Transposed-letter priming effects in reading aloud words and nonwords

A masked nonword prime generated by transposing adjacent inner letters in a word (e.g., jugde) facilitates the recognition of the target word (JUDGE) more than a prime in which the relevant letters are replaced by different letters (e.g., junpe). This transposed-letter (TL) priming effect has been widely interpreted as evidence that the coding of letter position is flexible, rather than precise. Although the TL priming effect has been extensively investigated in the domain of visual word recognition using the lexical decision task, very few studies have investigated this empirical phenomenon in reading aloud. In the present study, we investigated TL priming effects in reading aloud words and nonwords and found that these effects are of equal magnitude for the two types of items. We take this result as support for the view that the TL priming effect arises from noisy perception of letter order within the prime prior to the mapping of orthography to phonology.6 page(s

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

Plantar plate pathology is associated with erosive disease in the painful forefoot of patients with rheumatoid arthritis

Background: Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges. Together with the transverse metatarsal ligament they prevent splaying of the forefoot and subluxation of the MTP joints. Damage to the plantar plates is a plausible mechanism therefore, through which the forefoot presentation, commonly described as ‘walking on pebbles’, may develop in patients with RA. The aims of this study were to investigate the relationship between plantar plate pathology and clinical, biomechanical and plain radiography findings in the painful forefoot of patients with RA. Secondly, to compare plantar plate pathology at the symptomatic lesser (2nd-5th) MTP joints in patients with RA, with a group of healthy age and gender matched control subjects without foot pain. Methods: In 41 patients with RA and ten control subjects the forefoot was imaged using 3T MRI. Intermediate weighted fat-suppressed sagittal and short axis sequences were acquired through the lesser MTP joints. Images were read prospectively by two radiologists and consensus reached. Plantar plate pathology in patients with RA was compared with control subjects. Multivariable multilevel modelling was used to assess the association between plantar plate pathology and the clinical, biomechanical and plain radiography findings. Results: There were significant differences between control subjects and patients with RA in the presence of plantar plate pathology at the lesser MTP joints. No substantive or statistically significant associations were found between plantar plate pathology and clinical and biomechanical findings. The presence of plantar plate pathology was independently associated with an increase in the odds of erosion (OR = 52.50 [8.38–326.97], p < 0.001). Conclusion: The distribution of plantar plate pathology at the lesser MTP joints in healthy control subjects differs to that seen in patients with RA who have the consequence of inflammatory disease in the forefoot. Longitudinal follow-up is required to determine the mechanism and presentation of plantar plate pathology in the painful forefoot of patients with RA

Resequencing of genes for transforming growth factor β1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy

BACKGROUND: Diabetic nephropathy is the leading cause of end stage renal failure in the western world. There is substantial epidemiological evidence supporting a genetic predisposition to diabetic nephropathy, however the exact molecular mechanisms remain unknown. Transforming growth factor (TGFβ1) is a crucial mediator in the pathogenesis of diabetic nephropathy. METHODS: We investigated the role of five known single nucleotide polymorphisms (SNPs) in the TGFB1 gene for their association with diabetic nephropathy in an Irish, type 1 diabetic case (n = 272) control (n = 367) collection. The activity of TGFβ1 is facilitated by the action of type 1 and type 2 receptors, with both receptor genes (TGFBR1 and TGFBR2) shown to be upregulated in diabetic kidney disease. We therefore screened TGFBR1 and TGFBR2 genes for genomic variants using WAVE™ (dHPLC) technology and confirmed variants by direct capillary sequencing. Allele frequencies were determined in forty-eight healthy individuals. Data for all SNPs was assessed for Hardy Weinberg equilibrium, with genotypes and allele frequencies compared using the χ(2 )test for contingency tables. Patterns of linkage disequilibrium were established and common haplotypes estimated. RESULTS: Fifteen variants were identified in these genes, seven of which are novel, and putatively functional SNPs were subsequently genotyped using TaqMan™, Invader™ or Pyrosequencing(® )technology. No significant differences (p > 0.1) were found in genotype or allele distributions between cases and controls for any of the SNPs assessed. CONCLUSION: Our results suggest common variants in TGFB1, TGFBR1 and TGFBR2 genes do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture

Purpose: To evaluate the ability of human airway epithelial cell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo. Method: The permeability of seven compounds selected to possess a range of lipophilicity was measured in two airway cell lines (Calu-3 and 16HBE14o-), in normal human bronchial epithelial (NHBE) cells and using a simple isolated perfused lungs (IPL) technique. Data from the cell layers and ex vivo lungs were compared to published absorption rates from rat lungs measured in vivo. Results: A strong relationship was observed between the logarithm of the in vivo absorption half-life and the absorption half-life in the IPL (r = 0.97; excluding formoterol). Good log-linear relationships were also found between the apparent first-order absorption rate in vivo and cell layer permeability with correlation coefficients of 0.92, 0.93, 0.91 in Calu-3, 16HBE14o- and NHBE cells, respectively. Conclusion: The simple IPL technique provided a good prediction of drug absorption from the lungs, making it a useful method for empirical screening of drug absorption in the lungs. Permeability measurements were similar in all the respiratory epithelial cell models evaluated, with Calu-3 having the advantage for routine permeability screening purposes of being readily availability, robust and easy to culture

A behavioral database for masked form priming

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe–CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word’s susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments

Three allele combinations associated with Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. METHODS: 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. RESULTS: We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. CONCLUSION: These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles

Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial

Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse. Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis. Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary care centers in England. Participants: Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point. Intervention: Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care. Measurements: The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of −0.16 point (95% CI, −0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group). Limitation: Hydroxychloroquine dosage restrictions may have reduced efficacy. Conclusion: Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis