bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in symptomatic malaria prevalence through proactive community treatment in rural Senegal
Authors: Linn Annē M. , Ndiaye Youssoupha , Hennessee Ian , Gaye Seynabou , Linn Patrick , Nordstrom Karin , McLaughlin Matt
Published: July 2015

Objectives

We piloted a community‐based proactive malaria case detection model in rural Senegal to evaluate whether this model can increase testing and treatment and reduce prevalence of symptomatic malaria in target communities.

Methods

Home care providers conducted weekly sweeps of every household in their village throughout the transmission season to identify patients with symptoms of malaria, perform rapid diagnostic tests (RDT) on symptomatic patients and provide treatment for positive cases. The model was implemented in 15 villages from July to November 2013, the high transmission season. Fifteen comparison villages were chosen from those implementing Senegal's original, passive model of community case management of malaria. Three sweeps were conducted in the comparison villages to compare prevalence of symptomatic malaria using difference in differences analysis.

Results

At baseline, prevalence of symptomatic malaria confirmed by RDT for all symptomatic individuals found during sweeps was similar in both sets of villages (P = 0.79). At end line, prevalence was 16 times higher in the comparison villages than in the intervention villages (P = 0.003). Adjusting for potential confounders, the intervention was associated with a 30‐fold reduction in odds of symptomatic malaria in the intervention villages (AOR = 0.033; 95% CI: 0.017, 0.065). Treatment seeking also increased in the intervention villages, with 57% of consultations by home care providers conducted between sweeps through routine community case management.

Conclusions

This pilot study suggests that community‐based proactive case detection reduces symptomatic malaria prevalence, likely through more timely case management and improved care seeking behaviour. A randomised controlled trial is needed to further evaluate the impact of this model.
A tomato phloem‐mobile protein regulates the shoot‐to‐root ratio by mediating the auxin response in distant organs
Authors: Spiegelman Ziv , Ham Byung‐Kook , Zhang Zhaoliang , Toal Ted W. , Brady Siobhan M. , Zheng Yi , Fei Zhangjun , Lucas William J. , Wolf Shmuel
Published: July 2015

The plant vascular system serves as a conduit for delivery of both nutrients and signaling molecules to various distantly located organs. The anucleate sieve tube system of the angiosperm phloem delivers sugars and amino acids to developing organs, and has recently been shown to contain a unique population of RNA and proteins. Grafting studies have established that a number of these macromolecules are capable of moving long distances between tissues, thus providing support for operation of a phloem‐mediated inter‐organ communication network. Currently, our knowledge of the roles played by such phloem‐borne macromolecules is in its infancy. Here, we show that, in tomato, translocation of a phloem‐mobile cyclophilin, SlCyp1, from a wild‐type scion into a mutant rootstock results in restoration of vascular development and lateral root initiation. This process occurs through reactivation of auxin response pathways and reprogramming of the root transcriptome. Moreover, we show that long‐distance trafficking of SlCyp1 is associated with regulation of the shoot‐to‐root ratio in response to changing light intensities, by modulating root growth. We conclude that long‐distance trafficking of SlCyp1 acts as a rheostat to control the shoot‐to‐root ratio, by mediating root development to integrate photosynthesis and light intensity with requirements for access to water and mineral nutrients.
Mechanisms Regulating Protein Localization
Authors: Bauer Nicholas C. , Doetsch Paul W. , Corbett Anita H.
Published: July 2015

Cellular functions are dictated by protein content and activity. There are numerous strategies to regulate proteins varying from modulating gene expression to post‐translational modifications. One commonly used mode of regulation in eukaryotes is targeted localization. By specifically redirecting the localization of a pool of existing protein, cells can achieve rapid changes in local protein function. Eukaryotic cells have evolved elegant targeting pathways to direct proteins to the appropriate cellular location or locations. Here, we provide a general overview of these localization pathways, with a focus on nuclear and mitochondrial transport, and present a survey of the evolutionarily conserved regulatory strategies identified thus far. We end with a description of several specific examples of proteins that exploit localization as an important mode of regulation.
Zero carbon homes and zero carbon living: sociomaterial interdependencies in carbon governance
Authors: Walker Gordon , Karvonen Andrew , Guy Simon
Published: July 2015

We consider in this paper the relations between built form and everyday practices of home‐living. These we see as co‐constituting a combined domestic carbon space in which sociomaterial interdependencies are constantly at work. Carbon emissions are necessarily caught up in these interdependencies and not separable from them. We use the case of the mainstreaming of zero carbon (zero‐C) housing in the UK to explore whether conceiving of domestic carbon in properly sociomaterial terms reveals possibilities for, or resistances to, carbon governance objectives. We find strong resistances to the notion that zero‐C might mean simultaneously creating ‘new normals’ of built form and ways of living, with market values and governance delineations resisting any sharing of responsibility for achieving zero‐C between those building and those living in future homes. The slippery, contested and diminished calculation of zero‐C has also been closely coupled to these ends. This case shows that resistances to carbon control can emerge in interdependent sociomaterial forms and are strengthened through that interdependency, such that carbon lock‐in works through entwined forms of inertia. However, we argue that in other instances and spaces of carbon governance we might find alternative sociomaterial articulations that serve to configure the politics of change in more positive ways.
Long‐term experiences in cryopreservation of mobilized peripheral blood stem cells using a closed‐bag system: a technology with potential for broader application
Authors: Spoerl Silvia , Peter Robert , Wäscher Dagmar , Verbeek Mareike , Menzel Helge , Peschel Christian , Krackhardt Angela M.
Published: July 2015

BACKGROUND

In several European countries, preparation of cellular products with open manufacturing systems as used for cryopreservation of peripheral blood stem cells (PBSCs) needs to be performed in a clean‐room facility. However, this form of manufacturing is highly expensive and laborious. Thus, safe techniques providing improved efficacy regarding time and material, which are in accordance with legal requirements are highly desirable.

STUDY DESIGN AND METHODS

We have developed, validated, and applied a simple method for cryopreservation of PBSCs within a functionally closed‐bag system using the closed cryo freeze prep set. This process fulfills good manufacturing practice requirements and allows for the cryopreservation of PBSCs without a clean‐room facility. In addition to cryopreservation of PBSCs, we have recently successfully modified our system for processing, portioning, and cryopreservation of allogeneic donor lymphocytes.

RESULTS

Since 2010, cryopreservation of PBSCs using a closed‐bag system has been performed in our facility on a routine basis and 210 patients and healthy donors have been included in this analysis. No significant reduction in viability of CD34+ cells and no process‐related contamination were observed. Outcome of hematopoietic stem cell transplantation regarding time of engraftment and infectious complications is comparable to products manufactured in conventional clean‐room facilities.

CONCLUSION

Our data confirm that cryopreservation of PBSCs within a functionally closed‐bag system is safe, effective, and economical. Furthermore, the system has the potential to be extended to other manufacturing processes of cellular products.
Novel RHAG allele encoding the Rhnull phenotype in Brazil
Authors: Arnoni Carine Prisco , Muniz Janaína Guilhem , Gazito Diana , Person Rosangela de Medeiros , Vendrame Tatiane Aparecida de Paula , Castilho Lilian , Latini Flavia Roche Moreira
Published: July 2015

Rhnull is a rare phenotype characterized by the loss of Rh antigen expression. This phenotype can be related to several molecular backgrounds. In this study, we show a novel allele in a Brazilian pregnant woman encoding the Rhnull phenotype due to a change in RHAG exon2 c.310C>T, which leads to a premature stop codon (Gln104Stop).
FY*A silencing by the GATA‐motif variant FY*A(−69C) in a Caucasian family
Authors: Písačka Martin , Marinov Iuri , Králová Miroslava , Králová Jana , Kořánová Michaela , Bohoněk Miloš , Sood Chhavi , Ochoa‐Garay Gorka
Published: July 2015

BACKGROUND

The c.1‐67C variant polymorphism in a GATA motif of the FY promoter is known to result in erythroid‐specific FY silencing, that is, in Fy(a−) and Fy(b−) phenotypes. A Caucasian donor presented with the very rare Fy(a−b−) phenotype and was further investigated.

STUDY DESIGN AND METHODS

Genomic DNA was analyzed by sequencing to identify the cause of the Fy(a−b−) phenotype. Samples were collected from some of his relatives to establish a correlation between the serology and genotyping results. Red blood cells were analyzed by gel column agglutination and flow cytometry. Genomic DNA was analyzed on genotyping microarrays, by DNA sequencing and by allele‐specific PCR.

RESULTS

In the donor, a single‐nucleotide polymorphism T>C within the GATA motif was found at Position c.1‐69 of the FY promoter and shown to occur in the FY*A allele. His genotype was found to be FY*A(−69C), FY*BW.01. In six FY*A/FY*B heterozygous members of the family, a perfect correlation was found between the presence vs. absence of the FY*A(−69C) variant allele and a Fy(a−) vs. Fy(a+) phenotype.

CONCLUSION

The location of the c.1‐69C polymorphism in a GATA motif whose disruption is known to result in a Fy null phenotype, together with the perfect correlation between the presence of the FY*A(−69C) allele and the Fy(a−) phenotype support a cause–effect relationship between the two.
Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation
Authors: Schonewille Henk , Prinsen‐Zander Karin J.M. , Reijnart Mila , van de Watering Leo , Zwaginga Jaap‐Jan , Meerman Robertjan H. , van Kamp Inge L. , Brand Anneke
Published: July 2015

BACKGROUND

Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fya, Fyb, Jka, Jkb, and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported.

STUDY DESIGN AND METHODS

Data from February 2007 to August 2014 on IUT patients were retrieved from the Leiden University Medical Center database and from donors from the Sanquin National Donor Database. Maternal data included red blood cell (RBC) antigen profiles, RBC antibodies, and date and consecutive number of each IUT. From the fathers, children, and IUT donors the RBC antigen profiles were retrieved.

RESULTS

A total of 182 fetuses from 159 women were treated with 481 IUTs. Of these, 317 IUTs (66%) were matched for Duffy, Kidd, and S antigens. Only matched IUTs were received by 77 women (48%) and 82 (52%) received (partly) nonmatched IUTs. Evaluable for new antibodies were 142 women. Duffy, Kidd, or S antibodies were formed by three of 69 women (4.3%) after matched IUTs and by eight of 73 women (11.0%) after nonmatched IUTs.

CONCLUSION

Extended matching for all IUTs was not possible for approximately 50% of women. Strict adherence to Duffy, Kidd, and S antigens–matched IUTs decreased immunization against these antigens by 60% compared to nonmatched IUTs.
Comparison of biosimilar filgrastim with originator filgrastim for peripheral blood stem cell mobilization and engraftment in patients with multiple myeloma undergoing autologous stem cell transplantation
Authors: Pham Tina , Patil Sushrut , Fleming Shaun , Avery Sharon , Walker Patricia , Wei Andrew , Curtis David , Stuart Georgia , Klarica Daniela , O'Brien Maureen , Morris Karen , Das Tongted , Bollard Geraldine , Muirhead Jennifer , Coutsouvelis John , Spencer Andrew
Published: July 2015

BACKGROUND

Nivestim is a biosimilar approved for the same indications as Neupogen including the mobilization of autologous peripheral blood stem cells (PBSCs). The clinical efficacy and safety of Nivestim for this use have not been formally assessed in clinical trials.

STUDY DESIGN AND METHODS

In our retrospective single‐center study we compared variables of PBSC mobilization and engraftment of 60 patients mobilized with Nivestim to that of 38 patients mobilized with Neupogen.

RESULTS

We found no difference between Nivestim and Neupogen in peripheral blood CD34+ at first leukapheresis (47 × 106 cells/L vs. 60 × 106 cells/L, p = 0.48) nor the total CD34+ collected (5.37 × 106/kg vs. 4.59 × 106/kg, p = 0.22). However, a difference in the median number of leukapheresis procedures (one vs. two, p = 0.0007) was observed. Eighty‐one patients (51 Nivestim and 30 Neupogen mobilized) went on to transplantation. Median time to neutrophil engraftment (15 days vs. 13.5 days, p = 0.09) and platelet (PLT) engraftment (20 days vs. 18 days, p = 0.01) was longer in the Nivestim group. The significant delay in PLT engraftment did not, however, translate to increased PLT transfusions (two vs. three, p = 0.2) or impact significantly on hospitalization time for admissions within 30 days posttransplant (20 days vs. 18 days, p = 0.17).

CONCLUSION

Nivestim is as effective as Neupogen for PBSC mobilization; however, its use was associated with a delay in PLT recovery. A prospective study should be conducted to confirm our findings.
Effects of teriparatide retreatment in a patient with β‐thalassemia major
Authors: Tournis Symeon , Dede Anastasia D. , Savvidis Christos , Triantafyllopoulos Ioannis K. , Kattamis Antonis , Papaioannou Nikolaos
Published: July 2015

BACKGROUND

Bone disease is a frequent complication of β‐thalassemia major (β‐ΤΜ) and its etiology is multifactorial. Marrow expansion, chronic hypoxia, endocrine complications, and iron overload caused chiefly by chronic transfusion treatment are significant factors affecting skeletal health. Bone disease is prevalent even among patients on regular transfusions and adequate iron chelation. The life expectancy of patients with β‐thalassemia has increased during the past decade and so, nowadays, patients with thalassemia‐associated bone disease (TBD) often require long‐term management. There are limited data concerning their pharmacologic treatment. Bisphosphonates represent the most widely studied agents in such patients and there are no published studies about the effects of anabolic treatment. Retreatment with teriparatide has only occasionally been studied in patients with osteoporosis.

CASE REPORT

We present a male adult patient with β‐ΤΜ with a history of low bone mass and multiple vertebral fractures, who required sequential treatment for his longstanding bone disease. He had exhibited considerable, albeit delayed, response to a course of teriparatide treatment for 18 months but subsequently, and while on alendronate, sustained an insufficiency fracture at the left ischiopubic ramus. A second trial of teriparatide treatment resulted in further remarkable increase in total hip and femoral neck bone mineral density. We present the patient's response to sequential treatment during an 8‐year follow‐up.

CONCLUSION

Teriparatide could represent an alternative treatment for adults with TBD especially when long‐term, sequential treatment is needed. Although there are limited data concerning retreatment, in selected cases, this might be considered.
Cytologic analysis of the mammary papillar discharge in a canine micropapillary carcinoma
Authors: Cassali Geovanni Dantas , Monteiro Lidianne Narducci , Gamba Conrado de Oliveira , Damasceno Karine Araújo , de Campos Cecília Bonolo , Salgado Breno Souza
Published: July 2015

This is a report on the cytologic analysis of the mammary papillar discharge in a 7‐year‐old female Doberman dog with an invasive micropapillary carcinoma. Cytologic evaluation of nipple discharge is a well‐known method for the rapid diagnosis of breast cancer in women. However, there is no previous report regarding the use of this technique for assessing mammary tumors in dogs. The aim of this study was to describe the use of mammary papillar discharge cytology for diagnosing a micropapillary carcinoma in a dog. Cytologically, evaluation of the papillar discharge revealed cells arranged in clusters in a papillary pattern or in a morula‐like arrangement, suggesting the diagnosis of a micropapillary carcinoma, which was subsequently confirmed by histopathology. Thus, mammary papillar discharge cytology should be considered as an ancillary method for evaluating mammary diseases in dogs.
Serum concentrations of allergen‐specific IgE in horses with equine recurrent airway obstruction and healthy controls assessed byELISA
Authors: Niedzwiedz Artur , Jaworski Zbigniew , Kubiak Krzysztof
Published: July 2015

Background

Equine recurrent airway obstruction (RAO), also known as heaves, is one of the most common respiratory problems in older horses. WhenRAO‐affected horses stay pastured or in a dust‐free environment for a prolonged time, clinical signs as well as airway inflammation wane. A number of environmental, immunologic, infectious, and genetic factors play an important role in the pathogenesis ofRAO, and the immunologic basis of this disease is still poorly understood.

Objectives

The aim of this study was to investigate the concentrations of allergen‐specific IgE in the serum of horses suffering from RAO and healthy controls.

Material and methods

The study included a group of 14 adult Polish Konik horses, kept in a standardized environment, and divided into 2 groups: 7 horses which did not have any respiratory problems comprised the control group and 7 horses with a history ofRAOconstituted the study group. A clinical and laboratory evaluation, endoscopic examination, and bronchoalveolar lavage (BAL) were performed in all horses. Sera of all horses were tested against allergens from 9 molds and 3 mites using the Heska Allercept assay.

Results

In the serologic tests, a statistically significant difference between both groups was found for specific IgE against mites, whereinTyrophagus putrescentiacorrelated most clearly withRAO. There was no difference between groups for IgE specific against molds.

Conclusion

On the basis of our observations and results, we conclude thatRAOis associated with increased serum concentrations of specific serum IgE against mites, in particularT putrescentia.
Ultrastructural characterization of normal Merkel cells in the dog
Authors: Ramírez Gustavo A. , Rodríguez Francisco , Herráez Pedro , Castro‐Alonso Ayoze , Andrada Marisa , Espinosa‐de‐los‐Monteros Antonio
Published: July 2015

Background

Involvement of Merkel cells (MKs) in different cutaneous diseases as well as in the growth, differentiation and homeostasis of the skin has been previously documented.

Hypothesis/Objectives

The aim was to assess the ultrastructural features of MKs in canine skin, including morphometrics, highlighting their similarities with and differences from those described for other mammals.

Animals

Hard palate, nasal planum, lower lip and whisker pad samples were taken from two healthy young dogs destined for academic purposes.

Methods

Ultrathin sections of samples fixed in osmium tetroxide and embedded in Epon 812 resin were stained with uranyl acetate and lead citrate and examined using a JEOL JEM 2010 transmission electron microscope.

Results

Ultrastructural characteristics included the following: (i) arrangement in clusters in the basal layer of the epidermis, oral mucosa and external follicular root sheath; (ii) inconstant link with nerve terminal; (iii) oval (10.27 ± 1.64 μm major axis) cell shape with large lobulated nuclei (5.98 ± 1.16 μm major axis); (iv) spine‐like and thick cytoplasmic processes interdigitating with surrounding keratinocytes; (v) presence of desmosomes in the cell body or at the base of spine‐like processes attaching to neighbouring keratinocytes; and (vi) cytoplasm containing loosely arranged intermediate filaments (10.04 ± 1.17 nm) and numerous dense‐core granules (100.1 ± 17.12 nm) arranged in the basal portion of the cytoplasm.

Conclusions and clinical importance

This study provides the first complete description of the ultrastructural characteristics of MKs in the dog, enhancing our knowledge of the skin structure in this species and providing a basis for future physiological and pathological studies of the role of these cells in normal and damaged canine tissues.
Plasma iron, C‐reactive protein, albumin, and plasma fibrinogen concentrations in dogs with systemic inflammatory response syndrome
Authors: Torrente Carlos , Manzanilla Edgar G. , Bosch Luis , Fresno Laura , Rivera del Alamo Montserrat , Andaluz Anna , Saco Yolanda , Ruiz de Gopegui Rafael
Published: July 2015

Objective

To investigate the diagnostic and prognostic value over time of plasma iron compared with the inflammatory markers albumin, C‐reactive protein (CRP), and fibrinogen in dogs with systemic inflammatory response syndrome (SIRS).

Design

Prospective observational study of sequentially enrolled dogs.

Setting

ICU of a veterinary teaching hospital.

Animals

One hundred and sixteen client‐owned dogs: 54 dogs with SIRS or sepsis, 42 with focal inflammation, and 20 clinically healthy dogs.

Measurements and Main Results

Blood samples were obtained on admission in all study groups, and then on alternate days until discharge or death in both inflammation groups. On admission, dogs with SIRS had significantly lower plasma iron (65 ± 5.8 μg/dL,P= 0.001) concentrations than dogs with focal inflammation (89.5 ± 6.2 μg/dL,P= 0.001). Plasma iron, albumin, and CRP effectively discriminated the SIRS/sepsis group from those presenting with focal inflammation with areas under the curve for the receiver operating curves of 0.679, 0.834, and 0.704, respectively.

The admission values for these variables did not discriminate survivors from nonsurvivors within the SIRS/sepsis group. However, the magnitude of increase in iron concentration and the decrease in CRP concentration from admission to hospital discharge was higher in survivors than in nonsurvivors within the SIRS/septic group (22.8 vs. 2.51 μg/dL, respectively,P= 0.021 for iron; −67.1 vs. −4.1 mg/L, respectively,P= 0.002 for CRP), resulting in iron and CRP concentrations at hospital discharge for survivors similar to those in the focal inflammation group.

Conclusion

Hypoferremia is a sensitive marker of systemic inflammation in dogs. In this study, the increase in iron concentrations during the hospitalization period of SIRS/septic dogs was associated with a better prognosis, suggesting that plasma iron in combination with CRP and albumin concentrations might be used to monitor dogs with inflammatory disease processes.
Presumptive intraperitoneal envenomation resulting in hemoperitoneum and acute abdominal pain in a dog
Authors: Istvan Stephanie A. , Walker Julie M. , Hansen Bernard D. , Hanel Rita M. , Marks Steven L.
Published: July 2015

Objective

To describe the clinical features, diagnostic findings, treatment, and outcome of a dog with acute abdominal pain and hemoperitoneum secondary to a presumptive intraperitoneal (IP) snakebite.

Case Summary

A 10‐month‐old castrated male mixed‐breed dog was evaluated for suspected snake envenomation. The dog presented recumbent and tachycardic with signs of severe abdominal pain. Two cutaneous puncture wounds and hemoperitoneum were discovered during evaluation. Ultrasonographic examination revealed communication of the wounds with the peritoneal cavity. The dog was treated with supportive care, parenteral analgesia, packed red blood cell and fresh frozen plasma transfusions, crotalid antivenom, and placement of an IP catheter to provide local analgesia. The dog recovered fully and was discharged 5 days after initial presentation.

New or Unique Information Provided

To our knowledge, this is the first report of IP envenomation accompanied by hemorrhage treated with continuous IP analgesia in the veterinary literature.
Measuring the influence of blood component infusion rate on recipient vital signs
Authors: Gehrie E. A. , Hendrickson J. E. , Tormey C. A.
Published: July 2015

Background and Objectives

One of the challenges surrounding blood component administration is the determination of an appropriate rate of infusion. There are very few evidence‐based guidelines available to guide healthcare providers looking for a ‘standard’ infusion rate for red blood cells (RBCs), plasma or platelets (PLTs). Our objective was to determine the extent to which blood component infusion rates were associated with changes in transfusion recipient vital signs.

Materials and Methods

We retrospectively examined records of 3496 component infusions (RBCs, n = 2359; PLTs, n = 478; plasma, n = 659) over a 1‐year period at a 362‐bed multispecialty hospital. The following data were collected for each transfusion: blood product volume and infusion time, recipient pre‐ and post‐transfusion temperature, blood pressure and pulse rate, and hospital ward where transfusion occurred.

Results

Plasma (median 10·4 ml/min) was infused faster than PLTs (median 7·2 ml/min, P < 0·0001) or RBCs (median 2·3 ml/min, P < 0·0001). For all blood components, infusion rates varied based on the hospital unit performing the infusion. No association was found between relatively fast RBC, plasma or PLT infusion rates (>20 ml/min) and clinically significant reported changes in vital signs.

Conclusions

There does not appear to be a strong correlation between infusion rate and significant changes in recipient temperature, blood pressure or pulse rate. Based on these data, a reasonable rate for routine transfusion is 2–3 ml/min for RBCs and 7–10 ml/min for plasma and PLTs. Faster infusion rates (>20 ml/min) likely can be applied with close patient monitoring if there is a more urgent need for transfusion.
A national common massive transfusion protocol (MTP) is a feasible and advantageous option for centralized blood services and hospitals
Authors: Chay J. , Koh M. , Tan H. H. , Ng J. , Ng H. J. , Chia N. , Kuperan P. , Tan J. , Lew E. , Tan L. K. , Koh P. L. , Desouza K. A. , Bin Mohd Fathil S. , Kyaw P. M. , Ang A. L.
Published: July 2015

Background

A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals.

Methods

Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood‐derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non‐trauma general medical, surgical and obstetric patients.

Results

There were 434 activations of the MTP from October 2011 to October 2013. Thirty‐nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra‐operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri‐partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood‐derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation.

Conclusion

This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.
ABO alleles are linked with haplotypes of an erythroid cell‐specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination
Authors: Nakajima T. , Sano R. , Takahashi Y. , Watanabe K. , Kubo R. , Kobayashi M. , Takahashi K. , Takeshita H. , Kominato Y.
Published: July 2015

Recent investigation of transcriptional regulation of the ABO genes has identified a candidate erythroid cell‐specific regulatory element, named the +5·8‐kb site, in the first intron of ABO. Six haplotypes of the site have been reported previously. The present genetic population study demonstrated that each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles. Thus, investigation of these haplotypes could provide a clue to further elucidation of ABO alleles.
Treatment of refractory ITP and Evans syndrome by haematopoietic cell transplantation: is it indicated, and for whom?
Authors: Vaughn J. E. , Anwer F. , Deeg H. J.
Published: July 2015

Several lines of therapy have been established for patients with immune thrombocytopenia (ITP) and Evans syndrome. However, these therapies generally require prolonged administration, lead to profound immunosuppression and increased infectious risk, and are often poorly tolerated. While most patients with these disorders will respond to first‐line steroid therapy, others will prove refractory or intolerant to multiple treatments. In these patients (and possibly even selected patients who are not considered refractory), autologous or allogeneic haematopoietic stem cell transplantation (HCT) may provide definitive therapy. We review the literature on the treatment of ITP and Evans syndrome with HCT and discuss its use in the management of these disorders. We also pose, for the purpose of discussion, research questions that will be important to address if HCT is to be considered a viable option for more patients with these diseases.
High rate of HIV infection in voluntary, first time, young male donors at HEMOAM, a reference blood bank in the Brazilian Amazon: 1992–2012 historical series
Authors: Viga‐Yurtsever S. , Fraiji N. , Lira E. , Stefani M. M. , Kiesslich D.
Published: July 2015

Background and Objectives

There are significant regional differences in the Brazilian AIDS epidemic, which expands in the Amazonas State/north, while it is stable in the epicentre/southeast. This study evaluated incidence of HIV infection (1992–2012) at a main public blood bank in the Brazilian Amazon (Hematology and Hemotherapy Foundation from Amazonas State/HEMOAM, Manaus).

Methods

Retrospective analysis of institutional‐computerized data set (SPSS version 13; P < 0·05).

Results

Among 762 378 consecutive blood donations performed by 687 080 donors, replacement donations (56·8%), repeat donors (65·3%) and males (80·4%) prevailed. Among them, 685 confirmed cases of HIV infection with significantly higher frequency in: voluntary donations (0·14% vs. 0·08% replacement), first‐time donors (0·17% vs. 0·06% repeat) and males (0·11% vs. 0·07% females). Around 80% had 21–40 years. Overtime HIV positivity raised both in younger (16–20 years; P = 0·005) and older individuals (51–65 years; P = 0·03).

Conclusion

Higher rate of HIV in voluntary, first time, young males may orient recruitment of lower risk donors, especially in the Brazilian Amazon where AIDS incidence and mortality are rising.
Characterisation of Avena fatua populations with resistance to multiple herbicides
Authors: Keith B K , Lehnhoff E A , Burns E E , Menalled F D , Dyer W E
Published: July 2015

Avena fatua (wild oat) populations with resistance (R) to one or more herbicides have been described in numerous cropping systems worldwide. We previously reported that the R3 and R4 wild oat populations from Montana, USA, were resistant to four herbicides representing three different modes of action: tralkoxydim [acetyl‐CoA carboxylase (ACCase] inhibitor), imazamethabenz and flucarbazone [acetolactate synthase (ALS) inhibitors] and difenzoquat (growth inhibitor). We now quantify resistance levels of these populations to triallate [very long chain fatty acid (VLCFA) biosynthesis inhibitor], pinoxaden (ACCase inhibitor) and paraquat (photosystem I inhibitor). Glasshouse dose–response experiments showed that, compared with the means of two susceptible (S) populations, the R3 and R4 populations were 17.5‐ and 18.1‐fold more resistant to triallate, 3.6‐ and 3.7‐fold more resistant to pinoxaden, respectively, and 3.2‐fold (R3) more resistant to paraquat. Pre‐treatment of R plants with the cytochrome P450 inhibitor malathion partially reversed the resistance phenotype for flucarbazone (both populations), imazamethabenz (R4), difenzoquat (R4) and pinoxaden (R3), but not for tralkoxydim, fenoxaprop‐P‐ethyl or triallate. Target site point mutations known to confer resistance to ALS or ACCase inhibitors were not detected via DNA sequencing and allele‐specific PCR assays in R plants, suggesting the involvement of non‐target site resistance mechanism(s) for these herbicides. Together, our results complete the initial characterisation of wild oat populations that are resistant to seven (R3) or six (R4) herbicides from five or four mode of action families respectively.
Microclimate is an independent risk factor for the development of intraoperatively acquired pressure ulcers in the park‐bench position: A prospective observational study
Authors: Yoshimura Mine , Nakagami Gojiro , Iizaka Shinji , Yoshida Mikako , Uehata Yoko , Kohno Michihiro , Kasuya Yusuke , Mae Tomoko , Yamasaki Takashi , Sanada Hiromi
Published: July 2015

Preventing pressure ulcers is important in patients undergoing procedures in the park‐bench position. We hypothesized that the microclimate around the skin is a significant risk factor for developing pressure ulcers. This research continuously assessed factors of the microclimate in terms of skin temperature and perspiration as well as the interface pressure in order to determine whether the microclimate is an independent risk factor for the development of park‐bench position‐related pressure ulcers (PBP‐PUs). A prospective observational study was conducted among patients undergoing elective surgery in the park‐bench position at a general hospital in the metropolitan area of Japan between April and November 2014. Factors of the microclimate, including skin temperature and perspiration, in addition to the interface pressure were continuously measured throughout surgery. Twenty‐nine patients were analyzed (mean age 44.4 ± 13.2 years, male 44.8%). Of these 29 patients, seven (24.1%) developed Category I PBP‐PUs. The change in skin temperature from baseline to the end of surgery (2.7 ± 0.3 °C vs. 1.9 ± 0.8 °C) and the average peak pressure (119.1 ± 36.8 mmHg vs. 94.5 ± 23.1 mmHg) were significantly higher in the patients with PBP‐PUs than in those without PBP‐PUs. There were no significant differences in the amount of perspiration between the two groups. A hierarchical logistic regression analysis showed that the change in skin temperature was significantly related to the development of PBP‐PUs (unit = 0.1 °C: odds ratio 1.44, 95% confidential interval 1.09–2.33) when adjusted for the average peak pressure and length of surgery. Our results suggest that a change in skin temperature toward a higher value is an independent risk factor for the development of PBP‐PUs. Proper intraoperative management of skin temperature may therefore be a promising candidate as a preventive method against PBP‐PU development.
Evidence‐based chronic ulcer care and lower limb outcomes among Pacific Northwest veterans
Authors: Karavan Mahsa , Olerud John , Bouldin Erin , Taylor Leslie , Reiber Gayle E.
Published: July 2015

Evidence‐based ulcer care guidelines detail optimal components of care for treatment of ulcers of different etiologies. We investigated the impact of providing specific evidence‐based ulcer treatment components on healing outcomes for lower limb ulcers (LLU) among veterans in the Pacific Northwest. Components of evidence‐based ulcer care for venous, arterial, diabetic foot ulcers/neuropathic ulcers were abstracted from medical records. The outcome was ulcer healing. Our analysis assessed the relationship between evidence‐based ulcer care by etiology, components of care provided, and healing, while accounting for veteran characteristics. A minority of veterans in all three ulcer‐etiology groups received the recommended components of evidence‐based care in at least 80% of visits. The likelihood of healing improved when assessment for edema and infection were performed on at least 80% of visits (hazard ratio [HR] = 3.20, p = 0.009 and HR = 3.54, p = 0.006, respectively) in patients with venous ulcers. There was no significant association between frequency of care components provided and healing among patients with arterial ulcers. Among patients with diabetic/neuropathic ulcers, the chance of healing increased 2.5‐fold when debridement was performed at 80% of visits (p = 0.03), and doubled when ischemia was assessed at the first visit (p = 0.045). Veterans in the Pacific Northwest did not uniformly receive evidence‐based ulcer care. Not all evidence‐based ulcer care components were significantly associated with healing. At a minimum, clinicians need to address components of ulcer care associated with improved ulcer healing.
Severe hypoxia and malnutrition collectively contribute to scar fibroblast inhibition and cell apoptosis
Authors: Lynam Emily C. , Xie Yan , Dawson Rebecca , Mcgovern Jacqui , Upton Zee , Wang XiQiao
Published: July 2015

This study aims to investigate whether severe hypoxia and malnutrition in scar tissue play key roles to induce hypertrophic scar regression. And scar‐derived fibroblasts were treated with moderate/severe hypoxia and malnutrition to model condition of proliferative and regressive scar (5%O2+5%FCS and 0.5%O2 + 0.5%FCS), and normoxia with well nutrition as control (10%O2 + 10%FCS). Our results demonstrated that severe hypoxia and malnutrition resulted in significantly reduced cell viability and collagen production, as well as HIF‐1, VEGF, TGF‐β1, and Bcl‐2 protein expression when compared with control, and cell apoptosis occurred. Therefore, the severe hypoxia and malnutrition in scar tissue contribute to fibroblast inhibition and cell apoptosis, which is correlated with scar regression.
Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway‐regulatory protein
Authors: Azimzadeh Agnes M. , Kelishadi Sean S. , Ezzelarab Mohamed B. , Singh Avneesh K. , Stoddard Tiffany , Iwase Hayato , Zhang Tianshu , Burdorf Lars , Sievert Evelyn , Avon Chris , Cheng Xiangfei , Ayares David , Horvath Keith A. , Corcoran Philip C. , Mohiuddin Muhammad M. , Barth Rolf N. , Cooper David K. C. , Pierson Richard N.
Published: July 2015

We describe the incidence of early graft failure (EGF, defined as loss of function from any cause within 3 days after transplant) in a large cohort of GalTKO pig organs transplanted into baboons in three centers, and the effect of additional expression of a human complement pathway‐regulatory protein, CD46 or CD55 (GalTKO.hCPRP). Baboon recipients of life‐supporting GalTKO kidney (n = 7) or heterotopic heart (n = 14) grafts received either no immunosuppression (n = 4), or one of several partial or full immunosuppressive regimens (n = 17). Fourteen additional baboons received a GalTKO.hCPRP kidney (n = 5) or heart (n = 9) and similar treatment regimens. Immunologic, pathologic, and coagulation parameters were measured at frequent intervals. EGF of GalTKO organs occurred in 9/21 baboons (43%). hCPRP expression reduced the GalTKO EGF incidence to 7% (1/14; P < 0.01 vs. GalTKO alone). At 30 mins, complement deposits were more intense in organs in which EGF developed (P < 0.005). The intensity of peri‐transplant platelet activation (as β‐thromboglobulin release) correlated with EGF, as did the cumulative coagulation score (P < 0.01). We conclude that (i) the transgenic expression of a hCPRP on the vascular endothelium of a GalTKO pig reduces the incidence of EGF and reduces complement deposition, (ii) complement deposition and platelet activation correlate with early GalTKO organ failure, and (iii) the expression of a hCPRP reduces EGF but does not prevent systemic coagulation activation. Additional strategies will be required to control coagulation activation.
Multiple reversals of chirality in the land snail genus Albinaria (Gastropoda, Clausiliidae)
Authors: Kornilios Panagiotis , Stamataki Eirini , Giokas Sinos
Published: July 2015

Reversed chirality has frequently evolved in snails, although the vast majority coils dextrally. However, there are often sinistral species within a dextral genus or almost exclusively sinistral families, such as the Clausiliidae. Some populations of the predominantly sinistral clausiliid genus Albinaria, in the southern Greek mainland, coil dextrally. The origin, evolution and distribution of the dextral Albinaria are puzzling, and as there is no reliable phylogenetic reconstruction for this speciose genus, it remains unclear how many times a shift in chirality has really occurred. In this study, our aim was to elucidate the evolutionary pathways of dextrality in Albinaria. We undertook a molecular phylogenetic analysis of two mtDNA (16S and COI) and one nDNA marker (ITS1) and included dextral and sinistral representatives found in syntopy or not. Both mtDNA and nDNA tree topologies imply that dextrals did not evolve as a monophyletic lineage. Instead, dextral lineages have evolved from sinistral ancestors multiple times independently. The fragmented population structure in Albinaria facilitates genetic drift and contributes to fixation of the opposite chirality and overcoming of the mating disadvantage of left–right reversal. Stochastic phenomena and biogeographical barriers have trapped those reversals in a limited geographical area.
Biogeography of Australasian flightless weevils (Curculionidae, Celeuthetini) suggests permeability of Lydekker's and Wallace's Lines
Authors: Toussaint Emmanuel F. A. , Tänzler Rene , Rahmadi Cahyo , Balke Michael , Riedel Alexander
Published: July 2015

The Indo‐Australian region was formed by the collision of the Australian and Asian plates, and its fauna largely reflects this dual origin. Lydekker's and Wallace's Lines represent biogeographic transition boundaries between biotas although their permeability through geological times was rarely assessed. Here, we explore the evolutionary history of flightless weevils of the tribe Celeuthetini in this geologically highly complex region. We generated a DNA sequence data set of 2236 bp comprising two nuclear and two mitochondrial markers for 62 species of the Indo‐Australian tribe Celeuthetini. We used Bayesian Inference and Maximum Likelihood to reconstruct the first molecular phylogeny of the group. Based on this phylogenetic tree, we employed the program BioGeoBEARS to infer the biogeographical history of Celeuthetini in the region. The group's radiation begun east of Wallace's Line, probably during the mid‐Eocene. We unveil multiple transgressions of Lydekker's and Wallace's Lines mostly during the Miocene with a significant role of founder‐event speciation. The phylogeny of Celeuthetini is geographically highly structured with the first lineages occurring in New Guinea and the Moluccas, and a deep divergence between two clades largely confined to Sulawesi and their respective sister clades of the Lesser Sunda Islands. Wallace's Line was crossed once from Sulawesi and three times from the Lesser Sunda Islands to Java whilst Lydekker's Line was crossed once from New Guinea to the Moluccas. Although this beetle group shows extensive local diversification with little dispersal, the biogeographical demarcations of the Australasian region appear to have been rather porous barriers to dispersal.
Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2: role of carotid body CO2
Authors: Smith Curtis. A. , Blain Grégory M. , Henderson Kathleen S. , Dempsey Jerome A.
Published: July 2015

Key Points

The influence of specific carotid body (CB) normoxic hypocapnia, hypercapnia and normocapnia on the ventilatory sensitivity of central chemoreceptors to systemic hypercapnia was assessed in seven awake dogs with extracorporeal perfusion of the vascularly isolated CB.

Chemosensitivity in this preparation was similar to that in the intact animal.

Separation of CB circulation from that of the brain was confirmed.

When the isolated CB was hypercapnic vs. hypocapnic and when the isolated CB was normocapnic vs. hypocapnic, the group mean central CO2 response slopes of minute ventilation () (P ≤ 0.01) and mean inspiratory flow rate (VT/TI) (P ≤ 0.05) increased significantly. Tidal volume (VT), breathing frequency (fb)and rate of rise of diaphragm EMG were increased in 6 of 7 dogs but did not achieve statistical significance.

We propose that hyperaddition is the dominant form of chemoreceptor interaction under conditions of quiet wakefulness in intact animals and over a wide range of CB and .

We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO2. The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body  ≈ 22, 41 and 68 mmHg, respectively) on the ventilatory CO2 sensitivity of central chemoreceptors was studied in seven awake dogs with vascularly‐isolated and extracorporeally‐perfused CBs. Chemosensitivity with one CB was similar to that in intact dogs. In four CB‐denervated dogs, absence of hyper‐/hypoventilatory responses to CB perfusion with of 19–75 mmHg confirmed separation of the perfused CB circulation from the brain. The group mean central CO2 response slopes were increased 303% for minute ventilation ()(P ≤ 0.01) and 251% for mean inspiratory flow rate (VT/TI) (P ≤ 0.05) when the CB was hypercapnic vs. hypocapnic; central CO2 response slopes for tidal volume (VT), breathing frequency (fb) and rate of rise of the diaphragm EMG increased in 6 of 7 animals but the group mean changes did not reach statistical significance. Group mean central CO2 response slopes were also increased 237% for (P ≤ 0.01) and 249% for VT/TI(P ≤ 0.05) when the CB was normocapnic vs. hypocapnic, but no significant differences in any of the central ventilatory response indices were found between CB normocapnia and hypercapnia. These hyperadditive effects of CB hyper‐/hypocapnia agree with previous findings using CB hyper‐/hypoxia.We propose that hyperaddition is the dominant form of chemoreceptor interaction in quiet wakefulness when the chemosensory control system is intact, response gains physiological, and carotid body chemoreceptors are driven by a wide range of O2 and/or CO2.