P-n junction organic photovoltaics fabricated by all solution processing

We have prepared p-n junction organic photovoltaic cells using an all solution processing method with poly(3-hexylthiophene) (P3HT) as the donor and phenyl-C 61-butyric acid methyl ester (PCBM) as the acceptor. Interdigitated donor/acceptor interface morphology was observed in the device processed with the lowest boiling point solvent for PCBM used in this study. The influences of different solvents on donor/acceptor morphology and respective device performance were investigated simultaneously. The best device obtained had characteristically rough interface morphology with a peak to valley value ∼15 nm. The device displayed a power conversion efficiency of 1.78%, an open circuit voltage (V oc) 0.44 V, a short circuit current density (J sc) 9.4 mA/cm 2 and a fill factor 43%.

Remixing Canadian copyright law: A review essay on'An Emerging Intellectual Property Paradigm','Canadian Copyright: A Citizen's Guide'; and'RiP!: A Remix Manifesto', Prometheus, Vol. 27 (3), p. 297-305

In her album, Hymns of the 49th Parallel, the chanteuse K.D. Lang pays tribute to a series of great Canadian songwriters—such as Neil Young, Leonard Cohen, Joni Mitchell and Jane Siberry. In a similar spirit of celebration, this review essay pays homage to a number of recent texts and films dealing with Canadian intellectual property. First, it considers Ysolde Gendreau’s collection, An Emerging Intellectual Property Paradigm: Perspectives from Canada. Second, this essay looks at Laura Murray and Samuel Trosow’s manual, Canadian Copyright: A Citizen’s Guide. Finally, this review evaluates Brett Gaylor’s documentary, RiP! A Remix Manifesto. The three works share certain affinities—a spirit of scepticism about the legitimacy and the efficacy of existing networks of law, policy and bureaucracy; a populist interest in the impact of intellectual property on the everyday lives of citizens, creators and consumers; a passion for human rights; and a melioristic desire for sensible law reform of copyright law and related regimes of intellectual property.

Prognostic value of biochemical liver parameters in neonatal sepsis-associated cholestasis

Aims The aim of the study was to evaluate the significance of total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyltransferase (GGT) for predicting outcome in sepsis-associated cholestasis. Methods: A retrospective cohort review of the hospital records was performed in 181 neonates admitted to the Neonatal Care Unit. A comparison was performed between subjects with low and high liver values based on cut-off values from ROC analysis. We defined poor prognosis to be when a subject had prolonged cholestasis of more than 3.5 months, developed severe sepsis, septic shock or had a fatal outcome. Results: The majority of the subjects were male (56%), preterm (56%) and had early onset sepsis (73%). The poor prognosis group had lower initial values of GGT compared with the good prognosis group (P = 0.003). Serum GGT (cut-off value of 85.5 U/L) and AST (cut-off value of 51 U/L) showed significant correlation with the outcome following multivariate analysis. The odds ratio (OR) of low GGT and high AST were OR 4.3 (95% CI:1.6 to11.8) and OR 2.9 (95% CI:1.1 to 8), respectively, for poor prognosis. In subjects with normal AST values, those with low GGT value had relative risk of 2.52 (95% CI:1.4 to 3.5) for poorer prognosis compared with those with normal or high GGT. Conclusion: Serum GGT and AST values can be used to predict the prognosis of patients with sepsis-associated cholestasis

Cough and reflux esophagitis in children: their co-existence and airway cellularity

Background There are no prospective studies that have examined for chronic cough in children without lung disease but with gastroesophageal reflux (GER). In otherwise healthy children undergoing flexible upper gastrointestinal endoscopy (esophago-gastroscopy), the aims of the study were to (1) define the frequency of cough in relation to symptoms of GER, (2) examine if children with cough and reflux esophagitis (RE) have different airway cellularity and microbiology in bronchoalveolar lavage (BAL) when compared to those without. Methods Data specific for chronic cough (>4-weeks), symptoms of GER and cough severity were collected. Children aged <16-years (n = 150) were defined as 'coughers' (C+) if a history of cough in association with their GER symptoms was elicited before BAL were obtained during elective esophago-gastroscopy. Presence of esophagitis on esophageal biopsies was considered reflux esophagitis positive (E+). Results C+ (n = 69) were just as likely as C- (n = 81) to have esophagitis, odds ratio 0.87 (95%CI 0.46, 1.7). Median neutrophil percentage in BAL was significantly different between groups; highest in C+E- (7, IQR 28) and lowest in C-E+ (5, IQR 6). BAL positive bacterial culture occurred in 20.7% and were more likely present in current coughers (OR 3.37, 95%CI 1.39, 8.08). Airway neutrophilia (median 20%, IQR 34) was significantly higher in those with BAL positive bacterial cultures than those without (5%, 4; p = 0.0001). Conclusion In children without lung disease, the common co-existence of cough with symptoms of GER is independent of the occurrence of esophagitis. Airway neutrophilia when present in these children is more likely to be related to airway bacterial infection and not to esophagitis.

Conversion of n-type CuTCNQ into p-type nitrogen-doped CuO and the implication for room temperature gas sensing

Sensors to detect toxic and harmful gases are usually based on metal oxides that are operated at elevated temperature. However, enabling gas detection at room temperature (RT) is a significant ongoing challenge. Here, we address this issue by demonstrating that microrods of semiconducting CuTCNQ (TCNQ=7,7,8,8-tetracyanoquinodimethane) with nanostructured features can be employed as conductometric gas sensors operating at 50°C for detection of oxidizing and reducing gases such as NO2 and NH3. The sensor is evaluated at RT and up to 200°C. It was found that CuTCNQ is transformed into a N-doped CuO material with p-type conductivity when annealed at the maximum temperature. This is the first time that such a transformation, from a semiconducting charge transfer material into a N-doped metal oxide is detected. It is shown here that both the surface chemistry and the type of majority charge carrier within the sensing layer is critically important for the type of response towards oxidizing and reducing gases. A detailed physical description of NO2 and NH3 sensing mechanism at CuTCNQ and N-doped CuO is provided to explain the difference in the response. For the N-doped CuO sensor, a detection limit of 1 ppm for NO2 and 10 ppm for NH3 are achieved.

Evaluation of a mobile phone image-based dietary assessment method in adults with type 2 diabetes

Photographic and image-based dietary records have limited evidence evaluating their performance and use among adults with a chronic disease. This study evaluated the performance of a mobile phone image-based dietary record, the Nutricam Dietary Assessment Method (NuDAM), in adults with type 2 diabetes mellitus (T2DM). Criterion validity was determined by comparing energy intake (EI) with total energy expenditure (TEE) measured by the doubly-labelled water technique. Relative validity was established by comparison to a weighed food record (WFR). Inter-rater reliability was assessed by comparing estimates of intake from three dietitians. Ten adults (6 males, age=61.2±6.9 years, BMI=31.0±4.5 kg/m2) participated. Compared to TEE, mean EI was under-reported using both methods, with a mean ratio of EI:TEE 0.76±0.20 for the NuDAM and 0.76±0.17 for the WFR. There was moderate to high correlations between the NuDAM and WFR for energy (r=0.57), carbohydrate (r=0.63, p<0.05), protein (r=0.78, p<0.01) and alcohol (rs=0.85, p<0.01), with a weaker relationship for fat (r=0.24). Agreement between dietitians for nutrient intake for the 3-day NuDAM (ICC = 0.77-0.99) was marginally lower when compared with the 3-day WFR (ICC=0.82-0.99). All subjects preferred using the NuDAM and were willing to use it again for longer recording periods.

Incorporation of human recombinant tropoelastin into silk fibroin membranes with the view to repairing Bruch’s membrane

Bombyx mori silk fibroin membranes provide a potential delivery vehicle for both cells and extracellular matrix (ECM) components into diseased or injured tissues. We have previously demonstrated the feasibility of growing retinal pigment epithelial cells (RPE) on fibroin membranes with the view to repairing the retina of patients afflicted with age-related macular degeneration (AMD). The goal of the present study was to investigate the feasibility of incorporating the ECM component elastin, in the form of human recombinant tropoelastin, into these same membranes. Two basic strategies were explored: (1) membranes prepared from blended solutions of fibroin and tropoelastin; and (2) layered constructs prepared from sequentially cast solutions of fibroin, tropoelastin, and fibroin. Optimal conditions for RPE attachment were achieved using a tropoelastin-fibroin blend ratio of 10 to 90 parts by weight. Retention of tropoelastin within the blend and layered constructs was confirmed by immunolabelling and Fourier-transform infrared spectroscopy (FTIR). In the layered constructs, the bulk of tropoelastin was apparently absorbed into the initially cast fibroin layer. Blend membranes displayed higher elastic modulus, percentage elongation, and tensile strength (p < 0.01) when compared to the layered constructs. RPE cell response to fibroin membranes was not affected by the presence of tropoelastin. These findings support the potential use of fibroin membranes for the co-delivery of RPE cells and tropoelastin.

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10 -11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.

Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.66 x 10-10, odds ratio (OR) = 0.74, 95% CI:0.68-0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6×10-4. OR = 0.86 (95% CI:0.79-0.93); rs744166, P = 2.6×10-5, OR = 0.84 (95% CI:0.77-0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2×10-5, OR = 0.65 (95% CI:0.54-0.79)), and further associations were detected for IL12B (rs10045431, P = 5.261025, OR = 0.83 (95% CI:0.76-0.91)), CDKAL1 (rs6908425, P = 1.1×10-4, OR = 0.82 (95% CI:0.74-0.91)), LRRK2/MUC19 (rs11175593, P = 9.9×10-5, OR = 1.92 (95% CI: 1.38-2.67)), and chr13q14 (rs3764147, P = 5.9×10-4, OR = 1.19 (95% CI: 1.08-1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases.

The MS risk allele of CD40 is associated with reduced cell-membrane bound expression in antigen presenting cells: Implications for gene function

Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS. © 2015 Field et al.

Morphometric analysis of the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis using low dose computerized tomography

Introduction. The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). Methods. In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. Results. The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). Conclusion. Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Using low dose computerized tomography to morphometrically analyse the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis

INTRODUCTION The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). METHODS In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. RESULTS The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). CONCLUSION Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis

Objectives - It has long been suspected that susceptibility to ankylosing spondylitis (AS) is influenced by genes lying distant to the major histocompatibility complex. This study compares genetic models of AS to assess the most likely mode of inheritance, using recurrence risk ratios in relatives of affected subjects. Methods - Recurrence risk ratios in different degrees of relatives were determined using published data from studies specifically designed to address the question. The methods of Risch were used to determine the expected recurrence risk ratios in different degrees of relatives, assuming equal first degree relative recurrence risk between models. Goodness of fit was determined by χ2 comparison of the expected number of affected subjects with the observed number, given equal numbers of each type of relative studied. Results - The recurrence risks in different degrees of relatives were: monozygotic (MZ) twins 63% (17/27), first degree relatives 8.2% (441/5390), second degree relatives 1.0% (8/834), and third degree relatives 0.7% (7/997). Parent-child recurrence risk (7.9%, 37/466) was not significantly different from the sibling recurrence risk (8.2%, 404/4924), excluding a significant dominance genetic component to susceptibility. Poor fitting models included single gene, genetic heterogeneity, additive, two locus multiplicative, and one locus and residual polygenes (χ2 > 32 (two degrees of freedom), p < 10-6 for all models). The best fitting model studied was a five locus model with multiplicative interaction between loci (χ2 = 1.4 (two degrees of freedom), p = 0.5). Oligogenic multiplicative models were the best fitting over a range of population prevalences and first degree recurrence risk rates. Conclusions - This study suggests that of the genetic models tested, the most likely model operating in AS is an oligogenic model with predominantly multiplicative interaction between loci.

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom

Objective - To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. Methods - HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. Results - The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10-99). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10-5), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HkA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. Conclusion - HLA-B27 and -B60 are associated with susceptibility to AS, but differences in BLA-B27 subtype do not affect susceptibility to AS in this white population.