bluuebunny/crossref_metadata_2025 huggingface dataset:
Contingent Valuation of a Classic Cycling Race
Authors: Vekeman Andy , Meulders Michel , Praet Alain , Colpaert Jan , Van Puyenbroeck Tom
Published: February 2013

We provide a contingent valuation of a major cycling event, namely the Tour of Flanders. Starting from survey data, we estimate several models with different assumptions about (1) the latent willingness to pay (WTP) distribution and (2) the change in WTP when responding to the follow-up question in a double-bounded dichotomous framework. We relate the individual figures to explanatory factors and find that people residing in the event’s core region as well as spectators have a higher valuation. Incorporating the spatial effect, we arrive at an estimated aggregate value of 24.3 million euro.
Technique for Retrieval of a Knotted and Entrapped Guide Wire After Central Venous Catheterization
Authors: Yong Yao Pey , Abisi Said , Whitaker Simon , Braithwaite Bruce
Published: February 2013

Central venous catheterization is a common procedure performed in the critically ill patient. The complication associated with this invasive procedure is well established. However, complication related to the guide wire is rare. We present a case of knotted and entrapped guide wire following central venous catheterization using the Seldinger method and technique to retrieve it nonoperatively.
PKR regulates proliferation, differentiation, and survival of murine hematopoietic stem/progenitor cells
Authors: Liu Xiangfei , Bennett Richard L. , Cheng Xiaodong , Byrne Michael , Reinhard Mary K. , May W. Stratford
Published: February 2013

Key Points

PKR may be an unrecognized but important regulator of HSPC cell fate. PKR expression regulates the frequency of HSPCs in the bone marrow and their response to stress.
Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma
Authors: Daponte Antonio , Signoriello Simona , Maiorino Luigi , Massidda Bruno , Simeone Ester , Grimaldi Antonio Maria , Caracò Corrado , Palmieri Giuseppe , Cossu Antonio , Botti Gerardo , Petrillo Antonella , Lastoria Secondo , Cavalcanti Ernesta , Aprea Pasquale , Mozzillo Nicola , Gallo Ciro , Comella Giuseppe , Ascierto Paolo Antonio
Published: February 2013

Background

The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized 2x2 factorial design trial.

Methods

A total of 260 patients were randomly assigned to one of four treatment groups: (A) fotemustine and dacarbazine repeated on 3-week cycle; (B) same treatment as (A) plus IFN-α2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-α2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs. C+D) and IFN-α2b (groups A+C vs. B+D).

Results

Addition of fotemustine did not significantly improve overall survival (OS) (p=0.28) or progression-free survival (PFS) (p=0.55); Hazard ratio (HR) for OS was 0.93 (95% CI 0.71-1.21). Similarly, addition of IFN-α2b did not improve OS (p=0.68) or PFS (p=0.65); HR for OS was 0.92 (95% CI 0.70-1.20). Overall response rate was not improved by the addition of either fotemustine (p=0.87) or IFN-α2b (p=0.57). The combination of all three drugs resulted in the highest occurrence of adverse events.

Conclusions

No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.

Trial registration

ClinicalTrials.gov: NCT01359956
Active interference cancellation-aided QoS-aware distributed ARQ for cognitive radios with heterogeneous traffics
Authors: Liu Juan , Chen Wei , Cao Zhigang , Zhang Ying Jun
Published: February 2013

Relay-assisted Automatic Repeat reQuest (ARQ), which allows the relays instead of the source to carry out retransmissions of packets erroneously received at the destination, is an efficient cooperative transmission technique to improve link reliability with high spectrum efficiency in wireless networks. In cognitive radio (CR) systems, however, this relay-assisted ARQ could induce large latency, since a successful transmission of a packet may consume two idle timeslot or temporal spectrum holes. To overcome this limitation, an active interference cancellation (IC)-aided distributed relay-assisted ARQ method is proposed in this article to serve heterogeneous elastic traffics with diverse quality of service (QoS) demands in CR systems. Specifically, by applying our recently proposed distributed beamforming-based IC method in the physical layer, cognitive relays can exploit spatial spectrum holes (SSHs) to retransmit while keeping the interference to primary users at a tolerable level. Meanwhile, at the MAC layer, two scheduling policies, namely probabilistic and queue-length-based scheduling, are proposed to obtain an efficient allocation of temporal and SSHs to direct transmissions and retransmissions. The performance of the proposed schemes are analyzed and optimized by adjusting the scheduling parameters. As a result, the secondary users can obtain significant QoS gains, as validated by theoretical and simulation results.
The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence
Authors: Xiang Yu-zhu , Xiong Hui , Cui Zi-lian , Jiang Shao-bo , Xia Qing-hua , Zhao Yong , Li Guan-bin , Jin Xun-bo
Published: February 2013

Background

Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association.

Methods

We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs).

Results

The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96).

Conclusions

The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required.
CA-125–indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery
Authors: Wang Fang , Ye Yanfen , Xu Xia , Zhou Xuehui , Wang Jinhua , Chen Xiaoxiang
Published: February 2013

Background

There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS).

Methods

We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration.

Results

The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p < 0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31 days (ranging from 1 to 391 days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of < 1.68 × nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p = 0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level ≤ 1.68 × nadir at relapse (69.4 and 13.8 months) were longer than those with a CA-125 level > 1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p = 0.02 and 0.04 respectively).

Conclusions

The increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.
Sexual dimorphism in the feeding mechanism of threespine stickleback
Authors: McGee Matthew D. , Wainwright Peter C.
Published: February 2013

Sexual dimorphism is common in nature and has the potential to increase intraspecific variation in performance and patterns of resource use. We sought to determine whether anadromous threespine stickleback, Gasterosteus aculeatus, exhibit sexual dimorphism in feeding kinematics. We filmed four males and four females consuming live prey in a total of 51 sequences filmed at 500 Hz, then tested for differences in cranial kinematics using a combination of principal component analysis and linear mixed models. We document, for the first time in fishes, divergence between males and females in both the timing of key movements and the magnitude of excursions reached by the hyoid, jaws and neurocranium during prey capture. Some of the largest differences are in jaw protrusion, with males exhibiting faster time to peak jaw protrusion but females exhibiting greater maximum jaw protrusion. Measurements of morphological jaw protrusion on cleared and stained specimens significantly predict jaw protrusion in kinematics. This morphological divergence could reflect ecological divergence between the sexes, or the demands of nest building and territory defense compromising male feeding performance. Remarkably, the morphological jaw protrusion divergence in anadromous males and females is similar to jaw protrusion divergence between ecomorphs in a benthic–limnetic species pair, with limnetics exhibiting female-like patterns of protrusion and benthics exhibiting male-like patterns. These results suggest that sexual dimorphism in feeding functional morphology exists in nature and may have played an important role in the radiation of threespine stickleback.
Establishment of paediatric age-related reference intervals for serum prolactin to aid in the diagnosis of neurometabolic conditions affecting dopamine metabolism
Authors: Aitkenhead Helen , Heales Simon J
Published: February 2013

Background

There are a number of inborn errors of dopamine biosynthesis for which prolactin measurement may be a useful screening tool. However, the interpretation of prolactin results is difficult as age-related paediatric reference intervals are scant especially in infancy.

Methods

Serum prolactin reference intervals were calculated from the existing laboratory data using an indirect method, based on patients (n = 2369) attending a tertiary care hospital over a 10-year period. The data were log transformed and partitioned by age and sex.

Results

The prolactin results for all age and sex stratifications show non-Gaussian distributions (P < 0.0001). There are apparent age-related differences for prolactin during the first year of life with prolactin declining sharply during the first year of life and continuing to decline until five years of age when the concentrations stabilize. The sex differences are small until 13-17 years of age when prolactin is higher in girls than in boys.

Conclusions

This is the first published study to report age-related prolactin reference intervals spanning all paediatric age groups where the data are age partitioned in infants under one year of age using an ‘indirect’ approach. It is envisaged that these reference intervals will be used to aid in the selection of patients presenting with features of central dopamine deficiency for lumbar puncture. Also, these reference intervals have the potential for treatment monitoring of patients with diagnoses of inborn errors of dopamine biosynthesis.
Repairing Breaches with Rules: Maintaining Institutions in the Face of Everyday Disruptions
Authors: Heaphy Emily D.
Published: February 2013

This study reveals the institutional work required to maintain taken-for-granted beliefs about roles in the face of everyday breaches of role expectations. Through a comparative qualitative study of hospital-employed patient advocates in teaching and Veterans Health Administration hospitals, I demonstrate that patient advocates repair breaches in the taken-for-granted beliefs about the patient, family, and staff roles in hospitals. My research shows that patient advocates skillfully used rules—or formal policies and procedures—to restore, clarify, or initiate organizational changes in rules, all to maintain institutionalized role expectations. This analysis expands our understanding of the work of maintaining institutions by specifying how constellations of roles are maintained in the face of breaches of role expectations and across different institutional contexts. It highlights the roles of pressure specialists and furthers theorizing on individual agency by specifying how rules can be source of individual agency.
Embracing the Overriding Objective: Difficulties and Dilemmas in the New Criminal Climate
Authors: Garland Fae , McEwan Jenny
Published: February 2013

There has been little discussion to date of the impact of the new criminal case management system enshrined in the Criminal Procedure Rules for England and Wales upon the judges and practising lawyers who are expected to operate it. Detailed interviews were conducted with a number of these criminal law professionals in order to explore what, if any, problems they were experiencing in this context. It transpires that a number of practical problems confront them, and that defence lawyers may have difficulty reconciling their ethical obligations to the client with their considerably enhanced duties to the court. The issues that emerge from this small sample of interviews provide useful material to be taken into account in the design of any larger project to investigate the efficacy of case management or to compare local variations in practice. They also offer guidance to those developing the new criminal procedures in what obstacles to the desired cooperative culture need to be addressed.
The effects of thiol modulators on nitrergic nerve- and S-nitrosothiols-induced relaxation in duodenum
Authors: Kıroğlu Olcay Ergurhan , Aydinoglu Fatma , Öğülener Nuran
Published: February 2013

Background: The aim of this study was to investigate whether thiols are involved in the nitrergic neurotransmission in mouse duodenum.

Methods: The effects of thiol-modulating agents, ethacrynic acid (100 μM), a non-specific sulfhydryl alkylator, and diamide (100 μM), an alkylating agent that oxidizes protein sulfhydryl groups and depletes intracellular glutathione, on relaxations to nitrergic stimulation (electrical field stimulation, EFS;10 Hz, 25 V, 1 ms, 15 s-train), S-nitrosoglutathione (GSNO; 5 μM), S-nitroso-acetylpenicillamine (SNAP; 5 μM), and S-nitrosocysteine (CysNO; 10 μM) were investigated. Moreover, the effects of buthionine sulfoximine (100 μM), an inhibitor of γ-glutamylcysteine synthetase, and sulfobromophthalein (100 μM), an inhibitor of glutathione-S-transferase, were studied on relaxant responses to EFS and S-nitrosothiols in mouse duodenum.

Results: Exogenous free thiol, glutathione (GSH, 100 μM) did not influence relaxation to EFS, GSNO, SNAP, and CysNO. Ethacrynic acid and diamide significantly decreased relaxation of duodenum to EFS, GSNO, SNAP, and CysNO. This inhibition was prevented by addition of GSH. Buthionine sulfoximine and sulfobromophthalein significantly decreased relaxation to EFS and GSNO but did not influence relaxation to SNAP and CysNO. The inhibitory effect of buthionine sulfoximine and sulfobromophthalein on the relaxant response to EFS and GSNO was prevented by addition of GSH.

Conclusions: These results suggest that relaxation to nitrergic stimulation is thiol-dependent, and nitrosothiols, possibly S-nitrosoglutathione may play a role, as an intermediate compound in nitrergic neurotransmission in mouse duodenum.
Jobelyn® pretreatment ameliorates symptoms of psychosis in experimental models
Authors: Omogbiya Itivere Adrian , Umukoro Solomon , Aderibigbe Adegbuyi Oladele , Bakre Adewale Ganiyu
Published: February 2013

Background: Psychosis is a chronic neurological disorder and it remains a major medical and social problem in most African countries. Individuals with psychotic illness in this region tend to seek help from traditional medical practitioners, who prescribe herbal remedies as alternative forms of treatment for the disease. Jobelyn® (JB) is a commercial polyherbal formulation that has been acclaimed to show beneficial effects in neurological disorders. However, its usefulness in psychosis has not been scientifically validated. Thus, this study was undertaken to evaluate its effects on animal models predictive of human psychosis.

Methods: Antipsychotic activity of JB was assessed based on the inhibition of stereotyped behavior induced by amphetamine or apomorphine in mice. Amphetamine-induced hyperactivity and lethality in aggregated mice were additional tests employed to further evaluate the antipsychotic property of JB. The effect of JB on catalepsy was also assessed, using the inclined plane paradigm.

Results: JB (5–50 mg/kg, p.o.) significantly (p<0.05) inhibited stereotypy induced by amphetamine (10.0 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.), which suggests antipsychotic activity. Furthermore, JB (5–50 mg/kg, p.o.) reduced lethality in aggregated mice and inhibited hyperactivity induced by amphetamine, respectively. However, JB (5–50 mg/kg, p.o.) did not cause cataleptic behavior, as it failed to alter the duration of stay of the animals on the inclined plane.

Conclusions: Taken together, these findings suggest that JB exhibits antipsychotic-like activity, devoid of the adverse effect of cataleptic behavior, and may offer some beneficial effects in the symptomatic relief of psychotic ailments.
Severely ill-posed linear parabolic integro-differential problems
Authors: Lorenzi Alfredo
Published: February 2013

Via Carleman estimates we prove uniqueness and continuous dependence results for the temporal
traces of solutions to three overdetermined linear parabolic ill-posed problems with no initial condition, the first being integro-differential, the latter two being with deviating arguments. The overdetermination is prescribed in an open subset of the (space-time) lateral boundary.
Lion predation on livestock and native wildlife in Waza National Park, northern Cameroon
Authors: Tumenta Pricelia N. , Visser Hermen D. , van Rijssel Jacco , Müller Lana , de Iongh Hans H. , Funston Paul J. , Udo de Haes Helias A.
Published: February 2013

The feeding ecology of lions (Panthera leo, Linnaeus 1758) was investigated in and around Waza National Park, northern Cameroon. Diet was determined using global positioning system (GPS) data of lion kill sites (clusters of GPS location points) collected using radio collars. Lions consumed 14 different prey species, with five species that were either medium (50–200 kg) or large (>200 kg) in size forming the bulk of kills. The western kob (Kobus kob kob) was the most common (23.5%) wild prey of lions, but worryingly livestock (predominantly cattle) constituted as much as 21.6% of the diet. This creates a conservation problem resulting in lions being killed in retaliation. However, this conflict is strongly exacerbated by herders driving their cattle into the park for forage and water. Wild prey was also consumed outside the park (6.7%), suggesting excursions beyond the park boundary. Lions showed a preference for wild prey over livestock when relative abundances were considered. Management efforts to reduce livestock intrusion into the park and to reverse the declining trends of wild prey populations would significantly reduce predation of livestock and prevent persecution of lions in this park, but conflict mitigation measures outside the park are also urgently needed.
Microglia Are Essential to Masculinization of Brain and Behavior
Authors: Lenz Kathryn M. , Nugent Bridget M. , Haliyur Rachana , McCarthy Margaret M.
Published: February 2013

Brain sexual differentiation in rodents results from the perinatal testicular androgen surge. In the preoptic area (POA), estradiol aromatized from testosterone upregulates the production of the proinflammatory molecule, prostaglandin E2(PGE2) to produce sex-specific brain development. PGE2produces a two-fold greater density of dendritic spines in males than in females and masculinizes adult copulatory behavior. One neonatal dose of PGE2masculinizes the POA and behavior, and simultaneous treatment with an inhibitor of additional prostaglandin synthesis prevents this masculinization, indicating a positive feedforward process that leads to sustained increases in PGE2. The mechanisms underlying this feedforward process were unknown. Microglia, the primary immunocompetent cells in the brain, are active neonatally, contribute to normal brain development, and both produce and respond to prostaglandins. We investigated whether there are sex differences in microglia in the POA and whether they influence developmental masculinization. Neonatal males had twice as many ameboid microglia as females and a more activated morphological profile, and both estradiol and PGE2masculinized microglial number and morphology in females. Microglial inhibition during the critical period for sexual differentiation prevented sex differences in microglia, estradiol-induced masculinization of dendritic spine density, and adult copulatory behavior. Microglial inhibition also prevented the estradiol-induced upregulation of PGE2, indicating that microglia are essential to the feedforward process through which estradiol upregulates prostaglandin production. These studies demonstrate that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior.
Learning to be Lazy: Exploiting Redundancy in a Novel Task to Minimize Movement-Related Effort
Authors: Ranganathan Rajiv , Adewuyi Adenike , Mussa-Ivaldi Ferdinando A.
Published: February 2013

A key issue in motor control is to understand how the motor system chooses a solution from the multiple solutions that exist to achieve any particular task goal. One hypothesis is that redundancy may be resolved by minimizing movement-related costs. However, testing this prediction in motor learning has been problematic in simple laboratory tasks, like reaching, because the motor system already has extensive prior knowledge about redundancy in these tasks. Here, we used a novel task where healthy human participants performed finger movements to guide a computer cursor to different targets on the screen. Through training, all participants learned to perform successful goal-directed movements. Our findings showed that subjects did not develop a single inverse map from target to hand posture. Instead, they learned to use distinct hand postures to get to a single target, using a strategy in which the final hand posture at the target depended on the starting hand posture. Furthermore, postures chosen also depended upon the information content of visual feedback, with precise visual feedback resulting in postures that minimized movement-related costs. These results reinforce the idea that redundancy is exploited to minimize movement-related costs and that feedback plays a critical role in modulating this ability to effectively take advantage of the abundance of degrees of freedom.
Preventing Formation of Reticulon 3 Immunoreactive Dystrophic Neurites Improves Cognitive Function in Mice
Authors: Shi Qi , Prior Marguerite , Zhou Xiangdong , Tang Xiaoying , He Wanxia , Hu Xiangyou , Yan Riqiang
Published: February 2013

Neuritic dystrophy is one of the important pathological features associated with amyloid plaques in Alzheimer's disease (AD) and age-dependent neuronal dysfunctions. We reported previously that reticulon-3 (RTN3) immunoreactive dystrophic neurites (RIDNs) are abundantly present in the hippocampus of AD patients, in AD mouse models, and in aged wild-type mice. Transgenic mice overexpressing the human RTN3 transgene spontaneously develop RIDNs in their hippocampi, and the formation of RIDNs correlates with the appearance of RTN3 aggregation. To further elucidate whether the formation of RIDNs is reversible, we generated transgenic mice expressing wild-type human RTN3 under the control of a tetracycline-responsive promoter. Treatment with doxycycline for 2 months effectively turned off expression of the human RTN3 transgene, confirming the inducible nature of the system. However, the formation of hippocampal RIDNs was dependent on whether the transgene was turned off before or after the formation of RTN3 aggregates. When transgenic human RTN3 expression was turned off at young age, formation of RIDNs was essentially eliminated compared with the vehicle-treated transgenic mice. More importantly, a fear conditioning study demonstrated that contextual associative learning and memory in inducible transgenic mice was improved if the density of RIDNs was lowered. Additional mechanistic study suggested that a reduction in BDNF levels in transgenic mice might contribute to the reduced learning and memory in transgenic mice overexpressing RTN3. Hence, we conclude that age-dependent RIDNs cannot be effectively cleared once they have formed, and we postulate that successful prevention of RIDN formation should be initiated before RTN3 aggregation.
Olfactory Bulb Short Axon Cell Release of GABA and Dopamine Produces a Temporally Biphasic Inhibition–Excitation Response in External Tufted Cells
Authors: Liu Shaolin , Plachez Celine , Shao Zuoyi , Puche Adam , Shipley Michael T.
Published: February 2013

Evidence for coexpression of two or more classic neurotransmitters in neurons has increased, but less is known about cotransmission. Ventral tegmental area (VTA) neurons corelease dopamine (DA), the excitatory transmitter glutamate, and the inhibitory transmitter GABA onto target cells in the striatum. Olfactory bulb (OB) short axon cells (SACs) form interglomerular connections and coexpress markers for DA and GABA. Using an optogenetic approach, we provide evidence that mouse OB SACs release both GABA and DA onto external tufted cells (ETCs) in other glomeruli. Optical activation of channelrhodopsin specifically expressed in DAergic SACs produced a GABAAreceptor-mediated monosynaptic inhibitory response, followed by DA–D1-like receptor-mediated excitatory response in ETCs. The GABAAreceptor-mediated hyperpolarization activatesIhcurrent in ETCs; synaptically released DA increasesIh, which enhances postinhibitory rebound spiking. Thus, the opposing actions of synaptically released GABA and DA are functionally integrated byIhto generate an inhibition-to-excitation “switch” in ETCs. Consistent with the established role ofIhin ETC burst firing, we show that endogenous DA release increases ETC spontaneous bursting frequency. ETCs transmit sensory signals to mitral/tufted output neurons and drive intraglomerular inhibition to shape glomerulus output to downstream olfactory networks. GABA and DA cotransmission from SACs to ETCs may play a key role in regulating output coding across the glomerular array.
Patch-Clamp Recordings from Lateral Line Neuromast Hair Cells of the Living Zebrafish
Authors: Ricci Anthony J. , Bai Jun-Ping , Song Lei , Lv Caixia , Zenisek David , Santos-Sacchi Joseph
Published: February 2013

Zebrafish are popular models for biological discovery. For investigators of the auditory and vestibular periphery, manipulations of hair cell and synaptic mechanisms have relied on inferences from extracellular recordings of physiological activity. We now provide data showing that hair cells and supporting cells of the lateral line can be directly patch-clamped, providing the first recordings of ionic channel activity, synaptic vesicle release, and gap junctional coupling in the neuromasts of living fish. Such capabilities will allow more detailed understanding of mechano-sensation of the zebrafish.
The Disruption ofCelf6, a Gene Identified by Translational Profiling of Serotonergic Neurons, Results in Autism-Related Behaviors
Authors: Dougherty Joseph D. , Maloney Susan E. , Wozniak David F. , Rieger Michael A. , Sonnenblick Lisa , Coppola Giovanni , Mahieu Nathaniel G. , Zhang Juliet , Cai Jinlu , Patti Gary J. , Abrahams Brett S. , Geschwind Daniel H. , Heintz Nathaniel
Published: February 2013

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, of which 174 were highly enriched, including all known markers of these cells. Analysis of common variants near the corresponding genes in the AGRE collection implicated the RNA binding protein CELF6 in autism risk. Screening for rare variants inCELF6identified an inherited premature stop codon in one of the probands. Subsequent disruption ofCelf6in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. This work provides a reproducible and accurate method to profile serotonergic neurons under a variety of conditions and suggests a novel paradigm for gaining information on the etiology of psychiatric disorders.
Frequency and characterization of gastro–entero–pancreatic neuroendocrine tumor patients with high-grade of uptake at somatostatin receptor scintigraphy
Authors: Chougnet Cecile N , Leboulleux Sophie , Caramella Caroline , Lumbroso Jean , Borget Isabelle , Déandreis Désirée , Duvillard Pierre , Elias Dominique , de Baere Thierry , Vélayoudom-Céphise Fritz-Line , Guigay Joël , Ducreux Michel , Schlumberger Martin , Baudin Eric
Published: February 2013

Recent studies suggest that the somatostatin receptor scintigraphy (SRS) grade of uptake is a predictor of response to peptide receptor radionuclide therapy (PRRT). To identify and characterize patients with well-differentiated (WD) neuroendocrine neoplasm (NEN) displaying a high-grade uptake at SRS. Patients with WD-NEN, whose SRS films were available for review, were retrospectively included. SRS was reviewed by three independent readers and classified into four subgroups based on a modified Krenning's scale (mKS): no uptake (group-0), homogeneous grade 1–2 uptake (group-1), homogeneous grade 3–4 (group-2), and heterogeneous grade 1–4 (group-3). A simplified scale (sS) of SRS was also used to look for characteristics of patients with high-grade uptake. One hundred and six WD-NEN patients were enrolled. Group-0, group-1, group-2, and group-3 were found in 17, 8, 33, and 42% of cases respectively. High-grade uptake at sS (75% of cases) was correlated with older age, functioning NEN, high chromogranin-A level, and grade 1 (G1) NEN based on mitotic count. Based on the mKS or sS scales, no difference on survival was found. Thirty-three to seventy-five percent of metastatic NEN patients can be considered candidates for PRRT based on homogeneous or heterogeneous high-grade uptake. Functioning G1 NEN patients could be the best candidates for PRRT. Randomized trials are expected to confirm this result.
Penetrating keratoplasty and graft rejection in eight horses
Authors: Makra Zita , Tuboly Tamás , Bodó Gábor
Published: February 2013

The aim of this study was to describe long-term follow-up and difference in immune reactions in the tear film following penetrating keratoplasty (PK) in horses when differently preserved corneas were utilised. This report describes for the first time the use of corneal grafts preserved in tissue culture media in equine PK. Eight experimental horses with normal eyes were included and freshly harvested, frozen or preserved corneal grafts were used for the PK. The graft-taking technique and storage, PK surgery, postoperative treatments and complications are described. The mean postoperative follow-up time was 286 days. Tear film samples taken before and periodically after surgery were measured for IgM, IgG and IgA contents by direct ELISA. All grafts were incorporated into the donor horse but were rejected to some degree. The differently harvested corneal grafts healed in the same manner and looked similar. Preoperatively, the clear corneas meant low risk for graft failure, and the fresh or stored tissues provided intact endothelium, although there were no clear graft sites postoperatively. The presence of IgA, IgG and IgM was demonstrated in the tear film from the early postoperative period. IgG levels were lower than IgA or IgM and had a constant baseline in every case, as IgA and IgM had great variability with time and an individual pattern in each eye.
Isolation and molecular characterisation of a pestivirus from goats in Egypt
Authors: Abdel-Latif Ahmed , Goyal Sagar , Chander Yogesh , Abdel-Moneim Ahmed , Tamam Sabry , Madbouly Hanafy
Published: February 2013

Nine fetuses and neonates from sheep and goats in Egypt were screened for pestiviruses using immunohistochemistry (IHC), virus isolation, and reverse transcription-polymerase chain reaction (RT-PCR). Two goat kids with typical border disease (BD) were positive for pestivirus infection by immunohistochemistry (IHC) using polyclonal anti-BDV serum but not when four different monoclonal antibodies (MAbs) were used. On inoculation in MDBK cells, a cytopathic bovine viral diarrhoea virus (BVDV) was isolated from one of the two kids. PCR amplification followed by sequencing of the 5′-UTR region confirmed it as BVDV subtype 1b. Although the circulating virus in Egypt is considered to be BVDV 1a, this report confirms the existence of BVDV 1b in addition to BVDV 1a. To our knowledge, this is the first report of isolation of a pestivirus from goats in Egypt and is probably the second report worldwide of a goat kid showing central nervous signs associated with border disease.
Effect of the denervation of porcine ovaries on dexamethasone-induced cyst formation
Authors: Jana Barbara , Kozłowska Anna , Wojtkiewicz Joanna , Majewski Mariusz
Published: February 2013

Previously, we have shown that the activity of noradrenergic nerve fibres increased and the steroid content changed in porcine ovaries with dexamethasone-(DXM-) induced polycystic status. To better understand the role of the ovarian nerves in the formation of cystic status, the morphology and steroidogenic activity of the ovaries of DXM-treated gilts after denervation of the gonads were investigated in this study. Ovarian denervation was performed on day 3 of the first studied oestrous cycle and then, on days 7–21 of the cycle, DXM was administered. Following neurectomy and DXM treatment, cysts, medium-sized follicles and corpora lutea were not present, while the number of small-sized follicles increased. Denervation and DXM application led to a reduction in the number of dopamine-β-hydroxylase- and/or neuropeptide Y-immunoreactive nerve fibres. The concentrations of progesterone, androstenedione, testosterone and oestradiol-17β in the follicular fluid and/or in the wall of small-sized follicles of the experimental gilts were lower than in the controls. A similar result was demonstrated for P450scc, 3β-HSD and P450arom protein contents in the small follicles. Our data showed that DXM was not able to stimulate the formation of cysts in denervated porcine ovaries, indicating that the ovarian peripheral nerves might participate in the aetiopathogenesis of polycystic status.
Transcutaneous Oxygen Tension as a Potential Predictor of Cardiovascular Events in Type 2 Diabetes
Authors: Gazzaruso Carmine , Coppola Adriana , Falcone Colomba , Luppi Chiara , Montalcini Tiziana , Baffero Elisabetta , Gallotti Pietro , Pujia Arturo , Solerte Sebastiano B. , Pelissero Gabriele , Giustina Andrea
Published: February 2013

OBJECTIVE

Transcutaneous oxygen tension (TcPO2) measures tissue perfusion and is important in the management of peripheral artery disease (PAD). Ankle brachial index (ABI) is used for the diagnosis of PAD and represents a predictor of major adverse cardiovascular events (MACE), even if in diabetes its diagnostic and predictive value seems to be reduced. No study has evaluated TcPO2 as a predictor of cardiovascular events. Aim of this longitudinal study was to assess whether TcPO2 is better than ABI at predicting MACE in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

Among 361 consecutive patients with apparently uncomplicated diabetes, 67 MACE occurred during a follow-up period of 45.8 ± 23.2 months.

RESULTS

The percentage of both subjects with low ABI (≤0.9) and subjects with low TcPO2 (≤46 mmHg as measured by a receiver operating characteristic curve) was significantly (<0.001) greater among patients with than among those without MACEs (ABI 64.2 vs. 40.8; TcPO2 58.2 vs. 34%). The Kaplan-Meier method showed that both low ABI (Mantel log-rank test, 4.087; P = 0.043) and low TcPO2 (Mantel log-rank test, 33.748; P > 0.0001) were associated with a higher rate of MACEs. Cox regression analysis showed that low TcPO2 (hazard ratio 1.78 [95% CI 1.44–2.23]; P < 0.001) was a significant predictor of MACE, while ABI did not enter the model.

CONCLUSIONS

This longitudinal study showed that TcPO2 may be a potential predictor of MACE among patients with uncomplicated type 2 diabetes and that its predictive value seems to be greater than that of ABI.
Fasting Glucose Level and the Risk of Incident Atherosclerotic Cardiovascular Diseases
Authors: Park Chanshin , Guallar Eliseo , Linton John A. , Lee Duk-Chul , Jang Yangsoo , Son Dong Koog , Han Eun-Jeong , Baek Soo Jin , Yun Young Duk , Jee Sun Ha , Samet Jonathan M.
Published: February 2013

OBJECTIVE

Although diabetes increases the risk of cardiovascular disease (CVD) and mortality, the dose-response relationship between fasting glucose levels below those diagnostic of diabetes with cardiovascular events has not been well characterized.

RESEARCH DESIGN AND METHODS

A prospective cohort study of more than one million Koreans was conducted with a mean follow-up of 16 years. A total of 1,197,384 Korean adults with no specific medical conditions diagnosed were classified by baseline fasting serum glucose level. Associations of fasting glucose level with CVD incidence and mortality, stroke incidence and mortality, and all-cause mortality were analyzed using multivariate proportional hazards regression.

RESULTS

The relationships between fasting glucose levels and CVD risks generally followed J-shape curves, with lowest risk in the glucose range of 85–99 mg/dL. As fasting glucose levels increased to >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increased, but risk for hemorrhagic stroke did not. Fasting glucose levels <70 mg/dL were associated with increased risk of all stroke (hazard ratio 1.06, 95% CI 1.01–1.11) in men and (hazard ratio 1.11, 1.05–1.17) in women.

CONCLUSIONS

Both low glucose level and impaired fasting glucose should be considered as predictors of risk for stroke and coronary heart disease. The fasting glucose level associated with the lowest cardiovascular risk may be in a narrow range.
Schwarz Methods for a Preconditioned WOPSIP Method for Elliptic Problems
Authors: Antonietti Paola F. , Ayuso de Dios Blanca , Brenner Susanne C. , Sung Li-yeng
Published: February 2013

We propose and analyze several two-level non-overlapping Schwarz methods
for a preconditioned weakly over-penalized symmetric interior penalty (WOPSIP)
discretization of a second order boundary value problem. We show that the preconditioners
are scalable and that the condition number of the resulting preconditioned
linear systems of equations is independent of the penalty parameter and is of order
H/h, where H and h represent the mesh sizes of the coarse and fine partitions, respectively.
Numerical experiments that illustrate the performance of the proposed two-level Schwarz methods are also presented.
Regular Decompositions for H(div) Spaces
Authors: Kolev Tzanio , Vassilevski Panayot
Published: February 2013

We study regular decompositions for H(div) spaces. In particular, we show that such regular decompositions are
closely related to a previously studied ``inf-sup'' condition for parameter-dependent Stokes problems,
for which we provide an alternative, more direct, proof.
Polynomial of Best Uniform Approximation to and Smoothing in Two-level Methods
Authors: Kraus Johannes , Vassilevski Panayot , Zikatanov Ludmil
Published: February 2013

We derive defect correction scheme for constructing the sequence of
polynomials of best approximation in the uniform norm to 1/x on a
finite interval with positive endpoints. As an application, we
consider two-level methods for scalar elliptic partial differential
equation (PDE), where the relaxation on the fine grid uses the
aforementioned polynomial of best approximation. Based on a new
smoothing property of this polynomial smoother that we prove,
combined with a proper choice of the coarse space, we obtain as a
corollary, that the convergence rate of the resulting two-level
method is uniform with respect to the mesh parameters, coarsening
ratio and PDE coefficient variation.
A Simplified Calculation of Reduced HCT--Basis Functions in a Finite Element Context
Authors: Meyer Arnd
Published: February 2013

We present simple formulas for the definition of the basis functions
on a reduced Hsieh-Clough-Tocher (rHCT) element. These formulas use the
P_3-biorthogonal basis in the master triangle and form the resulting basis
with the help of the edge vectors of the triangle only. This allows
for a simple and efficient algorithm to compute the stiffness matrices.
Robust Two-level Domain Decomposition Preconditioners for High-contrast Anisotropic Flows in Multiscale Media
Authors: Efendiev Yalchin , Galvis Juan , Lazarov Raytcho , Margenov Svetozar , Ren Jun
Published: February 2013

In this paper we discuss robust two-level domain decomposition
preconditioners for highly anisotropic heterogeneous multiscale problems.
We present a construction of several coarse spaces that employ
standard finite element and multiscale
basis functions and discuss
techniques to reduce the dimensions of coarse spaces
without sacrificing the robustness. We experimentally study the
performance of the preconditioner on a variety two-dimensional test problems
with channels of high anisotropy. The numerical tests
confirm the robustness of the perconditioner with respect to the
underlying physical parameters.
Multi-label classification using error correcting output codes
Authors: Kajdanowicz Tomasz , Kazienko Przemysław
Published: February 2013

A framework for multi-label classification extended by Error Correcting Output Codes (ECOCs) is introduced and empirically examined in the article. The solution assumes the base multi-label classifiers to be a noisy channel and applies ECOCs in order to recover the classification errors made by individual classifiers. The framework was examined through exhaustive studies over combinations of three distinct classification algorithms and four ECOC methods employed in the multi-label classification problem. The experimental results revealed that (i) the Bode-Chaudhuri-Hocquenghem (BCH) code matched with any multi-label classifier results in better classification quality; (ii) the accuracy of the binary relevance classification method strongly depends on the coding scheme; (iii) the label power-set and the RAkEL classifier consume the same time for computation irrespective of the coding utilized; (iv) in general, they are not suitable for ECOCs because they are not capable to benefit from ECOC correcting abilities; (v) the all-pairs code combined with binary relevance is not suitable for datasets with larger label sets.
A rainfall forecasting method using machine learning models and its application to the Fukuoka city case
Authors: Sumi S. Monira , Zaman M. Faisal , Hirose Hideo
Published: February 2013

In the present article, an attempt is made to derive optimal data-driven machine learning methods for forecasting an average daily and monthly rainfall of the Fukuoka city in Japan. This comparative study is conducted concentrating on three aspects: modelling inputs, modelling methods and pre-processing techniques. A comparison between linear correlation analysis and average mutual information is made to find an optimal input technique. For the modelling of the rainfall, a novel hybrid multi-model method is proposed and compared with its constituent models. The models include the artificial neural network, multivariate adaptive regression splines, the k-nearest neighbour, and radial basis support vector regression. Each of these methods is applied to model the daily and monthly rainfall, coupled with a pre-processing technique including moving average and principal component analysis. In the first stage of the hybrid method, sub-models from each of the above methods are constructed with different parameter settings. In the second stage, the sub-models are ranked with a variable selection technique and the higher ranked models are selected based on the leave-one-out cross-validation error. The forecasting of the hybrid model is performed by the weighted combination of the finally selected models.