bluuebunny/crossref_metadata_2025 huggingface dataset:
Submacular haemorrhage after intravitreal bevacizumab compared with intravitreal ranibizumab in large occult choroidal neovascularization
Authors: Krishnan Radhika , Goverdhan Srinivas , Lochhead Jonathan
Published: April 2009

Abstract

Background:  Submacular haemorrhage may occur following intravitreal bevacizumab injection for large occult choroidal neovascularization (CNV) in age‐related macular degeneration (AMD). We report the occurrence of submacular haemorrhage following intravitreal ranibizumab compared with intravitreal bevacizumab for large occult CNV in AMD.

Methods:  Retrospective, comparative evaluation of two interventional case series. Evaluation of consecutive patients with occult CNV ≥ 15 mm2 treated with intravitreal bevacizumab (n = 14) and intravitreal ranibizumab (n = 22) over a 2‐year period within a single institution. Postoperative submacular haemorrhage, Early Treatment Diabetic Retinopathy Study‐derived visual acuity, preoperative blood pressure and anticoagulant use were noted. The two groups were compared using Fisher's exact test.

Results:  The mean surface area of occult CNV at presentation was 20.9 ± 5.4 mm2 in the bevacizumab group and 24.0 ± 11.0 mm2 in the ranibizumab group. Fresh submacular haemorrhage was seen in 4 out of 14 patients following bevacizumab compared with 0 out of 22 patients following ranibizumab (P = 0.017, odds ratio = 19.29). Mean preoperative blood pressures were very similar between the groups. 28.6% of patients in the bevacizumab group were on oral anticoagulants compared with 31.8% in the ranibizumab group. None of the patients who developed postoperative haemorrhage were on anticoagulants.

Conclusions:  Acute submacular haemorrhages appear to be a significant adverse event following intravitreal bevacizumab in occult CNV ≥ 15 mm2. Intravitreal ranibizumab appears to have a significantly lower incidence of postoperative submacular haemorrhage in occult CNV ≥ 15 mm2. Larger studies are required to identify the most appropriate agent for the treatment of large occult CNV.
To investigate the prevalence of polypoidal choroidal vasculopathy in presumed age‐related peripapillary subretinal neovascular membranes
Authors: Squirrell David M , Bacon James F , Brand Christopher S
Published: April 2009

Abstract

Background:  To investigate the prevalence and angiographic appearances of polypoidal choroidal vasculopathy (PCV) masquerading as age‐related peripapillary subretinal neovascular membranes (PSRNVM).

Methods:  A consecutive case series of all patients investigated for presumed age‐related PSRNVM in our tertiary referral centre over the period September 2006–2007. The presenting clinical features and fundus fluorescein angiographic (FFA) characteristics of each patient's lesion were identified. Any accompanying Indocyanine Green Angiogram (ICGA) was also reviewed, and on the basis of this investigation patients were classified into one of three groups: proven PCV, probable PCV and PSRNVM.

Results:  Thirty patients with presumed age‐related PSRNVM were identified. The FFA leakage pattern was occult in 21 patients and classic in nine patients. Sixteen patients also had ICGA performed. In 14 of these patients the original FFA leakage pattern was occult, and in two it was classic. Of the 14 patients with occult leakage on FFA who subsequently underwent ICGA all were found to have PCV.

Conclusions:  PCV is important and underrecognized in presumed age‐related PSRNVMs. In such cases, particularly when the pattern of leakage on the fluorescein angiogram is occult, ICGA should be performed to identify the site of the polyps and if required to direct treatment.
Kimura disease of the eyelid in an Indian man
Authors: Lee Jason KS , Almousa Radwan , Thamboo Thomas P , Amrith Shantha
Published: April 2009

Abstract

Kimura disease is a rare idiopathic chronic inflammatory disease, characterized by subcutaneous nodular lesions in the head and neck area. Ophthalmic manifestation of Kimura disease involves orbital and eyelid lesions mostly in Asian patients, but it has been described in White patients and Black Caribbean patients. Kimura disease is usually associated with eosinophilia and occasionally with renal disease. Here, we report a case of Kimura disease of the eyelid in a 50‐year‐old Indian man with eosinophilia. The main differential diagnosis was angiolymphoid hyperplasia with eosinophilia. Histology is crucial to separate these two entities, and our case was shown to be Kimura disease by histology. To our knowledge, this is the first report of a person of Indian origin to develop Kimura disease involving the eyelid.
A novel engineering method based on the critical plane concept to estimate the lifetime of weldments subjected to variable amplitude multiaxial fatigue loading
Authors: SUSMEL L. , TOVO R. , BENASCIUTTI D.
Published: April 2009

This paper summarizes an attempt at proposing a new engineering method suitable for estimating the fatigue lifetime of steel‐ and aluminium‐welded connections subjected to variable amplitude multiaxial fatigue loading. In particular, the proposed approach is based on the use of the so‐called Modified Wöhler Curve Method (MWCM), i.e. a bi‐parametrical critical plane approach, whose accuracy has been checked so far solely in addressing the constant amplitude multiaxial fatigue problem. In order to extend the use of our criterion to variable amplitude situations, the critical plane is suggested here as being determined by taking full advantage of the maximum variance concept, that is, such a plane is assumed to be the one containing the direction along which the variance of the resolved shear stress reaches its maximum value. The main advantage of such a strategy is that the cycle counting can directly be performed by considering the shear stress resolved along the maximum variance direction: by so doing, the problem is greatly simplified, allowing those well‐established cycle counting methods specifically devised to address the uniaxial variable amplitude problem to be extended to those situations involving multiaxial fatigue loading. The validity of the proposed methodology was checked by using two different datasets taken from the literature and generated by testing both steel and aluminium tube‐to‐plate welded connections subjected to in‐phase and 90° out‐of‐phase variable amplitude bending and torsion. This new fatigue life assessment technique was seen to be highly accurate allowing the estimates to fall within the calibration scatter bands not only when the constants in the governing equations were calculated by using the experimental uniaxial and torsional fully reversed fatigue curves, but also when they were determined by using the reference curves supplied, for the investigated geometry, by the available standard codes. These results seem to strongly support the idea that, thanks to its peculiar features, our method can be considered as an effective engineering approach capable of performing multiaxial fatigue assessment under variable amplitude loading which fully complies with the recommendations of the available standard codes.
Substance P and cocaine employ convergent mechanisms to depress excitatory synaptic transmission in the rat nucleus accumbens in vitro
Authors: Kombian Samuel B. , Ananthalakshmi Kethireddy V. V. , Zidichouski Jeffrey A. , Saleh Tarek M.
Published: April 2009

Substance P (SP) has been reported to produce effects on excitatory synaptic transmission in the nucleus accumbens (NAc) that are similar to those induced by cocaine. To address the question of whether SP serves as an endogenous mediator producing cocaine‐like effects that are known to be D1‐receptor‐mediated, we tested the hypothesis that the effects of SP and cocaine on excitatory postsynaptic currents (EPSCs) in the NAc occlude one another. We report here that SP and SP5–11 actions occlude the effect of cocaine and vice versa. SP, SP5–11 and cocaine all depressed evoked, non‐N‐methyl‐d‐aspartate (NMDA) receptor‐mediated synaptic currents in a concentration‐dependent manner, with EC50 values of 0.12, 0.17 and 8.3 μm, respectively. Although cocaine was the least potent, it was most efficacious. SP, SP5–11 and cocaine all suppressed isolated NMDA receptor‐mediated evoked EPSCs. SP5–11 (1 μm)‐induced EPSC depression was blocked by the neurokinin‐1 antagonist L732138 and by the D1‐like receptor antagonist SCH23390. Pretreatment of slices with cocaine (30 μm) depressed the EPSC by 39.1% ± 4.8%. Application of SP or SP5–11 (1 μm) at the peak of the cocaine depressive effect on the EPSC did not produce any additional diminution of the response (5.7% ± 2.8%). In the reverse experiments, in which either SP or SP5–11 was applied first, subsequent application of cocaine at the peak of the peptide’s effect (30.3% ± 2.3%) produced a further but smaller depression (15.5% ± 3.6%) of the remaining EPSC. These data indicate that cocaine and SP produce similar effects on excitatory synaptic transmission in the NAc, and that their actions occlude one another. This suggests that SP may act like cocaine in its absence, and may be an endogenous trigger for the reward and behaviors associated with cocaine.
Learning to filter out visual distractors
Authors: Gál Viktor , Kozák Lajos R. , Kóbor István , Bankó Éva M. , Serences John T. , Vidnyánszky Zoltán
Published: April 2009

When learning to master a visual task in a cluttered natural environment, it is important to optimize the processing of task‐relevant information and to efficiently filter out distractors. However, the mechanisms that suppress task‐irrelevant information are not well understood. Here we show that training leads to a selective increase in motion coherence detection thresholds for task‐irrelevant motion directions that interfered with the processing of task‐relevant directions during training. Furthermore, using functional magnetic resonance imaging we found that training attenuated neural responses associated with the task‐irrelevant direction compared with the task‐relevant direction in the visual cortical areas involved in processing of visual motion. The strongest suppression of functional magnetic resonance imaging responses to task‐irrelevant motion information was observed in human area MT+. These findings reveal that perceptual learning leads to the suppression and efficient filtering of task‐irrelevant visual information.
Comparing the role of the anterior cingulate cortex and 6‐hydroxydopamine nucleus accumbens lesions on operant effort‐based decision making
Authors: Walton Mark E. , Groves James , Jennings Katie A. , Croxson Paula L. , Sharp Trevor , Rushworth Matthew F. S. , Bannerman David M.
Published: April 2009

Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort‐related cost–benefit decision‐making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed‐ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)]. All animals initially preferred to put in work to gain the HR. Systemic administration of a D2 antagonist caused a significant switch in choices towards the LR option. Similarly, post‐operatively, excitotoxic ACC lesions caused a significant bias away from HR choices compared with sham‐lesioned animals. There was no slowing in the speed of lever pressing and no correlation between time to complete the FR requirement and choice performance. Unexpectedly, no such alteration in choice allocation was observed in animals following 6‐hydroxydopamine NAc lesions. However, these rats were consistently slower to initiate responding when cued to commence each trial and also showed a reduction in food hoarding on a species‐typical foraging task. Taken together, this implies that only ACC lesions, and not 6‐hydroxydopamine NAc lesions as performed here, cause a bias away from investing effort for greater reward when choosing between competing options.
Differential loss and preservation of glutamate receptor function in bipolar cells in the rd10 mouse model of retinitis pigmentosa
Authors: Puthussery Theresa , Gayet‐Primo Jacqueline , Pandey Shilpi , Duvoisin Robert M. , Taylor W. Rowland
Published: April 2009

Photoreceptor degenerations can trigger morphological alterations in second‐order neurons, however, the functional implications of such changes are not well known. We conducted a longitudinal study, using whole‐cell patch‐clamp, immunohistochemistry and electron microscopy to correlate physiological with anatomical changes in bipolar cells of the rd10 mouse – a model of autosomal recessive retinitis pigmentosa. Rod bipolar cells (RBCs) showed progressive changes in mGluR6‐induced currents with advancing rod photoreceptor degeneration. Significant changes in response amplitude and kinetics were observed as early as postnatal day (P)20, and by P45 the response amplitudes were reduced by 91%, and then remained relatively stable until 6 months. These functional changes correlated with the loss of rod photoreceptors and mGluR6 receptor expression. Moreover, we showed that RBCs make transient ectopic connections with cones during progression of the disease. At P45, ON‐cone bipolar cells (ON‐CBCs) retain mGluR6 responses for longer periods than the RBCs, but by about 6 months these cells also strongly downregulate mGluR6 expression. We propose that the relative longevity of mGluR6 responses in CBCs is due to the slower loss of the cones. In contrast, ionotropic glutamate receptor expression and function in OFF‐CBCs remains normal at 6 months despite the loss of synaptic input from cones. Thus, glutamate receptor expression is differentially regulated in bipolar cells, with the metabotropic receptors being absolutely dependent on synaptic input. These findings define the temporal window over which bipolar cells may be receptive to photoreceptor repair or replacement.
Patterns of 15N assimilation and growth of methanotrophic ANME‐2 archaea and sulfate‐reducing bacteria within structured syntrophic consortia revealed by FISH‐SIMS
Authors: Orphan Victoria J. , Turk Kendra A. , Green Abigail M. , House Christopher H.
Published: April 2009

Methane release from the oceans is controlled in large part by syntrophic interactions between anaerobic methanotrophic archaea (ANME) and sulfate‐reducing bacteria (DSS), frequently found as organized consortia. An understanding of the specifics of this symbiotic relationship and the metabolic heterogeneity existing between and within individual methane‐oxidizing aggregates is currently lacking. Here, we use the microanalytical method FISH‐SIMS (fluorescence in situ hybridization‐secondary ion mass spectrometry) to describe the physiological traits and anabolic activity of individual methanotrophic consortia, specifically tracking 15N‐labelled protein synthesis to examine the effects of organization and size on the metabolic activity of the syntrophic partners. Patterns of 15N distribution within individual aggregates showed enhanced 15N assimilation in ANME‐2 cells relative to the co‐associated DSS revealing a decoupling in anabolic activity between the partners. Protein synthesis in ANME‐2 cells was sustained throughout the core of individual ANME‐2/DSS consortia ranging in size range from 4 to 20 μm. This indicates that metabolic activity of the methane‐oxidizing archaea is not limited to, or noticeably enhanced at the ANME−2/DSS boundary. Overall, the metabolic activity of both syntrophic partners within consortia was greater than activity measured in representatives of the ANME‐2 and DSS observed alone, with smaller ANME‐2/DSS aggregates displaying a tendency for greater 15N uptake and doubling times ranging from 3 to 5 months. The combination of 15N‐labelling and FISH‐SIMS provides an important perspective on the extent of heterogeneity within methanotrophic aggregates and may aid in constraining predictive models of activity and growth by these syntrophic consortia.
Evidence for low‐titre infections in insect symbiosis:Wolbachiain the bark beetlePityogenes chalcographus(Coleoptera, Scolytinae)
Authors: Wolfgang Arthofer , Markus Riegler , Dimitrios N. Avtzis , Christian Stauffer
Published: April 2009

Wolbachiaare obligatory endosymbiotic α‐proteobacteria found in many insect species. They are maternally transmitted and often exhibit reproductive phenotypes like cytoplasmic incompatibility.Pityogenes chalcographusis a bark beetle causing severe damage in spruce stands. Its European populations are divided into several mitochondrial clades separated by partial crossing barriers. In this study, we tested a large sample set covering the natural range of the beetle in Europe for the presence ofWolbachiaand associations between infection pattern and mitotypes using a highly sensitive nested PCR technique. 35.5% of the individuals were infected with the endosymbiont and two distinct strains were identified. Both strains occur in low titre not accessible by conventional detection methods. The infections are present all over Europe, unlikely to cause the partial crossing barriers in this host and uncoupled from mitochondrial clades. This pattern is indicative for populations evolving towards endosymbiont loss and for repeated intraspecific horizontal transfer ofWolbachia. Alternatively, the low‐titre infections found inP. chalcographusare yet another example forWolbachiathat can persist in host species at low densities and frequencies.
Exenatide: a review from pharmacology to clinical practice
Authors: Gentilella R. , Bianchi C. , Rossi A. , Rotella C. M.
Published: April 2009

Background:  Exenatide is an incretin mimetic that activates glucagon‐like‐peptide‐1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose‐dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying.

Methods:  In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c ≤11%), or by thiazolidinediones (with or without metformin) and treated for periods from 16 weeks to 3 years, exenatide (5 μg b.i.d. s.c. for the first 4 weeks of treatment and 10 μg b.i.d. s.c. thereafter) reduced HbA1c, fasting and postprandial glucose, and body weight dose dependently, and was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c. Body weight diminished with exenatide, whereas it increased with both insulin preparations. Positive effects on the lipid profile and a reduction in C‐reactive protein were also recorded with exenatide. Treatment extensions up to 3 years showed that benefits were maintained in the long term. Adverse events were usually mild to moderate in intensity, and generally the frequency decreased with continued therapy. The most common was nausea (whose incidence may be reduced by gradual dose escalation from 5 μg b.i.d. to 10 μg b.i.d.), vomiting, diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated with a sulphonylurea).

Results and conclusions:  Exenatide is a new, promising therapeutic option for type 2 diabetic patients inadequately controlled by oral agents, before insulin therapy, offering the added benefits of body weight reduction and tight postprandial glucose control.
Long‐term 2‐year safety and efficacy of vildagliptin compared with rosiglitazone in drug‐naïve patients with type 2 diabetes mellitus
Authors: Rosenstock J. , Niggli M. , Maldonado‐Lutomirsky M.
Published: April 2009

Aims:  To assess the long‐term safety and the sustained glycaemic control of vildagliptin compared with rosiglitazone over 2‐year treatment in drug‐naïve type 2 diabetes mellitus patients.

Methods:  This was an additional 80‐week, multicentre, double‐blind and active‐controlled extension to a 24‐week core study comparing the treatments of vildagliptin (50 mg b.i.d., n = 396) to rosiglitazone (8 mg q.d., n = 202). The primary efficacy variable was the mean change in haemoglobin A1c (HbA1c) from the core study baseline (day 1) to the end of 104 weeks (the extension endpoint).

Results:  Vildagliptin and rosiglitazone showed statistically significant and sustained HbA1c reductions from a core mean baseline of 8.6 and 8.7% to 7.8 and 7.3% respectively (both significant, p < 0.001). However, rosiglitazone‐treated patients showed significantly greater mean HbA1c reductions (mean difference 0.62%, s.e. 0.13, p < 0.001) compared with vildagliptin. The overall lipid profile significantly improved with vildagliptin compared to rosiglitazone treatment. Body weight remained unchanged in vildagliptin‐treated patients despite improvements in glycaemic control but significantly increased (mean change from core study baseline 4.67 kg) in rosiglitazone‐treated patients (p < 0.001). Notably, a lower incidence of peripheral oedema was seen with vildagliptin (4.6%) compared with rosiglitazone treatment (11.1%). More serious adverse events (SAEs) occurred in vildagliptin‐ than rosiglitazone‐treated patients (12.5 and 9.1% respectively), but only one SAE each in both treatment group was suspected to be related to study drug. Three non‐study drug‐related deaths (vildagliptin: 2 and rosiglitazone: 1) were reported. Four mild hypoglycaemic events were observed with vildagliptin.

Conclusions:  This study showed that the similar short‐term HbA1c reductions seen with both vildagliptin and rosiglitazone treatments were more durable after 104 weeks of treatment with rosiglitazone than vildagliptin. However, this greater durability with rosiglitazone was at the expense of weight gain (almost 5 kg), higher incidences of peripheral oedema and a less favourable plasma lipid profile compared with vildagliptin.
Prodrug delivery of novel PTP1B inhibitors to enhance insulin signalling
Authors: Erbe D. V. , Klaman L. D. , Wilson D. P. , Wan Z.‐K. , Kirincich S. J. , Will S. , Xu X. , Kung L. , Wang S. , Tam S. , Lee J. , Tobin J. F.
Published: April 2009

A growing percentage of the population is resistant to two key hormones – insulin and leptin – as a result of increased obesity, often leading to significant health consequences such as type 2 diabetes. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of signalling by both of these hormones, so that inhibitors of this enzyme may provide promise for correcting endocrine abnormalities in both diabetes and obesity. As with other tyrosine phosphatases, identification of viable drug candidates targeting PTP1B has been elusive because of the nature of its active site. Beginning with novel phosphotyrosine mimetics, we have designed some of the most potent PTP1B inhibitors. However, their highly acidic structures limit intrinsic permeability and pharmacokinetics. Ester prodrugs of these inhibitors improve their drug‐like properties with the goal of delivering these nanomolar inhibitors to the cytoplasm of cells within target tissues. In addition to identifying prodrugs that is able to deliver active drugs into cells to inhibit PTP1B and increase insulin signalling, these compounds were further modified to gain a variety of cleavage properties for targeting activity in vivo. One such prodrug candidate improved insulin sensitivity in ob/ob mice, with lowered fasting blood glucose levels seen in the context of lowered fasting insulin levels following 4 days of intraperitoneal dosing. The results presented in this study highlight the potential for design of orally active drug candidates targeting PTP1B, while also delineating the considerable challenges remaining.
Autoradiographic observations on developing and growing claws of reptiles
Authors: Alibardi Lorenzo
Published: April 2009

Alibardi, L. 2010. Autoradiographic observations on developing and growing claws of reptiles. —Acta Zoologica (Stockholm) 91: 233–241

The present qualitative autoradiographic analysis aims to present the main features of morphogenesis and growth of claws in reptiles. Lizard embryos treated with tritiated thymidine reveal that epidermal cell proliferation in terminal digits is prevalent in the dorsal side and gives origin to the curved unguis of the claw. Less proliferation occurs in the ventral side of the digit tip where the concave sub‐unguis is derived. Adult claws of a turtle show that thymidine‐labelled cells are present along most of the epidermis of the claw, especially at the claw tip. Also, injection of tritiated histidine and proline, indicating active protein synthesis, confirm autoradiographic labelling along most of the epidermis of claws, in particular at the apical tip. The present study indicates that proximal matrix regions, as have been described in mammalian nails, are absent in reptiles. This pattern of claw growth probably derives from that of terminal digital scales. In fact reptilian (and avian) claws are formed from a modification of scales, a different condition from that present in mammals.
Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity
Authors: Kar P. , Laight D. , Rooprai H. K. , Shaw K. M. , Cummings M.
Published: April 2009

Objective  Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid‐rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high‐risk cardiovascular subjects with Type 2 diabetes.

Research design and methods  Thirty‐two Type 2 diabetes mellitus patients, prescribed diet or oral glucose‐lowering agents, received GSE (600 mg/day) or placebo for 4 weeks in a double‐blinded randomized crossover trial. Markers of endothelial function (measured by photoplethysmography), oxidative stress [total antioxidant status (TAOS), reduced glutathione (GSH)/oxidized glutathione (GSSG)], inflammation [highly sensitive C‐reactive protein (hsCRP), urinary albumin : creatinine ratio), insulin resistance [homeostasis model assessment–insulin resistance (HOMA–IR)] and metabolism (fructosamine, lipid profile) was measured at baseline and after intervention with GSE or placebo.

Results  Baseline characteristics (16 male and 16 female): age 61.8 ± 6.36 years; body mass index 30.2 ± 5.92 kg/m2; diabetes duration 5.9 ± 2.14 years. Following GSE (but not placebo), significant changes were noted in fructosamine (282 ± 40.9 vs. 273 ± 50.2 mmol/l; P = 0.0004); whole blood GSH (2359 ± 823 vs. 3595 ± 1051 mmol/l; P < 0.01) and hsCRP (3.2 ± 3.65 vs. 2.0 ± 2.2 mg/l; P = 0.0006). Total cholesterol concentration also decreased (4.5 ± 0.96 vs. 4.3 ± 0.99 mmol/l; P = 0.05). No statistically significant changes were shown in endothelial function, HOMA–IR or TAOS.

Conclusion  GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4‐week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk.
Effect of ABCA1 variant on atherogenic dyslipidaemia in patients with Type 2 diabetes treated with rosiglitazone
Authors: Park S. E. , Kang E. S. , Kim D. H. , Kim S. K. , Lee J. H. , Ahn C. W. , Lee H. C. , Cha B. S.
Published: April 2009

Aims  To investigate the effect of two common ATP‐binding cassette transporter 1 (ABCA1) polymorphisms (rs4149263 and rs2020927) on atherogenic dyslipidaemia in Korean Type 2 diabetic patients who were treated with rosiglitazone.

Patients and methods  Two hundred and fifty‐six patients with Type 2 diabetes who had never previously received peroxisome proliferator‐activated receptor gamma (PPAR‐γ) agonists or lipid‐lowering treatment were treated with 4 mg of rosiglitazone daily for 12 weeks without any adjustment to their glucose‐lowering regimen. The primary outcome was the change in atherogenic index of plasma (AIP), calculated as log [triglyceride (mmol/l)/high‐density lipoprotein cholesterol (mmol/l)], before and after rosiglitazone treatment. The effect of rosiglitazone on the change in AIP was compared across the ABCA1 single nucleotide polymorphisms (SNPs) rs41429263 and rs2020927.

Results  Before adjustment, the change in AIP at 12 weeks was significantly different across the rs4149263 genotypes [median (interquartile range): −0.05 (−0.21, 0.09) for TT; 0.02 (−0.09, 0.17) for TC; and 0.11 (0.03, 0.25) for CC; P = 0.003], but not across the rs2020927 [−0.04 (−0.18, 0.10) for TT; 0.03 (−0.17, 0.15) for TC; and −0.03 (−0.13, 0.10) for CC; P = 0.401]. After controlling for age, gender and duration of diabetes, the presence of the C‐allele was significantly associated with an increase in AIP by 0.13 [95% confidence interval (CI), 0.04–0.21; P = 0.003]. This association did not change significantly when body mass index and pretreatment metabolic parameters were additionally controlled for (the change in AIP: 0.14; 95% CI, 0.04–0.24; P = 0.007).

Conclusions  The ABCA1 SNP rs4149263 may be associated with the change in atherogenic lipid profile in Type 2 diabetes treated with rosiglitazone.
An ecosystem model‐based estimate of changes in water availability differs from water proxies that are commonly used in species distribution models
Authors: Hickler Thomas , Fronzek Stefan , Araújo Miguel B. , Schweiger Oliver , Thuiller Wilfried , Sykes Martin T.
Published: April 2009

Aim  To assess whether the water availability measures commonly used in species distribution models might be misleading because they do not account for the hydrological effects of changes in vegetation structure and functioning.

Location  Europe.

Methods  We compared different methods for estimating water availability in species distribution models with the soil water content predicted by a process‐based ecosystem model. The latter also accounted for the hydrological effects of dynamic changes in vegetation structure and functioning, including potential physiological effects of increasing CO2.

Results  All proxies showed similar patterns of water availability across Europe for current climate, but when projected into the future, the changes in the simpler water availability measures showed no correlation with those projected by the more complex ecosystem model, even if CO2 effects were switched off.

Main conclusions  Results from species distribution modelling studies concerning future changes in species ranges and biodiversity should be interpreted with caution, and more process‐based representations of the water balance of terrestrial ecosystems should be considered within these models.
Change in action: how infants learn to walk down slopes
Authors: Gill Simone V. , Adolph Karen E. , Vereijken Beatrix
Published: April 2009

A critical aspect of perception–action coupling is the ability to modify ongoing actions in accordance with variations in the environment. Infants’ ability to modify their gait patterns to walk down shallow and steep slopes was examined at three nested time scales. Across sessions, a microgenetic training design showed rapid improvements after the first session in infants receiving concentrated practice walking down slopes and in infants in a control group who were tested only at the beginning and end of the study. Within sessions, analyses across easy and challenging slope angles showed that infants used a ‘braking strategy’ to curb increases in walking speed across increasingly steeper slopes. Within trials, comparisons of infants’ gait modifications before and after stepping over the brink of the slopes showed that the braking strategy was planned prospectively. Findings illustrate how observing change in action provides important insights into the process of skill acquisition.
Children's use of gesture to resolve lexical ambiguity
Authors: Kidd Evan , Holler Judith
Published: April 2009

We report on a study investigating 3–5‐year‐old children's use of gesture to resolve lexical ambiguity. Children were told three short stories that contained two homonym senses; for example, bat (flying mammal) and bat (sports equipment). They were then asked to re‐tell these stories to a second experimenter. The data were coded for the means that children used during attempts at disambiguation: speech, gesture, or a combination of the two. The results indicated that the 3‐year‐old children rarely disambiguated the two senses, mainly using deictic pointing gestures during attempts at disambiguation. In contrast, the 4‐year‐old children attempted to disambiguate the two senses more often, using a larger proportion of iconic gestures than the other children. The 5‐year‐old children used less iconic gestures than the 4‐year‐olds, but unlike the 3‐year‐olds, were able to disambiguate the senses through the verbal channel. The results highlight the value of gesture to the development of children's language and communication skills.
Inferring the size of a goal object from an actor's grasping movement in 6‐ and 9‐month‐old infants
Authors: Daum Moritz M. , Vuori Maria T. , Prinz Wolfgang , Aschersleben Gisa
Published: April 2009

The present study applied a preferential looking paradigm to test whether 6‐ and 9‐month old infants are able to infer the size of a goal object from an actor's grasping movement. The target object was a cup with the handle rotated either towards or away from the actor. In two experiments, infants saw the video of an actor's grasping movement towards an occluded target object. The aperture size of the actor's hand was varied as between‐subjects factor. Subsequently, two final states of the grasping movement were presented simultaneously with the occluder being removed. In Experiment 1, the expected final state showed the actor's hand holding a cup in a way that would be expected after the performed grasping movement. In the unexpected final state, the actor's hand held the cup at the side which would be unexpected after the performed grasping movement. Results show that 6‐ as well as 9‐month‐olds looked longer at the unexpected than at the expected final state. Experiment 2 excluded an alternative explanation of these findings, namely that the discrimination of the final states was due to geometrical familiarity or novelty of the final states. These findings provide evidence that infants are able to infer the size of a goal object from the aperture size of the actor's hand during the grasp.
Categorical flexibility in preschoolers: contributions of conceptual knowledge and executive control
Authors: Blaye Agnès , Jacques Sophie
Published: April 2009

The current study evaluated the relative roles of conceptual knowledge and executive control on the development of categorical flexibility, the ability to switch between simultaneously available but conflicting categorical representations of an object. Experiment 1 assessed conceptual knowledge and executive control together; Experiment 2 differentiated conceptual knowledge from costly executive processes. In Experiment 1, 3‐ to 5‐year‐olds were given a three‐choice (taxonomic, thematic, and nonassociate) match‐to‐sample task and asked to match two associates. In Experiment 2, same‐aged children were assessed on another match‐to‐sample task that reduced executive costs by presenting thematic and taxonomic associates on separate trials. By comparing performance across tasks, age‐related changes resulting from conceptual knowledge and executive control indicated that conceptual knowledge of superordinate relations showed gains between 3 and 4 years, whereas gains in executive control were seen between 4 and 5 years, suggesting a décalage in the development of conceptual and executive processes underlying categorical flexibility.
Lifespan differences in cortical dynamics of auditory perception
Authors: Müller Viktor , Gruber Walter , Klimesch Wolfgang , Lindenberger Ulman
Published: April 2009

Using electroencephalographic recordings (EEG), we assessed differences in oscillatory cortical activity during auditory‐oddball performance between children aged 9–13 years, younger adults, and older adults. From childhood to old age, phase synchronization increased within and between electrodes, whereas whole power and evoked power decreased. We conclude that the cortical dynamics of perceptual processing undergo substantial reorganization from childhood to old age, and discuss possible reasons for the inverse relation between age trends in phase synchronization and power, such as lifespan differences in neural background activity, or a lifespan shift from rate coding in children to temporal coding in adults.
Language‐specific stress perception by 9‐month‐old French and Spanish infants
Authors: Skoruppa Katrin , Pons Ferran , Christophe Anne , Bosch Laura , Dupoux Emmanuel , Sebastián‐Gallés Núria , Limissuri Rita Alves , Peperkamp Sharon
Published: April 2009

During the first year of life, infants begin to have difficulties perceiving non‐native vowel and consonant contrasts, thus adapting their perception to the phonetic categories of the target language. In this paper, we examine the perception of a non‐segmental feature, i.e. stress. Previous research with adults has shown that speakers of French (a language with fixed stress) have great difficulties in perceiving stress contrasts (

Dupoux, Pallier, Sebastián & Mehler, 1997

), whereas speakers of Spanish (a language with lexically contrastive stress) perceive these contrasts as accurately as segmental contrasts. We show that language‐specific differences in the perception of stress likewise arise during the first year of life. Specifically, 9‐month‐old Spanish infants successfully distinguish between stress‐initial and stress‐final pseudo‐words, while French infants of this age show no sign of discrimination. In a second experiment using multiple tokens of a single pseudo‐word, French infants of the same age successfully discriminate between the two stress patterns, showing that they are able to perceive the acoustic correlates of stress. Their failure to discriminate stress patterns in the first experiment thus reflects an inability to process stress at an abstract, phonological level.
THE IMMACULATE BODY IN THE SISTINE CEILING
Authors: BUTLER KIM E.
Published: April 2009

A new reading of textual evidence roots the imagery of Michelangelo's Sistine Ceiling frescoes in contemporary theological commitment to the doctrine of the Immaculate Conception. The cluster of abstract metaphors contained in a sermon written by Pope Sixtus IV, dedicated to the Immaculate Conception, and the liturgical and devotional texts the sermon inspired, offers foundational source material for the ceiling programme. It is proposed that such an Immaculacy message exists alongside and mutually supports Incarnationist and Eucharistic ones, all rooted in a metaphor of bodily perfection that Michelangelo ‘figures’ at the level of gender as well.
HERRI MET DE BLES'S WAY TO CALVARY: A SILENIC LANDSCAPE
Authors: WEEMANS MICHEL
Published: April 2009

Herri met de Bles's Way to Calvary is a ‘visual exegesis’ closely related to Erasmus' exegetical theory. Erasmus conceived exegesis as a dialectical tension between the two extremes senses of the Biblical text (literal and spiritual), mediated by the figure of allegory. Not only does allegory designate Christ, but also the veiled language of the Scriptures and Christ's constant use of enigmatic, paradoxical and obscure figures. Interpreted in the light of the Erasmian exegetical model, and related to the figure of the Silenus popularized by the Christian humanist, Bles's landscape reveals the presence of a specific pictorial phenomenon of crypto‐anthropomorphosis. This landscape of a procession following a tiny mocked Christ‐Silenus, is also a portrait of a gigantic rocky mocking Silenus. This pictorial device is an integral part of the exegetical logic of the picture and is instrumental in inviting the beholder to conversion.
Using Speakers' Referential Intentions to Model Early Cross-Situational Word Learning
Authors: Frank Michael C. , Goodman Noah D. , Tenenbaum Joshua B.
Published: April 2009

Word learning is a “chicken and egg” problem. If a child could understand speakers' utterances, it would be easy to learn the meanings of individual words, and once a child knows what many words mean, it is easy to infer speakers' intended meanings. To the beginning learner, however, both individual word meanings and speakers' intentions are unknown. We describe a computational model of word learning that solves these two inference problems in parallel, rather than relying exclusively on either the inferred meanings of utterances or cross-situational word-meaning associations. We tested our model using annotated corpus data and found that it inferred pairings between words and object concepts with higher precision than comparison models. Moreover, as the result of making probabilistic inferences about speakers' intentions, our model explains a variety of behavioral phenomena described in the word-learning literature. These phenomena include mutual exclusivity, one-trial learning, cross-situational learning, the role of words in object individuation, and the use of inferred intentions to disambiguate reference.
When Intentions Go Public
Authors: Gollwitzer Peter M. , Sheeran Paschal , Michalski Verena , Seifert Andrea E.
Published: April 2009

Based on Lewinian goal theory in general and self-completion theory in particular, four experiments examined the implications of other people taking notice of one's identity-related behavioral intentions (e.g., the intention to read law periodicals regularly to reach the identity goal of becoming a lawyer). Identity-related behavioral intentions that had been noticed by other people were translated into action less intensively than those that had been ignored (Studies 1–3). This effect was evident in the field (persistent striving over 1 week's time; Study 1 ) and in the laboratory (jumping on opportunities to act; Studies 2 and 3), and it held among participants with strong but not weak commitment to the identity goal ( Study 3 ). Study 4 showed, in addition, that when other people take notice of an individual's identity-related behavioral intention, this gives the individual a premature sense of possessing the aspired-to identity.
Approximate Bayesian Inference for Latent Gaussian models by using Integrated Nested Laplace Approximations
Authors: Rue Håvard , Martino Sara , Chopin Nicolas
Published: April 2009

Structured additive regression models are perhaps the most commonly used class of models in statistical applications. It includes, among others, (generalized) linear models, (generalized) additive models, smoothing spline models, state space models, semiparametric regression, spatial and spatiotemporal models, log-Gaussian Cox processes and geostatistical and geoadditive models. We consider approximate Bayesian inference in a popular subset of structured additive regression models, latent Gaussian models, where the latent field is Gaussian, controlled by a few hyperparameters and with non-Gaussian response variables. The posterior marginals are not available in closed form owing to the non-Gaussian response variables. For such models, Markov chain Monte Carlo methods can be implemented, but they are not without problems, in terms of both convergence and computational time. In some practical applications, the extent of these problems is such that Markov chain Monte Carlo sampling is simply not an appropriate tool for routine analysis. We show that, by using an integrated nested Laplace approximation and its simplified version, we can directly compute very accurate approximations to the posterior marginals. The main benefit of these approximations is computational: where Markov chain Monte Carlo algorithms need hours or days to run, our approximations provide more precise estimates in seconds or minutes. Another advantage with our approach is its generality, which makes it possible to perform Bayesian analysis in an automatic, streamlined way, and to compute model comparison criteria and various predictive measures so that models can be compared and the model under study can be challenged.
THE CRISIS OF HISTORICISM: AND THE PROBLEM OF HISTORICAL MEANING IN NEW TESTAMENT STUDIES
Authors: McLEAN B. H.
Published: April 2009

The rapid rise of varieties of historicism in Germany, during the mid‐ to late‐nineteenth century, and subsequently in England and America, resulted in a radical transformation of the principles of coherence and methods of analysis within biblical studies.1This paper will argue that the foundational ‘subject/object’ metaphysics of historicism has been subverted over the past century. For this reason, historical positivism should no longer be accorded the status of ‘normative paradigm’ and ‘gatekeeper’ over and against other interpretive approaches. This paper next lays out five principles for a renewed practice of historical inquiry. It argues, first, that historical inquiry continues to serve a vital function within biblical studies in its ability to call attention to historical difference, and, thereby, to contribute to a strategy of resistance to ideology and to totalizing theories; second, that the traditional appeal to historical ‘context’ and ‘author’ in the interpretation of texts continues to be a useful practice – despite the provisional and constructed nature of both – as a way of taking into account extra‐lingual reference and of avoiding presentism; third, that the substitution of new ‘grand narratives’ of Christian origins in place of the (quasi‐theological) ‘historical’ narrative of traditional Christianity – under the claim of historical objectivity – should be abandoned because the very concept of ‘origins’ is the result of a literalizing of a metaphor. Such totalizing narratives always reduce history's inherent polycentricism. Fourth, I will argue that the continued use of historicism in the antiquarian attempt to reconstruct the past, disconnected from both a quest for social justice and a desire for personal self‐creation, represents a form of thought that alienates scholars from themselves and from their real material contexts. Finally, and following on the previous point, this paper submits that the practice of historical analysis has an ethical dimension by virtue of the fact that the personhood of the biblical historian is indissolubly linked to other dimensions of life including the social and ethical aspects of life. These added dimensions complicate the making of choices, which is implicit within all practices of interpretation. These five principles are here suggested as points of departure for the reconceptualization of the scope and function of historical inquiry within the discipline of New Testament studies.
Can An ‘Estimation Factor’ Help Explain Cross‐Sectional Returns?
Authors: Lundtofte Frederik
Published: April 2009

Abstract:  We show in a theoretical model that the expected excess return on any asset depends on its covariance not only with the market portfolio, but also with changes in the representative agent's estimate. We test our model using GMM and compare it to the CAPM. The results suggest that adding an ‘estimation factor’ to the CAPM helps explain cross‐sectional returns and that, unconditionally, this estimation factor carries a negative risk premium.