bluuebunny/crossref_metadata_2025 huggingface dataset:
Single dose kinetic study of the triple combination mefloquine/sulphadoxine/pyrimethamine (Fansimef) in healthy male volunteers.
Authors: Mansor SM , Navaratnam V. , Mohamad M. , Hussein S. , Kumar A. , Jamaludin A. , Wernsdorfer WH
Published: July 2012

A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC‐ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean +/‐ s.d. for mefloquine (5.70 +/‐ 0.95 h), sulphadoxine (3.75 +/‐ 2.03 h) and pyrimethamine (3.30 +/‐ 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half‐lives (t1/2). The t1/2s for mefloquine, sulphadoxine and pyrimethamine were 387 +/‐ 98 h, 255 +/‐ 61 h and 114 +/‐ 42 h, respectively.
Lack of effect of terfenadine on theophylline pharmacokinetics and metabolism in normal subjects.
Authors: Brion N. , Naline E. , Beaumont D. , Pays M. , Advenier C.
Published: July 2012

The pharmacokinetics of oral theophylline (250 mg) and the production of its metabolites (3‐methylxanthine, 1‐methyluric acid, 1,3‐ dimethyluric acid) were studied before and after the administration of oral terfenadine (120 mg twice daily for 16 days) in 10 healthy volunteers. Comparison of volumes of distribution, elimination half‐ lives, areas under the plasma concentration‐time curves, plasma clearance of theophylline and elimination of theophylline metabolites indicated that terfenadine had no significant effect on theophylline pharmacokinetics and metabolism.
A comparison of three mathematical models to describe the disappearance curves of subcutaneously injected 125I‐labelled insulin.
Authors: De Meijer PH , Russel FG , Van Lier HJ , Van Ginneken CA
Published: July 2012

1. The absorption of insulin in constant and varied volumes and concentration was studied in healthy volunteers. 2. Disappearance curves of radioactivity after subcutaneous injection of labelled insulin were fitted with three models: a diffusion rate‐limited, a dissolution rate‐limited and a capacity‐limited model. 3. For each curve and model goodness of fit (r2) and sum of weighted squared deviations (SWSD) were calculated. With constant volume and concentration r2 was greater than 0.097 for each curve. SWSDs with the second model were less than those with the first (NS) and third (P less than 0.01). 4. When volume and concentration were varied, the parameters of the first and third model also varied, arguing against the validity of these models. 5. It is concluded that each of the three models, although yielding an accurate description of the observed data is too simple conceptually. Suggestions for more appropriate modelling are discussed.
Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity.
Authors: Herrick AL , McColl KE , Moore MR , Brodie MJ , Adamson AR , Goldberg A.
Published: July 2012

1. Acute intermittent porphyria (AIP) is sometimes termed a ‘pharmacogenetic’ disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely exclude porphyria. 4. Acute porphyria should be suspected if clinical deterioration occurs during therapy with anticonvulsants, or other porphyrinogenic drugs, even in the absence of an underlying genetic defect in haem synthesis in peripheral blood cells.
Long lasting respiratory depression induced by morphine‐6‐glucuronide?
Authors: Hasselstrom J. , Berg U. , Lofgren A. , Sawe J.
Published: July 2012

We report a case of long lasting respiratory depression after intravenous administration of morphine to a 7 year old girl with haemolytic uraemic syndrome. The plasma concentrations of the active metabolite M6G were more than 10 times those normally seen and the half‐ lives of M6G and morphine were prolonged.
Low and conventional dose cyclopenthiazide on glucose and lipid metabolism in mild hypertension.
Authors: McVeigh GE , Dulie EB , Ravenscroft A. , Galloway DB , Johnston GD
Published: July 2012

In a double‐blind, placebo controlled, randomised parallel study we investigated the antihypertensive activity and metabolic adverse effects of three doses of cyclopenthiazide in 53 patients with mild hypertension. After a 4 week placebo washout period, patients with diastolic blood pressures between 90‐110 mm Hg were randomly assigned to receive 50 micrograms, 125 micrograms and 500 micrograms of cyclopenthiazide or matching placebo, over an 8 week active treatment period. Blood pressure was recorded at 2 weekly intervals during the trial. Venous samples were taken for evaluation of drug effect on indices of carbohydrate and lipid metabolism just prior to, and on completion of, the active treatment period. Systolic and diastolic blood pressure decreased significantly (P less than 0.05) with the 125 micrograms and 500 micrograms doses of cyclopenthiazide. No change was apparent in any index of glucose and lipid metabolism over time. Low and conventional doses of cyclopenthiazide lower blood pressure without alteration to the metabolic profile in the short term.
Ginkgo biloba for cerebral insufficiency.
Authors: Kleijnen J. , Knipschild P.
Published: July 2012

1. By means of a critical review we tried to establish whether there is evidence from controlled trials in humans on the efficacy of Ginkgo biloba extracts in cerebral insufficiency. 2. The methodological quality of 40 trials on Ginkgo and cerebral insufficiency was assessed using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. A comparison of the quality was made with trials of co‐dergocrine, which is registered for the same indication. 3. There were eight well performed trials out of a total of 40. Shortcomings were limited numbers of patients included, and incomplete description of randomization procedures, patient characteristics, effect measurement and data presentation. In no trial was double‐blindness checked. Virtually all trials reported positive results, in most trials the dosage was 120 mg Ginkgo extract a day, given for at least 4‐6 weeks. For the best trials, there were no marked differences in the quality of the evidence of the efficacy of Ginkgo in cerebral insufficiency compared with co‐dergocrine. The results of the review may be complicated by a combination of publication bias and other biases, because there were no negative results reported in many trials of low methodological quality. 4. Positive results have been reported for Ginkgo biloba extracts in the treatment of cerebral insufficiency. The clinical evidence is similar to that of a registered product which is prescribed for the same indication. However, further studies should be conducted for a more detailed assessment of the efficacy.
7‐Alkoxyquinoline O‐dealkylation by microsomes from human liver and placenta.
Authors: Hakkola J. , Maenpaa J. , Mayer RT , Park SS , Gelboin HV , Pelkonen O.
Published: July 2012

1. The O‐dealkylation of seven 7‐alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7‐alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O‐dealkylation of all of the 7‐ alkoxyquinoline derivatives, being greatest for 7‐butoxy‐ and 7‐ benzyloxyquinoline. 4. Placental 7‐alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1‐7‐1 raised against 3‐methylcholanthrene‐induced rat liver P450. 5. None of the 7‐alkoxyquinoline O‐dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
The effects of age and gender on the pharmacokinetics of tenidap sodium in patients with rheumatoid arthritis and osteoarthritis.
Authors: Caldwell JR , Kirby DS , Gardner MJ , Hansen RA
Published: July 2012

1. This open‐label study was conducted to evaluate the effects of age and gender on the pharmacokinetics of tenidap sodium in patients with either rheumatoid arthritis (RA) or osteoarthritis (OA). 2. A total of 145 male and female patients, 80 with RA (aged 22‐91 years) and 65 with OA (aged 45‐83 years) each received a single dose of 120 mg tenidap sodium. Pharmacokinetic parameters were estimated from individual tenidap plasma concentration‐time curves determined up to 120 h post‐ dose. Tenidap plasma protein binding was determined in the youngest and oldest age groups for both RA and OA patients. 3. In RA patients, age and gender did not significantly affect the disposition of tenidap or the percentage of unbound tenidap in plasma. Only for tmax were statistically significant effects in the analysis of covariance observed and these were attributed to very high tmax values in two female patients. Likewise, in patients with OA, age and gender did not significantly affect the pharmacokinetics of tenidap, although patients with larger body weights had lower Cmax values. 4. Pharmacokinetic parameters were not significantly different between RA and OA patients, except for t1/2, where two outlier RA patients had low values that caused the mean value to be significantly lower in RA (24 h) than in OA (26 h) patients. Pharmacokinetic parameters for pooled values from RA and OA patients were as follows: t1/2 = 25 h, AUC = 538.4 micrograms ml‐ 1 h, Cmax = 21.9 micrograms ml‐1, tmax = 3.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Disruption of redox homeostasis leads to oxidative DNA damage in spermatocytes of Wolbachia‐infected Drosophila simulans
Authors: Brennan L. J. , Haukedal J. A. , Earle J. C. , Keddie B. , Harris H. L.
Published: July 2012

Molecular interactions between symbiotic bacteria and their animal hosts are, as yet, poorly understood. The most widespread bacterial endosymbiont, Wolbachia pipientis, occurs in high density in testes of infected Drosophila simulans and causes cytoplasmic incompatibility (CI), a form of male‐derived zygotic lethality. Wolbachia grow and divide within host vacuoles that generate reactive oxygen species (ROS), which in turn stimulate the up‐regulation of antioxidant enzymes. These enzymes appear to protect the host from ROS‐mediated damage, as there is no obvious fitness cost to Drosophila carrying Wolbachia infections. We have now determined that DNA from Wolbachia‐infected mosquito Aedes albopictus (Aa23) cells shows a higher amount of the base 8‐oxo‐deoxyguanosine, a marker of oxidative DNA damage, than DNA from uninfected cells, and that Wolbachia infection in D. simulans is associated with an increase in DNA strand breaks in meiotic spermatocytes. Feeding exogenous antioxidants to male and female D. simulans dramatically increased Wolbachia numbers with no obvious effects on host fitness. These results suggest that ROS‐induced DNA damage in sperm nuclei may contribute to the modification characteristic of CI expression in Wolbachia‐infected males and that Wolbachia density is sensitive to redox balance in these flies.
Effects of chronic consumption of fruit and vegetable puree‐based drinks on vasodilation, plasma oxidative stability and antioxidant status
Authors: George T. W. , Paterson E. , Waroonphan S. , Gordon M. H. , Lovegrove J. A.
Published: July 2012

Background

Fruit and vegetable‐rich diets are associated with a reduced cardiovascular disease (CVD) risk. This protective effect may be a result of the phytochemicals present within fruits and vegetables (F&V). However, there can be considerable variation in the content of phytochemical composition of whole F&V depending on growing location, cultivar, season and agricultural practices, etc. Therefore, the present study investigated the effects of consuming fruits and vegetables as puree‐based drinks (FVPD) daily on vasodilation, phytochemical bioavailability, antioxidant status and other CVD risk factors. FVPD was chosen to provide a standardised source of F&V material that could be delivered from the same batch to all subjects during each treatment arm of the study.

Methods

Thirty‐nine subjects completed the randomised, controlled, cross‐over dietary intervention. Subjects were randomised to consume 200 mL of FVPD (or fruit‐flavoured control), daily for 6 weeks with an 8‐week washout period between treatments. Dietary intake was measured using two 5‐day diet records during each cross‐over arm of the study. Blood and urine samples were collected before and after each intervention and vasodilation assessed in 19 subjects using laser Doppler imaging with iontophoresis.

Results

FVPD significantly increased dietary vitamin C and carotenoids (P < 0.001), and concomitantly increased plasma α‐ and β‐carotene (P < 0.001) with a near‐significant increase in endothelium‐dependent vasodilation (P = 0.060).

Conclusions

Overall, the findings obtained in the present study showed that FVPD were a useful vehicle to increase fruit and vegetable intake, significantly increasing dietary and plasma phytochemical concentrations with a trend towards increased endothelium‐dependent vasodilation.
Added value of a mandible movement automated analysis in the screening of obstructive sleep apnea
Authors: MAURY GISELE , CAMBRON LAURENT , JAMART JACQUES , MARCHAND ERIC , SENNY FRÉDÉRIC , POIRRIER ROBERT
Published: July 2012

In‐laboratory polysomnography is the ‘gold standard’ for diagnosing obstructive sleep apnea syndrome, but is time consuming and costly, with long waiting lists in many sleep laboratories. Therefore, the search for alternative methods to detect respiratory events is growing. In this prospective study, we compared attended polysomnography with two other methods, with or without mandible movement automated analysis provided by a distance‐meter and added to airflow and oxygen saturation analysis for the detection of respiratory events. The mandible movement automated analysis allows for the detection of salient mandible movement, which is a surrogate for arousal. All parameters were recorded simultaneously in 570 consecutive patients (M/F: 381/189; age: 50 ± 14 years; body mass index: 29 ± 7 kg m−2) visiting a sleep laboratory. The most frequent main diagnoses were: obstructive sleep apnea (344; 60%); insomnia/anxiety/depression (75; 13%); and upper airway resistance syndrome (25; 4%). The correlation between polysomnography and the method with mandible movement automated analysis was excellent (r: 0.95; P < 0.001). Accuracy characteristics of the methods showed a statistical improvement in sensitivity and negative predictive value with the addition of mandible movement automated analysis. This was true for different diagnostic thresholds of obstructive sleep severity, with an excellent efficiency for moderate to severe index (apnea–hypopnea index ≥15 h−1). A Bland & Altman plot corroborated the analysis. The addition of mandible movement automated analysis significantly improves the respiratory index calculation accuracy compared with an airflow and oxygen saturation analysis. This is an attractive method for the screening of obstructive sleep apnea syndrome, increasing the ability to detect hypopnea thanks to the salient mandible movement as a marker of arousals.
N‐(2‐methyl‐6‐benzoxazolyl)‐N′‐1,5‐naphthyridin‐4‐yl urea (SB334867), a hypocretin receptor‐1 antagonist, preferentially prevents ethanol seeking: comparison with natural reward seeking
Authors: Martin‐Fardon Rémi , Weiss Friedbert
Published: July 2012

Orexins/hypocretins (Orx/Hcrt) are hypothalamic peptides that regulate a wide range of physiological processes and have been shown to be recruited by drugs of abuse. This study was designed to test the effect of the specific Orx/Hcrt receptor‐1 (Hcrt‐r1) antagonist, N‐(2‐methyl‐6‐benzoxazolyl)‐N′‐1,5‐naphthyridin‐4‐yl urea (SB334867), on reinstatement elicited by ethanol (EtOH)‐associated stimuli versus stimuli associated with a conventional reinforcer [i.e. SuperSac, consisting of 3% glucose and 0.125% saccharin (w/v)]. SB334867 (1–10 mg/kg, i.p.) dose‐dependently reduced reinstatement induced by the EtOH‐ but not SuperSac‐associated stimuli. These findings support a differential role of Hcrt‐r1 in mediating EtOH seeking versus natural reward seeking.
Measurement of Ara h 1‐, 2‐, and 3‐specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children
Authors: Ebisawa Motohiro , Movérare Robert , Sato Sakura , Maruyama Nobuyuki , Borres Magnus P. , Komata Takatsugu
Published: July 2012

To cite this article:Ebisawa M, Movérare R, Sato S, Maruyama N, Borres MP, Komata T. Measurement of Ara h 1‐, 2‐, and 3‐specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children.Pediatr Allergy Immunol2012:23: 573–581.

Background: Food challenges are time‐consuming, expensive, and not always possible to perform. Therefore, new tools to diagnose food allergy are desired. The aim was to evaluate IgE antibodies to peanut allergens in the diagnosis of peanut allergy in Japanese children using ImmunoCAP®and IgE immunoblotting.

Methods: The study included 2–13‐yr‐old consecutive patients (n = 57) referred to our specialist clinic for investigation of current peanut allergy using food challenge. All children had a previous doctor’s diagnosis of peanut allergy and were on elimination diet. Serum samples were analyzed for IgE reactivity to peanut, recombinant (r) Ara h 1, 2, 3, 5, 8, and 9. IgE immunoblotting (n = 23) was performed using extracts from raw and roasted peanut.

Results: Twenty‐six of the children failed (allergic group), and 31 passed the peanut challenge (tolerant group). The rAra h 2 ImmunoCAP test was superior in its ability to differentiate between children in the allergic and tolerant groups with a sensitivity and specificity of 88% and 84%, respectively (cutoff, 0.35 kUA/l). The combination of rAra h 1, 2, and 3 resulted in a higher specificity (94%) when IgE to all of them was the criteria for positivity. ImmunoCAP generally showed a good agreement with immunoblotting using both raw and roasted peanut for IgE reactivity to Ara h 1, 2, and 3.

Conclusions: Measurement of IgE antibodies to rAra h 1, 2, and 3 is useful in the diagnosis of peanut allergy and in the investigation of reactions to raw and roasted peanut.
A major quantitative trait allele for resistance to the Sugarcane yellow leaf virus (Luteoviridae)
Authors: Costet Laurent , Raboin Louis‐Marie , Payet Magali , D’Hont Angélique , Nibouche Samuel
Published: July 2012

With 1 figure and 1 table

The yellow leaf disease of sugarcane is distributed worldwide and causes important yield losses. This disease is caused by a member of the Luteoviridae family, the Sugarcane yellow leaf virus (SCYLV). The objective of this study was to characterize genetic factors for resistance to yellow leaf disease in a sugarcane clone resistant to infection by SCYLV. We analysed a progeny of 196 clones obtained from a cross between the susceptible cultivar ‘R570’ and the resistant cultivar ‘MQ76‐53’. This progeny was assessed for virus incidence using tissue‐blot immunoassay after 10 years of cultivation under natural infection conditions. The progeny was genotyped with various types of molecular markers resulting in 2822 polymorphic markers. Marker/trait association analysis revealed that SCYLV resistance in ‘MQ76‐53’ is controlled by Ryl1, a major quantitative trait allele (QTA) accounting for 32% of the phenotypic variance. Ryl1 is the first major QTA described to control a viral disease in sugarcane, and ‘MQ76‐53’ can already be used to introgress SCYLV resistance derived from Ryl1 in elite germplasm.
High production of interleukin‐10 and interferon‐γ in influenza‐associated MERS in the early phase
Authors: Morichi Shinichiro , Kawashima Hisashi , Ioi Hiroaki , Yamanaka Gaku , Kashiwagi Yasuyo , Hoshika Akinori
Published: July 2012

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) occurs in various diseases and pathologies, and the clinical symptoms are not consistent with the impaired region. The mechanism of the region specificity is unclear. We investigated the cytokine profiling in cerebrospinal fluid (CSF) and serum obtained from a child with MERS during influenza infection, and compared them with those of serious another serious type of influenza‐associated encephalopathy. There was no elevation of Interleukin (IL)‐1β, which induces convulsion. The inhibitory cytokines of IL‐10 and IFN‐γ were elevated in the early phase in CSF. Comparing them with other patients, the elevation of the cytokine levels were generally mild. Considering that the prognosis of this MERS case was favorable and high levels of inhibitory cytokines including IL‐10 and IFN‐γ might work to localize the lesion and to prevent sequelae.
Microscopic polyangiitis in a girl with severe anemia and no respiratory symptoms
Authors: Yamato Kazumi , Ishii Takafumi , Kawamura Tomoyuki
Published: July 2012

ANCA‐positive microscopic polyangiitis is a rare in children. We reported an 11‐year‐old girl without respiratory symptoms with sever anemia which shows signs of hemolytic anemia in test data. Chest X‐ray and computed tomography scans suggested alveolar hemorrhage. The patent developed night hypoxia and moderate proteinuria. Serum MPO‐antibody was highly positive and renal biopsy demonstrated segmental necrosis or crescent formation. A diagnosis of microscopic polyangiitis was made. She responded to pulsed methylprednisolon and pulsed Endoxan therapy. Microscopic polyangitiis should be considered early in the differential diagnosis of patients presenting with anemia of an unknown origin.
Left atrium thrombus in an extremely low‐birthweight infant with late‐onset circulatory dysfunction
Authors: Ina Shihomi , Futatani Takeshi , Higashiyama Hiroyuki , Hashida Nobuko , Fujita Shuhei , Shimura Shoetsu , Igarashi Noboru , Hatasaki Kiyoshi
Published: July 2012

A left atrium thrombus, potentially a life‐threatening complication, is an extremely rare in early infancy. Most cases are caused by mal‐placement of central venous catheters or related to congenital heart diseases with left atrial blood congestion. Here we present an extremely low birth weight infant who developed a left atrial thrombus during the course of late onset circulatory dysfunction. The thrombus was successfully treated by recombinant tissue plasminogen activator. A hemodynamically unstable condition like late onset circulatory dysfunction should be taken into consideration as a potential risk condition of this rare disease.
DESCARTES' ‘PROVISIONAL MORALITY’
Authors: CIMAKASKY JOSEPH , POLANSKY RONALD
Published: July 2012

Discourse on Method part 3 offers une morale par provision, usually translated as ‘a provisional moral code’. Occasionally it has been questioned that this code is temporary and restricted to those engaged in pure inquiry. We argue that Descartes intends the moral code to be his final ethical position universally applicable. Since the moral code is ‘derived from’ the rules of method, it should have their permanence, holding for the time pure inquiry commences and when it completes the sciences. Moreover, the four moral maxims replace the classical cardinal virtues. Thus they are meant to govern the lives of all persons.
Processio and The Place of Ontic Being: John Milbank and James K.A. Smith On Participation
Authors: Triffett Brendan Peter
Published: July 2012

James K.A. Smith argues that the ontology of participation associated with Radical Orthodoxy is incompatible with a Christian affirmation of the intrinsic being and goodness of creatures. In response, he proposes a Leibnizian view in which things are endowed with the innate dynamism of ‘force’. Creatures have a certain depth of being, and are intrinsically good, just because they each have an inner virtuality that they bring into expression. Such force is said to be a metaphysical component of the agent. In this paper it is asked whether John Milbank's ontology of participation can be defended by distinguishing between two senses of being a subject. Perhaps it is possible for a creature to bring into expression what is an infused ‘alien’ gift rather than a metaphysical component – to be expressive subject, but not ontic subject, for divine power. However, while this distinction promises to make sense of the reception of an indwelling ‘other’ in grace, knowledge and love, neither proper substance nor proper existence can be received in this way. A creature must be the ontic subject for its being, after all. Still, divine being might proceed from God as radical indwelling gift, as non‐ontic ground for ontic being.
IDENTIFICATION AND ESTIMATION OF AUCTION MODEL WITH TWO‐DIMENSIONAL UNOBSERVED HETEROGENEITY*
Authors: Krasnokutskaya Elena
Published: July 2012

This article investigates the empirical importance of allowing for multidimensional sources of unobserved heterogeneity in auction models with private information. It develops the estimation procedure to recover the distribution of private information in the presence of two sources of unobserved heterogeneity. It is shown that this estimation procedure identifies components of the model and produces uniformly consistent estimators of these components. The results of the estimation with highway procurement data indicate that allowing for two‐dimensional unobserved heterogeneity may significantly affect the results of estimation as well as policy‐relevant instruments derived from the estimated distributions of bidders’ costs.
THE IMPACT OF BESTSELLER RANK ON DEMAND: EVIDENCE FROM THE APP MARKET*
Authors: Carare Octavian
Published: July 2012

This article uses daily data on the ranking by sales of the top 100 apps sold through Apple’s App Store to provide evidence of the causal impact of today’s bestseller rank information on tomorrow’s demand. The estimates indicate that the willingness to pay of consumers is about $4.50 greater for a top ranked app than for the same unranked app. The results also indicate that the effects of bestseller status on willingness to pay decline steeply with rank at the top ranks, but remain economically significant for the apps in the first half of the top 100 list.
ASSET‐BASED UNEMPLOYMENT INSURANCE*
Authors: Rendahl Pontus
Published: July 2012

This article studies a model of consumption, savings, and job search in which a borrowing constraint limits self‐insurance. The government administers the unemployment insurance program that may condition on an individual’s asset position, but not on her efforts of finding a job. To compensate for the impediments to self‐insurance, benefit payments should optimally be set higher at lower wealth levels and peak for borrowing‐constrained individuals with zero liquid funds. A quantitative exercise reveals that the U.S. unemployment insurance program is surprisingly close to optimal for the asset poor, but far too generous for wealthier individuals.
MODEL UNCERTAINTY AND EXCHANGE RATE VOLATILITY*
Authors: Markiewicz Agnieszka
Published: July 2012

This article proposes an explanation for shifts in the volatility of exchange‐rate returns. Agents are uncertain about the true data generating model and deal with this uncertainty by making inference on the models and their parameters' approach, I call model learning. Model learning may lead agents to focus excessively on a subset of fundamental variables. Consequently, exchange‐rate volatility is determined by the dynamics of these fundamentals and changes as agents alter models. I investigate the empirical relevance of model learning and find that the change in volatility of GBP/USD in 1993 was triggered by a shift between models.
EX ANTE INVESTMENT, EX POST REMEDIES, AND PRODUCT LIABILITY*
Authors: Chen Yongmin , Hua Xinyu
Published: July 2012

A firm can increase product safety through ex ante investment and can remedy quality problems after sales. An increase in product liability raises returns to ex ante investment through higher consumer demand, but may also negatively affect the investment incentive due to more ex post remedial activities. The trade‐off between these “output” and “substitution” effects can result in an inverted U‐shaped relationship between product liability and ex ante investment. We find that the firm prefers full liability, but consumer surplus can be higher under partial liability. We further identify conditions under which full liability or partial liability is socially optimal.
FORECASTING INFLATION USING DYNAMIC MODEL AVERAGING*
Authors: Koop Gary , Korobilis Dimitris
Published: July 2012

We forecast quarterly US inflation based on the generalized Phillips curve using econometric methods that incorporate dynamic model averaging. These methods not only allow for coefficients to change over time, but also allow for the entire forecasting model to change over time. We find that dynamic model averaging leads to substantial forecasting improvements over simple benchmark regressions and more sophisticated approaches such as those using time varying coefficient models. We also provide evidence on which sets of predictors are relevant for forecasting in each period.
TAXES, REGULATIONS AND THE CORPORATE DEBT MARKET*
Authors: Atesagaoglu Orhan Erem
Published: July 2012

Outstanding credit market debt in the U.S. corporate sector increased dramatically over the second half of the 20th century. During this period, tax rates on dividend distributions and corporate income decreased. This article argues that the observed decline in dividend and corporate income tax rates generated an improvement in the collateral value of corporate assets and led to an increase in U.S. corporate debt. To analyze this conjecture, we build a general equilibrium model with enforcement constraints that induce endogenous limits on debt financing. We find that the model can account for the time‐series features of U.S. corporate debt data.
MATCHING MARKETS WITH MIXED OWNERSHIP: THE CASE FOR A REAL‐LIFE ASSIGNMENT MECHANISM*
Authors: Guillen Pablo , Kesten Onur
Published: July 2012

We consider a common indivisible good allocation problem whose popular applications include on‐campus housing, kidney exchange, and school choice. We show that the so‐called New House 4 (NH4) mechanism, which has been in use at MIT since the 1980s, is equivalent to a natural adaptation of the well‐known Gale–Shapley (GS) mechanism. We run two experiments comparing NH4 with the prominently advocated Top Trading Cycles (TTC) mechanism and NH4 with GS. We find that under NH4, the participation rate is significantly higher than under TTC. Based on a new ordinal test of efficiency, NH4 is more likely to Pareto dominate TTC.
DECORATED ARCHAIC POTTERY FROM THE HERACLES SANCTUARY AT THEBES: A MATERIALS, TECHNOLOGY AND PROVENANCE STUDY*
Authors: MASTROTHEODOROS G. , BELTSIOS K. G. , ZACHARIAS N. , ARAVANTINOS V. , KALLIGA K.
Published: July 2012

Forty‐seven decorated samples of Archaic pottery excavated at a Heracles sanctuary (Thebes, Boeotia) were studied through a combined surface and body approach, using non‐destructive techniques. Most of the samples were archaeologically classified as Theban/Boeotian, others as Corinthian and a few as possibly Euboean. The techniques employed were optical microscopy and SEM–EDAX (micromorphology and compositional analysis of the surfaces) and XRF for the analysis of the ceramic body. The results provided information on the technological level of the collected pottery as well as on the relation of the chemistry and micromorphology of the pigments, aimed at assisting provenance studies.
Expression of chondroitin‐glucuronate C5‐epimerase and cellular immune responses in patients with hepatocellular carcinoma
Authors: Mizukoshi Eishiro , Fushimi Kazumi , Arai Kuniaki , Yamashita Tatsuya , Honda Masao , Kaneko Shuichi
Published: July 2012

Background & Aims

Chondroitin‐glucuronate C5‐epimerase is an enzyme that converts D‐glucuronic acid to L‐iduronic acid residues in dermatan sulphate biosynthesis. It is also identified to be a tumour‐associated antigen recognized by cytotoxic T cells (CTLs) and its enhanced expression in many cancers has been reported. In the present study, we investigated the usefulness of this molecule as an immunotherapeutic target in hepatocellular carcinoma (HCC).

Methods

The expression of chondroitin‐glucuronate C5‐epimerase in hepatoma cell lines and HCC tissues was confirmed by immunofluorescence and immunohistochemical analysis. CTL responses were investigated by several immunological techniques using peripheral blood mononuclear cells (PBMCs) or tumour‐infiltrating lymphocytes. To determine the safety of immunotherapy using chondroitin‐glucuronate C5‐epimerase‐derived peptide, 12 patients with HCC were administered s.c. vaccinations of the peptides and analysed.

Results

Chondroitin‐glucuronate C5‐epimerase was expressed in HCC cell lines and human tissues including alpha‐foetoprotein (AFP)‐negative individuals. Chondroitin‐glucuronate C5‐epimerase‐specific CTLs could be generated by stimulating PBMCs of HCC patients with peptides and they showed cytotoxicity against HCC cells expressing the protein. The frequency of CTL precursors investigated by enzyme‐linked immunospot (ELISPOT) assay was 0–34 cells/3 × 105 PBMCs and the infiltration of interferon‐gamma‐producing CTLs into the tumour site was confirmed. In the vaccination study, no severe adverse events were observed and the peptide‐specific CTLs were induced in 4 of 12 patients tested.

Conclusions

Chondroitin‐glucuronate C5‐epimerase is a potential candidate for tumour antigen with immunogenicity and the peptides derived from this antigen could be useful in HCC immunotherapy.
Structural Confirmation of a Unique Carotenoid Lactoside, P457, in Symbiodinium sp. Strain nbrc 104787 Isolated from a Sea Anemone and its Distribution in Dinoflagellates and Various Marine Organisms
Authors: Wakahama Takahiro , Laza‐Martínez Aitor , Bin Haji Mohd Taha Ahmad Iskandar , Okuyama Hidetoshi , Yoshida Kiyohito , Kogame Kazuhiro , Awai Koichiro , Kawachi Masanobu , Maoka Takashi , Takaichi Shinichi
Published: July 2012

The molecular structure of the carotenoid lactoside P457, (3S,5R,6R,3′S,5′R,6′S)‐13′‐cis‐5,6‐epoxy‐3′,5′‐dihydroxy‐3‐(β‐d‐galactosyl‐(1→4)‐β‐d‐glucosyl)oxy‐6′,7′‐didehydro‐5,6,7,8,5′,6′‐hexahydro‐β,β‐caroten‐20‐al, was confirmed by spectroscopic methods using Symbiodinium sp. strain NBRC 104787 cells isolated from a sea anemone. Among various algae, cyanobacteria, land plants, and marine invertebrates, the distribution of this unique diglycosyl carotenoid was restricted to free‐living peridinin‐containing dinoflagellates and marine invertebrates that harbor peridinin‐containing zooxanthellae. Neoxanthin appeared to be a common precursor for biosynthesis of peridinin and P457, although neoxanthin was not found in peridinin‐containing dinoflagellates. Fucoxanthin‐containing dinoflagellates did not possess peridinin or P457; green dinoflagellates, which contain chlorophyll a and b, did not contain peridinin, fucoxanthin, or P457; and no unicellular algae containing both peridinin and P457, other than peridinin‐containing dinoflagellates, have been observed. Therefore, the biosynthetic pathways for peridinin and P457 may have been coestablished during the evolution of dinoflagellates after the host heterotrophic eukaryotic microorganism formed a symbiotic association with red alga that does not contain peridinin or P457.
High‐Risk Electrocardiographic Parameters are Ubiquitous in Patients with Ischemic Cardiomyopathy
Authors: Carey Mary G. , Al‐Zaiti Salah S. , Canty John M. , Fallavollita James A.
Published: July 2012

Background: The electrocardiogram (ECG) can be used to predict cardiovascular risk; however, like all risk factors with imperfect specificity, studies in low risk populations have been plagued by poor predictive accuracy. Although predictive accuracy might be improved among cohorts with a higher likelihood of cardiovascular events, this would also affect the prevalence of abnormal parameters and their exclusions.

Method: To determine the magnitude of these changes in a cohort with ischemic cardiomyopathy we analyzed 15 previously validated high‐risk parameters from the resting and ambulatory ECG in subjects enrolled in the Prediction of Arrhythmic Events with Positron Emission Tomography (PAREPET) study (n = 198).

Results: Using the published exclusion criteria from the validation studies (i.e., atrial fibrillation, persistent pacing, prolonged QRS), only 4 high‐risk ECG parameters (27%) could be evaluated in all subjects and only 42% of subjects could have all 15 ECG parameters assessed. Nevertheless, almost every subject (97%) had at least one abnormal parameter. On average, there were 3.4 ± 1.8 (range, 0–8) high‐risk ECG parameters per subject among the 11.7 ± 4.5 (range, 4–15) parameters that could be assessed.

Conclusions: Thus, 34% of all assessable parameters were abnormal. In conclusion, a significant proportion of ECG parameters cannot be assessed in patients with ischemic cardiomyopathy, but high‐risk results are ubiquitous. The influence of these issues will be clarified when the results of the PAREPET study are available to actually determine the predictive value of these parameters on cause‐specific mortality in a high‐risk cohort.
Relation between Beat‐to‐Beat QT Interval Variability and T‐Wave Amplitude in Healthy Subjects
Authors: Hasan Muhammad A. , Abbott Derek , Baumert Mathias
Published: July 2012

Objectives: Elevated beat‐to‐beat QT interval variability (QTV) has been associated with increased cardiovascular morbidity and mortality.The aim of this study was to investigate interlead differences in beat‐to‐beat QTV of 12‐lead ECG and its relationship with the T wave amplitude.

Methods: Short‐term 12‐lead ECGs of 72 healthy subjects (17 f, 38 ± 14 years; 55 m, 39 ± 13 years) were studied. Beat‐to‐beat QT intervals were extracted separately for each lead using a template matching algorithm. We calculated the standard deviation of beat‐to‐beat QT intervals as a marker of QTV as well as interlead correlation coefficients. In addition, we measured the median T‐wave amplitude in each lead.

Results: There was a significant difference in the standard deviation of beat‐to‐beat QT intervals between leads (minimum: lead V3 (2.58 ± 1.36 ms), maximum: lead III (7.2 ± 6.4 ms), ANOVA: P < 0.0001). Single measure intraclass correlation coefficients of beat‐to‐beat QT intervals were 0.27 ± 0.18. Interlead correlation coefficients varied between 0.08 ± 0.33 for lead III and lead V1 and 0.88 ± 0.09 for lead II and lead aVR. QTV was negatively correlated with the T‐wave amplitude (r =–0.62, P < 0.0001). There was no significant affect of mean heart rate, age or gender on QT variability (ANOVA: P > 0.05).

Conclusions: QTV varies considerably between leads in magnitude as well as temporal patterns. QTV is increased when the T wave is small.
Risk Stratification for Serious Arrhythmic Events Using Nonsustained Ventricular Tachycardia and Heart Rate Turbulence Detected by 24‐Hour Holter Electrocardiograms in Patients with Left Ventricular Dysfunction
Authors: Miwa Yosuke , Yoshino Hideaki , Hoshida Kyoko , Miyakoshi Mutsumi , Tsukada Takehiro , Yusu Satoru , Ikeda Takanori
Published: July 2012

Background: Previous studies have described the clinical usefulness of the presence of nonsustained ventricular tachycardia (NSVT) and defined heart rate turbulence (HRT) in stratifying patients at risk. We prospectively assessed whether HRT can facilitate the predictive accuracy of NSVT for identifying patients at risk for serious arrhythmic events in patients with left ventricular (LV) dysfunction.

Methods: We enrolled 299 consecutive patients with LV dysfunction (ejection fraction ≤ 40%) including ischemic (n = 184) and nonischemic causes (n = 115). The presence of NSVT was assessed on Holter electrocardiograms (ECGs). HRT was simultaneously measured from Holter ECGs, assessing two parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO and TS were abnormal. The end point was defined as of sudden cardiac death (SCD) and sustained ventricular tachyarrhythmias (VTs).

Results: NSVT was documented in 93 patients (32.7%). For HRT assessment, 17 patients (5.6%) were not utilized. Of 282 patients, 68 (24.1%) were HRT positive. During follow‐up of 960 ± 444 days, 14 patients (5.0%) reached the end point. NSVT, HRT, and diabetes were significantly associated with the end point. On multivariate analysis, NSVT had  the strongest value for the end point, with an HR of 4.4 (95%CI, 1.4–14.3; P = 0.0138). When NSVT combined with HRT, the predictive accuracy is more increased, with an HR of 8.2 (95%CI, 2.9–23.3; P < 0.0001). The predictive values of the combination were higher than single use of NSVT or HRT.

Conclusions: HRT can facilitate the predictive accuracy of NSVT for identifying patients at risk for serious arrhythmic events in patients with LV dysfunction.
Optimal QT/JT Interval Assessment in Patients with Complete Bundle Branch Block
Authors: Chiladakis John , Kalogeropoulos Andreas , Koutsogiannis Nikolaos , Zagkli Fani , Vlassopoulou Niki , Chouchoulis Konstantinos , Alexopoulos Dimitrios
Published: July 2012

Background: Prolonged ventricular repolarization duration confers increased risk for malignant ventricular arrhythmias. We sought to clarify the optimal method of QT/JT interval assessment in patients with complete bundle branch block (BBB).

Methods: Study patients (n = 71) were dual‐chamber device recipients with baseline left or right BBB who preserved intrinsic ventricular activation during incremental atrial pacing. Patients were classified according to the presence or not of structural heart disease. The former group received chronic amiodarone therapy. QT and JT intervals were recorded at baseline heart rate of 51 ± 4 beats/min and during atrial pacing at 60, 80, and 100 beats/min. We used linear mixed‐effects models to assess the effect of heart rate on the derived QTc and JTc values with the use of six different heart rate correction formulae.

Results: Heart rate had a significant effect on the QTc and the JTc intervals regardless of the correction formula used (P < 0.001 for all formulae). The formula of Hodges demonstrated the least variability in QTc and JTc measurements across the different heart rates in both patients groups without (F = 15.05 and F = 13.53, respectively) and with structural heart disease (F = 5.71 and F = 7.69, respectively), followed by the Nomogram and Framingham methods, whereas the uncorrected QT and JT intervals showed comparable heart rate–dependency. The application of Bazett's JTc and QTc led to the most pronounced interval variations in any case with BBB.

Conclusions: The Hodges, Nomogram and Framingham correction methods provide best assessment of QT/JT intervals in BBB, whereas Bazett's formula exaggerates heart rate–dependency of ventricular repolarization intervals.
Multicenter Automatic Defibrillator Implantation Trial: Reduce Inappropriate Therapy (MADIT‐RIT): Background, Rationale, and Clinical Protocol
Authors: Schuger Claudio , Daubert James P. , Brown Mary W. , Cannom David , Estes N.A. Mark , Hall W. Jackson , Kayser Torsten , Klein Helmut , Olshansky Brian , Power Keith A. , Wilber David , Zareba Wojciech , Moss Arthur J.
Published: July 2012

The implantable cardioverter defibrillator (ICD) is highly effective in reducing mortality due to cardiac arrhythmias in high‐risk cardiac patients. However, inappropriate therapies caused predominantly by supraventricular tachyarrhythmias (SVTs) remain a significant side effect of ICD therapy despite medical treatment, affecting 8–40% of patients. The MADIT‐RIT is a global, prospective, randomized, nonblinded, three‐arm, multicenter clinical investigation to be performed in the Unites States, Europe, Canada, Israel and Japan, and will utilize approximately 90 centers with plan to enroll 1500 patients programmed to three treatment arms. The objective of the MADIT‐RIT trial is to determine if dual‐chamber ICD or CRT‐D devices with high rate cutoff (MADIT‐RIT‐Arm B) and/or long delay in combination with detection enhancements (MADIT‐RIT‐Arm C) are associated with fewer patients experiencing inappropriate therapies than standard programming (MADIT‐RIT‐Arm A) during postimplant follow‐up of patients with indication for primary prevention device therapy. This paper describes design and analytic plan for the MADIT‐RIT trial.
P‐Wave Morphology: Underlying Mechanisms and Clinical Implications
Authors: Platonov Pyotr G.
Published: July 2012

Increasing awareness of atrial fibrillation (AF) and its impact on public health revives interest in identification of noninvasive markers of predisposition to AF and ECG‐based risk stratification. P‐wave duration is generally accepted as the most reliable noninvasive marker of atrial conduction, and its prolongation has been associated with history of AF. However, patients with paroxysmal AF without structural heart disease may not have any impressive P‐wave prolongation, thus suggesting that global conduction slowing is not an obligatory requirement for development of AF. P‐wave morphology is therefore drawing increasing attention as it reflects the three‐dimensional course of atrial depolarization propagation and detects local conduction disturbances. The factors that determine P‐wave appearance include (1) the origin of the sinus rhythm that defines right atrial depolarization vector, (2) localization of left atrial breakthrough that defines left atrial depolarization vector, and (3) the shape and size of atrial chambers. However, it is often difficult to distinguish whether P‐wave abnormalities are caused by atrial enlargement or interatrial conduction delay. Recent advances in endocardial mapping technologies have linked certain P‐wave morphologies with interatrial conduction patterns and the function of major interatrial conduction routes. The value of P‐wave morphology extends beyond cardiac arrhythmias associated with atrial conduction delay and can be used for prediction of clinical outcome of a wide range of cardiovascular disorders, including ischemic heart disease and congestive heart failure.
Comparison of diagnostic values of thyroid aspiration samples using liquid‐based preparation and conventional smear: one‐year experience in a single institution
Authors: Chang Hyeyoon , Lee Eunjung , Lee Hyunjoo , Choi Jongsang , Kim Aeree , Kim Baek‐hui
Published: July 2012

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Fine‐needle aspiration (FNA) is the most useful tool in the diagnosis of thyroid nodules. Liquid‐based preparation (LBP) in FNA of thyroid nodules is now widely used and is replacing the conventional smear (CS). We compared the diagnostic value of the LBP method with that of CS in thyroid lesions. A total of 1767 CS FNA samples and 2523 LBP FNA samples were included in this comparison of diagnostic values. We also assessed the differences in cytomorphologic features in 41 randomly selected cases of PTC. The measured sensitivities of CS and LBP were 78.9% and 76.3%, respectively, and the specificities were 64.2% and 54.9%, respectively, whereas the positive predictive values were 92.3% and 94.3%, respectively, and the negative predictive values were 89.5% and 81.8%, respectively. The cytomorphological features of LBP showed better‐preserved nuclear details, cleaner background and fewer large papillae than were evident in CS. The results indicate that LBP reduces the diagnosis of non‐diagnostic or unsatisfactory/atypia of undetermined significance or follicular lesion of undetermined significance, although the diagnostic values for CS and LBP are not appreciably different.