of divergence in freezing tolerance among a group of Arabidopsis thaliana populations along the Yangtze River in China
Authors: Kang Juqing , Zhang Huiting , Sun Tianshu , Shi Yihao , Wang Jianqiao , Zhang Baocai , Wang Zhiheng , Zhou Yihua , Gu Hongya
Published: May 2013

We used a monophyletic group of four natural populations of Arabidopsis thaliana expanded from a single ancestor along the Yangtze River c. 90 000 yr ago to study the molecular mechanism of the divergence in their freezing tolerance, in order to gain an insight into the genetic basis of their local adaption to low temperatures.

Freezing tolerance assays, measurements of metabolites in the raffinose biosynthesis pathway and transactivation‐activity assays of variation in forms of cold‐responsive transcription factors were conducted on the four populations. Quantitative trait locus mapping was adopted with F2 populations of the most‐ and least freezing‐tolerant populations.

The degree of freezing tolerance among the four populations was negatively correlated with the lowest monthly average temperature of January in their native habitats, and positively correlated to the expression level of some cold‐regulated genes. We identified a major locus harboring three cold‐responsive transcription factor genes CBF1–3, and found a nucleotide insertion in CBF2 in all populations except SXcgx, which generated a dysfunctional CBF2 protein.

The CBF2 in SXcgx experienced a stronger natural selection in the cooler environment after CBF3 lost its response to low temperature, which possibly reflects a local adaptation of these populations during the expansion from a common ancestor.
FRAGMENTED OR CONNECTIVE PROFESSIONALISM? STRATEGIES FOR PROFESSIONALIZING THE WORK OF STRATEGISTS AND OTHER (ORGANIZATIONAL) PROFESSIONALS
Authors: NOORDEGRAAF MIRKO , VAN DER STEEN MARTIJN , VAN TWIST MARK
Published: May 2013

Many professionals, especially organizational ones (managers, controllers, strategists), face difficulties in organizing their professional fields. Work ambiguities and dependencies on outsiders make it difficult to set homogeneous standards and shelter occupational domains. Professionalism tends to be fragmented. It is questionable, however, whether professionalization is a matter of either enforced regulation or fragmented regulatory forms. More connective forms of professional control might enable groups to establish professional domains, despite ambiguities and dependencies. In order to understand professionalization dynamics in public domains and the relevance of connective professionalism, we study the development of one particular field, strategists in government. We show that the professionalization of Dutch strategists is fragmented: strategists are a varied and mobile group; they have different ideas about work; they depend on many other actors and factors. We also show that strategists opt for either more enforced forms of professionalism, or less professional control. Finally, we show how they might establish connective professionalism. By enacting embedded work spaces, strategists can reconfigure their work. This is also relevant for other (organizational) professionals.
Does The Necessity of Mathematical Truths Imply Their Apriority?
Authors: McEvoy Mark
Published: May 2013

It is sometimes argued that mathematical knowledge must be a priori, since mathematical truths are necessary, and experience tells us only what is true, not what must be true. This argument can be undermined either by showing that experience can yield knowledge of the necessity of some truths, or by arguing that mathematical theorems are contingent. Recent work by Albert Casullo and Timothy Williamson argues (or can be used to argue) the first of these lines; W. V. Quine and Hartry Field take the latter line. I defend a version of the argument against these, and other objections.
Successful outcome of severe Amanita phalloides poisoning in children
Authors: Grabhorn Enke , Nielsen Dirk , Hillebrand Georg , Brinkert Florian , Herden Uta , Fischer Lutz , Ganschow Rainer
Published: May 2013

Amanita phalloides intoxication can lead to FHF with high mortality, especially in children. There is still ongoing discussion about the optimal treatment and decision criteria for emergency liver transplantation (LTx). Here, we summarize our experience with outcomes in five children. Five children with severe A. phalloides intoxication were treated at our tertiary center from 1995 to 2010 and studied retrospectively with respect to clinical and laboratory aspects that might help to decide between LTx or conservative therapy only. The findings are discussed with regard to recommended treatment and transplantation criteria for adults. All patients survived, of whom two of five received emergency LTx. Three patients survived with conservative treatment consisting of intravenous silibinin, NAC, detoxification measures, and intensive care. Indications for LTx in two children were progressive brain edema and cardiovascular failure. Children with FHF due to A. phalloides intoxication should be considered early for emergency LTx but should be monitored closely for the necessity of definite LTx. Early detoxification with active charcoal as well as silibinin and NAC seems to improve the outcome. Late recovery of liver function after day 4 post‐ingestion is possible.
A novel morphological response of maize (Zea mays) adult roots to heterogeneous nitrate supply revealed by a split‐root experiment
Authors: Yu Peng , Li Xuexian , Yuan Lixing , Li Chunjian
Published: May 2013

Approximately 35–55% of total nitrogen (N) in maize plants is taken up by the root at the reproductive stage. Little is known about how the root of an adult plant responds to heterogeneous nutrient supply. In this study, root morphological and physiological adaptations to nitrate‐rich and nitrate‐poor patches and corresponding gene expression of ZmNrt2.1 and ZmNrt2.2 of maize seedlings and adult plants were characterized. Local high nitrate (LoHN) supply increased both lateral root length (LRL) and density of the treated nodal roots of adult maize plants, but only increased LRL of the treated primary roots of seedlings. LoHN also increased plant total N acquisition but not N influx rate of the treated roots, when expressed as per unit of root length. Furthermore, LoHN markedly increased specific root length (m g−1) of the treated roots but significantly inhibited the growth of the lateral roots outside of the nitrate‐rich patches, suggesting a systemic carbon saving strategy within a whole root system. Surprisingly, local low nitrate (LoLN) supply stimulated nodal root growth of adult plants although LoLN inhibited growth of primary roots of seedlings. LoLN inhibited the N influx rate of the treated roots and did not change plant total N content. The gene expression of ZmNrt2.1 and ZmNrt2.2 of the treated roots of seedlings and adult plants was inhibited by LoHN but enhanced by LoLN. In conclusion, maize adult roots responded to nitrate‐rich and nitrate‐poor patches by adaptive morphological alterations and displayed carbon saving strategies in response to heterogeneous nitrate supply.
Microtopography and the Properties of Residual Peat Are Convenient Indicators for Restoration Planning of Abandoned Extracted Peatlands
Authors: Triisberg Triin , Karofeld Edgar , Liira Jaan , Orru Mall , Ramst Rein , Paal Jaanus
Published: May 2013

The natural recovery of vegetation on abandoned peat extraction areas lasts for decades and the result of restoration succession can be unpredictable. The aim of the study was to specify environmental factors that affect the formation of the pioneer stages of mire communities and, therefore, be helpful in the prediction of the resulting ecosystem properties. We used the national inventory data from 64 milled peatlands in Estonia, distributed over the region of 300 × 200 km. This is the first national‐scale statistical evaluation of abandoned extracted peatlands. During surveys, vascular plants, bryophytes, and residual peat properties were recorded on three microtopographic forms: flats, ditch margins, and ditches. The microtopography was the main factor distinguishing the composition of plant communities on flats and ditches, while ditch margins resembled flats. The extracted indicator species suggested two successional pathways, toward fen or raised bog community. A single indicator trait—the depth of residual peat, which combines the information about peat properties (e.g.pH, ash content, and trophicity status), predicted the plant community succession in microtopographic habitats. We suggest that peatland management plans about the cost‐efficient restoration of abandoned peat mining areas should consider properties of residual peat layer as the baseline indicator: milled peatfields with thin (<2.3 m) and well‐decomposed residual peat should be restored toward fen vegetation types, whereas sites with thick (>2.3 m) and less decomposed residual peat layer should be restored toward transitional mires or raised bogs. Specific methodological suggestions are provided.
Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin‐6, High‐Sensitivity C‐Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?
Authors: Almroth G. , Lönn J. , Uhlin F. , Nayeri F. , Brudin L. , Andersson B. , Hahn‐Zoric M.
Published: May 2013

Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF‐23), hepatocyte growth factor (HGF), interleukin‐6 (Il‐6), high‐sensitivity C‐reactive protein (hs‐CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF‐23 and HGF with the earlier recognized inflammatory markers Il‐6 and hs‐CRP or suPAR. All patients studied had significantly elevated levels of FGF‐23, HGF, hs‐CRP and suPAR as compared to the controls. Il‐6 and hs‐CRP correlated for patients (R = 0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il‐6 and Ln CRP (R 0.28–0.37). Ln FGF‐23 correlated only with Ln HGF (r = −0.25) in controls. Ln HGF correlated with ln suPAR (r = 0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF‐23 with the recognized inflammatory markers Il‐6, hs‐CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il‐6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF‐23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.
Testing for established viruses: from the screening to the confirmation
Authors: Laperche S.
Published: May 2013

Enzyme Immunoassays (EIAs) detecting antibodies (Ab) or antigen (Ag) used to avoid viral transmissions by transfusion, are the most suitable methods for blood screening because they are economical and adaptable to high‐throughput testing. The continuing need to improve screening for HIV and HCV, led to develop Ag/Ab combination assays. The benefit of such assays has been widely demonstrated, since they are able to detect infected individuals in viremic pre‐seroconversion phase, making them particularly attractive for ensuring blood safety when nucleic acid testing (NAT) cannot be implemented.

In resource‐limited countries, especially in remote‐areas, blood safety is often based upon rapid tests (RT) which are easy to handle and can be used with whole blood. Nevertheless, the poor sensitivity of RT compared to EIAs could significantly impair blood safety.

Because NAT could efficiently detect serologically negative donors, many developed countries have implemented this method in blood screening. NAT yields vary depending on epidemiological situations. NAT is subjected to false‐negative results due to viral diversity or to extremely low viral loads, but also to false‐positive due to sample cross‐contamination. A repeatedly NAT reactive sample with multiplexed NAT is submitted to a virus‐specific amplification testing to discriminate between the viruses, creating some problematic situations consisting of samples reactive with the screening assay but non‐reactive with the discriminatory assay.

Although the primary purpose of viral screening testing is to prevent pathogen transmission to recipients, confirmatory testing intends to manage donors with adverse test results and to guarantee an optimal blood supply. As EIAs show a low positive predictive value in low‐prevalence countries due to frequent non‐specific reactions, the use of confirmatory assays is justified. Nevertheless confirmatory tests are known to be less sensitive than EIAs in the early phase of infection and show also nonspecific reactivity leading to indeterminate results which create difficulties in managing donors.

As in limited‐resource countries, specific confirmatory assay cannot be used, alternate strategies for confirmatory testing have been proposed, as to simultaneously test blood with two assays and to exclude donors reactive with both, or to use screening test signal values to support confirmation.

Although the direct detection of the virus through its genome might be considered as the best solution to ensure blood safety, the choice of blood screening strategy should be adapted to local epidemiology and organization constraints.
Transfusion risk reduction: Testing for bacteria
Authors: McDonald C. P.
Published: May 2013

Bacterial transmission by transfusion remains a significant problem in transfusion medicine and several Blood Services have introduced bacterial testing of platelet components. Platelet components present the greatest risk due to their storage at 18–22°C, which enhances the proliferation of most bacterial species. Platelet components were involved in 87% of bacterial fatalities in the USA between 2005 to 2009 and in 83% of bacterial transmissions in the UK between 1996 and 2011.

The major challenge for testing is that (unlike viruses) bacteria may multiply in blood components. Key testing issues are when to test, what volume to test and which assay or assays to use?

An ideal screening test needs to be rapid (2 h), sensitive (approximately 1 cfu/ml), specific, inexpensive and simple to use. No current tests fit these criteria. Culture assays are the most widely used for the detection of bacteria. BacT/ALERT™ is the most commonly used system world wide and can be regarded as the gold standard in this field. The sensitivity of culture is 1–10 cfu/ml and detection times are generally 18‐24 h.

Rapid tests currently available include the Bacti‐Flow™ (sensitivity 102 cfu/ml) flow cytometric assay; the Verax (sensitivity 103–105 cfu/ml) and BacTx™ (sensitivity 103–104 cfu/ml) assays which detect bacterial cell wall antigens and the pH SAFE™ which detects pH change. In house molecular assays (sensitivity <50 cfu/ml) have been developed, but none are commercially available.

Bacterial screen testing of blood components is a complex topic, but its implementation has undoubtedly increased the safety of the blood supply. In the USA, bacterial culture methods reduced the number of adverse bacterial transmissions by 50–75%, and in England no transmissions have been reported since implementation of routine culture in February 2011.
Blood donor profiling using donation patterns
Authors: Veldhuizen I. J. T.
Published: May 2013

To have a better insight in the donor career, blood establishments need to have a reliable donor profiling system. Keeping track of the regularity of donating behaviour is crucial. Yet, different viewpoints exist on what is to be understood with the term regular donor. The article will present and compare two useful approaches of donor profiling.

The first approach distinguishes different donor groups by using the total number of donations. This method uses the total number of donations to create donor groups. These donor groups are then studied in order to try to define factors that accurately describe differences between them. Up till now, the concrete number of donations that is used as a cut‐off value to create donor group varies widely among studies, as do the names allocated to describe the groups.

The second approach uses donation frequency, thus donations made within a certain time frame, to allocate donors into different groups. Not only the number of donations is important, but donation frequency as well. Recently, a European wide project on blood donor management, called DOMAINE (Donor Management in Europe) has created a new set of donor types by using both the total number of donations but also the different donation patterns. The newly defined donor types are mutually exclusive and present donors in different stages of their donor career. The donor types range from first‐time, regular, returning, lapsing and inactive donor, to the last type, the stopped donor. This classification provides blood banks with relevant information on the current ‘activity’ status of their donors.

A blood donor profiling system based on the number of blood donations has the clear advantage of getting a quick insight in the career of the donor. However, only focusing on the number of donations leaves out important information about the current activity status of the donor. By using both the total number of donations as well as donation patterns, a more clear‐cut classification of donor types is possible. In the short run, this may require a more time‐consuming and/or costly method of keeping track of donations, yet it has the advantage of keeping better track of donor activity and employability. It is a useful addition to donor profiling based solely on the total number of donations. Knowing the composition of the donor base and understanding accompanying donor behaviour allows for immediate directed retention, and if necessary, recruitment activities.
Recent insights into the mechanism of TRALI
Authors: Sachs U. J.
Published: May 2013

This paper will summarize the experimental and clinical literature on the pathogenesis of transfusion‐related acute lung injury (TRALI). Several mechanisms by which leukocyte antibodies including, HLA class I, HLA class II, and HNA‐3a antibodies, induce TRALI have been unraveled, although some aspects remain a matter of debate. Significant advances have also been made in the field of recipient‐related factors that contribute to the development of TRALI. In contrast, the pathomechanism behind antibody‐negative TRALI (associated with the transfusion of blood components which do not contain antibodies) is less well understood, and further research is urgently required.
Complement: new therapies and emergence of the complotype
Authors: Paul Morgan B.
Published: May 2013

Complement, an ancient and rather neglected part of the innate immune system, is undergoing a renaissance. Informed by basic discoveries on structure and function of complement proteins and fuelled by discovery of genetic links to diverse diseases, complement is rapidly emerging from the shadows. The recognition that aberrant complement activation is a drive to pathology in many degenerative and inflammatory disorders has driven the development of new drugs targeting the complement system that are proving effective in haemolytic, renal, rheumatological and neurological diseases. In this brief overview, I will attempt to give a flavour of the key current developments that are transforming the field and provide signposts to guide the interested reader to more detailed and scholarly reviews.
Transfusion support for Trauma
Authors: Allard S.
Published: May 2013

Severely injured patients are at a risk of acute traumatic coagulopathy contributing to high mortally rates. The early use of tranexamic acid in this setting has been shown to be safe and improves survival. Optimal FFP: Red cell ratios needed with respect to outcomes are yet to be defined. Slow turnaround times associated with the use of laboratory based coagulation testing can lead to delays in appropriate component support with a need for validated algorithms for near patient global tests of haemostasis. Multidisciplinary protocols are required for managing traumatic haemorrhage with emphasis on good communication supported by training, audit and on‐going review of cases to optimise patient care.
Whole blood as an alternative for component transfusion?
Authors: Thomas S.
Published: May 2013

Blood services commonly separate whole blood (WB) into its components of red cells, platelets and plasma. This enables storage of the components under conditions that optimise their quality for as long as possible, and enables transfusion of only the required components to each recipient. However, there are certain situations where separation and storage of components is not possible, and some evidence that components may not be the best therapy for major trauma. Nevertheless, there are significant risks associated with WB transfusion such as transfusion transmitted infections, alloimmunisation to human leucocyte antigens (HLA), post‐transfusion purpura (PTP), and transfusion associated graft versus host disease (TA‐GvHD).

The use of leucodepletion (LD) filters is relatively simple and has significant benefits such as reduced incidence of febrile transfusion reactions, reduced HLA immunisation, and reduced risk of TA‐GvHD and PTP. The LD process reliably reduces the transmission risk of cytomegalovirus (CMV) and of Human T‐cell lymphotropic virus (HTLV). There is also interest in the use of WB that has undergone a pathogen inactivation (PI) process, with storage either at refrigerated or ambient temperature. Initial studies suggest acceptable blood quality, killing of parasites, viruses and bacteria, and inactivation of any residual leucocytes. The transfusion of FWB in the developing world is a relatively common practice, as not all hospital or blood bank facilities can support component production, but there are arguments against the use of component therapy such as the delay in obtaining components, the cost (to the patient's family) of the treatment, and the wastage of the plasma.

It is clear that the use of component therapy may not be the most appropriate practice for all healthcare systems and the ability to use safely WB, whether fresh or stored, may be of significant benefit. The associated risks may be mitigated to some extent by the use of established and novel techniques, such as LD and PI.
Loading of dendritic cells for immunotherapy
Authors: Van Nuffel A. M. T. , Benteyn D. , Wilgenhof S. , Corthals J. , Heirman C. , Neyns B. , Bonehill A. , Thielemans K.
Published: May 2013

Dendritic cell therapy has been optimized a lot aiming to induce a strong and broad immune response in terms of the recognized epitopes by both CD8+ and CD4+ T cells and the use of the patients' complete unique set of HLA molecules. We here give an overview of our approach for antigen loading and maturation of dendritic cells and describe the consequences to evaluate the immune response after treatment as well as the Brussels experience in clinical trials.
Characterization of blood donors with high haemoglobin concentration
Authors: Magnussen K. , Hasselbalch H. , Ullum H. , Bjerrum O. W.
Published: May 2013

The literature contains little on the prevalence and causes of high predonation haemoglobin levels among blood donors. This study aimed to characterize and develop an algorithm to manage would‐be donors with polycythaemia. Between November 2009 and November 2011, we offered haematology consultations to blood donors with repeated haemoglobin concentration (Hb) above the WHO limit for polycythaemia vera (PV) (10.2 and 11.5 mm ⁄ 16.5 and 18.5 g/dl for women and men, respectively). Investigation of such donors included Hb, haematocrit, mean cell volume, erythropoietin, ferritin, platelet count and leucocyte count, JAK2 V617F and JAK2 exon12 analysis, as well as other routine measurements. Among 46 such donors, 39 had a history of smoking, which contributes to erythrocytosis. Two had PV, five had severe hypertension, one of them because of renal artery stenosis, and two had diabetes mellitus. Thus, we found a high morbidity among such donors. Of the 36 others, 30 donated again before May 2012, at which time the Hb was significantly lower. We recommend JAK2 V617F and JAK2 exon12 screening and clinical investigation for donors with concurrently high Hb, high haematocrit and iron deficiency. We also recommend that they stop or cut down on smoking to reduce the risk of thrombosis in general. We disqualified 10 of the donors.
Blood collection management in romanian transfusion network; current and perspective features
Authors: Burta O. L. , Rosin A. , Parvu S.
Published: May 2013

The presentation of blood collection management in Romania, is structured in 4 parts: the first part is devoted to general presentation of organization of National Network, with afferent legislation and regulations; the second one displays certain social‐economic and demographic data, such as ageing/gender, gross domestic product, and unemployment rate, aiming to have a general view about Romanian historical, current and forecasted data, each of them being partly involved in future national strategy in transfusion field. The third part refers to certain interconditioned situations, which fingerprint the national policy regarding quality system in transfusion field, represented by: ‐ general population evolution in terms of impact upon donors' pool ‐having as references: the total number of donations, and donations/1000 inhabitants‐ historical data and forecast for the next 6 years; ‐ an approach of identification of the most reliable and safer potential blood donors' groups, by displaying the evolution of first time donations, according to period of time, number, age, gender; ‐ “meet of demand” with explanation of the existing huge gap; ‐ the complexity of specific activity in collection/processing, refering to: number of collected units/separation rate of total blood, and number of platelets apheresis procedures, and testing regarding the total number of laboratory tests, aiming the maximum security for transfusion therapy; ‐ taken into account the evolution of medical staff, at to both levels: national and transfusion network, with obvious evidence of undersized in number and overloaded in job description. Based on the above objective parameters, and on EC missions conclusions, with the interest of drawing the future policies in transfusion field, the fourth part presents a questionnaire designed for fraiming each blood establishment, regarding blood donation promotion, and blood donors recruitment, operational marketing in blood donation process, blood supply management, and blood collection activity; the answers were interpreted according to a predetermined evaluation scale about strategies: short‐, medium‐ and long term /degrees of priority, and actions: presence, number and efficiency. Further, were selected and displayed part of the answers to above mentioned criteria, with concurrent SWOT analyse, and afferent codification for future national policy. Some pertinent conclusions arose, about the correlation of human resources (number and training) with: acquisition of modern equipment, use of an unique computerized soft for recruitment and retention activities, and hemovigillance purpose, standardized reporting system, authorized vehicles for mobile collections, and renovation and modernization of the infrastructures, all of these based on performance criteria/blood collection management, thus security requirement and satisfaction of the medical staff (prehospital and hospital), blood donors and recipients, being fulfilled, as major objective of national policy.
The role of blood transfusion in Sickle Cell Disease
Authors: Howard J.
Published: May 2013

Blood transfusion is used in the treatment and prevention of acute and chronic complications of Sickle Cell Disease. Blood may be administered in the emergency situation as a simple top‐up transfusion or as an automated or manual exchange procedure. Elective transfusions may be offered as an one‐off procedure, often pre‐operatively or as a long‐term regime, usually for primary or secondary stroke prevention. The main complications of transfusion in this patient population are alloimmunization, hyperhaemolytic transfusion reactions and iron overload.
Rozrolimupab, a mixture of recombinant human monoclonal anti‐D antibodies, for the treatment of primary immune thrombocytopenia – a review
Authors: Robak T. , Trelinski J. , Flensburg M. F. , Næsted H. , Petersen J.
Published: May 2013

Background

In patients with immune thrombocytopenia (ITP) who are Rhesus (Rh) D positive and who have not undergone splenectomy, the platelet count can be supported by anti‐D Ig therapy. The response rate to plasma‐derived intravenous anti‐D at a dose of 50–75 μg/kg is 70–80% with an increase in platelet count after 24–72 h and duration for more than 21 days in 50% of responders. Rozrolimupab is a mixture of 25 fully human IgG1 recombinant monoclonal anti‐D antibodies produced in CHO cells using a single‐batch manufacturing strategy from a polyclonal cell bank.

Materials & Methods

The primary objective of the phase I/II study was to evaluate safety of a single dose in adult RhD‐positive non‐splenectomized patients with ITP. The secondary objectives were evaluations of the efficacy and appropriate dose for pivotal study. Patients were dosed with a single rozrolimupab dose ranging from 75 to 300 μg/kg, infused intravenously over 15–20 min.

Results

Rozrolimupab was well tolerated with no unexpected toxicities. The most frequent adverse events were headache, pyrexia, chills and fatigue. Serious adverse events were observed in nine patients, mainly in cohorts treated with doses of 200 μg/kg and 250 μg/kg, but only considered related to rozrolimupab in four patients: decrease in Hb (one patient), extravascular haemolysis (one patient) and transient increase of D‐dimers (two patients). Hb decreased by ≥3.0 g/dl in six patients, but decrease by ≥5 g/dl was not observed. Seven patients required blood transfusions. Across all cohorts, 21 of 61 patients (34%) met the response criterion on day 7. The best response was noted in the 300 μg/kg dose cohort with response observed in eight of 13 patients (62%). Median time to response was 2 days and median duration of response was 14 days.

Discussion

The advantage of rozrolimupab over polyclonal anti‐D immunoglobulin is unlimited supply, high and reproducible specificity and activity, and an improved safety profile.

Conclusion

In conclusion, our data suggest that rozrolimupab is safe, well tolerated and has efficacy similar to plasma‐derived anti‐D immunoglobulin in the treatment of primary ITP.