bluuebunny/crossref_metadata_2025 huggingface dataset:
Current and future HCV therapy: do we still need other anti‐HCV drugs?
Authors: Petta Salvatore , Craxì Antonio
Published: December 2014

Eradication of hepatitis C virus (HCV) infection, at least in compensated patients, can help improve the outcomes of liver disease such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation, as well as perhaps extra‐hepatic complications such as diabetes and cardiovascular risk. In the past few years, the landscape of antiviral therapy has evolved at a breathtaking pace from pegylated interferon (PEG‐IFN) plus ribavirin (RBV) (PEG‐IFN/RBV) to IFN‐based strategies combining direct acting antivirals (DDAs) with PEG‐IFN/RBV and finally IFN‐free combinations of DAAs. In particular with these most recent developments, treatment regimens have become shorter, safer and even more effective, with a wide range of indications. Nevertheless, research continues and newer antiviral drugs are still under development. At a point when a >90% sustained virological response (SVR) is being claimed with all new available regimens, pharmacological and clinical research should be addressing unresolved areas, such as cases of suboptimal SVR or to increase effectiveness rather than pursuing the development of new ‘me‐too’ drugs. The issues which should be given priority for further development include the following:

Improving the results of IFN‐free regimens in patients with genotype 3 (HCV‐3) infection.

Identifying the indications for the treatment in patients with compensated and decompensated cirrhosis.

Identifying standardized or personalized backup strategies in patients who do not respond to IFN‐free regimens.

Finally, because of financial constraints, the high cost of IFN‐free strategies prevents their universal use in CHC patients and coverage by national healthcare systems. Thus, efforts must be made to document cost‐effectiveness in all clinical scenarios and to develop more affordable IFN‐free regimens.
Pegylated interferon based therapy with second‐wave direct‐acting antivirals in genotype 1 chronic hepatitis C
Authors: Welch Nicole M. , Jensen Donald M.
Published: December 2014

Within the last few years, treatment of chronic hepatitis C infection has progressed beyond regimens containing the first‐wave direct‐acting antiviral agents (DAAs) boceprevir and telaprevir, which had high pill burdens as well as low efficacy and safety in treatment‐experienced patients. Triple therapy regimens with newer second‐wave DAAs combined with pegylated interferon (PEG‐IFN) and ribavirin (RBV), have shown rates of sustained virological response never before achieved with previous regimens in treatment‐naïve genotype 1 (HCV‐1) patients. Additionally, increased response rates have been found with quadruple agent therapy in prior non‐responders, partial‐responders, and relapsers, including those with cirrhosis. This review will focus on the second‐wave DAAs including protease inhibitors (PI), nucleotide inhibitors, and NS5B inhibitors combined with PEG‐IFN and RBV for both treatment‐naïve and treatment‐experienced genotype 1 hepatitis C virus (HCV‐1) infected patients. The current standard of care for treatment‐naïve HCV‐1 is the second‐wave PI, sofosbuvir, plus PEG‐IFN/RBV and sofosbuvir plus the second‐wave nucleotide inhibitor simeprevir with or without RBV in treatment‐experienced HCV‐1 patients. These recommendations could change, especially for treatment‐experienced patients based on the positive results obtained with the newest quadruple therapy studies.
Optimal interferon‐free therapy in treatment‐experienced chronic hepatitis C patients
Authors: Peter Joy , Nelson David R.
Published: December 2014

Over the past year, interferon (IFN) free dosing regimens have become available to treat chronic hepatitis C. Offering high rates of sustained virological response (SVR), short treatment and improved tolerability, IFN‐free treatment now represents the paradigm for both treatment‐naïve and ‐experienced patients. Patients with prior treatment failure, in particular those with cirrhosis, still represent some of the most difficult to treat, but the availability of multiple agents that can interrupt several steps of the HCV lifecycle affords providers and patients with options that can be combined and individually tailored to each patient's unique needs to obtain high rates of SVR.
Optimal therapy of chronic hepatitis B: how do I treat HBeAg‐positive patients?
Authors: Vlachogiannakos Jiannis , Papatheodoridis George V.
Published: December 2014

Current agents for the treatment of chronic hepatitis B (CHB) can be classified into interferon‐α (standard or pegylated) (IFN) and nucleos(t)ide analogues (NAs). IFN therapy has the advantage of a finite duration (48 weeks) with a chance for durable sustained off‐treatment response in HBeAg positive CHB patients. However, these benefits are limited to approximately 30% of HBeAg positive patients, while parenteral administration and potential side effects are common patient concerns. Thus, patients who can benefit from IFN therapy must be carefully selected and monitored. Recently, stopping rules for IFN non‐responders were developed based on 12‐week HBsAg levels. NAs are currently used in most CHB patients. They are administered in one tablet daily and can be used in all patients with excellent tolerability and a good safety profile. The current first‐line options, entecavir (ETV) and tenofovir (TDF), are highly potent with a minimal risk of resistance during long‐term monotherapy. Prolongation of entecavir or tenofovir maintains the initially high virological remission rates in adherent HBeAg positive patients and modifies the long‐term outcomes. The need for a long‐term, perhaps indefinite, treatment duration is the main limitation of ETV or TDF, which may sometimes be safely discontinued in HBeAg positive patients who achieve stable HBeAg seroconversion. Since there will always be safety concerns and family planning issues with long‐term therapy, NAs should be used carefully particularly in young HBeAg positive patients with minimal‐mild liver disease.
How to optimize current therapy in hepatitis C virus genotype 1 patients. Predictors of response to interferon‐based therapy with second wave direct acting antivirals
Authors: Serfaty Lawrence
Published: December 2014

Second wave direct acting antivirals such as sofosbuvir, simeprevir and daclatasvir can be combined with pegylated interferon alpha and ribavirin (PEG‐IFN/RBV) as triple therapy in patients with hepatitis C virus (HCV) infection. In patients with HCV genotype 1 (HCV‐1), a PEG‐IFN/RBV‐based regimen with sofosbuvir is highly effective but the presence of cirrhosis and the non‐CC IFNL3 genotype have been associated with a poorer response. A PEG‐IFN/RBV‐based regimen with simeprevir or daclatasvir is based on response‐guided therapy and its efficacy depends on predictors of response to IFN. HCV‐1 subtype is also a major predictor of response. In HCV‐1a infected patients, the K80Q mutation in NS3 or the presence of NS5A variants at baseline are associated with poor response with simeprevir‐ or daclatasvir‐containing regimens respectively. Thus, these regimens should be only used in HCV‐1b patients with good predictors of response to IFN.
Cure of HCV related liver disease
Authors: Shiffman Mitchell L , Benhamou Yves
Published: December 2014

Chronic hepatitis C virus (HCV) causes chronic liver injury and can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV can also interact with the immune system to cause several HCV related disorders including essential mixed cryoglobulinemia, vasculitis, dermatitis, glomerulonephritis and lymphoma. A strong association between HCV and diabetes mellitus also exists. These extrahepatic features may lead to increased fatigue and a reduced quality of life. It is now possible to cure most patients with chronic HCV using oral antiviral therapy. Many of these HCV‐related disorders and symptoms can be cured when HCV is eradicated. However, some patients may have irreversible injury to extrahepatic sites, cirrhosis that cannot resolve, an increased risk for HCC, persistent fatigue and a reduced quality of life, despite achieving sustained virological response.
HBsAg quantification to optimize treatment monitoring in chronic hepatitis B patients
Authors: Martinot‐Peignoux Michelle , Asselah Tarik , Marcellin Patrick
Published: December 2014

Hepatitis B surface antigen (HBsAg) levels in serum have been shown to reflect active intrahepatic covalently closed circular DNA (cccDNA) and to have additional value as a marker of on‐treatment efficacy. In the past few years, immunoassays to quantify HBsAg have been developed to monitor HBsAg kinetics during treatment. Although HBsAg quantification cannot replace HBV DNA measurement in clinical practice, the combined use of HBsAg quantification and HBV DNA measurements could help predict treatment outcome. One of the most important results of the studies in this new marker is that a decline in HBsAg titres during pegylated‐interferon (PEG‐IFN) treatment is a strong predictor of response so that a ‘week 12 stopping rule’ could be established for both Hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative patients. However, the positive predictive value (PPV) for a sustained viral response (SVR) remains low. The role of HBsAg measurements during nucloes(t)ides analogue (NAs) treatment is unclear. It may be a useful marker for stopping NAs by limiting the chance of relapse or for add‐on strategies. Monitoring serum HBsAg levels in chronic hepatitis B (CHB) patients during treatment may provide significant complementary information to HBV DNA measurements.
Ketone body production is differentially altered in steatosis and non‐alcoholic steatohepatitis in obese humans
Authors: Männistö Ville T. , Simonen Marko , Hyysalo Jenni , Soininen Pasi , Kangas Antti J. , Kaminska Dorota , Matte Ananda K. , Venesmaa Sari , Käkelä Pirjo , Kärjä Vesa , Arola Johanna , Gylling Helena , Cederberg Henna , Kuusisto Johanna , Laakso Markku , Yki‐Järvinen Hannele , Ala‐Korpela Mika , Pihlajamäki Jussi
Published: December 2014

Background & Aims

Levels of ketone bodies have been reported to be both increased and decreased in individuals with non‐alcoholic fatty liver disease. We investigated whether the metabolism of ketone bodies is different in simple steatosis and in non‐alcoholic steatohepatitis (NASH).

Methods

Serum low molecular weight molecules including ketone bodies were measured using high‐throughput proton (1H) nuclear magnetic resonance in 116 (76 categorized unequivocally to those with normal liver, simple steatosis or NASH) morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, body mass index 45.1 ± 6.1 kg/m2, 39 men and 77 women] with histological assessment of NASH and analysis of gene expression in the liver. Finally, we correlated β‐hydroxybutyrate (β‐OHB) levels with NASH predicting score in Metabolic Syndrome in Men Study (METSIM) population study (n = 8749 non‐diabetic men).

Results

Levels of ketone bodies were lower in individuals with NASH compared to individuals with simple steatosis (P = 0.004 and P = 0.018 for β‐OHB and acetoacetate respectively). Lower levels of β‐OHB were associated with the NASH predicting score in the METSIM study (P = 0.001). Liver inflammation correlated with mRNA expression of genes regulating ketolysis in the liver (Spearman correlation 0.379–0.388, P < 0.0006 for ACAT1, ACSS2 and BDH1).

Conclusion

Lower levels of ketone bodies in individuals with NASH compared to individuals with simple steatosis suggest a decrease in ketone body metabolism in NASH.
Sex‐related differences in size, function and regeneration of the major cheliped in the hermit crab Pagurus filholi
Authors: Matsuo Kento , Tanikawa Daisuke , Yasuda Chiaki I. , Wada Satoshi
Published: December 2014

Pagurus hermit crabs have a well‐developed right cheliped (major cheliped) and in some species the major cheliped of males is longer than that of females. This paper describes sex‐related differences in major cheliped length and regeneration pattern of the major cheliped in the hermit crab Pagurus filholi. We also examined the function of the major cheliped in male–male competition. Major cheliped length of males was longer than that of females in P. filholi. Males regenerated larger chelipeds than females at the first molt after experimentally induced autotomy. Body size growth in males of the regeneration group was less than that in intact males of the control group while there was no significant difference in body size growth of females between regeneration and control groups. Major cheliped length was included in the best model to explain the outcome of male–male competition and thus sexual selection appears to be a causative factor in the sex‐related difference of the major cheliped length. Sex‐related differences in the regeneration pattern may reflect differences in evolutionary pressures on males for large major chelipeds and females for large body size.
Challenges in Cultivating Knowledge in University‐Industry‐Government Partnerships — Qatar as a Case Study
Authors: Abduljawad Haytham
Published: December 2014

In 2008, the state of Qatar articulated a national vision to transform its hydrocarbon‐based economy to a knowledge based economy (KBE) by the year 2030. A KBE derives its value from intangible assets (knowledge) where production, distribution, and utilization of such assets are the main drivers for economic growth and wealth generation. Knowledge assets are created through various intra and inter organization processes. University‐Industry‐Government (UIG) collaborations are major contributors to knowledge assets at organizational and national levels. UIG partnership is a fairly new concept and a complex process that has not been formally implemented, supported, or monitored in the state of Qatar. To explore the UIG partnership, and to assess the effectiveness of knowledge creation and exchange, a single case study method was used to capture and reveal perspectives of participants involved in the partnership. Based on perspectives from 31 participants from (a) Qatar University, (b) Oil and Gas industry organizations and (c) government and semi government institutions in the state of Qatar, organizations are indeed taking initial steps to stimulate and deepen university‐industry partnerships. This paper identifies challenges in cultivating the knowledge created and transferred from UIG partnerships and recommends key solutions to the challenges organizations are faced with in efforts to institutionalize the knowledge that is produced from collaborations with academia.
Randomised, multicentre trial of micafungin vs. an institutional standard regimen for salvage treatment of invasive aspergillosis
Authors: Cornely Oliver A. , Meems Lambertus , Herbrecht Raoul , Viscoli Claudio , van Amsterdam Ronald G. M. , Ruhnke Markus
Published: December 2014

Invasive aspergillosis remains associated with significant morbidity and mortality, necessitating new options for salvage therapy. The objective of this study was to evaluate the efficacy and safety of micafungin as salvage monotherapy in patients with invasive aspergillosis. Patients with proven or probable invasive aspergillosis, who were refractory or intolerant to previous systemic antifungal therapy, were randomised 2 : 1 to receive 300 mg day−1 intravenous micafungin monotherapy or an intravenous control monotherapy [lipid amphotericin B (5 mg kg−1 day−1), voriconazole (8 mg kg−1 day−1) or caspofungin (50 mg day−1)] for 3–12 weeks. Patients underwent final assessment 12 weeks after treatment start. Seventeen patients with invasive aspergillosis (proven, n = 2; probable, n = 14; not recorded, n = 1) participated in the study (micafungin arm, n = 12; control arm, n = 5). Three patients each in the micafungin (25.0%; 95% CI: 5.5–57.2) and control arm (60.0%; 95% CI: 14.7–94.7) had successful therapy at end of treatment as assessed by an Independent Data Review Board. Eleven patients died; six due to invasive aspergillosis. No deaths were considered related to study treatment. During this study it became increasingly common to use combination treatment for salvage therapy. Consequently, enrolment was low and the study was discontinued early. No clear trends in efficacy and safety can be concluded.
Design and participant baseline characteristics of ‘A Clinical Trial of IntensiVE Dialysis’: The ACTIVE Dialysis Study
Authors: Jardine Meg J , Zuo LI , Gray Nicholas A , de Zoysa Janak , Chan Christopher T , Gallagher Martin P , Howard Kirsten , Hertier Stephane , Cass Alan , Perkovic Vlado ,   ACTIVE Dialysis Steering Committee
Published: December 2014

Aims

Observational reports suggest extended dialysis hours are associated with improved outcomes. These findings are confounded by better prognostic characteristics among people practising extended hours. The aim of this article is to provide an overview of the methods and baseline characteristics for ACTIVE Dialysis Study participants.

Methods

This multicentre, randomized, open‐label, blinded endpoint‐assessment trial randomized participants receiving maintenance haemodialysis therapy to either extended (≥24 h) or standard (12–18 h) weekly haemodialysis for 12 months. A web‐based randomization system used minimization to ensure balanced allocation across regions, dialysis setting and dialysis vintage. The primary outcome is the change in quality of life over 12 months of study treatment assessed by EQ‐5D. Secondary outcomes include change in left ventricular mass index assessed by magnetic resonance imaging and safety outcomes including dialysis access events.

Results

A total of 200 participants were recruited between 2009 and 2013 from Australia (29.0%), China (62.0%), Canada (5.5%) and New Zealand (3.5%). Participants had a mean age of 52 (± 12) years and 11.5% were dialysing at home, with a mean duration of 13.9 h per week over a median of three sessions. At baseline, 32.5% had a history of cardiovascular disease and 36.5% had diabetes.

Conclusion

The ACTIVE Dialysis Study has met its planned recruitment target. The participant population are drawn from a range of health service settings in a global context. The study will contribute important evidence on the benefits and harms of extending weekly dialysis hours. The trial is registered at clinicaltrials.gov (NCT00649298).
A change in anticoagulation monitoring improves safety, reduces transfusion, and reduces costs in infants on cardiopulmonary bypass
Authors: Machovec Kelly A. , Jooste Edmund H. , Walczak Richard J. , Homi Hercilia Mayumi , Jaquiss Robert D. B. , Lodge Andrew J. , Ames Warwick A.
Published: December 2014

Background

An immature coagulation system coupled with the hypothermia and hemodilution associated with cardiopulmonary bypass (CPB) in infants makes the activated clotting time (ACT) an ineffective monitor for anticoagulation in this population. The Medtronic HMS Plus Hemostasis Management System (HMS; Medtronic, Inc., Minneapolis, MN, USA) is shown to decrease thrombin generation and blood product requirements.

Aim

We conducted a quality improvement initiative to test our hypothesis that the use of HMS results in reduced incidence of subtherapeutic ACT values, blood product usage, and operating room time for infants undergoing cardiac surgery.

Methods

Fifty consecutive patients weighing <10 kg having cardiac surgery requiring CPB had anticoagulation managed by the HMS. Data were compared to that of 50 consecutive patients weighing <10 kg having cardiac surgery who had their anticoagulation monitored by the ACT alone. Comparisons between categorical variables were performed with chi‐square tests. Comparisons between continuous variables were performed with the Wilcoxon rank‐sum test. Statistical significance was defined as two‐tailed P value < 0.05.

Results

The HMS group had a 61% decrease in incidence of ACT values <480 s and elimination of ACT values < 400 s at any time on bypass. The HMS group received fewer blood products and spent fewer minutes in the operating room after protamine administration, translating to fewer donor exposures and a savings of $403 in transfusion costs and $440 in operating room time costs.

Conclusion

Our findings highlight the benefits of individualized heparinization for pediatric patients undergoing CPB with a monitored heparinization system.
Ventral Midline Blanching in the Setting of Segmental Infantile Hemangiomas: Clinical Observations and Pathogenetic Implications
Authors: Feigenbaum Dana F. , Sybert Virginia P. , Vanderhooft Sheryll L. , Siegel Dawn , Drolet Beth A. , Frieden Ilona J. , Mathes Erin F. D.
Published: December 2014

Areas of blanched skin in children may be seen as an independent finding or in association with vascular birthmarks. We performed a retrospective chart review to identify and describe infants with areas of ventral midline blanching in the presence of segmental infantile hemangiomas. We identified nine full‐term infants with partial or full segmental hemangiomas and areas of midline ventral blanching. Additional ventral wall defects were seen in five patients. Six had cardiac anomalies and six had intracranial anomalies. Five were diagnosed with definite PHACE (posterior fossa, hemangioma, arterial, cardiac, and eye abnormalities) syndrome and three had possible PHACE syndrome. Eight were complicated by ulceration. Treatment varied according to the case. Ventral blanching, even in the absence of overt midline defects, can be seen in infants with segmental hemangiomas at risk for PHACE syndrome. We hypothesize that midline blanching may represent a minor manifestation of a developmental ventral defect.
Exploring the effects of social anxiety similarity in newly developed same‐sex friendships
Authors: BOUCHER ELIANE M. , JACOBSON JILL A. , CUMMINGS JORDEN A.
Published: December 2014

In studying the interpersonal consequences of social anxiety (SA), researchers generally have neglected to account for partner levels of SA. Therefore, in the current study, we examined how SA similarity would influence interpersonal closeness and uncertainty during the early stages of friendship development. Fifty‐six same‐sex friend pairs completed measures of SA, closeness, and uncertainty after knowing each other for approximately 1 month and then again 6 weeks later. Although higher levels of SA at Time 1 were related to more uncertainty, similarity had no effect on closeness or uncertainty at Time 1. However, friends matched on SA experienced increased closeness and decreased uncertainty over the 6 weeks, suggesting SA similarity may become increasingly important as friendships develop.
Spectroscopic Properties of Morin in Various CH3OH–H2O and CH3CN–H2O Mixed Solvents
Authors: Park Hyoung‐Ryun , Im Seo‐Eun , Seo Jung‐Ja , Kim Bong‐Gon , Yoon Jin Ah , Bark Ki‐Min
Published: December 2014

The specific fluorescence properties of morin (3,2′,4′,5,7‐pentahydroxyflavone) were studied in various CH3OH–H2O and CH3CN–H2O mixed solvents. Although the dihedral angle is large in the S0 state, morin has an almost planar molecular structure in the S1 state owing to the very low rotational energy barrier around the interring bond between B and the A, C ring. The excited state intramolecular proton transfer (ESIPT) at the S1 state cannot occur immediately after excitation, S1 → S0 fluorescence can be observed. Two conformers, Morin A and B have been known. At the CH3OH–H2O, Morin B will be the principal species but at the CH3CN–H2O, Morin A is the principal species. At the CH3OH–H2O, owing to the large Franck–Condon (FC) factor for S2 → S1 internal convernal (IC) and flexible molecular structure, only S1 → S0 fluorescence was exhibited. At the CH3CN–H2O, as the FC factor for S2 → S1 IC is small and molecular structure is rigid, S2 → S0 and S1 → S0 dual fluorescence was observed. This abnormal fluorescence property was further supported by the small pK1 value, effective delocalization of the lone pair electrons of C(2′)–OH to the A, C ring, and a theoretical calculation.
Staffing Call Centers with Uncertain Arrival Rates and Co‐sourcing
Authors: Koçağa Yaşar Levent , Armony Mor , Ward Amy R.
Published: December 2014

In a call center, staffing decisions must be made before the call arrival rate is known with certainty. Once the arrival rate becomes known, the call center may be over‐staffed, in which case staff are being paid to be idle, or under‐staffed, in which case many callers hang‐up in the face of long wait times. Firms that have chosen to keep their call center operations in‐house can mitigate this problem by co‐sourcing; that is, by sometimes outsourcing calls. Then, the required staffing N depends on how the firm chooses which calls to outsource in real time, after the arrival rate realizes and the call center operates as a M/ M/ N +  M queue with an outsourcing option. Our objective is to find a joint policy for staffing and call outsourcing that minimizes the long‐run average cost of this two‐stage stochastic program when there is a linear staffing cost per unit time and linear costs associated with abandonments and outsourcing. We propose a policy that uses a square‐root safety staffing rule, and outsources calls in accordance with a threshold rule that characterizes when the system is “too crowded.” Analytically, we establish that our proposed policy is asymptotically optimal, as the mean arrival rate becomes large, when the level of uncertainty in the arrival rate is of the same order as the inherent system fluctuations in the number of waiting customers for a known arrival rate. Through an extensive numerical study, we establish that our policy is extremely robust. In particular, our policy performs remarkably well over a wide range of parameters, and far beyond where it is proved to be asymptotically optimal.
Frontal midline theta as a neurophysiological correlate for deficits of attentional orienting in children with developmental coordination disorder
Authors: Wang Chun‐Hao , Lo Yu‐Hui , Pan Chien‐Yu , Chen Fu‐Chen , Liang Wei‐Kuang , Tsai Chia‐Liang
Published: December 2014

Children with developmental coordination disorder (DCD) have been demonstrated to show attentional orienting deficits. The neural mechanism, however, has thus far remained elusive. Here, we measure oscillations in the EEG associated with attentional orienting to address this issue. The EEG was recorded from DCD children and typical developing (TD) controls during an eye‐gaze cueing paradigm. DCD group responded more slowly than TD group across all conditions. Additionally, TD group showed higher frontal midline theta activities in both valid and invalid conditions relative to a neutral condition, with such an effect absent in the DCD group. Theta oscillations might reflect attentional processing in relation to the cues being performed in TD group, with the lessened modulation of theta in DCD group possibly reflecting a deficit in attentional orienting. Possible explanations for the DCD‐TD differences in theta oscillation and attentional orienting are discussed.
Representation and Inclusion in Public Organizations: Evidence from the U.K. Civil Service
Authors: Andrews Rhys , Ashworth Rachel
Published: December 2014

Theories of workforce diversity in the public sector assume that organizations that are more representative of the population they serve are more likely to foster an inclusive work climate in which individuals from different sections of society can thrive. The authors examine this assumption by studying whether gender and minority ethnic representativeness are related to perceptions of inclusiveness and the experience of discrimination and bullying within U.K. civil service organizations. Findings suggest that gender representativeness and minority ethnic representativeness are both associated with an inclusive work climate, with each aspect of representativeness positively related to higher perceptions of inclusion and lower levels of discrimination and bullying. The theoretical and practical implications of the findings are discussed.
Identification of blue staining vaccine‐derived material in inflammatory lesions using cultured canine macrophages
Authors: Scruggs Jennifer L. , LeBlanc Casey J.
Published: December 2014

Background

Vaccine reactions are described in cytology textbooks as having eosinophilic to magenta colored globules within and admixed with inflammatory cells. Recently, we have seen increased numbers of inflammatory lesions containing blue to blue‐gray globular material, with historical information suggesting an association with rabies vaccination.

Objectives

The purpose of the study was to confirm the blue‐gray and the eosinophilic material observed microscopically in some inflammatory lesions as being vaccine‐derived.

Methods

Three different vaccines were cytocentrifuged and Wright stained. Vaccine aliquots were also added to the culture media of canine‐derived macrophages for 24 hours and the cells subsequently harvested, cytocentrifuged, and Wright stained. The globular material present in both preparations was compared to that observed in vaccine‐induced inflammatory lesions. Morin staining was used to identify metal within vaccine material in both in vitro‐ and in vivo‐derived cytology samples.

Results

Vaccine‐derived material has a characteristic color and appearance. Appearance of the material was consistent in cytologic samples, in cells incubated with the vaccine, and in cytocentrifuged preparations of the vaccine vial contents. The blue‐gray globules stained positively for Morin stain, while the eosinophilic material did not stain.

Conclusions

Vaccine‐induced inflammatory lesions may contain blue to blue‐gray or magenta stained globular material. Blue‐gray material was associated with administration of rabies vaccine Imrab 3TFand the observed material may be metal‐containing adjuvant. Magenta material was associated with other vaccines and negative for Morin stain, suggesting a metal‐free adjuvant.
Tracking the history of an invasion: the freshwater croakers (Teleostei: Sciaenidae) in South America
Authors: Boeger Walter A. , Marteleto Flávio M. , Zagonel Letícia , Braga Mariana P.
Published: December 2014

In this study, the competing hypotheses of single vs. double colonisation events for freshwater Pachyurinae (Sciaenidae) in South America is tested and the historical biogeography of the expansion of this clade within the continent is reconstructed based on phylogenetic analysis. Parsimony and Bayesian inference (BI) for 19 marine and freshwater species assigned to Sciaenidae, Haemulidae and Polypteridae were determined based on partial sequences of the mitochondrial 16S and cytochrome b genes and fragments of the nuclear Tmo‐4C4 and rhodopsin genes. A parsimonious ancestral character reconstruction of euryhalinity was performed on a clade of families of closely related fishes to evaluate the role of ecological fitting in the colonisation of freshwater by a marine sciaenid. The parsimony and BI phylogenetic hypotheses for the concatenated sequences supported the monophyly of the freshwater Sciaenidae. Divergence of the two freshwater clades of Sciaenidae, Pachyurinae and Plagioscion, occurred within the Amazon Basin. Within Pachyurinae, two clades were recovered: one composed of species from the Amazon and the Paraná Basin and a second with representatives from the São Francisco and south‐eastern Atlantic basins. The results were compatible with the hypothesis of a single colonisation event of South American freshwater habitats by a marine lineage. The hypothesis of gradual adaptation to freshwater was rejected in favour of the hypothesis of ecological fitting. Sciaenidae, or a subordinate lineage within the family, is ancestrally capable of withstanding exposure to low‐salinity habitats, which putatively facilitated the colonisation of freshwater habitats. The subsequent diversification and expansion of Pachyurinae across South America followed this colonisation and replicated the general pattern of the area relationships of South American river basins for several other fish groups.
Coherent presentations of Artin monoids
Authors: Gaussent Stéphane , Guiraud Yves , Malbos Philippe
Published: December 2014

We compute coherent presentations of Artin monoids, that is, presentations by generators, relations, and relations between the relations. For that, we use methods of higher-dimensional rewriting that extend Squier’s and Knuth–Bendix’s completions into a homotopical completion–reduction, applied to Artin’s and Garside’s presentations. The main result of the paper states that the so-called Tits–Zamolodchikov 3-cells extend Artin’s presentation into a coherent presentation. As a byproduct, we give a new constructive proof of a theorem of Deligne on the actions of an Artin monoid on a category.
Gating of dopamine transmission by calcium and axonal N‐, Q‐, T‐ and L‐type voltage‐gated calcium channels differs between striatal domains
Authors: Brimblecombe Katherine R. , Gracie Caitlin J. , Platt Nicola J. , Cragg Stephanie J.
Published: December 2014

Key points

The voltage‐gated Ca2+ channels (VGCCs) that catalyse striatal dopamine transmission are critical to dopamine function and might prime subpopulations of neurons for parkinsonian degeneration.

However, the VGCCs that operate on mesostriatal axons are incompletely defined; previous studies encompassed channels on striatal cholinergic interneurons that strongly influence dopamine transmission.

We define that multiple types of axonal VGCCs operate that extend beyond classic presynaptic N/P/Q channels to include T‐ and L‐types.

We reveal differences in VGCC function between mouse axon types that in humans are vulnerable versus resistant to Parkinson's disease. We show for the first time that this is underpinned by different sensitivity of dopamine transmission to extracellular Ca2+ and by different spatiotemporal intracellular Ca2+ microdomains.

These data define key principles of how Ca2+ and VGCCs govern dopamine transmission in the healthy brain and reveal differences between neuron types that might contribute to vulnerability in disease.

The axonal voltage‐gated Ca2+ channels (VGCCs) that catalyse dopamine (DA) transmission are incompletely defined. Yet, they are critical to DA function and might prime subpopulations of DA neurons for parkinsonian degeneration. Previous studies of VGCCs will have encompassed those on striatal cholinergic interneurons, which strongly influence DA transmission. We identify which VGCCs on DA axons govern DA transmission, we determine their dynamic properties and reveal an underlying basis for differences between the caudate putamen (CPu) and nucleus accumbens (NAc). We detected DA release evoked electrically during nicotinic receptor blockade or optogenetically by light activation of channel rhodopsin‐expressing DA axons in mouse striatal slices. Subtype‐specific VGCC blockers indicated that N‐, Q‐, T‐ and L‐VGCCs govern DA release in CPu, but in NAc, T and L‐channels are relatively silent. The roles of the most dominant channels were inversely frequency‐dependent, due to low‐pass filtering of DA release by Ca2+‐dependent relationships between initial release probability and short‐term plasticity. Ca2+ concentration–response curves revealed that differences between CPu and NAc were due to greater underlying Ca2+ sensitivity of DA transmission from CPu axons. Functions for ‘silent’ L‐ and T‐channels in NAc could be unmasked by elevating extracellular [Ca2+]. Furthermore, we identified a greater coupling between BAPTA‐sensitive, fast Ca2+ transients and DA transmission in CPu axons, and evidence for endogenous fast buffering of Ca2+ in NAc. These data reveal that a range of VGCCs operate dynamically on DA axons, depending on local driving forces. Furthermore, they reveal dramatic differences in Ca2+ handling between axonal subpopulations that show different vulnerability to parkinsonian degeneration.
Fracture Toughness Evaluation of Reactor Pressure Vessel Steels by Master Curve Method Using Miniature Compact Tension Specimens
Authors: Tobita Tohru , Nishiyama Yutaka , Ohtsu Takuyo , Udagawa Makoto , Katsuyama Jinya , Onizawa Kunio
Published: December 2014

We conducted fracture toughness testing on five types of commercially manufactured steel with different ductile-to-brittle transition temperatures. This was performed using specimens of different sizes and shapes, including the precracked Charpy-type (PCCv), 0.4T-CT, 1T-CT, and miniature compact tension specimens (0.16T-CT). Our objective was to investigate the applicability of 0.16T-CT specimens to fracture toughness evaluation by the master curve method for reactor pressure vessel (RPV) steels. The reference temperature (To) values determined from the 0.16T-CT specimens were overall in good agreement with those determined from the 1T-CT specimens. The scatter of the 1T-equivalent fracture toughness values obtained from the 0.16T-CT specimens was equivalent to that obtained from the other larger specimens. Furthermore, we examined the loading rate effect on To for the 0.16T-CT specimens within the quasi-static loading range prescribed by ASTM E1921. The higher loading rate gave rise to a slightly higher To, and this dependency was almost the same for the larger specimens. We suggested an optimum test temperature on the basis of the Charpy transition temperature for determining To using the 0.16T-CT specimens.
Force Modeling and Control of SiC Monocrystal Wafer Processing
Authors: Li Shujuan , Du Siming , Tang Aofei , Landers Robert G. , Zhang Yang
Published: December 2014

Wire saws with fixed diamond abrasive are often used to cut hard and brittle materials owning to the wire saw's narrow kerf, low cutting force, and minimal material waste. Typically, the cutting force changes during the operation since the part diameter and the contact length between the wire saw and part (i.e., contact length) continuously change, even if the process parameters (i.e., wire saw velocity, part feed rate, part rotation speed, and wire saw tension) are fixed, leading to wire saw breakage, wafer collapse, and inferior surface roughness. This study addresses this issue by regulating the force via feedback control. The most significant process parameter affecting the normal force, namely, part feed rate, is taken as the control variable. A system identification routine is used to obtain the transfer function relating the normal force and commanded part feed rate and the model parameters are identified online. An adaptive force controller is designed, and simulation and experimental studies for SiC monocrystal wafer wire saw machining are conducted. The results show the dynamic model well characterizes the normal force generated when wire saw machining SiC monocrystal, and the adaptive controller can effectively track various normal reference force trajectories (i.e., constants, ramps, and sine waves). The experimental results demonstrate that the wire saw machining process with adaptive force control can improve the cutting productivity and significantly decrease wafer surface roughness as compared to the cutting process with a constant part feed rate.
Electrical Discharge Grinding of Polycrystalline Diamond—Effect of Machining Parameters and Finishing In-Feed
Authors: Zulafif Rahim M. , Ding Songlin , Mo John
Published: December 2014

Electrical discharge grinding (EDG) is becoming more prevalent in the manufacturing of polycrystalline diamond (PCD) tools. This paper concerns investigation of the effects of machining parameters, as well as finishing in-feed, to the surface quality obtained when using EDG to erode PCD. With the aid of the morphological findings, different PCD erosion mechanisms are discussed. Experimental results demonstrated that the eroded surface quality of PCD was significantly affected by the selected parameters. High temperature due to the erosion process resulted in the partial conversion of diamond to graphite phase under the surface. Higher finishing in-feed produced better surface quality and caused lower surface graphitization and lower tensile residual stress. A model for the thermal stress prediction was developed and found to have good agreement with the experimental findings.
Millimeter-Scale Robotic Mechanisms Using Carbon Nanotube Composite Structures
Authors: Tanner Jordan D. , Grames Clayton , Jensen Brian D. , Magleby Spencer P. , Howell Larry L.
Published: December 2014

This paper presents a method for fabricating millimeter-scale robotic components for minimally invasive surgery. Photolithographic patterning is used to create a framework of carbon nanotubes (CNTs) that can be infiltrated with a variety of materials, depending on the desired material properties. For the examples shown in this paper, amorphous carbon is used as the infiltration material. The planar frameworks are then stacked to create the 3D device. The detail and precision are affected by large changes in cross section in the direction of stacking. Methods for improving the definition of the 3D object due to changing cross section are discussed. The process is demonstrated in a two-degree-of-freedom (2DOF) wrist mechanism and a 2DOF surgical gripping mechanism, which have the potential of decreasing the size of future minimally invasive surgical instruments.
Design and Optimization of a Five-Finger Haptic Glove Mechanism
Authors: Ma Zhou , Ben-Tzvi Pinhas
Published: December 2014

This paper describes the design and optimization of a novel five-finger haptic glove mechanism, which uses a worm-geared motor and an antagonistically routed cable mechanism at each finger as both active and passive force display actuators. Existing haptic gloves either restrict the natural motion and maximum output force of the hand or are bulky and heavy. In order to tackle these challenges, the five-finger haptic glove is designed to minimize the size and weight and maximize the workspace and force output range of the glove. The glove is a wireless and self-contained mechatronic system that mounts over the dorsum of a bare hand and provides haptic force feedback to each finger. This paper describes the mechatronic design of the glove and the method to optimize the link length with the purpose of enhancing workspace and the force transmission ratio. Simulation and experimental results are reported, showing the future potential of the proposed system in haptic applications and rehabilitation therapy.
Damage Evolution in Lead Free Solder Joints in Isothermal Fatigue
Authors: Qasaimeh Awni , Hamasha Sa’d , Jaradat Younis , Borgesen Peter
Published: December 2014

The extrapolation and generalization of accelerated test results for lead free solder joints require the identification of a damage function that can be counted on to apply beyond the region of the test. Individual ball grid array (BGA) scale Sn3Ag0.5Cu (SAC305) solder joints were subjected to isothermal shear fatigue testing at room temperature and 65 °C. The resulting mechanical response degradation and crack behavior, including strain hardening, crack initiation, and propagation, were correlated with the inelastic work and effective stiffness derived from load–displacement hysteresis loops. Crack initiation was found to scale with the accumulated work, independently of cycling amplitude and strain rate. The subsequent damage rate varied slightly with amplitude.
Modeling of Melt-Pool Formation and Material Removal in Micro-Electrodischarge Machining
Authors: Mujumdar Soham S. , Curreli Davide , Kapoor Shiv G. , Ruzic David
Published: December 2014

This paper presents a micro-electrodischarge machining (EDM) melt-pool model to predict workpiece (anode) material removal from a single discharge micro-EDM process. To model the melt-pool, heat transfer and fluid flow equations are solved in the domain containing dielectric and workpiece material. A level set method is used to identify solid and liquid fractions of the workpiece material when the material is molten by micro-EDM plasma heat flux. The plasma heat flux, plasma pressure and the radius of the plasma bubble have been estimated by a micro-EDM plasma model and serve as inputs to the melt-pool model to predict the volume of material removed from the surface of the workpiece. Experiments are carried out to study the effect of interelectrode voltage and gap distance on the crater size. For interelectrode voltage in the range of 200–300 V and gap distance of 1,2 μm, the model predicts crater diameter in the range of 78–96 μm and maximum crater depth of 8–9 μm for discharge duration of 2 μs. The crater diameter values for most of experimental craters show good agreement with the simulated crater shapes. However, the model over-predicts the crater depths compared to the experiments.
Numerical Simulation of Francis Turbine
Authors: Saeed Raza A.
Published: December 2014

This paper presents the results of modelling of the complete three-dimensional fluid flow through the spiral casing, stay vanes, guide vanes, and then through the Francis turbine runner to the draft tube of the Derbendikhan power station. To investigate the flow in the Francis turbine and also to compute stress distribution in the runner blades, a three-dimensional model was prepared according to specifications provided. The two topics discussed in this study are: (i) the simulation of the 3D fluid flow through the inter blade channels for the Francis turbine runner by using Computational Fluid Dynamics (CFD) and, (ii) the simulation of the stress analysis of the turbine runner by using Finite Element Analysis (FEA). In this study, the water pressure obtained from the CFD analysis for different boundary conditions are incorporated into a Finite Element model to calculate stress distributions in the runner.
Turbulent Flow and Jet-Interaction in a Smooth Lid-Driven-Cavity
Authors: Uhkoetter Stephan , aus der Wiesche Stefan
Published: December 2014

Experiments were carried out to study the flow and mixing behavior in a smooth lid-driven cavity. In contrast to a simple lid-driven cavity configuration, narrow gaps with finite thickness at inlet and outlet and an additional jet into the cavity were considered, too. It was found that a thin shear layer close to the moving wall occurred whereas the larger part of the flow domain was characterized by large fluctuating eddies. Due to the smooth cavity shape, a pressure gradient in flow direction resulted. The combined effects of that pressure gradient and the moving wall were investigated by measurements of the velocity and fluctuation profiles using Laser-Doppler-Anemometry (LDA). Special attention was spent to the interaction of the inflowing jet with the main flow within the cavity, and different regimes of jet-cavity-interaction were visualized. In addition to the experiments, an extensive Large-Eddy-Simulation (LES) study was conducted, and a reasonable agreement between the experimental data and the LES results were found.
Determination of Pressure Drop of Pure Water Flowing Upward Direction in a Double Tube Heat Exchanger Having Smooth and Microfin Tubes
Authors: Çebi Alican , Celen Ali , Dalkılıç Ahmet Selim , Sevindir Mustafa Kemal , Wongwises Somchai
Published: December 2014

Single phase friction factor and pressure drop behavior of smooth and microfin tubes are studied experimentally. The vertical test section was working as a counter flow double tube heat exchanger with water flowing in the inner smooth and microfin tubes having varying inner diameters and cooling water flowing in the annulus. Pressure drop of water due to cooling in upward flow in inner tubes is determined by experiments. Inner tube mass flow rate was between 0.023 kg/s to 0.100 kg/s while test section inlet temperatures were 40°C and 60°C. Effect of Reynolds number on pressure drop is also investigated and Blasius type friction factor correlations are developed for both smooth and microfin tubes.