bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Brix refractometer as an on‐farm tool for the detection of passive transfer of immunity in dairy calves
Authors: Thornhill JB , Krebs GL , Petzel CE
Published: January 2015

Objectives

To investigate the accuracy of both the optical and digital Brix refractometers compared with radial immunodiffusion (RID) for determining the immunoglobulin G (IgG) concentrations in dairy calf serum.

Design

The experiment design was a cross‐sectional survey of four dairy farms. Serum was sampled from 12 calves from each farm at approximately 48 hours of age.

Methods

Serum IgG concentrations of 48 calves were measured using RID and both types of Brix refractometer.

Results

IgG concentrations measured by Brix refractometer scores correlated with RID results: 0.74 and 0.71 for the digital and optical devices, respectively. The minimum Brix score that identified calf serum with success of passive immunity (>1000 mg/dL RID IgG) with 100% accuracy was 10% for both devices. The optical and digital devices performed similarly at identifying IgG concentrations in calf serum, with a concordance of 87%.

Conclusion

Brix refractometer score ≥10% can be used to classify calves with successful transfer of passive immunity and the devices are sufficiently accurate for use as a simple, inexpensive on‐farm tool for the monitoring of neonatal dairy calf immunity levels.
Herpesvirus in a captive Australian Krefft's river turtle (Emydura macquarii krefftii)
Authors: Cowan ML , Raidal SR , Peters A
Published: January 2015

Case report

A mature, captive Krefft's river turtle (Emydura macquarii krefftii) was presented with severe proliferative and ulcerative lesions of the skin and shell. The areas were biopsied and histopathological examination demonstrated orthokeratotic hyperkeratosis with keratinocytes containing eosinophilic intranuclear inclusions. Molecular diagnostics confirmed the presence of a herpesvirus in the affected tissues.

Conclusion

This is the first recorded case of herpesvirus infection in an Australian freshwater turtle species.
Milrinone for the Treatment of Acute Heart Failure After Acute Myocardial Infarction: A Systematic Review and Meta‐Analysis
Authors: Tang Xiuying , Liu Peng , Li Runjun , Jing Quanmin , Lv Junhao , Liu Li , Liu Yingfeng
Published: January 2015

Despite advancements in modern medicine, the treatment of acute heart failure (AHF) after acute myocardial infarction (AMI) remains challenging. Milrinone is effective in the treatment of chronic congestive heart failure, but its safety and efficacy in patients with AHF after AMI have not been systematically evaluated. This meta‐analysis was performed to assess the safety and efficacy of milrinone in patients with AHF after AMI. We used a pre‐designed protocol to search electronic databases for randomized trials assessing milrinone for the treatment of AHF after AMI. Data were abstracted from relevant studies. Heterogeneity was assessed qualitatively using a Q test and quantified using the I2 statistic. Pooled risk estimates with 95% confidence intervals (CIs) were obtained using fixed‐effects models unless substantial heterogeneity was observed (I2 ≥ 50% and heterogeneity p ≤ 0.1). Four randomized trials met the inclusion criteria. However, there were no significant differences in deaths, blood pressure, premature ventricular contractions, gastrointestinal reactions, or ventricular tachycardia or fibrillation (all p > 0.05) between control group and milrinone treatment group. Pooled estimates showed that milrinone significantly increased the left ventricular ejection fraction (MD 5.69; 95% CI 4.27 to 7.10; p < 0.00001) and cardiac output (MD 0.35, 95% CI: 0.13 to 0.56; p = 0.002, I2 = 24%). While studies to date are few and limited by small sample sizes and poor quality, they suggest that treatment with milrinone may be safe and effective for patients with AHF after AMI. However, this meta‐analysis did not show that milrinone could improve prognosis or the survival rate.
Wentzel, Kathryn R & Brophy, Jere E (2014) Motivating students to learnRoutledge (New York & London) isbn 978‐0‐415‐89352‐7 301 pp £39.99 http://www.routledge.com/books/details/9780415893527/
Authors: Hammer Sara
Published: January 2015

The authors of Motivating students to learn offer teachers evidence‐based classroom strategies to motivate their students. This fourth edition draws comprehensively on current psychological and educational research on student motivation and extrapolates this to implications for teaching practice in the classroom. This book's aim is primarily school teachers but it may also be of interest to people in further and higher education. If you think this book's content could be relevant, I suggest you borrow a copy to decide whether it's worth buying.

Sara Hammer
The orphan receptor NOR1 participates in isoprenaline‐induced cardiac hypertrophy by regulating PARP‐1
Authors: Feng Xiao‐Jun , Gao Hui , Gao Si , Li Zhuoming , Li Hong , Lu Jing , Wang Jiao‐Jiao , Huang Xiao‐Yang , Liu Min , Zou Jian , Ye Jian‐Tao , Liu Pei‐Qing
Published: January 2015

Background and Purpose

The orphan nuclear receptor NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, and is involved in glucose and fat metabolism. However, its potential contribution to cardiovascular diseases remains to be assessed. Here, the roles of NOR1 in cardiac hypertrophy induced by isoprenaline and the underlying molecular mechanisms were investigated.

Experimental Approach

NOR1 was expressed in cardiomyocytes treated with isoprenaline. After NOR1 overexpression or knockdown in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA of hypertrophic biomarkers. Interactions between NOR1 and PARP‐1 were investigated by co‐immunoprecipitation. NOR1 expression and PARP‐1 activity were measured in rats with cardiac hypertrophy induced by isoprenaline.

Key Results

Treatment with isoprenaline significantly up‐regulated NOR1 expression and PARP‐1 activity both in vivo and in vitro. Specific gene silencing of NOR1 attenuated isoprenaline‐induced cardiomyocyte hypertrophy, whereas NOR1 overexpression exacerbated cardiac hypertrophy. We identified a physical interaction between NOR1 and PARP‐1, which was enhanced by NOR1 transfection and thereby led to PARP‐1 activation. Overexpression of NOR1, but not C293Y, a NOR1 mutant lacking the PARP‐1 binding activity, increased cellular surface area and the mRNA levels of atrial natriuretic factor and brain natriuretic polypeptide, effects blocked by the PARP‐1 inhibitor 3‐aminobenzamide or siRNA for PARP‐1.

Conclusions and Implications

This is the first evidence that NOR1 was involved in isoprenaline‐induced cardiac hypertrophy. The pro‐hypertrophic effect of NOR1 can be partly attributed to its regulation of PARP‐1 enzymic activity.
A novel selective and orally bioavailable Nav1.8 channel blocker, PF‐01247324, attenuates nociception and sensory neuron excitability
Authors: Payne Claire Elizabeth , Brown Adam R , Theile Jonathon W , Loucif Alexandre J C , Alexandrou Aristos J , Fuller Mathew D , Mahoney John H , Antonio Brett M , Gerlach Aaron C , Printzenhoff David M , Prime Rebecca L , Stockbridge Gillian , Kirkup Anthony J , Bannon Anthony W , England Steve , Chapman Mark L , Bagal Sharan , Roeloffs Rosemarie , Anand Uma , Anand Praveen , Bungay Peter J , Kemp Mark , Butt Richard P , Stevens Edward B
Published: January 2015

Background and Purpose

NaV1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers for the treatment of chronic pain. Here, we describe the effects of PF‐01247324, a new generation, selective, orally bioavailable Nav1.8 channel blocker of novel chemotype.

Experimental Approach

The inhibition of Nav1.8 channels by PF‐01247324 was studied using in vitro patch‐clamp electrophysiology and the oral bioavailability and antinociceptive effects demonstrated using in vivo rodent models of inflammatory and neuropathic pain.

Key Results

PF‐01247324 inhibited native tetrodotoxin‐resistant (TTX‐R) currents in human dorsal root ganglion (DRG) neurons (IC50: 331 nM) and in recombinantly expressed h Nav1.8 channels (IC50: 196 nM), with 50‐fold selectivity over recombinantly expressed TTX‐R hNav1.5 channels (IC50: ∼10 μM) and 65–100‐fold selectivity over TTX‐sensitive (TTX‐S) channels (IC50: ∼10–18 μM). Native TTX‐R currents in small‐diameter rodent DRG neurons were inhibited with an IC50 448 nM, and the block of both human recombinant Nav1.8 channels and TTX‐R from rat DRG neurons was both frequency and state dependent. In vitro current clamp showed that PF‐01247324 reduced excitability in both rat and human DRG neurons and also altered the waveform of the action potential. In vivo experiments n rodents demonstrated efficacy in both inflammatory and neuropathic pain models.

Conclusions and Implications

Using PF‐01247324, we have confirmed a role for Nav1.8 channels in both inflammatory and neuropathic pain. We have also demonstrated a key role for Nav1.8 channels in action potential upstroke and repetitive firing of rat and human DRG neurons.
Embedded (Lead) Users as Catalysts to Product Diffusion
Authors: Schweisfurth Tim G. , Herstatt Cornelius
Published: January 2015

Firms can harness social user networks not only for ideation, but also to accelerate and facilitate diffusion of new product introductions. They select individuals whose own product adoptions and opinions influence adoption decisions of others. In this paper we transfer this rationale to firm employees. We focus on ‘embedded users’ who are employees of a firm, but at the same time users of the firm's products. We aim to find out if their access to user networks, use experience and lead userness impact their opinion leadership and domain‐specific innovativeness. We also show how cognitive empathy towards external users is a mechanism to explain these relationships. Drawing on the user innovation and consumer behaviour literature, we derive and test eight hypotheses on a sample of 54 firm employees in gaming hardware firms. We find that lead userness is positively related to domain‐specific innovativeness and opinion leadership, but use experience only to the former. Cognitive empathy mediates all relationships in our study. To facilitate embedded users' tendency to act as opinion leaders and to adopt new products, managers should encourage their employees to use the firm's products to build use experience and thus develop cognitive empathy towards external users.
Glucocorticoid receptor function in health and disease
Authors: Caratti Giorgio , Matthews Laura , Poolman Toryn , Kershaw Stephen , Baxter Matthew , Ray David
Published: January 2015

Glucocorticoid hormones are essential for life in vertebrates. They act through the glucocorticoid receptor (GR), which is expressed in virtually all cells of the human body. Yet the actions of glucocorticoids (GCs) are specific to particular cell types. Broadly GCs regulate carbohydrate metabolism, inflammation, stress and cell fate. Synthetic GCs are widely used in medicine and are by far the most frequent cause of Cushing's syndrome in routine practice. The advent of novel drugs targeting the GR offers new opportunities to treat patients with immune, or malignant disease, and may also offer new opportunities to manage patients with adrenal insufficiency also. This review covers the latest understanding of how GCs work, how their actions are affected by disease, and where the new drugs may take us.
Trial and error: attending to language barriers in child welfare service provision from the perspective of frontline workers
Authors: Maiter Sarah , Alaggia Ramona , Chan Adrienne S. , Leslie Bruce
Published: January 2015

This paper reports on a qualitative study that used focus groups to gather data from the perspective of child protection workers on their experiences in providing services to clients with limited English proficiency (LEP). The goals of the study were to understand processes of relationship building and service provision that could contribute to improved practice. Focus groups are ideal in obtaining data on how a group deals with particular situations and for understanding their decision‐making processes. Measures to ensure rigour and trustworthiness were taken throughout the study. Findings provide rich and multilayered insights into the complexity of providing services for families with LEP showing that agencies use bilingual workers as well as interpreters for services. Participants noted, however, that services continued to be inconsistent with unclear guidelines and training about how and when to access interpreters. Lack of training for bilingual workers was also identified. Confidentiality issues, barriers to engaging with clients, problems with the quality of interpretation and role confusion together with benefits including interpreters being cultural and language ‘conduits’ and links to culturally specific services; enhanced communication decreasing the possibility of inaccurate assessments and lessening power differentials; and help with workload were noted.
Guidelines for diagnosis, prevention and treatment of hand eczema
Authors: Diepgen Thomas L , Andersen Klaus E , Chosidow Oliver , Coenraads Peter Jan , Elsner Peter , English John , Fartasch Manigé , Gimenez‐Arnau Ana , Nixon Rosemary , Sasseville Denis , Agner Tove
Published: January 2015

The guidelines aim to provide advice on the management of hand eczema (HE), using an evidence‐ and consensus‐based approach. The guidelines consider a systematic Cochrane review on interventions for HE, which is based on a systematic search of the published literature (including hand‐searching). In addition to the evidence‐ and consensus‐based recommendation on the treatment of HE, the guidelines cover mainly consensus‐based diagnostic aspects and preventive measures (primary and secondary prevention). Treatment recommendations include non‐pharmacological interventions, topical, physical and systemic treatments. Topical corticosteroids are recommended as first line treatment in the management of HE, however continuous long‐term treatment beyond six weeks only when necessary and under careful medical supervision. Alitretinoin is recommended as a second line treatment (relative to topical corticosteroids) for patients with severe chronic HE. Randomized control trials (RCT) are missing for other used systemic treatments and comparison of systemic drugs in “head‐to‐head” RCTs are needed.

The guidelines development group is a working group of the European Society of Contact Dermatitis (ESCD) and has carefully tried to reconcile opposite views, define current optimal practice and provide specific recommendations, and meetings have been chaired by a professional moderator of the AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften; Association of the Scientific Medical Societies in Germany).

No financial support was given by any medical company. The guidelines are expected to be valid until December 2017 at the latest.
Elevation of plasma 1‐deoxy‐sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy?
Authors: Dohrn M. F. , Othman A. , Hirshman S. K. , Bode H. , Alecu I. , Fähndrich E. , Karges W. , Weis J. , Schulz J. B. , Hornemann T. , Claeys K. G.
Published: January 2015

Background and purpose

Diabetic distal sensorimotor polyneuropathy (DSPN) is a frequent, disabling complication of diabetes mellitus. There is increasing evidence that sphingolipids play a role in insulin resistance and type 2 diabetes (T2DM). Whether neurotoxic 1‐deoxy‐sphingolipids are elevated in DSPN patients' plasma and whether levels correlate to the DSPN stage were examined.

Methods

The plasma profile of 12 sphingoid bases in patients with DSPN and T2DM(n = 39) were cross‐sectionally compared to other nerve disorders including chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 13), transthyretin‐related familial amyloid polyneuropathy (FAP) (n = 10), amyotrophic lateral sclerosis (ALS) (n = 13) and small fibre neuropathy (n = 12) by liquid chromatography mass spectrometry. Correlations to the DSPN stage were additionally performed. Furthermore, the sphingoid base distribution in sural nerve specimens was measured in patients with DSPN (n = 6) compared to CIDP (n = 3).

Results

A significantly increased amount of 1‐deoxy‐sphingolipids [1‐deoxy‐sphinganine (0.11 ± 0.06 μmol/l), 1‐deoxy‐sphingosine (0.24 ± 0.16 μmol/l)] in patients with DSPN was observed compared to age‐matched healthy controls (0.06 ± 0.03 μmol/l; 0.12 ± 0.05 μmol/l) and to the other groups. (Para)clinical parameters including sensory loss, neuropathic pain, weakness, vibration perception, nerve conduction velocity, sensory nerve action potentials (sural nerve) and duration of T2DM did not correlate with plasma 1‐deoxy‐sphingolipid levels, neither did the clinical stage according to the Dyck classification for DSPN. Sphingolipid levels in sural nerve biopsies showed no differences between DSPN and CIDP. Contrarily, patients with a small fibre neuropathy had decreased C20‐sphingosine plasma levels.

Conclusion

1‐deoxy‐sphingolipid plasma levels are significantly elevated in DSPN. They are already detectable in early disease stages but do not correlate with the clinical course. Further knowledge on 1‐deoxy‐sphingolipids might lead to a better pathophysiological understanding and future treatment options in DSPN.
The challenge of managing the Columbia River Basin for energy and fish
Authors: Leonard N. J. , Fritsch M. A. , Ruff J. D. , Fazio J. F. , Harrison J. , Grover T.
Published: January 2015

The Columbia River Basin (Basin) is located in the Pacific Northwest, United States. The 370 hydroelectric dams in the Basin provide the Pacific Northwest with many services including hydropower generation, flood control, agricultural irrigation and navigation. The basin also provides habitat for a variety of anadromous and resident fishes and wildlife species. Balancing the energy demands with the needs of fish and wildlife is a daunting task. Through the implementation of the Pacific Northwest Electric Power Planning and Conservation Act (Power Act), the Council, in collaboration with state, federal, tribal and non‐governmental partners, attempts to address the needs of fish and wildlife with that of hydropower generation. The implementation has become increasingly challenging as the Basin's ecosystem continues to be impacted by societal demands and the resulting environmental impacts. The focus of this paper is the ongoing challenge of meeting the demands on hydropower generation and of the basin's fish species.
Large amounts of labile organic carbon in permafrost soils of northern Alaska
Authors: Mueller Carsten W. , Rethemeyer Janet , Kao‐Kniffin Jenny , Löppmann Sebastian , Hinkel Kenneth M. , G. Bockheim James
Published: January 2015

Permafrost‐affected soils of the northern circumpolar region represent 50% of the terrestrial soil organic carbon (SOC) reservoir and are most strongly affected by climatic change. There is growing concern that this vast SOC pool could transition from a net C sink to a source. But so far little is known on how the organic matter (OM) in permafrost soils will respond in a warming future, which is governed by OM composition and possible stabilization mechanisms. To investigate if and how SOC in the active layer and adjacent permafrost is protected against degradation, we employed density fractionation to separate differently stabilized SOM fractions. We studied the quantity and quality of OM in different compartments using elemental analysis, 13C solid‐phase nuclear magnetic resonance (13C‐NMR) spectroscopy, and 14C analyses. The soil samples were derived from 16 cores from drained thaw lake basins, ranging from 0 to 5500 years of age, representing a unique series of developing Arctic soils over time. The normalized SOC stocks ranged between 35.5 and 86.2 kg SOC m−3, with the major amount of SOC located in the active layers. The SOC stock is dominated by large amounts of particulate organic matter (POM), whereas mineral‐associated OM especially in older soils is of minor importance on a mass basis. We show that tremendous amounts of over 25 kg OC per square meter are stored as presumably easily degradable OM rich in carbohydrates. Only about 10 kg OC per square meter is present as presumably more stable, mineral‐associated OC. Significant amounts of the easily degradable, carbohydrate‐rich OM are preserved in the yet permanently frozen soil below the permafrost table. Forced by global warming, this vast labile OM pool could soon become available for microbial degradation due to the continuous deepening of the annually thawing active layer.
PHT3D‐UZF: A Reactive Transport Model for Variably‐Saturated Porous Media
Authors: Wu Ming Zhi , Post Vincent E.A. , Salmon S. Ursula , Morway Eric D. , Prommer Henning
Published: January 2015

A modified version of the MODFLOW/MT3DMS‐based reactive transport model PHT3D was developed to extend current reactive transport capabilities to the variably‐saturated component of the subsurface system and incorporate diffusive reactive transport of gaseous species. Referred to as PHT3D‐UZF, this code incorporates flux terms calculated by MODFLOW's unsaturated‐zone flow (UZF1) package. A volume‐averaged approach similar to the method used in UZF‐MT3DMS was adopted. The PHREEQC‐based computation of chemical processes within PHT3D‐UZF in combination with the analytical solution method of UZF1 allows for comprehensive reactive transport investigations (i.e., biogeochemical transformations) that jointly involve saturated and unsaturated zone processes. Intended for regional‐scale applications, UZF1 simulates downward‐only flux within the unsaturated zone. The model was tested by comparing simulation results with those of existing numerical models. The comparison was performed for several benchmark problems that cover a range of important hydrological and reactive transport processes. A 2D simulation scenario was defined to illustrate the geochemical evolution following dewatering in a sandy acid sulfate soil environment. Other potential applications include the simulation of biogeochemical processes in variably‐saturated systems that track the transport and fate of agricultural pollutants, nutrients, natural and xenobiotic organic compounds and micropollutants such as pharmaceuticals, as well as the evolution of isotope patterns.
Novel characterization of a breakpoint in F8: an individualized approach to gene analysis when PCR and MLPA results contradict
Authors: Pezeshkpoor B. , Theophilus B. D. M. , Guilliatt A. M. , Oldenburg J. , Williams M. D. , El‐Maarri O.
Published: January 2015

Haemophilia A is an X‐linked bleeding disorder caused by heterogeneous mutations in the F8 gene. Two inversion hotspots in intron 22 and intron 1, as well as point mutations, small insertions and deletions in the F8 gene account for causal mutations leading to severe haemophilia A. Rarely, novel molecular mechanisms lead to a haemophilia A phenotype which cannot be completely characterized by routine molecular diagnostic methods. Here, we characterized the molecular abnormality in a boy with a severe haemophilia A phenotype. On investigation by PCR and DNA sequencing, exon 18 of F8 repeatedly failed to amplify. However, analysis by multiplex ligation‐dependent probe amplification demonstrated the presence of exon 18 sequence, suggesting a more complex rearrangement than a single exon deletion. The analysis of exon 18 and its flanking regions by inverse PCR revealed a complex mutation comprising insertions of extragenic sequences from Xq28 along with a partial duplication of exon 18. Based on the successful analysis and characterization of the familial breakpoint, we developed a PCR‐based diagnostic approach to detect this defect in family members in whom no diagnostic test could be offered until this time.
Efficacy and safety of OBI‐1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A
Authors: Kruse‐Jarres R. , St‐Louis J. , Greist A. , Shapiro A. , Smith H. , Chowdary P. , Drebes A. , Gomperts E. , Bourgeois C. , Mo M. , Novack A. , Farin H. , Ewenstein B.
Published: January 2015

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI‐1 is an investigational, B‐domain deleted, recombinant FVIII, porcine sequence, with low cross‐reactivity to anti‐hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI‐1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg−1, OBI‐1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI‐1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti‐porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI‐1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI‐1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients.
Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre
Authors: Santoro C. , Di Mauro R. , Baldacci E. , De Angelis F. , Abbruzzese R. , Barone F. , Bochicchio R. A. , Ferrara G. , Guarini A. , Foà R. , Mazzucconi M. G.
Published: January 2015

Bleeding phenotype in factor XI (FXI)‐deficient patients is variable, and not related to baseline FXI:Act. Aims of our study were to describe the characteristics and the management of surgery and deliveries in FXI‐deficient patients, and to investigate the relationship between the haemorrhagic phenotype and the baseline FXI:Act. Ninety‐five patients were diagnosed and followed in our centre for a median follow‐up of 0.9 years (0.1–36.2); median FXI:Act of all patients: 38% (0.5–69%). Fifty‐six patients (59%) experienced bleeding episodes not surgery‐related. Prior to diagnosis, 64 patients underwent 132 surgeries, and after diagnosis, 23 patients underwent 36 surgeries. Globally 26 of 168 surgeries were prophylactically treated, whereas 142 of 168 were not. As regard as surgeries performed without prophylaxis, 30 bleeding events (21%) occurred in 21 patients. At diagnosis, the median FXI:Act of bleeding and non‐bleeding patients was 28% and 37%, respectively, without statistically significant difference between the two groups (P = 0.26). As regard as surgeries performed under prophylactic treatment just 1 bleeding event occurred. Prior to diagnosis, 31 spontaneous deliveries (SD) and eight caesarian sections (CS) were performed without prophylaxis: 4 postpartum haemorrhages (10.5%) occurred (patients FXI:Act: 2%, 6%, 27%, 52.3% respectively). After diagnosis, four SD and five CS were performed with prophylaxis: no postpartum haemorrhages occurred. We confirm the wide bleeding phenotype variability in FXI‐deficient patients, not related to the baseline FXI:Act levels. We highlight the importance of performing a correct diagnosis and follow‐up, because a good management of prophylactic treatment, dramatically reduces the bleeding rate in case of surgery or deliveries.
Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators
Authors: Dodt J. , Hubbard A. R. , Wicks S. J. , Gray E. , Neugebauer B. , Charton E. , Silvester G.
Published: January 2015

A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28–29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one‐stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed.
Point‐of‐care musculoskeletal ultrasound is critical for the diagnosis of hemarthroses, inflammation and soft tissue abnormalities in adult patients with painful haemophilic arthropathy
Authors: Kidder W. , Nguyen S. , Larios J. , Bergstrom J. , Ceponis A. , von Drygalski A.
Published: January 2015

We previously demonstrated in adult patients with haemophilia (PWH) that hemarthrosis is present in only ~1/3rd of acutely painful joints by using point‐of‐care‐musculoskeletal ultrasound (MSKUS). Therefore, other unrecognized tissue abnormalities must contribute to pain. Using high resolution MSKUS, employing grey scale and power Doppler, we sought to retrospectively (i) investigate soft tissue abnormalities in painful haemophilic joints and (ii) to determine to what extent MSKUS findings, functional or radiographic joint scores correlate with biomarkers of inflammation in PWH. Findings were correlated with Hemophilia Joint Health Scores (HJHS), Pettersson scores, high sensitivity C‐reactive protein and von Willebrand factor activity and antigen levels. A total of 65 MSKUS examinations for acute and chronic joint pains were performed for 34 adult haemophilia patients, mostly for chronic joint pains (72.3%). The most prominent findings (66.5%) pertained to inflammatory soft tissue changes including synovitis, tendinitis, enthesitis, bursitis and fat pad inflammation. Effusions were present in 55.5% and 46.8% of MSKUS performed for acute and chronic pain, respectively. Of those, 90.0% were bloody during acute and 47.6% during persistent pains. While inflammatory biomarkers correlated well with overall HJHS and total Pettersson scores (P < 0.05), they did not differ between those patients with synovitis and those without. MSKUS is emerging as an important modality to diagnose treatable musculoskeletal abnormalities contributing to pain in haemophilic arthropathy, and therefore seems critical for a personalized approach to haemophilia care. The role of biomarkers in this setting remains less clear and requires further investigation.
Evidence‐based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH‐HCC Guidelines)
Authors: Kokudo Norihiro , Hasegawa Kiyoshi , Akahane Masaaki , Igaki Hiroshi , Izumi Namiki , Ichida Takafumi , Uemoto Shinji , Kaneko Shuichi , Kawasaki Seiji , Ku Yonson , Kudo Masatoshi , Kubo Shoji , Takayama Tadatoshi , Tateishi Ryosuke , Fukuda Takashi , Matsui Osamu , Matsuyama Yutaka , Murakami Takamichi , Arii Shigeki , Okazaki Masatoshi , Makuuchi Masatoshi
Published: January 2015

The 3rd version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence‐based medicine, which was published in October 2013 in Japanese. Here, we briefly describe new or changed recommendations with a special reference to the two algorithms for surveillance, diagnosis, and treatment.
Low‐Temperature Sintering and Electrical Properties of 0.5Pb(Ni1/3Nb2/3)O3‐0.35PbTiO3‐0.15PbZrO3 Thick Films
Authors: Vadla Samba Siva , Kulkarni Ajit. R. , Narayanan Venkataramani
Published: January 2015

The effect of sintering time on phase, grain size, dielectric, ferroelectric, and piezoelectric properties of 0.5Pb(Ni1/3Nb2/3)O3‐0.35PbTiO3‐0.15PbZrO3 thick films has been investigated. The thick films used in this study were fabricated by a double‐doctor‐blade tape‐casting technique. Green tapes were sintered at relatively low sintering temperature of 1050°C for 6, 8, 10, and 12 h. Among these, tapes sintered for 10 h were found to exhibit better electrical properties. Based on the obtained properties, prepared thick films could be categorized as soft piezoelectric materials and may be used for fabricating sensors, low‐power transducers, and actuators.
Effect of reduction of lactose in yogurts by addition of β‐galactosidase enzyme on volatile compound profile and quality parameters
Authors: Wolf Irma V. , Vénica Claudia I. , Perotti María C.
Published: January 2015

A comparative study between reduced‐lactose yogurts made with added β‐galactosidase (E yogurts) and controls (C yogurts) was performed. The evolution of lactose content, pH, acidity and volatile compounds was measured during fermentation and storage at 5 °C. The hydrolysis percentages of lactose ranged from 75% to 78% in E yogurts and from 10% to 13% in C yogurts at the end of manufacture and stayed without changes throughout storage. There were no significant differences in pH and titratable acidity values among yogurts. A total of 22 volatile compounds were identified. The change in lactose level by the action of β‐galactosidase influenced the production of some volatile compounds derived from this sugar. At the end of fermentation, minor differences in volatile composition were recorded among yogurt samples. During storage, acetaldehyde and diketone levels were always higher in hydrolysed yogurts than their respective controls.
Expert and Target Scoring: Their relation, corresponding test instructions, and their effects on the construct validity of the video‐based social understanding test (VSU)
Authors: Conzelmann Kristin , Goerke Panja
Published: January 2015

This study investigated the relation between expert and target scoring of a video‐based social understanding test (VSU) under two different types of instructions (internal and observer). The effects of the scoring methods and instructions on the VSU's construct validity were also examined. A total of 529 pilot applicants completed the VSU (some with internal and some with observer instructions), cognitive ability and knowledge tests, and a personality questionnaire. A subsample (n = 132) completed the VSU again with the other instructions and participated in an assessment center (AC). The two scores were moderately correlated; correlations decreased when the instructions were considered. Neither expert nor target scores showed convergent validity with AC variables; none of the scoring‐instruction combinations showed significant associations with the remaining measures.
Estimating Coefficients of Equivalence and Stability for Job Performance Ratings: The importance of controlling for transient error on criterion measurement
Authors: Salgado Jesús F.
Published: January 2015

Previous research on measurement error in job performance ratings estimated reliability using coefficients: alpha, test–retest, and interrater correlation. None of these three coefficients control for the four main sources of error in performance ratings. For this reason, coefficient of equivalence and stability (CES) has been suggested as the ideal estimate of reliability. This article presents the estimates of CES for a time interval of 1, 2, and 3 years. The values obtained for a single rater were .51, .48, and .44, respectively. For two raters, the values were .59, .55, and .51. The findings suggest that previous reliability estimates based on alpha, test–retest, and interrater coefficients overestimated the reliability of job performance ratings. In the present study, the interrater coefficient overestimates reliability by 13.6–25.4% for an interval time of 1–3 years, as it does not control for transient error. Results also showed that the importance of transient error increases as the length of the interval between the measures increases. Based on the results, it is suggested that corrected validities based on interrater reliability underestimate the magnitude of the validity. The implications of these findings for future efforts to estimate criterion reliability and predictor validity are discussed.
Neoliberal reform for greater competitiveness: labour market deregulation in Japan and Italy
Authors: Watanabe Hiroaki Richard
Published: January 2015

According to ‘varieties of capitalism’ (VoC) perspective, coordinated market economies (CMEs) attain comparative advantages by coordinating industrial relations and maintaining regulation to a greater extent than liberal market economies and mixed market economies (MMEs). Yet, Japan, a typical CME in the VoC literature, introduced greater labour market flexibility than Italy, an MME. This article analyses why this is the case and claims that the institutional complementarities that had functioned well previously in Japan have been unraveling since the early 1990s and neoliberal deregulation of the labour market ensued. This comparative study of Japan and Italy shows that economic stagnation and the globalisation of finance and production exerted neoliberal pressures on the state and employers to increase competitiveness by introducing market‐oriented policies and business strategies. However, the power resources of labour unions and the partisan composition of the government affected the characteristics of neoliberal changes in labour market policy.
Field and laboratory investigations of budding in the tetillid sponge Cinachyrella cavernosa
Authors: Singh Anshika , Thakur Narsinh L.
Published: January 2015

The budding process of the tetillid sponge Cinachyrella cavernosa was studied for one year in the low intertidal zone near Mhapan (15°55′27.48″N, 73°33′29.89″E), on the central west coast of India. The sponges showed the highest budding frequency when the average water temperature of intertidal rock pools was 32.4±0.23°C (February–March), followed by a significant decrease in budding frequency at 28.2±0.12°C (April–July), and no budding at ≤25.9±0.12°C (August–November). Stepwise multiple regression analysis of physico‐chemical factors revealed temperature as the most prominent factor regulating the intensity of budding. Based on size and morphology, three stages of sponge buds were defined. The production of buds was found to be asynchronous, as adult sponges possessed buds of all three stages. Differences among these stages were examined at ultrastructural (in terms of spicules) and molecular (in terms of RNA/DNA) levels. Stage I (<0.5 mm dia‐meter) buds showed a complete absence of microscleres (sigmaspires), whereas stage II (0.5–1 mm) and stage III (>1 mm) buds contained all spicules characteristic of the adult sponge. There was a significant increase in RNA/DNA ratio from stage I to III, suggestive of a progressive increase in physiological activity during the developmental process. Additionally, we studied post‐settlement bud growth under field and laboratory conditions. Newly settled buds displayed a lower average‐specific growth rate in the field, owing to variability in environmental conditions, but more rapid growth under controlled conditions in the laboratory. This study highlights the role of abiotic factors in regulating the budding process and stresses the ecological significance of budding in maintaining natural sponge populations. Our data suggest that an increased frequency of budding under stressful conditions, such as high temperature, is an advantageous adaptation for these sponges. Buds showed rapid development, as no metamorphosis is involved, and retained the genotype of the parents, yielding high reproductive outputs and survival rates.
Genetic data from the red alga Palmaria palmata reveal a mid‐Pleistocene deep genetic split in the North Atlantic
Authors: Li Jing‐Jing , Hu Zi‐Min , Duan De‐Lin
Published: January 2015

Aim

We examined the biogeographical divergence, population‐level genetic differentiation and historical genetic exchange of the red macroalga Palmaria palmata in order to test whether populations on opposite sides of the North Atlantic underwent different demographic histories.

Location

North Atlantic rocky intertidal zones between c. 42 and 65° N.

Methods

We compiled mitochondrial (mtDNA) cox2–3 and plastid rpl12–rps31–rpl9 sequences from 333 and 310 individuals of P. palmata, respectively. Median‐joining networks were constructed to evaluate the genetic relationships among haplotypes. Pairwise genetic differentiation (FST) was calculated to elucidate population genetic structure. Spatial analysis of molecular variance was used to define genetic differentiation between groups. Extended Bayesian skyline plots and IMa2 were used to estimate historical demography, genetic divergence and gene flow between regions.

Results

The mtDNA cox2–3 haplotype network and phylogenetic trees consistently showed that North Atlantic P. palmata divided into two genetic lineages in association with mid‐Pleistocene (0.126–0.781 Ma) climate change. The demographic expansion time for European populations was c. 0.169–0.320 Ma. North American populations underwent demographic expansion c. 0.400 Ma but, for the populations in the Bay of Fundy, a sharp population‐size contraction happened c. 0.013–0.160 Ma. IMa2 analysis revealed no gene flow between the European and North American coasts.

Main conclusions

Our results suggest significant genetic differentiation in P. palmata both at a trans‐Atlantic continental scale and at a European basin scale, and that multiple glacial refugia may have existed for this species. Long‐term isolation within the Atlantic may have contributed greatly to structuring the population‐genetic differentiation of P. palmata. Our results also stress the importance of combining different gene markers to understand the phylogeographical history and genetic structure of marine biota.
Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro‐chemo‐gene therapy
Authors: Cutrera Jeffry , King Glenn , Jones Pamela , Kicenuik Kristin , Gumpel Elias , Xia Xueqing , Li Shulin
Published: January 2015

Electroporation improves the anti‐tumour efficacy of chemotherapeutic and gene therapies. Combining electroporation‐mediated chemotherapeutics with interleukin 12 (IL‐12) plasmid DNA produces a strong yet safe anti‐tumour effect for treating primary and refractory tumours. A previously published report demonstrated the efficacy of a single cycle of IL‐12 plasmid DNA and bleomycin in canines, and, similarly, this study further demonstrates the safety and efficacy of repeated cycles of chemotherapy plus IL‐12 gene therapy for long‐term management of aggressive tumours. Thirteen canine patients were enrolled in this study and received multiple cycles of electro‐chemo‐gene therapy (ECGT) with IL‐12 pDNA and either bleomycin or gemcitabine. ECGT treatments are very effective for inducing tumour regression via an antitumour immune response in all tested histotypes except for sarcomas, and these treatments can quickly eradicate or debulk large squamous cell carcinomas. The versatility of ECGT allows for response‐based modifications which can overcome treatment resistance for affecting refractory lesions. Importantly, not a single severe adverse event was noted even in animals receiving the highest doses of chemotherapeutics and IL12 pDNA over multiple treatment cycles. This report highlights the safety, efficacy and versatility of this treatment strategy. The data reveal the importance of inducing a strong anti‐tumour response for successfully affecting not only the treated tumours, but also non‐treated metastatic tumours. ECGT with IL12 pDNA plus chemotherapy is an effective strategy for treating multiple types of spontaneous cancers including large, refractory and multiple tumour burdens.
Complication Rates for Fluoroscopic Guided Interlaminar Lumbar Epidural Steroid Injections Performed by Certified Registered Nurse Anesthetists in Diverse Practice Settings
Authors: Beissel Donald E.
Published: January 2015

Study question:

What is the complication rate for Certified Registered Nurse Anesthetists (CRNAs) performing fluoroscopic guided lumbar epidural steroid injections (LESIs)?

Methods:

CRNA pain practitioners responded to questionnaires regarding their education level, experience, and practice locations. Participants also collected data on number of fluoroscopic guided LESIs performed and each of 20 complications for a 6-month period, and answered a poll regarding satisfaction with the data collection process.

Results:

Participants represented urban (23%) and rural (77%) practices; as well as office/clinic (31%) hospital (62%) and mixed (7%) practice settings. Both Masters (62%) and Doctoral prepared (38%) CRNAs participated. Their experience in performing fluoroscopic guided LESIs ranged from 1 to 17 years and 50 to 12,000 procedures. Rate of occurrence for each complication was below 1%. Participants had higher rates of bruising and vasovagal reactions than other complications. No paralysis or death occurred. Neither practice setting nor experience level was related to complication rates. Participants expressed interest in participating in additional studies of complication rates.

Conclusion:

CRNAs were able to safely and effectively perform fluoroscopic guided LESIs with complication rates similar to physician rates cited in the literature. Additional study of definitions of complications and CRNA complication rates for other pain management procedures is recommended.
ABCB1 and ABCB19 auxin transporters have synergistic effects on early and late Arabidopsis anther development
Authors: Cecchetti Valentina , Brunetti Patrizia , Napoli Nadia , Fattorini Laura , Altamura Maria Maddalena , Costantino Paolo , Cardarelli Maura
Published: January 2015

Arabidopsis abcb1 abcb19 double mutants defective in the auxin transporters ABCB1/PGP1 and ABCB19/PGP19 are altered in stamen elongation, anther dehiscence and pollen maturation. To assess the contribution of these transporters to stamen development we performed phenotypic, histological analyses, and in situ hybridizations on abcb1 and abcb19 single mutant flowers. We found that pollen maturation and anther dehiscence are precocious in the abcb1 but not in the abcb19 mutant. Accordingly, endothecium lignification is altered only in abcb1 anthers. Both abcb1 and abcb1 abcb19 stamens also show altered early development, with asynchronous anther locules and a multilayer tapetum. DAPI staining showed that the timing of meiosis is asynchronous in abcb1 abcb19 anther locules, while only a small percentage of pollen grains are non‐viable according to Alexander's staining. In agreement, TAM (TARDY ASYNCHRONOUS MEIOSIS), as well as BAM2 (BARELY ANY MERISTEM)—involved in tapetal cell development—are overexpressed in abcb1 abcb19 young flower buds. Correspondingly, ABCB1 and ABCB19 mRNA localization supports the observed phenotypes of abcb1 and abcb1 abcb19 mutant anthers. In conclusion, we provide evidence that auxin transport plays a significant role both in early and late stamen development: ABCB1 plays a major role during anther development, while ABCB19 has a synergistic role.