bluuebunny/crossref_metadata_2025 huggingface dataset:
How the tobacco industry built its relationship with Hollywood
Authors: Mekemson C , Glantz S A
Published: January 2010

Objective: To describe the development of the relationship between the tobacco industry and the entertainment industry.

Methods: Review of previously secret tobacco industry documents available on the internet.

Results: Both the entertainment and tobacco industries recognised the high value of promotion of tobacco through entertainment media. The 1980s saw undertakings by four tobacco companies, Philip Morris, RJ Reynolds (RJR), American Tobacco Company, and Brown and Williamson to place their products in movies. RJR and Philip Morris also worked to place products on television at the beginning of the decade. Each company hired aggressive product placement firms to represent its interests in Hollywood. These firms placed products and tobacco signage in positive situations that would encourage viewers to use tobacco and kept brands from being used in negative situations. At least one of the companies, RJR, undertook an extensive campaign to hook Hollywood on tobacco by providing free cigarettes to actors on a monthly basis. Efforts were also made to place favourable articles relating to product use by actors in national print media and to encourage professional photographers to take pictures of actors smoking specific brands. The cigar industry started developing connections with the entertainment industry beginning in the 1980s and paid product placements were made in both movies and on television. This effort did not always require money payments from the tobacco industry to the entertainment industry, suggesting that simply looking for cash payoffs may miss other important ties between the tobacco and entertainment industries.

Conclusions: The tobacco industry understood the value of placing and encouraging tobacco use in films, and how to do it. While the industry claims to have ended this practice, smoking in motion pictures increased throughout the 1990s and remains a public health problem.
Evolution of abbreviated development in the ophiuroid Ophiarachnella gorgonia involves heterochronies and deletions
Authors: Cisternas P A , Byrne M
Published: January 2010

The ophiuroid Ophiarachnella gorgonia Müller and Troschel, 1842 has the Type II mode of ophiuroid development through a short-lived (lecithotrophic) vitellaria larva that settles 3 days after fertilization. Development in O. gor gonia is characterized by a reduction in larval structures and settlement of a precocious juvenile. In comparison with other ophiuroid vitellariae, the larva of O. gorgonia has reduced ciliated bands that lack prominent epithelial ridges. Ab breviated development in O. gorgonia is achieved through prompt formation of a radial hydrocoel and radial juvenile skeleton. Newly settled juvenile O. gorgonia also lack the feeding and locomotory structures found in the settlement stage of species with ophioplutei. Juveniles of O. gorgonia settle with one pair of buccal podia, and the mouth is not functional. The first arm segment forms before the mouth opens. In comparison, in species with ophioplutei the first two pairs of buccal podia and the first two arm segments develop before the mouth opens and before settlement occurs. Comparison of development of O. gorgonia and that of other species with vitellariae suggests that hetero chron ies and deletions in the metamorphic and settlement programs may be involved in the evolution of abbreviated development.
Seasonal feeding-mode changes in the marine facultative kleptoparasite Trichotropis cancellata (Gastropoda, Capulidae): trade-offs between trophic strategy and reproduction
Authors: Iyengar E V
Published: January 2010

I report the first field study of seasonal patterns of host use by a marine kleptoparasite. Trichotropis cancellata Hinds, 1843, a marine snail, is a facultative kleptoparasite, able to suspension-feed and steal food from hosts. I investigated the incidence of kleptoparasitism and suspension feeding in T. cancellata populations at six sites around the San Juan Islands, Washington State, USA, through field surveys spanning 2 years. Facultative kleptoparasitism was the dominant feeding mode in the summer (>65% of the population) for T. cancellata of all sizes at all sites, with the highest frequency of parasitism in the summer and the lowest in the winter (the snail mating season). Sexually immature snails (smaller than 5 mm) formed the only group that predominantly did not leave hosts in the winter. Females returned to hosts after their egg masses hatched (late March to early April), while males returned earlier. Tube-dwelling worms from three families are the usual hosts of T. cancellata. Snail and worm host densities were correlated. Surprisingly, host size was not a primary trait determining host use. Prevalence of infection was less than 40%, suggesting that hosts are not in limited supply. Single-snail infections were the most common, although multiple-snail infections occurred. Parasite load was not randomly distributed; an excess of infections with three or more parasites suggests that snails nonrandomly cluster on hosts. Understanding the population dynamics of this facultative kleptoparasite may shed light on the selection pressures driving the evolution of kleptoparasitism and suspension feeding and of snail adaptations to exploit their most common hosts.
When and how do predator starting distances affect flight initiation distances?
Authors: Cooper, Jr. W E
Published: January 2010

The distance separating predator and prey when the predator begins to approach, starting distance, was recently shown to affect flight initiation distance in many bird species, raising questions about the effect's generality, variation with ecological factors, and economic basis. I studied the effect in two lizard species that forage by ambush and escape into nearby refuges. Monitoring costs during approach are absent because ambushers remain immobile while scanning for prey and predators. Risks are minimized because of the proximity to refuge. Flight initiation distance increased weakly with starting distance in Sceloporus virgatus Smith, 1938 significantly only at rapid approach speed. It was not significant in Urosaurus ornatus (Baird and Girard, 1852) at slow approach speed. Flight initiation distance is predicted to increase with starting distance, owing to monitoring costs and assessment by prey of greater risk during prolonged approaches. The significant effect in S. virgatus, which lacks monitoring costs, is the first indication that risk affects the relationship between starting distance and flight initiation distance. Conditions in which starting distance is important and its possible effects in earlier studies are discussed, as well as standardizing approaches and possible artifactual effects of starting distance.
Size-related performance variation in the wood frog (Rana sylvatica) tadpole tactile-stimulated startle response
Authors: Eidietis L
Published: January 2010

I described the initial response of the Rana sylvatica LeConte, 1825 tadpole to predator contact, that is, the tactile-stimulated startle response (TSR). Because tadpole survival from predation increases with tadpole size and with exposure to chemical predator cues during development, I anticipated that TSR performance would vary accordingly among tadpoles. Startle responses were stimulated in a laboratory setting and filmed using high-speed video. This method allowed analysis of performance at fine spatial and temporal scales. Maximum acceleration performance increased with tadpole length, as did cumulative distance covered after the first 0.016 s of the response. In contrast, the cumulative distance covered during the initial instants of the response did not depend on tadpole size. Exposure to a predator cue (odor of the dragonfly naiad Anax junius (Drury, 1773)) during development had no effect on tadpole morphology. Predator-cue exposure negatively affected cumulative distance traveled after the first 0.072 s of the startle response. I concluded that size-dependent variation in performance of the TSR may partially explain differential survival of tadpoles, but there was no evidence that exposure to this predator cue increased TSR performance.
Nesting snakes (Tropidonophis mairii, Colubridae) selectively oviposit in sites that provide evidence of previous successful hatching
Authors: Brown Gregory P , Shine Richard
Published: January 2010

In oviparous species without parental care, nesting females must select an oviposition site that provides incubation conditions favourable to the developing eggs. Abiotic cues (e.g., temperature, moisture) are well known to influence oviposition-site selection, but the potential role of biotic cues (e.g., the presence of eggshells from previous successfully hatched clutches or the scent of egg predators) has rarely been examined in this respect. To test whether nesting females use such cues, we collected gravid keelback snakes (Tropidonophis mairii (Gray, 1841), Colubridae) in tropical Australia and gave them a choice of potential nesting sites in captivity. Females selectively oviposited in sites containing empty eggshells rather than in control sites but did not avoid the scent of a sympatric egg predator (the slatey-grey snake, Stegonotus cucullatus (Duméril, Bibron and Duméril, 1854)); indeed, eggshells of this taxon were as effective as keelback eggs in attracting oviposition. Our study adds to growing evidence that nesting females assess and respond to a diverse array of biotic as well as abiotic cues that predict the probability of successful incubation for their eggs.
NOISE-INDUCED BACKWARD BIFURCATIONS OF STOCHASTIC 3D-CYCLES
Authors: BASHKIRTSEVA I. , RYASHKO L. , STIKHIN P.
Published: January 2010

We study stochastically forced multiple limit cycles of nonlinear dynamical systems in a period-doubling bifurcation zone. Noise-induced transitions between separate parts of the cycle are considered. A phenomenon of a decreasing of the stochastic cycle multiplicity with a noise intensity growth is investigated. We call it by a backward stochastic bifurcation (BSB). In this paper, for the BSB analysis we suggest a stochastic sensitivity function technique. As a result, a method for the estimation of critical values of noise intensity corresponding to BSB is proposed. The constructive possibilities of this general method for the detailed BSB analysis of the multiple stochastic cycles of the forced Roessler system are demonstrated.
Motif discovery in physiological datasets
Authors: Syed Zeeshan , Stultz Collin , Kellis Manolis , Indyk Piotr , Guttag John
Published: January 2010

In this article, we propose a methodology for identifying predictive physiological patterns in the absence of prior knowledge. We use the principle of conservation to identify activity that consistently precedes an outcome in patients, and describe a two-stage process that allows us to efficiently search for such patterns in large datasets. This involves first transforming continuous physiological signals from patients into symbolic sequences, and then searching for patterns in these reduced representations that are strongly associated with an outcome.

Our strategy of identifying conserved activity that is unlikely to have occurred purely by chance in symbolic data is analogous to the discovery of regulatory motifs in genomic datasets. We build upon existing work in this area, generalizing the notion of a regulatory motif and enhancing current techniques to operate robustly on non-genomic data. We also address two significant considerations associated with motif discovery in general: computational efficiency and robustness in the presence of degeneracy and noise. To deal with these issues, we introduce the concept of active regions and new subset-based techniques such as a two-layer Gibbs sampling algorithm. These extensions allow for a framework for information inference, where precursors are identified as approximately conserved activity of arbitrary complexity preceding multiple occurrences of an event.

We evaluated our solution on a population of patients who experienced sudden cardiac death and attempted to discover electrocardiographic activity that may be associated with the endpoint of death. To assess the predictive patterns discovered, we compared likelihood scores for motifs in the sudden death population against control populations of normal individuals and those with non-fatal supraventricular arrhythmias. Our results suggest that predictive motif discovery may be able to identify clinically relevant information even in the absence of significant prior knowledge.
VOGUE
Authors: Zaki Mohammed J. , Carothers Christopher D. , Szymanski Boleslaw K.
Published: January 2010

We present VOGUE, a novel, variable order hidden Markov model with state durations, that combines two separate techniques for modeling complex patterns in sequential data: pattern mining and data modeling. VOGUE relies on a variable gap sequence mining method to extract frequent patterns with different lengths and gaps between elements. It then uses these mined sequences to build a variable order hidden Markov model (HMM), that explicitly models the gaps. The gaps implicitly model the order of the HMM, and they explicitly model the duration of each state. We apply VOGUE to a variety of real sequence data taken from domains such as protein sequence classification, Web usage logs, intrusion detection, and spelling correction. We show that VOGUE has superior classification accuracy compared to regular HMMs, higher-order HMMs, and even special purpose HMMs like HMMER, which is a state-of-the-art method for protein classification. The VOGUE implementation and the datasets used in this article are available as open-source.
1
Bimodal perception of audio-visual material properties for virtual environments
Authors: Bonneel Nicolas , Suied Clara , Viaud-Delmon Isabelle , Drettakis George
Published: January 2010

High-quality rendering of both audio and visual material properties is very important in interactive virtual environments, since convincingly rendered materials increase realism and the sense of immersion. We studied how the level of detail of auditory and visual stimuli interact in the perception of audio-visual material rendering quality. Our study is based on perception of material discrimination, when varying the levels of detail of modal synthesis for sound, and bidirectional reflectance distribution functions for graphics. We performed an experiment for two different models (a Dragon and a Bunny model) and two material types (plastic and gold). The results show a significant interaction between auditory and visual level of detail in the perception of material similarity, when comparing approximate levels of detail to a high-quality audio-visual reference rendering. We show how this result can contribute to significant savings in computation time in an interactive audio-visual rendering system. To our knowledge, this is the first study that shows interaction of audio and graphics representation in a material perception task.
Multidimensional scaling analysis of haptic exploratory procedures
Authors: Cooke Theresa , Wallraven Christian , Bülthoff Heinrich H.
Published: January 2010

Previous work in real and virtual settings has shown that the way in which we interact with objects plays a fundamental role in the way we perceive them. This article uses multidimensional scaling (MDS) analysis to further characterize and quantify the effects of using different haptic exploratory procedures (EPs) on perceptual similarity spaces. In Experiment 1, 20 participants rated similarity on a set of nine novel, 3D objects varying in shape and texture after either following their contours, laterally rubbing their centers, gripping them, or sequentially touching their tips. MDS analysis was used to recover perceptual maps of the objects and relative weights of perceptual dimensions from similarity data. Both the maps and relative weights of shape/texture properties were found to vary as a function of the EP used. In addition, large individual differences in the relative weight of shape/texture were observed. In Experiment 2, 17 of the previous participants repeated Experiment 1 after an average of 105 days. The same patterns of raw similarity ratings, perceptual maps, dimension weights, and individual differences were observed, indicating that perceptual similarities remained stable over time. The findings underscore the role of hand movements and individual biases in shaping haptic perceptual similarity. A framework for validating multimodal virtual displays based on the approach used in the study is also presented.
The 21

st

ACM international conference on hypermedia and multimedia
Authors: Chin Alvin
Published: January 2010

The ACM Hypertext Conference is the main venue for high quality, peer-reviewed, double-blind research on "linking" and interconnectivity. The Web, the Semantic Web, Web 2.0, Social Networks, and Web Science all demonstrate the value of the link concept.
Myelodysplastic Syndromes
Authors: Scott Bart L. , Deeg H. Joachim
Published: January 2010

Myelodysplastic syndromes (MDS) represent a collection of stem cell disorders characterized by impaired hematopoiesis resulting in low peripheral blood counts. The majority of patients with MDS present with symptoms related to anemia; however, bleeding and infection are the most common causes of death. The median age of diagnosis is 72 and the median survival is 2.5 years. Lenalidomide, azacitidine, and decitabine are all FDA-approved agents to treat MDS; however, the only potential cure for MDS remains stem cell transplantation.
Nanotechnology Applications in Surgical Oncology
Authors: Singhal Sunil , Nie Shuming , Wang May D.
Published: January 2010

Surgery is currently the most effective and widely used procedure in treating human cancers, and the single most important predictor of patient survival is a complete surgical resection. Major opportunities exist to develop new and innovative technologies that could help the surgeon to delineate tumor margins, to identify residual tumor cells and micrometastases, and to determine if the tumor has been completely removed. Here we discuss recent advances in nanotechnology and optical instrumentation, and how these advances can be integrated for applications in surgical oncology. A fundamental rationale is that nanometer-sized particles such as quantum dots and colloidal gold have functional and structural properties that are not available from either discrete molecules or bulk materials. When conjugated with targeting ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target malignant tumor cells and tumor microenvironments with high specificity and affinity. In the “mesoscopic” size range of 10–100 nm, nanoparticles also have large surface areas for conjugating to multiple diagnostic and therapeutic agents, opening new possibilities in integrated cancer imaging and therapy.
Emerging Molecular Targets for the Treatment of Nonalcoholic Fatty Liver Disease
Authors: Musso Giovanni , Gambino Roberto , Cassader Maurizio
Published: January 2010

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, viral infection, or other specific causes of liver disease. Currently the most common chronic liver disease, affecting 30% of the Western world, NAFLD may progress to cirrhosis and end-stage liver disease and may increase the risk of developing diabetes and cardiovascular disease. Although its pathogenesis is unclear, NAFLD is tightly associated with insulin resistance and the metabolic syndrome. No established treatment exists, and current research is targeting new molecular mechanisms that underlie NAFLD and associated cardiometabolic disorders. This review discusses some of these emerging molecular mechanisms and their therapeutic implications for the treatment of NAFLD: microRNAs, incretin analogs/antagonists, liver-specific thyromimetics, AMP-activated protein kinase activators, and nuclear receptors farnesoid X receptor and pregane X receptor.
RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform
Authors: Bennett C. Frank , Swayze Eric E.
Published: January 2010

Dramatic advances in understanding of the roles RNA plays in normal health and disease have greatly expanded over the past 10 years and have made it clear that scientists are only beginning to comprehend the biology of RNAs. It is likely that RNA will become an increasingly important target for therapeutic intervention; therefore, it is important to develop strategies for therapeutically modulating RNA function. Antisense oligonucleotides are perhaps the most direct therapeutic strategy to approach RNA. Antisense oligonucleotides are designed to bind to the target RNA by well-characterized Watson-Crick base pairing, and once bound to the target RNA, modulate its function through a variety of postbinding events. This review focuses on the molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligonucleotides behave in the body.
TLR2 ligands attenuate cardiac dysfunction in polymicrobial sepsis via a phosphoinositide 3-kinase-dependent mechanism
Authors: Ha Tuanzhu , Lu Chen , Liu Li , Hua Fang , Hu Yulong , Kelley Jim , Singh Krishna , Kao Race L. , Kalbfleisch John , Williams David L. , Gao Xiang , Li Chuanfu
Published: January 2010

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. In the present study, we examined the effect of Toll-like receptor 2 (TLR2) ligands, peptidoglycan (PGN), and Pam3CSK4 (Pam3) on cardiac function in cecal ligation and puncture (CLP)-induced sepsis in mice. We also investigated whether the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in the effect of TLR2 ligands on cardiac function in CLP mice. PGN was administered to C57B6/L mice 1 h before the induction of CLP. Sham surgically operated mice served as a control. Cardiac function indexes (rate of change in left ventricular pressure, stroke work, cardiac output, and ejection fraction) were examined by a microconductance pressure catheter. Cardiac function was significantly decreased 6 h after CLP-induced sepsis compared with sham-operated control. In contrast, PGN administration attenuated CLP-induced cardiac dysfunction. Importantly, the therapeutic treatment with Pam3 1 h after CLP also significantly attenuated cardiac dysfunction in CLP mice. However, the beneficial effect of TLR2 ligands on cardiac dysfunction in CLP-mice was abolished in TLR2-deficient mice. PGN administration significantly increased the levels of phospho-Akt and phospho-GSK-3β in the myocardium compared with the levels in untreated CLP mice. PI3K inhibition abolished the PGN-induced attenuation of cardiac dysfunction in CLP mice. In conclusion, these data demonstrate that the administration of TLR2 ligands, PGN, or Pam3 attenuates cardiac dysfunction in septic mice via a TLR2/PI3K-dependent mechanism. More significantly, Pam3 therapeutic treatment will have a potential clinical relevance.
The role of nicotine on respiratory sensory gating measured by respiratory-related evoked potentials
Authors: Chan Pei-Ying Sarah , Davenport P. W.
Published: January 2010

Respiratory perception can be altered by changes in emotional or psychological states. This may be due to affective (i.e., anxiety) modulation of respiratory sensory gating. Nicotine withdrawal induces elevated anxiety and decreased somatosensory gating. Respiratory sensory gating is evidenced by decreased amplitude of the respiratory-related evoked potentials (RREP) N1 peak for the second occlusion (S2) when two 150-ms occlusions are presented with a 500-ms interval during an inspiration. The N1 peak amplitude ratio of the S2 and first occlusion (S1) (S2/S1) is <0.5 and due to central neural sensory gating. We hypothesized that withdrawal from nicotine is anxiogenic and reduces respiratory gating in smokers. The RREP was recorded in smokers with 12-h withdrawal from nicotine and nonsmokers using a paired occlusion protocol. In smokers, the RREP was measured after nicotine withdrawal, then with either nicotine or placebo gum, followed by the second RREP trial. Nonsmokers received only placebo gum. After nicotine withdrawal, the smokers had a higher state anxiety compared with nonsmokers. There was a significant interaction between groups (nonsmokers vs. smokers with nicotine vs. smokers with placebo) and test (pre- vs. posttreatment) in RREP N1 peak amplitude S2/S1. The S2/S1 in the smokers were larger than in nonsmokers before treatment. After gum treatment, the smoker-with-placebo group had a significantly larger S2/S1 than the other two groups. The S2/S1 was significantly decreased after the administration of nicotine gum in smokers due to significantly decreased S2 amplitudes. The RREP Nf and P1 peaks were unaffected. These results demonstrated that respiratory sensory gating was decreased in smokers after nicotine withdrawal. Nicotine increased respiratory sensory gating in smokers with a S2/S1 similar to that of the nonsmokers. Nicotine did not change respiratory sensory information arrival, but secondary information processing in respiratory sensation.
The effect of oxygen on dynamic cerebral autoregulation: critical role of hypocapnia
Authors: Ogoh Shigehiko , Nakahara Hidehiro , Ainslie Philip N. , Miyamoto Tadayoshi
Published: January 2010

Hypoxia is known to impair cerebral autoregulation (CA). Previous studies indicate that CA is profoundly affected by cerebrovascular tone, which is largely determined by the partial pressure of arterial O2 and CO2. However, hypoxic-induced hyperventilation via respiratory chemoreflex activation causes hypocapnia, which may influence CA independent of partial pressure of arterial O2. To identify the effect of O2 on dynamic cerebral blood flow regulation, we examined the influence of normoxia, isocapnia hyperoxia, hypoxia, and hypoxia with consequent hypocapnia on dynamic CA. We measured heart rate, blood pressure, ventilatory parameters, and middle cerebral artery blood velocity (transcranial Doppler). Dynamic CA was assessed ( n = 9) during each of four randomly assigned respiratory interventions: 1) normoxia (21% O2); 2) isocapnic hyperoxia (40% O2); 3) isocapnic hypoxia (14% O2); and 4) hypocapnic hypoxia (14% O2). During each condition, the rate of cerebral regulation (RoR), an established index of dynamic CA, was estimated during bilateral thigh cuff-induced transient hypotension. The RoR was unaltered during isocapnic hyperoxia. Isocapnic hypoxia attenuated the RoR (0.202 ± 0.003/s; 27%; P = 0.043), indicating impairment in dynamic CA. In contrast, hypocapnic hypoxia increased RoR (0.444 ± 0.069/s) from normoxia (0.311 ± 0.054/s; +55%; P = 0.041). These findings indicated that hypoxia disrupts dynamic CA, but hypocapnia augments the dynamic CA response. Because hypocapnia is a consequence of hypoxic-induced chemoreflex activation, it may provide a teleological means to effectively maintain dynamic CA in the face of prevailing arterial hypoxemia.
Aquaporin-6 Expression in the Cochlear Sensory Epithelium Is Downregulated by Salicylates
Authors: Perin Paola , Tritto Simona , Botta Laura , Fontana Jacopo Maria , Gastaldi Giulia , Masetto Sergio , Tosco Marisa , Laforenza Umberto
Published: January 2010

We characterize the expression pattern of aquaporin-6 in the mouse inner ear by RT-PCR and immunohistochemistry. Our data show that in the inner ear aquaporin-6 is expressed, in both vestibular and acoustic sensory epithelia, by the supporting cells directly contacting hair cells. In particular, in the Organ of Corti, expression was strongest in Deiters' cells, which provide both a mechanical link between outer hair cells (OHCs) and the Organ of Corti, and an entry point for ion recycle pathways. Since aquaporin-6 is permeable to both water and anions, these results suggest its possible involvement in regulating OHC motility, directly through modulation of water and chloride flow or by changing mechanical compliance in Deiters' cells. In further support of this role, treating mice with salicylates, which impair OHC electromotility, dramatically reduced aquaporin-6 expression in the inner ear epithelia but not in control tissues, suggesting a role for this protein in modulating OHCs' responses.
The Gut: The Forgotten Organ in Uremia?
Authors: Schepers Eva , Glorieux Griet , Vanholder Raymond
Published: January 2010

Part of the uremic retention solutes are generated in the intestine, but this option is rarely discussed in the literature. In this publication, we describe consecutively the role of the intestine in generating uremic retention solutes, the pathophysiological importance of the generated solutes and therapeutic options that are inspired by this knowledge. Apart from its role as a route via which uremic toxins or their precursors enter the body, the intestine also acts as an active player by presenting more precursors for fermentation due to disturbances in assimilation caused by uremia, followed by alterations in further processing related to changes in the composition of the fermenting flora. Many of the toxins generated or introduced into the body via the intestine (advanced glycation end products, indoles, phenols) play an active role in vascular damage. Intestinal therapeutic interventions that could help decrease solute concentration are restriction of dietary intake, however at the expense of increasing the risk of malnutrition, rerouting of intestinal metabolism by administration of prebiotics or probiotics and/ or the administration of active sorbents such as AST-120 (Kremezin®).
Clinical Experience with Adalimumab in a Multicenter Swiss Cohort of Patients with Crohn’s Disease
Authors: Nichita Cristina , Stelle Marc , Vavricka Stephan , El-Wafa Ali Abdou , Ballabeni Pierluigi , de Saussure Philippe , Straumann Alex , Rogler Gerhard , Michetti Pierre
Published: January 2010

Background: Controlled clinical trials have demonstrated the efficacy and safety of adalimumab in patients with moderate-to-severe Crohn’s disease (CD), but there is, however, only limited long-term experience with adalimumab in daily practice. Aim: To assess the long-term effectiveness and safety of adalimumab in a multicenter cohort of practice-based patients with moderate-to-severe CD. Methods: We retrospectively reviewed the charts of CD patients who received adalimumab over a 3-year period. Disease severity was scored using the Harvey-Bradshaw index (HBI). Remission was defined as an HBI of ≤4 and response as a reduction in the HBI of >3 points at evaluation compared to the baseline. Univariate logistic regression analysis was used to identify the predictive variables associated with response. Results: The charts of 55 patients were reviewed; remission and response rates observed at weeks 4–6 were 52.7 and 83.6%, respectively. Remission was maintained at weeks 12, 24 and 52 in 89.6, 72.4 and 44.7% of patients, respectively. Remission and response rates were not influenced by smoking status, disease location or duration, the first month total dose, or previous infliximab therapy. The remission rate at weeks 4–6 was significantly higher in patients intolerant of infliximab as compared to those who lost response to this drug. Adalimumab was well tolerated overall. Conclusion: Adalimumab can be considered a suitable option in patients with moderate-to-severe CD, demonstrating sustained long-term effectiveness.
Current Trends in Treating Hearing Loss in Elderly People: A Review of the Technology and Treatment Options – A Mini-Review
Authors: Sprinzl G.M. , Riechelmann H.
Published: January 2010

Background: According to the World Health Organization (WHO), by 2025 there will be approximately 1.2 billion people in the world over the age of 60, which marks a shift in world population to a greater proportion of older people. An estimated 70–80% of adults between 65 and 75 years of age suffer from presbycusis, or age-related, bilateral sensorineural hearing loss (HL) in the high frequencies. Presbycusis is correlated with decreased quality of life (QoL) and depression and according to WHO, is a leading cause of years lived with disability in the adult years. Objective: The purpose of the current study was to review the body of literature on treatment options and considerations for the elderly population, as there is a variety of audio-technology available today to treat presbycusis. Methods: A PubMed literature search was conducted using the keywords ‘presbycusis/presbyacusis/geriatric AND hearing aids/cochlear implants/electric acoustic stimulation/middle ear implants’ and ‘elderly AND cochlear implants’. References were also mined from papers found. Results: 431 articles were considered in this review of treatment options for elderly patients suffering from presbycusis. Conclusion: Hearing aids and cochlear implants (CIs) are the most commonly used devices for treating mild-severe presbycusis. Reported outcomes with hearing aids indicate they are an effective method for treating mild-moderate HL in cases where the patient is appropriately fitted and is willing, motivated, and able to use the device. Depending on the type and severity of the HL and the specific needs of the patient, electric-acoustic stimulation and active middle ear implants may also be appropriate solutions for treating presbycusis. Finally, very positive QoL and speech perception outcomes have been documented in treating severe-profound presbycusis with CIs. In some studies, QoL outcomes have even exceeded expectations of elderly patients.
Genetic Deletion of Myostatin From the Heart Prevents Skeletal Muscle Atrophy in Heart Failure
Authors: Heineke Joerg , Auger-Messier Mannix , Xu Jian , Sargent Michelle , York Allen , Welle Stephen , Molkentin Jeffery D.
Published: January 2010

Background—

Cardiac cachexia is characterized by an exaggerated loss of skeletal muscle, weakness, and exercise intolerance, although the cause of these effects remains unknown. Here, we hypothesized that the heart functions as an endocrine organ in promoting systemic cachexia by secreting peptide factors such as myostatin. Myostatin is a cytokine of the transforming growth factor-β superfamily that is known to control muscle wasting.

Methods and Results—

We used a Cre/loxP system to ablate myostatin (
Mstn
gene) expression in a cell type-specific manner. As expected, elimination of
Mstn
selectively in skeletal muscle with a myosin light chain 1f (
MLC1f
)-
cre
allele induced robust hypertrophy in all skeletal muscle. However, heart-specific deletion of
Mstn
with an
Nkx2.5-cre
allele did not alter baseline heart size or secondarily affect skeletal muscle size, but the characteristic wasting and atrophy of skeletal muscle that typify heart failure were not observed in these heart-specific null mice, indicating that myocardial myostatin expression controls muscle atrophy in heart failure. Indeed, myostatin levels in the plasma were significantly increased in wild-type mice subjected to pressure overload-induced cardiac hypertrophy but not in
Mstn
heart-specific deleted mice. Moreover, cardiac-specific overexpression of myostatin, which increased circulating levels of myostatin by 3- to 4-fold, caused a reduction in weight of the quadriceps, gastrocnemius, soleus, and even the heart itself. Finally, to investigate myostatin as a potential therapeutic target for the treatment of muscle wasting in heart failure, we infused a myostatin blocking antibody (JA-16), which promoted greater maintenance of muscle mass in heart failure.

Conclusions—

Myostatin released from cardiomyocytes induces skeletal muscle wasting in heart failure. Targeted inhibition of myostatin in cardiac cachexia might be a therapeutic option in the future.
Rescue of Cardiomyopathy in Peroxisome Proliferator-Activated Receptor-α Transgenic Mice by Deletion of Lipoprotein Lipase Identifies Sources of Cardiac Lipids and Peroxisome Proliferator-Activated Receptor-α Activators
Authors: Duncan Jennifer G. , Bharadwaj Kalyani G. , Fong Juliet L. , Mitra Riddhi , Sambandam Nandakumar , Courtois Michael R. , Lavine Kory J. , Goldberg Ira J. , Kelly Daniel P.
Published: January 2010

Background—

Emerging evidence in obesity and diabetes mellitus demonstrates that excessive myocardial fatty acid uptake and oxidation contribute to cardiac dysfunction. Transgenic mice with cardiac-specific overexpression of the fatty acid–activated nuclear receptor peroxisome proliferator-activated receptor-α (myosin heavy chain [MHC]-PPARα mice) exhibit phenotypic features of the diabetic heart, which are rescued by deletion of CD36, a fatty acid transporter, despite persistent activation of PPARα gene targets involved in fatty acid oxidation.

Methods and Results—

To further define the source of fatty acid that leads to cardiomyopathy associated with lipid excess, we crossed MHC-PPARα mice with mice deficient for cardiac lipoprotein lipase (hsLpLko). MHC-PPARα/hsLpLko mice exhibit improved cardiac function and reduced myocardial triglyceride content compared with MHC-PPARα mice. Surprisingly, in contrast to MHC-PPARα/CD36ko mice, the activity of the cardiac PPARα gene regulatory pathway is normalized in MHC-PPARα/hsLpLko mice, suggesting that PPARα ligand activity exists in the lipoprotein particle. Indeed, LpL mediated hydrolysis of very-low-density lipoprotein activated PPARα in cardiac myocytes in culture. The rescue of cardiac function in both models was associated with improved mitochondrial ultrastructure and reactivation of transcriptional regulators of mitochondrial function.

Conclusions—

MHC-PPARα mouse hearts acquire excess lipoprotein-derived lipids. LpL deficiency rescues myocyte triglyceride accumulation, mitochondrial gene regulatory derangements, and contractile function in MHC-PPARα mice. Finally, LpL serves as a source of activating ligand for PPARα in the cardiomyocyte.
Proton Magnetic Resonance Spectroscopy Detection of Neurotransmitters in Dorsomedial Medulla Correlate With Spontaneous Baroreceptor Reflex Function
Authors: Garcia-Espinosa Maria A. , Shaltout Hossam A. , Olson John , Westwood Brian M. , Robbins Mike E. , Link Kerry , Diz Debra I.
Published: January 2010

Control of heart rate variability via modulation of sympathovagal balance is a key function of nucleus tractus solitarii and the dorsal motor nucleus of the vagus localized in the dorsomedial medulla oblongata. Normal blood pressure regulation involves precise balance of glutamate (Glu)-glutamine-γ-aminobutyric acid transmitter systems, and angiotensin II modulates these transmitters to produce tonic suppression of reflex function. It is not known, however, whether other brain transmitters/metabolites are indicators of baroreflex function. This study establishes the concept that comprehensive baseline transmitter/metabolite profiles obtained using in vivo
1
H magnetic resonance spectroscopy in rats with well-characterized differences in resting blood pressure and baroreflex function can be used as indices of autonomic balance or baroreflex sensitivity. Transgenic rats with over-expression of renin [m(Ren2)27] or under-expression of glial-angiotensinogen (ASrAogen) were compared with Sprague-Dawley rats. Glu concentration in the dorsal medulla is significantly higher in ASrAogen rats compared with either Sprague-Dawley or (mRen2)27 rats. Glu levels and the ratio of Glu:glutamine correlated positively with indices of higher vagal tone consistent with the importance of these neurotransmitters in baroreflex function. Interestingly, the levels of choline-containing metabolites showed a significant positive correlation with spontaneous baroreflex sensitivity and a negative correlation with sympathetic tone. Thus, we demonstrate the concept that noninvasive assessment of neurochemical biomarkers may be used as an index of baroreflex sensitivity.
Glutamatergic Receptor Activation in the Rostral Ventrolateral Medulla Mediates the Sympathoexcitatory Response to Hyperinsulinemia
Authors: Bardgett Megan E. , McCarthy John J. , Stocker Sean D.
Published: January 2010

Hyperinsulinemia increases sympathetic nerve activity (SNA) and has been linked to cardiovascular morbidity in obesity. The rostral ventrolateral medulla (RVLM) plays a key role in the regulation of SNA and arterial blood pressure (ABP). Many sympathoexcitatory responses are mediated by glutamatergic receptor activation within the RVLM, and both the central renin–angiotensin and melanocortin systems are implicated in the sympathoexcitatory response to hyperinsulinemia. Therefore, we hypothesized that one or more of these neurotransmitters in the RVLM mediate the sympathoexcitatory response to insulin. Hyperinsulinemic–euglycemic clamps were performed in α-chloralose anesthetized, male Sprague–Dawley rats by infusion of insulin (3.75 mU/kg per minute, IV) and 50% dextrose solution for 120 minutes. Physiological increases in plasma insulin elevated lumbar SNA, with no change in renal SNA, ABP, or blood glucose. Microinjection of the ionotropic glutamate receptor antagonist kynurenic acid into the RVLM significantly reduced lumbar SNA and ABP. Selective blockade of NMDA but not non-NMDA glutamate receptors resulted in similar reductions of lumbar SNA. In marked contrast, microinjection of the angiotensin II type 1 receptor antagonist losartan or the melanocortin 3/4 antagonist SHU9119 had no effect on lumbar SNA or ABP. Western blot analysis showed that insulin receptor expression is significantly lower in the RVLM than the hypothalamus, and direct microinjection of insulin into the RVLM did not significantly increase lumbar SNA. These findings suggest that hyperinsulinemia increases lumbar SNA by activation of a glutamatergic NMDA-dependent projection to the RVLM.
Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI
Authors: Richard Edo , Gouw Alida A. , Scheltens Philip , van Gool Willem A.
Published: January 2010

Background and Purpose—

White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts.

Methods—

A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up.

Results—

Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3,
P
=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups.

Conclusions—

Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.
Five Defining Issues: The International Classical Pentecostal/Roman Catholic Dialogue
Authors: McDonnell Kilian
Published: January 2010

In the previous article on the international Classical Pentecostal/Roman Catholic dialogue I looked at a range of issues affecting the conversations, reserving to this article a more focused look at five theological areas. The range of topics over the first three quinquennia is extensive and merits attention. The fourth is not complete and is at issue here only in an incidental way.1 In a preliminary way the two sides agree of the basic content of the Christian faith: trinity,2 the divinity of Christ, virgin birth, centrality of the death and resurrection of Jesus, Pentecost as constitutive of the church, forgiveness of sins, promise of eternal life. We may look at these areas differently, but there is a measure of agreement on them. Beyond these theological areas of basic Christian faith, a number of issues emerged in the first three quinquennia which define the dialogue and give it an unmistakable profile. In this essay, I treat five of these defining issues: the hermeneutical moment, infant and believers' baptism, baptism in the Holy Spirit, the church as koinonia, and Mary.
The Influence of Dr. J. E. Purdie's Reformed Anglican Theology on the Formation and Development of the Pentecostal Assemblies of Canada
Authors: Althouse Peter
Published: January 2010

The Pentecostal Assemblies of Canada (PAOC) has had many similarities with its United States counterpart, the Assemblies of God. In fact, in its early years the PAOC was affiliated with the Assemblies of God.1 Yet the PAOC was unique in that it had a friendly relationship with the Anglican Church of Canada2 vis-à-vis the Toronto low-church Anglican theological school, Wycliffe College.3 This relationship centered on one man, a Wycliffe College graduate and Anglican priest, who was asked to be principal of the first Canadian Pentecostal Bible school in 1925, a position he held until 1950. This man was James Eustace Purdie, arguably the most influential person in the formation and development of PAOC doctrine through the theological education of Pentecostal ministers.4
Cameroonian light on the propagation of Christianity in Kenjo Jumbam's The white man of God
Authors: Hale F.
Published: January 2010

In this article the author shows how the arrival of Christianity in Cameroon is portrayed in the work of Cameroonian writer KenjoJumbam. Writing some time after independence, Jumbam's work (especially The White man of God) exhibits a balanced valuation of Christian missionary work in contrast to other Cameroonian authors writing around the time of independence who displayed a more negative valuation of Christianity as a result of anti-colonialist feelings. In Jumbam's portrayal of the work of Christian missionaries the issue of inculturation of Christianity in indigenous culture is also raised.
Situating biblical narrative studies in literary theory and literary approaches
Authors: de Klerk Johannes C
Published: January 2010

In literary studies of biblical texts one often encounters amazing ignorance of the intricacies of literary theory and the complexity of literary issues. This article addresses this problem from the viewpoint of biblical narrative studies. General trends of these studies are discussed, then biblical narrative studies are situated in the phenomena of 'literature', and consequently in narrative theories and some crucial literary issues. Finally the article focuses on whether biblical narrative studies should persist in an old-fashioned literary approach, and some cardinal pointers ahead are presented.