bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auxin influx importers modulate serration along the leaf margin
Authors: Kasprzewska Ania , Carter Ross , Swarup Ranjan , Bennett Malcolm , Monk Nick , Hobbs Jamie K. , Fleming Andrew 
Published: June 2015

SummaryLeaf shape in Arabidopsis is modulated by patterning events in the margin that utilize a PIN‐based auxin exporter/CUC2 transcription factor system to define regions of promotion and retardation of growth, leading to morphogenesis. In addition to auxin exporters, leaves also express auxin importers, notably members of the AUX1/LAX family. In contrast to their established roles in embryogenesis, lateral root and leaf initiation, the function of these transporters in leaf development is poorly understood. We report that three of these genes (AUX1, LAX1 and LAX2) show specific and dynamic patterns of expression during early leaf development in Arabidopsis, and that loss of expression of all three genes is required for observation of a phenotype in which morphogenesis (serration) is decreased. We used these expression patterns and mutant phenotypes to develop a margin‐patterning model that incorporates an AUX1/LAX1/LAX2 auxin import module that influences the extent of leaf serration. Testing of this model by margin‐localized expression of axr3–1 (AXR17) provides further insight into the role of auxin in leaf morphogenesis.
Structural Reforms and Labour‐market Outcomes: International Panel‐data Evidence
Authors: Hollweg Claire H. , Lederman Daniel , Mitra Devashish 
Published: June 2015

AbstractThis paper explores the impact of structural reforms on a comprehensive set of macro‐level labour‐market outcomes, including the unemployment rate, the average wage index, and overall and female employment levels and labour force participation rates. Together, these outcome variables capture the overall health of the labour market and the aggregate welfare of workers. Yet, to our knowledge, there seems to be no other comprehensive empirical investigation in the existing literature of the impact of structural reforms at the cross‐country macro‐level on labour‐market outcomes other than the unemployment rate. After documenting the average trends across countries in the labour‐market outcomes up to 10 years on either side of each country's structural reform year, we run fixed‐effects ordinary least squares and instrumental variables regressions to account for the likely endogeneity of structural reforms to labour‐market outcomes. Overall, the results suggest that structural reforms lead to positive outcomes for labour. Redistributive effects in favour of workers, along the lines of the Stolper‐Samuelson effect, may be at work.
Treatment of feline intermediate‐ to high‐grade lymphoma with a modified university of Wisconsin–Madison protocol: 119 cases (2004–2012)
Authors: Collette S. A. , Allstadt S. D. , Chon E. M. , Vernau W. , Smith A. N. , Garrett L. D. , Choy K. , Rebhun R. B. , Rodriguez C. O. , Skorupski K. A. 
Published: June 2015

AbstractCHOP‐based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance‐freeCHOP‐based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance‐free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate‐ to high‐grade lymphoma that were prescribed a modified 25‐week University of Wisconsin–Madison (UW‐25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with aUW‐25‐based protocol were included. The Kaplan–Meier median progression‐free interval (PFI) and survival time (MST) were 56 and 97 (range 2–2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longerPFIandMSTthan those with partial or no response (PFI205 versus 54 versus 21 days, respectively,P < 0.0001 andMST318 versus 85 versus 27 days, respectively,P < 0.0001).
Generalized vitiligo in a dog with primary hypoadrenocorticism
Authors: Malerba Eleonora , Morini Maria , Fracassi Federico 
Published: June 2015

BackgroundVitiligo is presumed to be an autoimmune disorder in the dog; primary adrenal insufficiency (Addison's disease) is associated with immune‐mediated destruction of the adrenal cortex.Hypothesis/ObjectivesIn this case report we describe a dog with primary hypoadrenocorticism that developed generalized vitiligo.Case reportA 4‐year‐old spayed female cross‐bred dog developed signs of Addison's disease and this was confirmed by biochemical testing; the dog was treated with fludrocortisone acetate and then desoxycorticosterone pivalate. Three months after the diagnosis, the dog developed depigmentation of the whole hair coat and of several focal areas of the skin. Histopathological findings were consistent with vitiligo.Conclusions and clinical importanceDogs with immune‐mediated disease may develop other manifestations of immune‐mediated disease, including a combination of Addison's disease and vitiligo. The cause in this case was not determined.
Cross‐resistance patterns to acetyl coenzyme A carboxylase (ACCase) inhibitors associated with different ACCase mutations in Beckmannia syzigachne
Authors: Pan L , Li J , Zhang T , Zhang D , Dong L Y 
Published: June 2015

SummaryBeckmannia syzigachne (American sloughgrass) is a competitive grass weed found in China. Fenoxaprop‐P‐ethyl is widely used for control of this species in China. Resistance to fenoxaprop‐P‐ethyl in B. syzigachne has been reported to be conferred by an isoleucine(Ile)‐1781‐leucine(Leu) substitution in the gene encoding the herbicide target, acetyl‐CoA carboxylase (ACCase). In this study, three mutations were detected by derived cleaved amplified polymorphic sequence (dCAPS) method in fenoxaprop‐P‐ethyl‐resistant B. syzigachne populations: Ile‐1781‐Leu in population JCWL‐R, Ile‐2041‐Asn in JCJT‐R and Gly‐2096‐Ala in JYJD‐R. The data indicated they were genetically homogeneous (homozygous mutant) at the ACCase locus. The use of cytochrome P450 inhibitors was shown to slightly reduce the GR50 value of fenoxaprop‐P‐ethyl‐resistant populations, from which we inferred a combination of target‐site resistance (TSR) and non‐target‐site resistance (NTSR) was involved in fenoxaprop‐P‐ethyl‐resistance. We characterised the cross‐resistance patterns to ACCase inhibitors in B. syzigachne. The plants in the JCWL‐R population were highly resistant to all tested APPs (aryloxyphen‐oxypropionates), sethoxydim and pinoxaden, and moderately resistant to clethodim. The plants in the JCJT‐R population were highly resistant to fluazifop‐P‐butyl, clodinafop‐propargyl, cyhalofop‐butyl, metamifop and pinoxaden; moderately resistant to haloxyfop‐R‐methyl, quizalofop‐P‐ethyl and sethoxydim; and sensitive to clethodim. The plants in the JYJD‐R population were highly resistant to clodinafop‐propargyl, metamifop and pinoxaden; moderately resistant to haloxyfop‐R‐methyl, cyhalofop‐butyl, quizalofop‐P‐ethyl, fluazifop‐P‐butyl and sethoxydim; and sensitive to clethodim. If resistance to ACCase inhibitors is present in B. syzigachne populations in the field, then our results indicate that clethodim should be used. While we demonstrated the cross‐resistance patterns of TSR resulting from three mutations in B. syzigachne, we also demonstrated that NTSR plays a role in resistance, which will complicate weed management.
Globular adiponectin ameliorates metabolic insulin resistance via AMPK‐mediated restoration of microvascular insulin responses
Authors: Zhao Lina , Fu Zhuo , Wu Jing , Aylor Kevin W. , Barrett Eugene J. , Cao Wenhong , Liu Zhenqi 
Published: June 2015

Key points
Adiponectin is an adipokine with anti‐inflammatory and anti‐diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes.
Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle.
In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment.
We demonstrated that a high‐fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK‐ and nitric oxide‐dependent mechanism.
This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses.
AbstractHypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high‐fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low‐fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre‐constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP‐activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin‐stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin's microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK‐ and nitric oxide‐dependent mechanism in male rats.
Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques
Authors: White A. D. , Sarfas C. , West K. , Sibley L. S. , Wareham A. S. , Clark S. , Dennis M. J. , Williams A. , Marsh P. D. , Sharpe S. A. 
Published: June 2015

ABSTRACT

Nine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.d.) injection, the
Mycobacterium bovis
BCG vaccine provides limited protection, whereas aerosol delivery has been shown to enhance efficacy in experimental models. In this study, we used the rhesus macaque model to characterize the mucosal and systemic immune response induced by aerosol-delivered BCG vaccine. Aerosol delivery of BCG induced both Th1 and Th17 cytokine responses. Polyfunctional CD4 T cells were detected in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) 8 weeks following vaccination in a dose-dependent manner. A similar trend was seen in peripheral gamma interferon (IFN-γ) spot-forming units measured by enzyme-linked immunosorbent spot (ELISpot) assay and serum anti-purified protein derivative (PPD) IgG levels. CD8 T cells predominantly expressed cytokines individually, with pronounced tumor necrosis factor alpha (TNF-α) production by BAL fluid cells. T-cell memory phenotype analysis revealed that CD4 and CD8 populations isolated from BAL fluid samples were polarized toward an effector memory phenotype, whereas the frequencies of peripheral central memory T cells increased significantly and remained elevated following aerosol vaccination. Expression patterns of the α4β1 integrin lung homing markers remained consistently high on CD4 and CD8 T cells isolated from BAL fluid and varied on peripheral T cells. This characterization of aerosol BCG vaccination highlights features of the resulting mycobacterium-specific immune response that may contribute to the enhanced protection previously reported in aerosol BCG vaccination studies and will inform future studies involving vaccines delivered to the mucosal surfaces of the lung.
Gait modifications to change lower extremity gait biomechanics in runners: a systematic review
Authors: Napier Christopher , Cochrane Christopher K , Taunton Jack E , Hunt Michael A 
Published: June 2015

BackgroundAbnormal biomechanics have been cited as a potential risk factor for running-related injury. Many modifiable biomechanical risk factors have also been proposed in the literature as interventions via gait retraining.AimTo determine which interventions have successfully modified biomechanical variables linked to running-related injury.Study designSystematic literature review.MethodsMEDLINE, EMBASE, CINAHL, SportDiscus and PSYCINFO were searched using key terms related to running biomechanics and gait retraining. Quality of included studies was assessed using the modified Downs and Black Quality Index and a best evidence synthesis was performed.Results27 studies investigating the effect of biomechanical interventions on kinetic, kinematic and spatiotemporal variables were included in this review. Foot strike manipulation had the greatest effect on kinematic measures (conflicting evidence for proximal joint angles; strong evidence for distal joint angles), real-time feedback had the greatest effect on kinetic measures (ranging from conflicting to strong evidence), and combined training protocols had the greatest effect on spatiotemporal measures (limited to moderate evidence).ConclusionsOverall, this systematic review shows that many biomechanical parameters can be altered by running modification training programmes. These interventions result in short term small to large effects on kinetic, kinematic and spatiotemporal outcomes during running. In general, runners tend to employ a distal strategy of gait modification unless given specific cues. The most effective strategy for reducing high-risk factors for running-related injury—such as impact loading—was through real-time feedback of kinetics and/or kinematics.
Near-normoglycaemia and development of neuropathy: a 24-year prospective study from diagnosis of type 1 diabetes
Authors: Ziegler Dan , Behler Margarete , Schroers-Teuber Maria , Roden Michael 
Published: June 2015

ObjectiveComplete prevention of diabetic neuropathies has not been previously demonstrated. We sought to determine whether long-term near-normoglycaemia maintained from the diagnosis of type 1 diabetes is associated with polyneuropathy and cardiac autonomic dysfunction.DesignProspective observational study over 24 years.SettingAmbulatory care.Participants32 newly diagnosed patients with type 1 diabetes aged 20.3±1.0 years, duration of diabetes 2.7±0.3 weeks.InterventionInsulin therapy according to standards of care.Primary and secondary outcome measuresMotor and sensory nerve conduction velocity (MNCV and SNCV), heart rate variability (HRV), and confirmed clinical polyneuropathy measured at 15 time points over 24 years and quantitative sensory testing (QST) determined over 20–22 years.Results11 patients were well controlled over 24 years with mean glycated haemoglobin (HbA1c) <7.0% (6.5±0.1%; group 1), whereas 21 patients were poorly controlled (mean HbA1c ≥7.0%: 8.3±0.2%; group 2). After 24 years, MNCV was faster in group 1 versus group 2 in the median (55.5±1.6 vs 48.9±1.6 m/s), ulnar (56.5±1.5 vs 49.3±1.7 m/s) and peroneal nerve (44.7±1.6 vs 36.8±2.5 m/s), while SNCV was faster in the median (53.6±1.6 vs 45.5±2.8 m/s), ulnar (54.7±1.8 vs 43.0±3.9 m/s), and sural nerve (44.5±1.8 vs 35.5±2.6 m/s; all p<0.05). The annual decline in peroneal MNCV and sural SNCV in group 1 was sixfold and threefold faster in group 2 than in group 1, respectively. Likewise, impairment in QST and HRV developed at faster rates in group 2. After 24 years, 64% of patients in group 2, but none in group 1, developed confirmed clinical polyneuropathy.ConclusionsNear-normoglycaemia maintained from the diagnosis of type 1 diabetes over 24 years was associated with a complete prevention of the decline in hyperglycaemia-related peripheral and autonomic nerve function, and development of confirmed clinical polyneuropathy.
Effectiveness of community-based health services by nurse practitioners: protocol for a systematic review and meta-analysis
Authors: Kanda Mikiko , Ota Erika , Fukuda Hiromi , Miyauchi Shinji , Gilmour Stuart , Kono Yuko , Nakagama Erika , Murashima Sachiyo , Shibuya Kenji 
Published: June 2015

IntroductionTo realise universal health coverage in an ageing society, adequate provision of appropriately trained human resources is essential. The nurse practitioner (NP) is an autonomous and independent, advanced practice nurse capable of providing treatment and care that can be substituted for some aspects of a medical doctor's (MD's) role, especially in a community setting. Previous systematic reviews found higher levels of patient satisfaction with services provided by NPs than those provided by MDs. As non-communicable diseases become a major health burden requiring long-term healthcare in community settings, this systematic review aims to assess the equivalence of NP services to standard care provided by MDs, and to determine whether their practice is an effective alternative to that of MDs in community settings.Methods and analysisRelevant randomised controlled trials (RCTs) and cluster RCTs will be searched in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and the British Nursing Index. We will assess patient and health system utilisation outcomes of interventions comparing treatment and care provided by NPs in community settings with that provided by MDs. Two authors will independently screen studies for inclusion, consulting with a third author where necessary to resolve discrepancies. The risk of bias of included studies will be assessed using the Cochrane Collaborationrisk of biastool, and quality of evidence using the GRADE approach. Meta-analysis of included studies will be conducted using fixed-effect or random-effects models depending on the degree of between-study heterogeneity. Results will be presented using risk ratios with 95% CI for dichotomous outcomes and standardised mean differences with 95% CI for continuous outcomes.Ethics and disseminationThis systematic review and meta-analysis protocol does not require ethical approval. We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.Trial registration numberPROSPEROCRD42014009627.
Effectiveness, safety and costs of orphan drugs: an evidence-based review
Authors: Onakpoya Igho J , Spencer Elizabeth A , Thompson Matthew J , Heneghan Carl J 
Published: June 2015

IntroductionSeveral orphan drugs have been approved by the European Medicines Agency (EMA) over the past two decades. However, the drugs are expensive, and in some instances, the evidence for effectiveness is not convincing at the time of regulatory approval. Our objective was to evaluate the clinical effectiveness of orphan drugs that have been granted marketing licenses in Europe, determine the annual costs of each drug, compare the costs of branded orphan drugs against their generic equivalents, and explore any relationships between orphan drug disease prevalence and annual costs.MethodsWe searched the EMA database to identify orphan drugs granted marketing authorisation up to April 2014. Electronic searches were also conducted in PubMed, EMBASE and Google Scholar, to assess data on effectiveness, safety and annual costs. 2 reviewers independently evaluated the levels and quality of evidence, and extracted data.ResultsWe identified 74 orphan drugs, with 54 (73%) demonstrating moderate quality of evidence. 85% showed significant clinical effects, but serious adverse events were reported in 86.5%. Their annual costs were between £726 and £378 000. There was a significant inverse relationship between disease prevalence and annual costs (p=0.01); this was largely due to the influence of the ultra-orphan diseases. We could not determine whether the balance between effectiveness and safety influenced annual costs. For 10 drugs where generic alternatives were available, the branded drugs were 1.4 to 82 000 times more expensive.ConclusionsThe available evidence suggests that there is inconsistency in the quality of evidence of approved orphan drugs, and there is no clear mechanism for determining their prices. In some cases, far cheaper generic agents appear to be available. A more robust, transparent and standard mechanism for determining annual costs is imperative.
Randomised controlled trial of topical kanuka honey for the treatment of rosacea
Authors: Braithwaite Irene , Hunt Anna , Riley Judith , Fingleton James , Kocks Janwillem , Corin Andrew , Helm Colin , Sheahan Davitt , Tofield Christopher , Montgomery Barney , Holliday Mark , Weatherall Mark , Beasley Richard 
Published: June 2015

ObjectiveTo investigate the efficacy of topical 90% medical-grade kanuka honey and 10% glycerine (Honevo) as a treatment for rosacea.DesignRandomised controlled trial with blinded assessment of primary outcome variable.SettingOutpatient primary healthcare population from 5 New Zealand sites.Participants138 adults aged ≥16, with a diagnosis of rosacea, and a baseline blinded Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) of ≥2. 69 participants were randomised to each treatment arm. 1 participant was excluded from the Honevo group, and 7 and 15 participants withdrew from the Honevo and control groups, respectively.InterventionsParticipants were randomly allocated 1:1 to Honevo or control cream (Cetomacrogol), applied twice daily for 8 weeks.Main outcome measuresThe primary outcome measure was the proportion of participants who had a ≥2 improvement in the 7-point IGA-RSS at week 8 compared to baseline. Secondary outcomes included change in IGA-RSS and subject-rated visual analogue score of change in severity (VAS-CS) on a 100 mm scale (0 mm ‘much worse’, 100 mm ‘much improved’) at weeks 2 and 8.Results24/68 (34.3%) in the Honevo group and 12/69 (17.4%) in the control group had a ≥2 improvement in IGA-RSS at week 8 compared to baseline (relative risk 2.03; 95% CI 1.11 to 3.72, p=0.020). The change in IGA-RSS for Honevo compared to control at week 2 minus baseline was −1 (Hodges-Lehman estimate, 95% CI −1 to 0, p=0.03), and at week 8 minus baseline was −1 (Hodges-Lehman estimate, 95% CI −1 to 0, p=0.005). The VAS-CS at week 2 was 9.1 (95% CI 3.5 to 14.7), p=0.002, and at week 8 was 12.3 (95% CI 5.7 to 18.9)¸ p<0.001 for Honevo compared to control.ConclusionsHonevo is an effective treatment for rosacea.Trial registration numberThis trial was registered in the Australian and New Zealand Clinical Trials Registry ACTRN12614000004662.