bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent effects of Tlr9 deletion in experimental late venous thrombosis resolution and vein wall injury
Authors: Luke Catherine E. , Elfline Megan , Kittan Nicolai , Allen Ron , Laser Adriana , Oostra Carson , Comerota Anthony , Hogaboam Cory , Kunkel Steven L. , Dewyer Nicholas A. , El-Sayed Osama M. , Henke Peter K.
Published: July 2015

Deep-vein thrombosis (DVT) resolves via a sterile inflammatory response. Defining the inflammatory response of DVT may allow for new therapies that do not involve anticoagulation. Previously, we have shown that Toll-like receptor 9 (Tlr9) gene deleted mice had impaired venous thrombosis (VT) resolution. Here, we further characterise the role of Tlr9 signalling and sterile inflammation in chronic VT and vein wall responses. First, we found a human precedent exists with Tlr9 + cells present in chronic post thrombotic intraluminal tissue. Second, in a stasis VT mouse model, endogenous danger signal mediators of uric acid, HMGB-1, and neutrophil extracellular traps marker of citrullinated histone-3 (and extracellular DNA) were greater in Tlr9-/- thrombi as compared with wild-type (WT), corresponding with larger VT at 8 and 21 days. Fewer M1 type (CCR2+) monocyte/macrophages (MØ) were present in Tlr9-/- thrombi than WT controls at 8 days, suggesting an impaired inflammatory cell influx. Using bone marrow-derived monocyte (BMMØ) cell culture, we found decreased fibrinolytic gene expression with exposure to several endogenous danger signals. Next, adoptive transfer of cultured Tlr9+/+ BMMØ to Tlr9-/- mice normalised VT resolution at 8 days. Lastly, although the VT size was larger at 21 days in Tlr9-/- mice and correlated with decreased endothelial antigen markers, no difference in fibrosis was found. These data suggest that Tlr9 signalling in MØ is critical for later VT resolution, is associated with necrosis clearance, but does not affect later vein wall fibrosis. These findings provide insight into the Tlr9 MØ mechanisms of sterile inflammation in this disease process.
Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes
Authors: Andreotti Felicita , Kołodziejczak Michalina , Schulze Volker , Wolff Georg , Dias Sofia , Claessen Bimmer , Brouwer Marc , Tarantini Giuseppe , Iliceto Sabino , Brockmeyer Maximilian , Kowalewski Mariusz , Lin Yingfeng , Eikelboom John , Musumeci Giuseppe , Lee Leong , Lip Gregory Y. H. , Valgimigli Marco , Berti Sergio , Kelm Malte , Navarese Eliano Pio
Published: July 2015

International guidelines differ in strengths of recommendation for anticoagulation strategies in acute coronary syndromes (ACS). We performed a comprehensive network meta-analysis (NMA) of randomised controlled trials (RCTs) to investigate the comparative efficacy and safety of parenteral anticoagulants in ACS. MEDLINE, Cochrane, EM-BASE, Google Scholar, major cardiology websites, and abstracts/presentations were searched. Six treatments were identified: 1) unfractionated heparin (UFH) + glycoprotein IIb/IIIa inhibitor (GPI) [UFH+GPI], 2) UFH±GPI, 3) bivalirudin, 4) low-molecular-weight heparins (LMWHs), 5) otamixaban, and 6) fondaparinux. Prespecified outcomes (death, myocardial infarction [MI], revascularisation, major bleeding [MB], minor bleeding, and stent thrombosis [ST]) were evaluated up to 30 days. Forty-two RCTs involving 117,353 patients were included. No significant differences in mortality rates were found among strategies. Compared to UFH+GPI, bivalirudin reduced the odds of MB but increased the odds of ST and MI. LMWHs vs bivalirudin reduced MI risk at the price of MB excess. UFH±GPI significantly increased the odds of MI vs LMWHs, of ST vs UFH+GPI, and of MB vs bivalirudin. Reduced ST risk with otamixaban vs UFH±GPI and vs bivalirudin was offset by a marked 2.5- to four-fold MB excess. Fondaparinux showed an intermediate profile. Results for ST-segment elevation MI were consistent with the overall findings. Early anticoagulant strategies for ACS differ in efficacy and safety, with UFH+GPI and LMWHs reducing ischaemic but increasing bleeding risk, and bivalirudin reducing MB but increases MI and ST. The findings support individualised therapy based on patients´ bleeding and ischaemic risks.
The effect of acenocoumarol on the antiplatelet effect of clopidogrel
Authors: Bergmeijer Thomas , Kelder Johannes , Hackeng Christian , ten Berg Jurriën , Dewilde Willem , Janssen Paul
Published: July 2015

Patients exhibiting high on-clopidogrel platelet reactivity (HPR) are at an increased risk of atherothrombotic events following percutaneous coronary interventions (PCI). The use of concomitant medication which is metabolised by the hepatic cytochrome P450 system, such as phenprocoumon, is associated with HPR. We assessed the level of platelet reactivity on clopidogrel in patients who received concomitant treatment with acenocoumarol (another coumarin derivative). Patients scheduled for PCI were included in a prospective, single centre, observational registry. Patients who were adequately pre-treated with clopidogrel were eligible for this analysis, which included 1,582 patients, of whom 104 patients (6.6 %) received concomitant acenocoumarol treatment. Platelet reactivity, as measured with the VerifyNow P2Y12 assay and expressed in P2Y12 Reaction Units (PRU), was significantly higher in patients on concomitant acenocoumarol treatment (mean PRU 229 ± 88 vs 187 ± 95; p< 0.001). In patients with concomitant acenocoumarol use, the proportion of patients with HPR was higher, defined as PRU > 208 (57.7 % vs 41.1 %; p=0.001) and PRU236 (49.0 % vs 31.4 %; p< 0.001). In multivariable analysis, concomitant acenocoumarol use was independently associated with a higher PRU and the occurrence of HPR defined as PRU236 (OR 2.00, [1.07–3.79]), but not with HPR defined as PRU > 208 (OR 1.37, [0.74–2.54]). PRU also was significantly increased after 1:1 propensity matching (+28.2; p< 0.001). As this was an observational study, confounding by indication cannot be excluded, although multivariable analyses and propensity matching were performed. The impact of the findings from this hypothesis-generating study on clinical outcome requires further investigation.
Mesenchymal Stem Cells as a Biological Drug for Heart Disease
Authors: Sanina Cristina , Hare Joshua M.
Published: July 2015

Cell-based treatment represents a new generation in the evolution of biological therapeutics. A prototypic cell-based therapy, the mesenchymal stem cell, has successfully entered phase III pivotal trials for heart failure, signifying adequate enabling safety and efficacy data from phase I and II trials. Successful phase III trials can lead to approval of a new biological therapy for regenerative medicine.
Harnessing the Power of Integrated Mitochondrial Biology and Physiology
Authors: Ping Peipei , Gustafsson Åsa B. , Bers Don M. , Blatter Lothar A. , Cai Hua , Jahangir Arshad , Kelly Daniel , Muoio Deborah , O’Rourke Brian , Rabinovitch Peter , Trayanova Natalia , Van Eyk Jennifer , Weiss James N. , Wong Renee , Schwartz Longacre Lisa
Published: July 2015

Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles.
The Canon of Love against the Use of Force in Islamic and Public International Law. Part I: The Chamber of Love within Legal Discipline
Authors: Malekian Farhad
Published: July 2015

To attempt to speak coherently about the philosophy of love in conjunction with the law is an eccentric undertaking for an international lawyer. This work asserts the view that “love” plays a significant jurisprudential role in both the writing and philosophical interpretation of the law. It is a powerful norm. If the law is written and interpreted with love for human beings, the position of the use of force will be modified and concede its place to the approbation of equal justice and peace based on the primary value of human integrity. The work will be a comparative discussion, as the adherence of European states to both public international law and European Union norms suggests that neither need there be an inevitable divergence between adherence to both these and to Islamic legal norms. It brings into recognition the principle that the use of armed force for any purpose is a serious violation of the jurisprudence of law and runs contrary to the inherent integrity of humankind and the canon of love for justice.
The Formation of a Customary International Crime: Global Terrorism Human (In) Security
Authors: Gal-Or Noemi
Published: July 2015

The article studies the concept of human security (hs) as embraced by the un General Assembly and Secretary Generals, and its instrumentality in the promotion of a customary international crime of global terrorism. Such a crime exists in the opinion of the Appellate Chamber of the Special Tribunal for Lebanon. Regarding terrorism in international criminal law (icl), not in armed conflict, I maintain that the concept of hs has been pivotal in furthering the “criminalisation” of terrorism in matters peace and security. I submit that (i) that the absence of a universally agreed upon definition of (global) terrorism does not suffice to detract from the finding that such a transnational crime exists, and (ii) in addition to the various and largely agreed constitutive elements of customary law, normative paradigmatic developments – here in the case of terrorism, and in the past two decades – have significantly supported this customarisation trend.
Sisymbrium isatidifolium (Brassicaceae): a new species from southern Spain, and the identity of S. hispanicum Jacq.
Authors: Blanca Gabriel , Cueto Miguel , Fuentes Julián
Published: July 2015

A new species of the genus Sisymbrium is described, illustrated, and compared with the most closely related ones of the genus, S. chrysanthum, S. hispanicum, S. crassifolium, and S. assoanum, and the identity of S. hispanicum is discussed. The new species occurs on gypsiferous marls, forming part of the esparto grasslands and cultivated fields in the provinces of Albacete, Jaén, Granada, and Almería (southern Spain). In addition, a distribution map, illustrations, and a description of the habitat of the new species are presented.
Illustrated larval key to lepidopteran pests of rice in Malaysia
Authors: NUR ATHIQAH M. Y. , NUR AZURA A. , LAU W. H.
Published: July 2015

Here we provide an illustrated key to lepidopteran larvae that occur as pests on rice (Oryza) in Malaysia. We are unaware of a published key for this region for this vital commercial crop, and hence provide one based on easily observable features that could be useful for identification, early detection, and pest management by specialists and non-specialists alike (see discussion in Mukerji & Singh 1951, Sri et al. 2010, Timm et al. 2007, Tillmon et al. 2000, Wagener et al. 2004).
Trends and Natural Variability of Spring Onset in the Coterminous United States as Evaluated by a New Gridded Dataset of Spring Indices
Authors: Ault Toby R. , Schwartz Mark D. , Zurita-Milla Raul , Weltzin Jake F. , Betancourt Julio L.
Published: July 2015

Climate change is expected to modify the timing of seasonal transitions this century, impacting wildlife migrations, ecosystem function, and agricultural activity. Tracking seasonal transitions in a consistent manner across space and through time requires indices that can be used for monitoring and managing biophysical and ecological systems during the coming decades. Here a new gridded dataset of spring indices is described and used to understand interannual, decadal, and secular trends across the coterminous United States. This dataset is derived from daily interpolated meteorological data, and the results are compared with historical station data to ensure the trends and variations are robust. Regional trends in the first leaf index range from −0.8 to −1.6 days decade−1, while first bloom index trends are between −0.4 and −1.2 for most regions. However, these trends are modulated by interannual to multidecadal variations, which are substantial throughout the regions considered here. These findings emphasize the important role large-scale climate modes of variability play in modulating spring onset on interannual to multidecadal time scales. Finally, there is some potential for successful subseasonal forecasts of spring onset, as indices from most regions are significantly correlated with antecedent large-scale modes of variability.
Canalplasty for Exostoses With Maximal Skin Preservation With Temporoparietal Fascia Grafting and Use of Bone Wax for Skin Flap Protection
Authors: Moss William J. , Lin Harrison W. , Cueva Roberto A.
Published: July 2015

Background:

External auditory canal exostoses are benign, bony overgrowths that arise in patients who experience chronic cold water exposure. While considerable advancement has been made in canalplasty techniques in recent decades, many patients continue to experience prolonged healing periods and recurrent stenosis following surgery.

Objective:

To perform a retrospective outcomes analysis of our experience with a skin-preserving canalplasty technique with temporoparietal fascia grafting and use of bone wax for skin flap protection.

Study Design:

Retrospective review.

Subjects and Methods:

Thirty-four patients (41 ears) underwent canalplasty from 2008 to 2014 at a tertiary referral center. Primary outcome measures included rates of prolonged healing and restenosis, need for revision surgery, and audiometric results. Rates of intraoperative and postoperative complications were also tabulated.

Results:

No patient experienced recurrent stenosis or required a revision surgery within the follow-up period. All but one patient (97%) achieved complete healing within 8 weeks. Minimal intraoperative complications were found. Statistically significant improvements in air pure tone averages and air-bone gaps were achieved.

Conclusion:

The proposed technique is a safe and effective method of canalplasty for exostoses that imparts accelerated wound healing and minimizes the rate of recurrent stenosis.
Effects of Balloon Dilation for Idiopathic Laryngotracheal Stenosis on Voice Production
Authors: Hoffman Matthew R. , Brand William T. , Dailey Seth H.
Published: July 2015

Objective:

To evaluate the effects of balloon dilation for idiopathic laryngotracheal stenosis on voice production.

Methods:

Retrospective review of 10 female patients with idiopathic laryngotracheal stenosis undergoing balloon dilation. Voice outcomes were evaluated by comparing pre- and posttreatment patient-reported, perceptual, aerodynamic, and acoustic parameters. Complete data sets were not available for all subjects; sample size for each parameter is reported with the corresponding result.

Results:

Total Voice Handicap Index (VHI) decreased significantly (22.9 ± 13.5 to 6.8 ± 6.5; n = 8; p = .015), as did glottal function index (7.2 ± 4.9 to 1.5 ± 2.0; n = 6; p = .022). No changes were observed in the GRBAS (grade, roughness, breathiness, asthenia, strain) scale. Changes in aerodynamic parameters were not statistically significant. Percent jitter decreased (1.32 ± 1.37 to 0.60 ± 0.29; n = 7; P = .078), and fundamental frequency range was preserved (507 ± 325 to 612 ± 281; n = 7; P = .309).

Conclusions:

Our sample of patients with idiopathic laryngotracheal stenosis had a mild-moderate dysphonia that improved with balloon dilation. Importantly, adverse effects on voice that can occur with open procedures were not observed. Patient perception of dysphonia improved while fundamental frequency range was maintained and aerodynamic parameters remained within or moved toward the normal range. Larger prospective studies are warranted to further evaluate changes in voice production associated with balloon dilation.
Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition
Authors: Zaloga Gary P.
Published: July 2015

Phytosterols are plant‐derived sterols that are structurally and functionally analogous to cholesterol in vertebrate animals. Phytosterols are found in many foods and are part of the normal human diet. However, absorption of phytosterols from the diet is minimal. Most lipid emulsions used for parenteral nutrition are based on vegetable oils. As a result, phytosterol administration occurs during intravenous administration of lipid. Levels of phytosterols in the blood and tissues may reach high levels during parenteral lipid administration and may be toxic to cells. Phytosterols are not fully metabolized by the human body and must be excreted through the hepatobiliary system. Accumulating scientific evidence suggests that administration of high doses of intravenous lipids that are high in phytosterols contributes to the development of parenteral nutrition–associated liver disease. In this review, mechanisms by which lipids and phytosterols may cause cholestasis are discussed. Human studies of the association of phytosterols with liver disease are reviewed. In addition, clinical studies of lipid/phytosterol reduction for reversing and/or preventing parenteral nutrition associated liver disease are discussed.
Review of extended producer responsibility: A case study approach
Authors: Gupt Yamini , Sahay Samraj
Published: July 2015

Principles of extended producer responsibility have been the core of most of the recent policies and legislation dealing with the end-of-life management of recyclable goods. This article makes an exploratory review of 27 cases of extended producer responsibility from developed and developing economies with and without informal recycling, to ascertain the most important aspect of extended producer responsibility. A comparative analysis of the cases with respect to role of stakeholders in the upstream and downstream stages of the extended producer responsibility has been carried out. Further, the study uses exploratory factor analysis to determine the important aspects of the extended producer responsibility in practice using 13 variables identified from the review. Findings of the comparative analysis reveal that financial responsibility of the producers and separate collecting and recycling agencies contributed significantly to the success of the extended producer responsibility-based environmental policies. Regulatory provisions, take-back responsibility and financial flow come out to be the three most important aspects of the extended producer responsibility. Presence of informal sector had a negative impact on the regulatory provisions. The outcomes of this study could serve as a guideline for designing of effective extended producer responsibility-based policies.
Damage Control and the Open Abdomen
Authors: Griggs Cornelia , Butler Kathryn
Published: July 2015

Background:

As strategies in acute care surgery focus on damage control to restore physiology, intensivists spanning all disciplines care for an increasing number of patients requiring massive transfusion, temporary abdominal closures, and their sequelae.

Objective:

To equip the nonsurgical intensivist with evidence-based management principles for patients with an open abdomen after damage control surgery.

Data Source:

Search of PubMed database and manual review of bibliographies from selected articles.

Data Synthesis and Conclusions:

Temporary abdominal closure improves outcomes in patients with abdominal compartment syndrome, hemorrhagic shock, and intra-abdominal sepsis but creates new challenges with electrolyte derangement, hypovolemia, malnutrition, enteric fistulas, and loss of abdominal wall domain. Intensive care of such patients mandates attention to resuscitation, sepsis control, and expedient abdominal closure.
Whole school behaviour management and perceptions of behaviour problems in Australian primary schools
Authors: De Nobile John , London Teola , El Baba Mariam
Published: July 2015

Over the past decade and a half, whole school behaviour management systems have been implemented in many Australian schools in efforts to reduce undesirable behaviours and improve outcomes for students with behaviour problems. There is evidence in the literature suggesting that whole school approaches are more effective at managing student behaviour problems than the individual practices of teachers. However, much of the research is concentrated on individual schools or small clusters of schools. This exploratory, mixed methods study, employed qualitative data to develop a schema for assessing the level of implementation of whole school behaviour management approaches, and subsequent quantitative data to examine the association between their level of implementation and perceptions of behaviour problems. Higher levels of implementation were found to be associated with lower levels of perceived behaviour problems. Potential links with job satisfaction and stress were also identified. The article concludes with implications for school leadership and policy.
Empirics in Family Business Research
Authors: Evert Robert E. , Martin John A. , McLeod Michael S. , Payne G. Tyge
Published: July 2015

Competent research methods and data analysis are essential components for the progression of family business research. To identify and evaluate empirical trends, and make suggestions for future research, we examine 319 empirical articles published in Family Business Review since 1988. These studies are compared with 146 family business research articles published in top-tier journals not dedicated to family business research over the same timeframe. While we substantiate growth in rigor and sophistication, we address specific family business research challenges regarding construct validity, generalizability, causality, temporality, and multilevel issues. Suggestions are provided for future empirical research across six major topical areas.
Viewing Family Firm Behavior and Governance Through the Lens of Agency and Stewardship Theories
Authors: Madison Kristen , Holt Daniel T. , Kellermanns Franz W. , Ranft Annette L.
Published: July 2015

Agency and stewardship theories are prominent perspectives to examine myriad issues within family firms. Although considered opposing theories, both address the same phenomena: the individual-level behaviors and firm-level governance mechanisms that predict organizational outcomes. Accordingly, we review and synthesize these theories concurrently, using the concepts of behavior and governance as our organizing framework. Our review encompasses 107 family firm articles grounded in agency and/or stewardship theory, published between 2000 and 2014 in 24 journals across several disciplines. Additionally, we identify future research areas that provide scholars opportunities to push theoretical boundaries and offer further insights into the family firm.
Radial force modeling for bearingless motors based on analyze of field origins
Authors: Lapôtre Blaise , Takorabet Noureddine , Meilbody-Tabar Farid , Lateb Ramdane , Silva Joaquim Da
Published: July 2015

This article proposes a global harmonic analysis of normal and tangential field components in air gap of multiphase bearingless permanent magnet motor topology to determine the radial force. This allows establishing the semi-analytical expressions of the radial force considering the location of field sources. The accuracy of the model is verified by full finite element method model using a statistic approach. An important result of this approach of modeling is that it permits to choose the most convenient topology for the bearingless permanent magnet motors by taking into account the location of the field sources in stator and rotor. In addition, the semi-analytic model allows predicting the force waveforms according to the stator and rotor topologies. The analysis of two different rotor topologies is carried out and it highlights the influence of the tangential component of the air-gap magnetic field on the motor performances. Moreover, the influence of the radial or parallel magnetization of the rotor magnet on the force ripples is discussed. The reduction of CPU time using the semi-analytical model makes it suitable to be implemented in a design optimization process.
Serial ammonia measurement in patients poisoned with glufosinate ammonium herbicide
Authors: Moon JM , Chun BJ
Published: July 2015

This study investigated whether ammonia concentrations can predict delayed neurotoxicity development and neurotoxicity latency in glufosinate ammonium (GLA) herbicide-poisoned patients presenting with an alert mental state and stable hemodynamics. This retrospective observational case study included 26 patients divided into 2 groups: neurotoxicity during hospitalization (complicated group) and without neurotoxicity (noncomplicated group). Thirteen patients (50.0%) experienced neurotoxicity at 16 h post-ingestion. Although ammonia concentrations at presentation did not differ significantly between the two groups, the ammonia level in the complicated group increased significantly at the next measurement and remained significantly higher than that in the noncomplicated group until 48 h after ingestion. The peak ammonia concentration before neurotoxicity development was an independent predictor of neurotoxicity (odds ratio: 1.047, 95% confidence interval: 1.010–1.087, p value = 0.014), and the optimal cutoff value of peak ammonia concentration for predicting neurotoxicity was 101.5 μg/dL. The rate of ammonia increase was not associated with the time latency from ingestion to neurotoxicity development. This study showed that serial ammonia measurements in GLA-poisoned patients may identify those who are at high risk of developing neurotoxicity. However, as this study enrolled few patients, further qualified trials are required to confirm our results and to reveal the etiology of hyperammonemia and its causality in neurotoxicity.
Performance characteristics of polymerase chain reaction and histological methods for the detection of Haplosporidium nelsoni in the eastern oyster (Crassostrea virginica)
Authors: Gagné Nellie , Veniot Anne , Stephenson Mary , McClure Carol
Published: July 2015

Fitness for purpose and validation are increasingly becoming a benchmark in the development of test methods for the diagnosis of infectious diseases in aquatic animals. The design of the evaluation and the analysis of data are critical to demonstrate test method performance characteristics and fitness for purpose, as stated in the World Organization for Animal Health pathway for test validation. Three test methods for the detection of the oyster parasite Haplosporidium nelsoni were selected for the validation study described herein: histology, end-point polymerase chain reaction (PCR), and real-time PCR (qPCR). Preliminary work evaluated the analytical sensitivity and specificity of the PCR and qPCR assay in development. The following stage used test results on 100 oysters in 3 different laboratories to assess diagnostic sensitivity (DSe), diagnostic specificity (DSp), repeatability, and reproducibility. Repeatability and reproducibility were within 68–95%. The final part of the project evaluated DSe and DSp using test results on 400 oysters and results from the first 100 oysters tested. In the absence of a 100% gold standard test, latent class modeling methods were explored to characterize the tests (i.e., Bayesian analyses). For both PCR methods, DSe was >90%, and in the 60% range for histology, whereas DSp was >90% for all methods. Based on the results of this validation, a threshold cycle value of 30 for qPCR corresponds to the limit of sensitivity for histology where unreliable detection becomes more frequent, thus providing a threshold helpful in diagnostic settings where both histology and qPCR are used.
Evidence of Anaplasma phagocytophilum and Borrelia burgdorferi infection in cats after exposure to wild-caught adult Ixodes scapularis
Authors: Lappin Michael R. , Chandrashekar Ramaswamy , Stillman Brett , Liu Jiayou , Mather Thomas N.
Published: July 2015

Cats are infected by Anaplasma phagocytophilum and Borrelia burgdorferi when exposed to infected Ixodes scapularis (black-legged ticks). The purpose of our study was to allow wild-caught I. scapularis to feed on healthy research cats ( n = 4) and temporally evaluate for A. phagocytophilum DNA in blood by a polymerase chain reaction (PCR) assay as well as for antibody responses to the B. burgdorferi C6 peptide, to the A. phagocytophilum P44 peptide, and to a novel A. phagocytophilum peptide (P44-4). Prior to I. scapularis infestation, all cats were negative for antibodies against both organisms based on a kit optimized for dog serum, and negative for A. phagocytophilum DNA in blood using a conventional PCR assay. Using the pre-infestation samples, an enzyme-linked immunosorbent assay for detecting antibodies against the P44-4 peptide was optimized. Cats were infested with wild-caught I. scapularis for 7 days. Genomic DNA of A. phagocytophilum was amplified from the blood before antibodies were detected in all 4 cats. Antibodies against the C6 peptide, P44 peptide, and P44-4 peptide were detected in the sera of all 4 cats. Antibodies against P44-4 were detected prior to those against P44 in 3 out of 4 cats. The results suggest that a PCR assay should be considered in acutely ill cats with suspected anaplasmosis that are seronegative.
Canine dysautonomia in a litter of Havanese puppies
Authors: Hull Noah C. , O’Toole Donal , Miller Myrna M. , Shoults Hannah , Deck Robin , Jones Warren , Johnson Gayle C. , Shaw Daniel P. , Schumaker Brant A.
Published: July 2015

Canine dysautonomia is a sporadic, generally fatal disease that rarely affects groups of related animals. Four 10-week-old Havanese puppies from a litter of 5 developed clinical signs of canine dysautonomia. The 4 affected dogs were exposed to an outdoor environment, whereas the fifth littermate was not exposed to the outdoors and remained clinically healthy. Clinical signs of dysautonomia developed 10–16 days after going outside the house. An unrelated dog also developed dysautonomia after exposure to 1 of the affected Havanese littermates. All 5 dogs had morphological changes consistent with dysautonomia (widespread neuronal degeneration in autonomic ganglia, select brainstem nuclei, and ventral horn motor neurons). Differential diagnoses were excluded through negative toxicological evaluation, fecal parasite screening, negative Canine distemper virus reverse transcription polymerase chain reaction, fluorescent antibody testing, attempted virus isolation, and electron microscopy. The 5 affected dogs were in the Kansas City, Missouri area, where there is a high incidence of dysautonomia.
Initial conditions-independent limit cycles of a fractional-order van der Pol oscillator
Authors: Liu QX , Liu JK , Chen YM
Published: July 2015

The fractional-order van der Pol (vdP) oscillator, which is a typical self-excited system containing fractional derivatives, has increasingly stimulated the interest of many researchers. To the best of our knowledge, the existence and uniqueness of its limit cycle (LC) remains an open question. The major purpose of this study is to reveal the initial conditions independence of the LC. In order to solve the considered system accurately and efficiently, we propose a modified predictor–corrector numerical algorithm and a semi-analytical approach based on the homotopy analysis method. Numerical examples show that, similar to the integer-order vdP oscillator, the phase trajectories starting with different initial conditions converge to the same LC as the solution domain is long enough. It is also found that the convergence rate strongly depends on the initial conditions. On some occasions, the transient responses approach the steady state so slowly that it is possible to come to the misjudgment that there are a series of LCs depending on initial conditions.
Effect of pretreatment with hydromorphone or buprenorphine on thermal antinociception induced by fentanyl in awake cats
Authors: Ambros Barbara
Published: July 2015

Objectives

The aim of this study was to determine the effect of pretreatment with hydromorphone or buprenorphine on thermal antinociception induced by fentanyl in cats.

Methods

Seven healthy cats received five different treatments consisting of two drugs. Drug 1 was administered intravenously 1 h before drug 2. Drug 2 was given as an intravenous loading dose followed by an infusion for 4 h. The drug combinations used were: buprenorphine 20 µg/kg followed by fentanyl (BF; 7 μg/kg, 7 μg/kg/h), buprenorphine 20 µg/kg followed by 0.9% saline solution (B), hydromorphone 0.07 mg/kg followed by 0.9% saline solution (H), hydromorphone 0.07 mg/kg followed by fentanyl (HF; 7 μg/kg, 7 μg/kg/h) and 0.9% saline solution followed by fentanyl (F; 7 μg/kg, 7 μg/kg/h). Thermal thresholds were obtained prior to treatment and at predetermined times up to 7 h after drug 1.

Results

Thermal thresholds were significantly higher than baseline in all treatment groups as follows: H from 0.25 to 2.50 h; B from 0.25 to 2.50 h; F from 1.25 to 5.50 h; HF from 0.25 to 5.50 h and BF from 0.25 to 5.25 h. Thermal thresholds were significantly higher in HF and BF than in F treatment before the fentanyl infusion was commenced (from 0.25 to 1.00 h). During the fentanyl infusion thermal thresholds in BF compared with F were lower at 1.75 h and from 2.50 to 3.50 h. After the constant rate infusion of fentanyl was started, thermal thresholds were significantly lower in HF compared with F at one time point (3 h).

Conclusions and relevance

Pretreatment with buprenorphine did partially inhibit the antinociceptive action of fentanyl. Hydromorphone did inhibit the antinociceptive action of fentanyl at one single time point in cats.
Laser Therapy for an Acquired Glomuvenous Malformation (Glomus Tumour)
Authors: Rivers Jason K. , Rivers Catherine A. , Li Monica K. , Martinka Magdalena
Published: July 2015

Background:

Glomuvenous malformations (GVMs) (previously known as glomus tumours) are uncommon, benign, vascular neoplasms. Current treatments include surgical excision and sclerotherapy, often with high recurrence rates and poor cosmetic results.

Objective:

We sought to use a nonsurgical approach for treatment of a GVM.

Methods:

We present a patient with an acquired, biopsy-proven GVM of the heel unamenable to surgical excision, treated with a long pulsed 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser.

Results:

Excellent cosmesis and long-term remission were achieved after several treatment sessions.

Conclusion:

Our experience provides further evidence to support the safety and effectiveness of the 1064-nm Nd:YAG laser in the management of large and surgically challenging GVMs.
Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients
Authors: Ackerley Suzanne J. , Byblow Winston D. , Barber P. Alan , MacDonald Hayley , McIntyre-Robinson Andrew , Stinear Cathy M.
Published: July 2015

Background. Recovery of upper limb function is important for regaining independence after stroke. Objective. To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation. Methods. Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention. Results. Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip. Conclusions. Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage.
Intensity, Duration, and Location of High-Definition Transcranial Direct Current Stimulation for Tinnitus Relief
Authors: Shekhawat Giriraj Singh , Sundram Frederick , Bikson Marom , Truong Dennis , De Ridder Dirk , Stinear Cathy M. , Welch David , Searchfield Grant D.
Published: July 2015

Background and Objective. Tinnitus is the perception of a phantom sound. The aim of this study was to compare current intensity (center anode 1 mA and 2 mA), duration (10 minutes and 20 minutes), and location (left temporoparietal area [LTA] and dorsolateral prefrontal cortex [DLPFC]) using 4 × 1 high-definition transcranial direct current stimulation (HD-tDCS) for tinnitus reduction. Methods. Twenty-seven participants with chronic tinnitus (>2 years) and mean age of 53.5 years underwent 2 sessions of HD-tDCS of the LTA and DLPFC in a randomized order with a 1 week gap between site of stimulation. During each session, a combination of 4 different settings were used in increasing dose (1 mA, 10 minutes; 1 mA, 20 minutes; 2 mA, 10 minutes; and 2 mA, 20 minutes). The impact of different settings on tinnitus loudness and annoyance was documented. Results. Twenty-one participants (77.78%) reported a minimum of 1 point reduction on tinnitus loudness or annoyance scales. There were significant changes in loudness and annoyance for duration of stimulation, F(1, 26) = 10.08, P < .005, and current intensity, F(1, 26) = 14.24, P = .001. There was no interaction between the location, intensity, and duration of stimulation. Higher intensity (2 mA) and longer duration (20 minutes) of stimulation were more effective. Conclusions. A current intensity of 2 mA for 20-minute duration was the most effective setting used for tinnitus relief. The stimulation of the LTA and DLPFC were equally effective for suppressing tinnitus loudness and annoyance.
Intra-aneurysmal microcatheter looping technique for stent-assisted embolization of complex intracranial aneurysms
Authors: Wang C-C , Lv N , Feng Z-Z , Li Z-F , Zhao R , Li Q , Liu J-M , Huang Q-H
Published: July 2015

The endovascular treatment of wide-necked, large and giant aneurysms remains challenging. This retrospective study investigated the feasibility and safety of an intra-aneurysmal microcatheter looping technique for stent-assisted embolization of complicated intracranial aneurysms.

This technique was used for 31 patients with complicated cerebral aneurysms from January 2007 to November 2013. The clinical and angiographic results were retrospectively evaluated.

The target aneurysms were successfully treated in all cases (100%). A flow diverter was used in seven procedures. There were no aneurysmal perforations or ischemic complications, except for a microguidewire perforation of the distal vessel in one case. Among the 24 cases with conventional stent-assisted embolization, complete embolization or neck residual was obtained in 21 cases. Partial occlusion occurred in three cases.

In conclusion, the intra-aneurysmal microcatheter looping technique is a safe and feasible alternative treatment of complicated intracranial aneurysms. This approach is a reasonable choice for patients and leads to successful outcomes.
Bilinear load-deflection model of fiber-reinforced polymer–concrete composite beam with interface slip
Authors: Wang Jingquan , Zou Xingxing , Feng Yu
Published: July 2015

The design of fiber-reinforced polymer–concrete hybrid beam is usually governed by deformation. Due to the rigidity degradation caused by fiber-reinforced polymer–concrete slip, the load–slip and load–deflection curves demonstrate a bilinear characteristic. The originality of this article is to propose a bilinear analytical model and to determine two dominant parameters in this model, namely, initial bond stress and slip modulus of the interconnection. This model consists of two distinct linear stages. In Stage I, full composite action between fiber-reinforced polymer and concrete is obtained, and no slip exists; Stage II commences once interfacial bond force diminishes, when slip increases linearly versus load, and the overall beam rigidity drops compared with that in Stage I, indicating only partial composite action is realized. Finally, three large-scale specimens were tested to validate the proposed bilinear model and to calculate the two parameters.
LMI–based robust controller design approach in aircraft multidisciplinary design optimization problem
Authors: Zeng Qinghua , Chen Longzhi
Published: July 2015

This article proposes a linear matrix inequality–based robust controller design approach to implement the synchronous design of aircraft control discipline and other disciplines, in which the variation in design parameters is treated as equivalent perturbations. Considering the complicated mapping relationships between the coefficient arrays of aircraft motion model and the aircraft design parameters, the robust controller designed is directly based on the variation in these coefficient arrays so conservative that the multidisciplinary design optimization problem would be too difficult to solve, or even if there is a solution, the robustness of design result is generally poor. Therefore, this article derives the uncertainty model of disciplinary design parameters based on response surface approximation, converts the design problem of the robust controller into a problem of solving a standard linear matrix inequality, and theoretically gives a less conservative design method of the robust controller which is based on the variation in design parameters. Furthermore, the concurrent subspace approach is applied to the multidisciplinary system with this kind of robust controller in the design loop. A multidisciplinary design optimization of a tailless aircraft as example is shown that control discipline can be synchronous optimal design with other discipline, especially this method will greatly reduce the calculated amount of multidisciplinary design optimization and make multidisciplinary design optimization results more robustness of flight performance.
Informed consent in clinical research: Consensus recommendations for reform identified by an expert interview panel
Authors: Lorell Beverly H , Mikita J Stephen , Anderson Annick , Hallinan Zachary P , Forrest Annemarie
Published: July 2015

Background

Informed consent is the cornerstone for protection of human subjects in clinical trials. However, a growing body of evidence suggests that reform of the informed consent process in the United States is needed.

Methods

The Clinical Trials Transformation Initiative conducted interviews with 25 experienced observers of the informed consent process to identify limitations and actionable recommendations for change.

Results

There was broad consensus that current practices often fail to meet the ethical obligation to inform potential research participants during the informed consent process. The most frequent single recommendation, which would affect all participants in federally regulated clinical research, was reform of the informed consent document. The interviews also identified the need for reform of clinical research review by institutional review boards, including transitioning to a single institutional review board for multi-site trials.

Conclusion

The consensus recommendations from the interviewees provide a framework for meaningful change in the informed consent process. Although some proposed changes are feasible for rapid implementation, others such as substantive reform of the informed consent document may require change in federal regulations.
Paediatric toe-to-hand transfer: an assessment of outcomes from a single unit
Authors: Nikkhah D. , Martin N. , Pickford M.
Published: July 2015

Toe-to-hand transfer is an acceptable treatment option for children born with absent digits. Toe transfer can provide functionally useful digits and may enhance patient wellbeing. A total of 19 children had 31 free second-toe-to-hand microsurgical transfers between 1998 and 2012. The mean age of these children at the time of the first operation was 45 months. All transferred toes survived. The donor site was satisfactory in all 19 patients. Twelve children (19 toes) attended a special review clinic; all children could grasp large objects (Duplo bricks) after toe transfer. The total passive range of motion was greater than total active range of motion by an average of 54 degrees. Static 2-point discrimination was generally excellent (mean = 5 mm). Eleven out of 12 children strongly agreed that their toe transfer had improved hand function. Microsurgical toe-to-hand transfer is a safe and reliable technique that can provide useful function for children with congenital differences. Our series compares favourably with the published literature.

Level of evidence: IV
Diabetes Device Interoperability for Improved Diabetes Management
Authors: Silk Alain D.
Published: July 2015

Scientific and technological advancements have led to the increasing availability and use of sophisticated devices for diabetes management, with corresponding improvements in public health. These devices are often capable of sharing data with a few other specific devices but are generally not broadly interoperable; they cannot work together with a wide variety of other devices. As a result of limited interoperability, benefits of modern diabetes devices and potential for development of innovative new diabetes technologies are not being fully realized. Here we discuss diabetes device interoperability in general, then focus on 4 examples that show how diabetes management could benefit from enhanced interoperability: remote monitoring and data sharing, integrating data from multiple devices to better inform diabetes management strategies, device consolidation, and artificial pancreas development.
Ibrutinib in mantle cell lymphoma patients: glass half full? Evidence and opinion
Authors: Stephens Deborah M. , Spurgeon Stephen E.
Published: July 2015

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin’s lymphoma typically marked by an aggressive clinical course and a predilection for relapse. The B-cell receptor (BCR) signaling survival pathway is chronically activated in MCL, contributing to its pathogenesis. Ibrutinib is an inhibitor of Bruton’s tyrosine kinase, a vital component of this pathway. This article details the current clinical experience with ibrutinib in the treatment of patients with MCL, including completed and published clinical trials and reviews potential adverse events (AEs) and pitfalls associated with ibrutinib therapy. Although most AEs experienced by patients treated with ibrutinib are mild, some can be severe and treatment limiting and may be attributed to off-target effects. Ibrutinib is a very promising agent for patients with MCL with notable response rates. However, when used as a single agent, around one third of patients relapse in the first 2 years of treatment. Recently reported combination therapies have shown significant activity. Emerging data evaluating potential mechanisms of drug resistance and the poor clinical outcomes after treatment failure are also discussed. Further understanding of resistance and its implications not only in relapsed disease but in the frontline setting are needed. Investigation of strategies to overcome resistance remains an area of high unmet clinical need. Evaluation of the impact of shorter treatment duration, effects on minimal residual disease, and incorporation of novel combinations are also warranted.