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We use a Monte Carlo model to predict the effect of composition, domain size, and energetic disorder upon the mobility of carriers in an organic donor-acceptor blend. These simulations show that, for the changes in local morphology expected within the thickness of a typical bulk heterojunction photovoltaic device, changes in mobility of more than an order of magnitude are expected. The impact of nonuniform mobility upon space-charge-limited diode and photovoltaic (PV) device performance is examined using a drift-diffusion model. The current passing through a space-charge-limited diode is shown to depend upon the position of the layers with differing mobility. Accurate modeling of the current in such devices can only be achieved using a drift-diffusion model incorporating nonuniform mobility. Inserting a 20 nm thick layer in which the mobility is less by one order of magnitude than in the rest of the 70 nm thick PV device reduced the device efficiency by more than 20%. Therefore it seems vital to exert a high degree of control over the morphology throughout the entire blend PV device, otherwise potential PV performance may be lost. [ABSTRACT FROM AUTHOR]

A Monte Carlo model is used to examine geminate pair dissociation in polymer-polymer photovoltaic devices. It is found that increasing one or both carrier mobilities aids geminate separation yield ηGS particularly at low fields. This, in turn, leads to improved maximum power output from polymer-polymer blend photovoltaics, even when carrier mobilities are unbalanced by a factor of 10. The dynamic behaviors of geminate charges that eventually separate and recombine are examined for the first time. It is shown that geminate pairs in a bilayer become effectively free when separated by ∼4 nm, which is far smaller than the thermal capture radius of 16 nm here. This may lead one to expect that ηGS would not be limited by the separation allowed by the morphology once the domain size has increased above 4 nm. In fact it is found that ηGS in a blend improves continuously as the average domain size increases from 4 to 16 nm. We show that although a small degree of separation may be available in a blend, the limited number of possible routes to further separation makes charge pairs in blends more susceptible to recombination than charge pairs in a bilayer. [ABSTRACT FROM AUTHOR]

We present a Monte Carlo model of carrier separation and recombination in nanostructured organic photovoltaic (OPV) devices which takes into account all electrostatic interactions, energetic disorder, and polaronic effects. This permits a detailed analysis of the strong morphology dependence of carrier collection efficiency. We find that performance is determined both by the orientation of the heterojunction relative to the external electric field as well as by carrier confinement due to polymer intermixing. The model predicts that an idealized interdigitated structure could achieve overall efficiencies twice as high as blends. The model also reproduces the weakly sublinear intensity dependence of short-circuit photocurrent (ISC) seen in experiment. We show that this is not the result of space-charge effects but of bimolecular recombination. Disconnected islands of polymer in coarser blends result in bimolecular recombination even at low intensities and should therefore be minimized. By including a microscopic description of dark injection, the model can describe the full current-voltage (J-V) characteristics of different OPV structures. We examine the effect of morphology, intensity, mobility, and recombination rate on key parameters such as short-circuit current, open-circuit voltage (VOC), and fill factor (FF). The model reproduces the intensity-dependent contribution to VOC in a bilayer above that of a blend observed in experiment. We find that performance in both bilayers and blends is very sensitive to the recombination rate across the heterojunction. The model also predicts a striking dependence of performance on mobility. Indeed it is shown that a tenfold increase in mobility dramatically improves ISC and FF and doubles the maximum power output in a bilayer device. As well as informing routes for improving device performance, the model also offers an improved microscopic understanding of OPV operation. [ABSTRACT FROM AUTHOR]

A simple Monte Carlo model is used to simulate the avalanche process in a multiplication region which incorporates a heterojunction, intended to introduce localization into the ionization process and reduce excess avalanche noise. The results are compared with those of models where the ionization path length distribution is represented by an exponential decay, displaced from the origin by a ballistic dead space. While the latter results depend sensitively on the arbitrary choice of scheme used to evaluate the model parameters, they agree remarkably well with Monte Carlo, considering the simplicity of the model. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

An outdoor grazing study on kale was conducted with pregnant, nonlactating (dry) dairy cows over a 42‐day winter grazing period commencing 9 June 2008. Kale treatments consisted of two kale cultivars varying in leaf:stem proportion ("Regal," a leafy variety and "Caledonian," a stemmy variety) and two sowing dates (8 November and 15 December). Measurements were made for dry‐matter (DM) utilization, apparent DM intake, liveweight gain and changes in body condition score (BCS) for a total of 120 cows allocated to three replicate groups of the four factorial treatments. Cows were offered a daily allowance of 10 kg DM/cow of kale and 2.2 kg DM/cow of straw. Pregrazing DM yield was higher for kale sown in November (16,517 kg DM/ha) than December (13,867 kg DM/ha), but was unaffected by cultivar (average 15,192 kg DM/ha). "Regal" kale had a higher percentage of leaf compared with "Caledonian" (33.6% vs. 25.6%), lower content of NDF (32.4% vs. 34.1%), but similar metabolizable energy content (12.1 MJ/kg DM for both) in the whole plant. Despite the differences in pregrazing DM yield and forage quality among treatments, no differences were found in DM utilization (between 88.5% and 90.2%), apparent DM intake (between 9.4 and 9.6 kg DM/cow.day), liveweight gain (between 0.53 and 0.67 kg/cow.day) and BCS gain (between 0.43 and 0.46 unit/cow over 42 days). Manipulation of kale yield and quality through choice of cultivar and sowing date had no effect on the performance of pregnant, nonlactating dairy cows. [ABSTRACT FROM AUTHOR]

Avalanche breakdown voltage has been measured in a series of AlxGa1-xAs (0

Objective. To compare scores for the Leeds enthesitis index in psoriatic arthritis and rheumatoid arthritis using clinical assessment and ultrasonography (US). Design. Swelling and tenderness of the enthesis was assessed at six sites: lateral epicondyles of humerus (LE), medial condyles of femur (MC), and the insertion of the Achilles tendon (AT). US assessed "inflammatory activity" (power Doppler signal, oedema, tendon thickening, and bursal swelling) and "damage" (erosions and enthesophytes). Results. 94 patients were included, 71 with PsA and 23 with RA. The patients with RA were significantly older (PsA 47.6 years; RA 62.6 years; (mean difference in ages =15.0 years, 95% CI 9.3-20.7 years)). US scores were higher in RA at the LE, significantly so for the "damage" scores. No differences between RA and PsA were seen at the other sites. As a result, the odds ratio for PsA, given an US score above the median, was 0.41 (0.13-1.03). However, using the clinical score, the odds ratio for PsA was 2.16 (0.81-5.70). Conclusions. Although clinical scores of enthesitis are greater in PsA compared to RA, US enthesitis scores did not distinguish between RA and PsA. This may in part be due to more frequent juxta-articular involvement in RA and in part due to the older age of the subjects with RA. [ABSTRACT FROM AUTHOR]

Aims The maternally inherited mt3243A > G mutation is associated with a variable clinical phenotype including diabetes and deafness (MIDD). We aimed to determine the prevalence and clinical characteristics of MIDD in a large South Asian cohort of young adult-onset diabetic patients from Sri Lanka. Methods DNA was available from 994 subjects (age of diagnosis 16–40 years, age at recruitment ≤ 45 years). Mutation screening was performed using a QRT-PCR method on an ABI 7900HT system using sequence-specific probes. Samples with heteroplasmy ≥ 5.0% were considered positive. Results Nine (four males) mutation-positive subjects were identified (prevalence 0.9%). They were diagnosed at a younger age (25.9 ± 4.8 years vs. 31.9 ± 5.6 years, P = 0.002) and were lean (body mass index [BMI] 18.7 ± 2.7 kg/m2 vs. 24.7 ± 4.0 kg/m2, P < 0.001) compared to NMCs. One mutation-positive subject (11.1%) had metabolic syndrome, compared to 633 (64.3%) of NMCs. Insulin therapy within 6 months of diagnosis was used in four (44.0%) carriers compared to 6.9% of NMCs ( P = 0.002). Combined screening criteria of any two of maternal history of diabetes, personal history of hearing impairment and family history of hearing impairment only identified five (55%) of the carriers, with a positive predictive value of 7.4%. Conclusions The prevalence of mt3243A > G mutation among young adult-onset diabetic subjects from Sri Lanka was 0.9%. Our study demonstrates that a maternal family history of diabetes and either a personal and/or family history of deafness only distinguish half of patients with MIDD from Sri Lankan subjects with young-onset diabetes. [ABSTRACT FROM AUTHOR]

The author comments on a study on kouprey by G. Galbreath and colleagues. It examines if kouprey Bos sauveli is a feral hybrid form with banteng Bos javanicus and zebu Bos indicus ancestry. Moreover, it asserts that kouprey appear to be homogenous. Observations on the appearance, size range and colour of kouprey are presented.

The mean avalanche current impulse response in an avalanche photodiode exhibits an initial transient and then grows or decays, above or below breakdown, at exponential rates which depend only on the probability distributions of the electron and hole ionization events. The process continues while the electric field profile remains unchanged by the applied bias or the evolving space charge. Below breakdown the distribution in the avalanche duration also exhibits an initial transient and then decays exponentially at the same rate as the mean current. Below breakdown the standard deviation in current decays exponentially at one half of the rate of the mean current, while above breakdown it grows exponentially at the same rate as the mean. Consequently the jitter in a Geiger mode avalanche photodiode becomes independent of time after the initial transients have decayed away. This behavior is quite general and independent of the electric field profile or of the presence of heterojunctions in the multiplication region. Using simple models for carrier transport we find the predicted enhancement in the velocity to ionization of those carriers which ionise shortly after their ballistic dead space significantly speeds up the avalanche dynamics in short devices. [ABSTRACT FROM AUTHOR]

Avalanche multiplication and excess noise have been measured on a series of AlxGa1-xAs-GaAs and GaAs-AlxGa1-xAs (x = 0.3, 0.45, and 0.6) single heterojunction p+-i-n+ diodes. In some devices excess noise is lower than in equivalent homojunction devices with avalanche regions composed of either of the constituent materials, the heterojunction with x = 0.3 showing the greatest improvement. Excess noise deteriorates with higher values of x because of the associated increase in hole ionization in the AlxGa1-xAs layer. It also depends critically upon the carrier injection conditions and Monte Carlo simulations show that this dependence results from the variation in the degree of noisy feedback processes on the position of the injected carriers. [ABSTRACT FROM AUTHOR]

The temperature dependence of electron and hole impact ionization in gallium arsenide (GaAs) has been determined from photomultiplication measurements at temperatures between 20 K and 500 K. It is found that impact ionization is suppressed by increasing temperature because of the increase in phonon scattering. Temperature variations in avalanche multiplication are shown to decrease with decreasing avalanching region width, and the effect is interpreted in terms of the reduced phonon scattering in the correspondingly reduced ionization path length. Effective electron and hole ionization coefficients are derived and are shown to predict accurately multiplication characteristics and breakdown voltage as a function of temperature in p[sup +] in[sup +] diodes with i-regions as thin as 0.5 µm. [ABSTRACT FROM AUTHOR]

The article presents the abstract of the paper "Species and Subspecies of Mangabeys: A Craniometric Approach," by C.P. Groves and M. Hawkins to be presented at the 21st Congress of the International Primatological Society in Entebbe, Uganda from June 25-30, 2006.

Anterior cruciate ligament (ACL) injuries occur most commonly in individuals between 18 and 29 years of age and are strongly correlated with sporting activity, with female athletes being at higher risk of ACL rupture than their male counterparts. ACL reconstruction is one of the most frequently performed procedures in orthopaedic surgery, having a reported incidence of 85 per 100,000 head of population in the at-risk age group. Subsequent graft failure is most commonly caused by recurrent trauma, followed by tunnel malpositioning, although the choice of graft type does not appear to affect outcome. The Danish ACL registry reported that ACL revisions accounted for 7.5% of all ACL reconstruction surgery performed between 2005 and 2008. Revision of ACL reconstruction is recognized to carry a worse outcome than primary reconstruction. Preoperative imaging has become a crucial part of surgical planning in these patients, with great reliance placed on computed tomography (CT). The radiologist should be able to recognize the types of primary repair and must be able to assess for the complications of primary surgery, such as tunnel malpositioning, tunnel widening, and fixation device failure. Revision is commonly a two-stage procedure with bone grafting of the tunnels prior to the definitive ligament repair. The radiologist should be able to asses for adequate bone graft incorporation. The purpose of this article is to present a review of the use of CT in the management of ACL revision surgery with examples of commonly used fixation devices; complications, such as tunnel widening and tunnel malpositioning; and bone graft incorporation. [Copyright &y& Elsevier]

A letter to the editor in response to "Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit," by S. A. Hearnshaw, R. F. Logan, D. Lowe et al. that was published a previous issue in 2011.

A response by C. Groves, J. Cao, and C. Zhang is presented to a letter to the editor regarding the article "An unsung carbon sink" by C. Larson from the November 18, 2011 issue.

Post-traumatic myositis ossificans is a benign condition of heterotopic ossification of unknown aetiology which typically is related to trauma from a single blow or repeated episodes of microtrauma. A case of myositis ossificans that developed after hamstring autograft harvest for an open cruciate ligament and posterolateral corner reconstruction is described, a previously unrecognised complication of this procedure. [ABSTRACT FROM AUTHOR]

Characterisation of the interactions between susceptibility loci (epistasis) is central to a full understanding of the genetic aetiology and the molecular pathology of complex diseases. We have examined, in British and French pedigrees, evidence for epistasis between the type 2 diabetes susceptibility loci on chromosomes 1q21-25 and 10q23-26 using two complementary linkage-based approaches. Joint two-locus linkage analysis of 1q and 10q in British pedigrees provided significant evidence for interaction (P ≤ 0.003) when comparing a general epistasis model with multiplicative or additive-effects-only models. Conditional linkage analysis (which models epistasis as a deviation from multiplicativity only) confirmed these findings, with significant LOD score increases at the 1q (P = 0.0002) and 10q (P = 0.0023) loci. These analyses provided sizeable reductions in the 1-LOD support intervals for both loci. Analyses of the British and French pedigrees together yielded comparable, but not enhanced, findings, with significant (P ≤ 0.003) evidence for epistasis in joint two-locus linkage analysis, and during conditional linkage analysis significant increases in linkage evidence at the 1q (P = 0.0002) and 10q (P = 0.0036) loci. Our findings of epistasis nevertheless substantiate the evidence for genuine genetic effects at both loci, facilitate endeavours to fine-map these loci in population samples, and support further examination of this interaction at the nucleotide level by providing a robust prior hypothesis. [ABSTRACT FROM AUTHOR]

(1) Radiation dose rates received by deer mice (Peromyscus maniculatus (Wagner)) and Ord's kangaroo rats (Dipodomys ordii (Woodhouse) inhabiting a solid radio- active waste disposal area and a control area in south-eastern Idaho were determined by surgically implanting lithium-floride thermoluminescent dosimeter (TLD) packets. Fifty-three percent of the 542 and 135 TLD packets implanted in deer mice and kangaroo rats, respectively, were recovered. (2) The radiation dose rates received by animals from the radioactive waste disposal area varied from 4 to 418 000 µGy day-1 (0.4-42 000 mrad day-1) and were significantly (P < 0.01) higher than the dose rate of 4 µGy day-1 (0.4 mrad day-1) received by control animals. Doses resulted primarily from radiation from buried activation and fission products and not from radionuclides in/on tissues. (3) Ninety-six percent of the waste disposal area deer mice in the autumn-winter had radiation dose rates higher than the rates of the control animals, whereas in the spring-summer 73% of the deer mice received dose rates greater than the rates of control animals. Differences in seasonal data were probably related to increased subsurface time in autumn-winter. (4) Autumn-winter dose rates received by kangaroo rats were significantly (P < 0.05) higher than spring-summer rates and were attributed to the species entering torpor beneath the soil surface during winter. (5) Conservative comparisons between the radiation. dose rates received by implanted TLD packets in individual small mammals and the potential dose rates received by individual animals on the surface of the area indicated a minimum of 49 and 20% of the deer mice and kangaroo rat populations, respectively, encountered areas of buried activation and fission waste and/or contaminated soil. [ABSTRACT FROM AUTHOR]

Abstract: Computed tomography (CT) arthrography of the shoulder is an imaging modality of great diagnostic accuracy with regard to glenohumeral instability and in particular labral lesions. Interpretation of the scans is made difficult by the frequent occurrence of normal anatomic variants and the complexity of injuries to the bone and soft tissues. We selected a continuous sample of 50 CT arthrograms of the shoulder and they were reported by two consultant musculoskeletal radiologists. The results were collated and analysed for the level of agreement. Hill–Sachs showed Kappa (K) statistic to be 0.37 (fair agreement), soft tissue Bankart 0.32 (fair agreement), bony Bankart 0.61 (substantial agreement), anterior capsular laxity 0.41 (moderate agreement) and glenohumeral osteoarthritis 0.20 (slight agreement). All the results were significant with a p value of <0.05. Nine (18%) of the 50 scans were in complete agreement. The results demonstrate that there can be considerable interobserver variation (IOV) in the reports of a CT arthrogram of a shoulder. They highlight the potential difficulties in reporting such images and suggests ways in which the report could be more focussed to provide a clinically reliable report and one which matches the surgical findings accurately. [Copyright &y& Elsevier]

The case reported is of a 46 year old male who presented with a history of acute on chronic knee pain. The clinical features and investigations suggested a tear of the quadriceps tendon, with pre-existing chronic calcific enthesopathy. The operative findings were of an acute collection of calcific material within the quadriceps tendon. This acute presentation and calcific collection have not previously been reported in the quadriceps tendon. [ABSTRACT FROM AUTHOR]

Summary: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder whose pathology involves multiple immune cell types, including B and T lymphocytes as well as myeloid cells. While it is clear that autoantibody‐producing B cells, as well as CD4+ T cell help, are key contributors to disease, little is known regarding the role of innate lymphoid cells such as natural killer (NK) cells in the pathogenesis of SLE. We have characterized the phenotype of NK cells by multi‐color flow cytometry in a large cohort of SLE patients. While the overall percentage of NK cells was similar or slightly decreased compared to healthy controls, a subset of patients displayed a high frequency of NK cells expressing the proliferation marker, Ki67, which was not found in healthy donors. Although expression of Ki67 on NK cells correlated with Ki67 on other immune cell subsets, the frequency of Ki67 on NK cells was considerably higher. Increased frequencies of Ki67+ NK cells correlated strongly with clinical severity and active nephritis and was also related to low NK cell numbers, but not overall leukopenia. Proteomic and functional data indicate that the cytokine interleukin‐15 promotes the induction of Ki67 on NK cells. These results suggest a role for NK cells in regulating the immune‐mediated pathology of SLE as well as reveal a possible target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Sclerotinia sclerotiorum population variability directly affects Sclerotinia stem rot (SSR) resistance breeding programs. In the north-central United States, however, soybean germplasm selection has often involved only a single isolate. Forty-four S. sclerotiorum isolates from Illinois, Michigan, Minnesota, Nebraska, Wisconsin, Poland, and across 11 different host species were evaluated for variation in isolate in vitro growth, in vitro oxalate production, and in planta aggressiveness on the susceptible soybean 'Williams 82'. Significant differences (P < 0.0001) were detected in isolate in planta aggressiveness, in vitro growth, and in vitro oxalate production. Furthermore, diverse isolate characteristics were observed within all hosts and locations of collection. Aggressiveness was not correlated to colony growth and was only weakly correlated (r = 0.26, P< 0.0001) to isolate oxalate production. In addition, the host or location of collection did not explain isolate aggressiveness. Isolate oxalic acid production, however, may be partially explained by the host (P < 0.05) and location (P < 0.01) of collection. Using a representative subset of nine S. sclerotiorum isolates and soybean genotypes exhibiting susceptible or resistant responses (determined using a single isolate), a significant interaction (P = 0.04) was detected between isolates and genotypes when SSR severity was evaluated. Our findings suggest that screening of S. sclerotiorum-resistant soybean germplasm should be performed with multiple isolates to account for the overall diversity of S. sclerotiorum isolates found throughout the soybean-growing regions of the United States. [ABSTRACT FROM AUTHOR]

Aim: To demonstrate the benefits of fluoroscopy-guided intra-articular steroid injection in the hip with varying degrees of disease severity, and to investigate the financial aspects of the procedure and impact on waiting time.Materials and Methods: A prospective study was undertaken of patients who underwent fluoroscopic intra-articular steroid injection over the 9-month study period. Comparative analysis of the Oxford hip pain score pre- and 6-8 weeks post-intra-articular injection was performed. Hip radiographs of all patients were categorised as normal, mild, moderate, or severe disease (four categories) based on the modified Kellgren-Lawrence severity scale, and improvement on the Oxford hip pain score on each of these four severity categories were assessed.Results: Within the study cohort of 100 patients, the mean increase in post-procedure hip score of 7.32 points confirms statistically significant benefits of the therapy (p<0.001, 95% confidence interval: 5.55-9.09). There was no significant difference in pre-injection hip score or change in score between the four severity categories (p=0.51). Significant improvement in hip score (p<0.05) was demonstrated in each of the four severity categories 6-8 weeks post-injection. No associated complications were observed.Conclusion: The present study confirms that fluoroscopy-guided intra-articular steroid injection is a highly effective therapeutic measure for hip osteoarthritis across all grades of disease severity with significant cost savings and the potential to reduce waiting times. [ABSTRACT FROM AUTHOR]

Spondylitis is the most common osseous manifestation of Mycobacterium tuberculosis infection. Although treatable, it continues to cause significant mortality and morbidity. Early diagnosis through familiarity with its imaging characteristics is essential to permit rapid treatment and prevent potential life-limiting consequences. In this review, we demonstrate the key magnetic resonance imaging features of this disease. [ABSTRACT FROM AUTHOR]

The article focuses on the Maryland Cancer Survey (MCS), initiated by the state Department of Health and Mental Hygiene. The MCS was launched to assess testing prevalence and risk behaviors for seven types of cancer including colorectal cancer. According to the 2006 MCS data, the percentage of Maryland residents who reported being up to date with colonoscopy or fecal occult blood test (FOBT) plus sigmoidoscopy has already exceeded the 2008 target of 57%.

Objective Ileal inflammation in ulcerative colitis can occur as backwash ileitis or prestomal ileitis. After restorative proctocolectomy (RPC), ileal inflammation may be present in the pouch (pouchitis) but inflammation proximal to the pouch in the neo-terminal ileum, so called pre-pouch ileitis (PI), has also been observed. As pouchitis is increasingly common and PI can mimic it, our aim was to characterize this condition. Subjects and methods A review of prospectively collected data on 571 inflammatory bowel disease patients undergoing follow-up after RPC in a single centre over 22 years was performed. The histology of biopsy material was reviewed and staining for colonic mucosal phenotypic changes was undertaken. It was not routine practice to prospectively assess all patients for pre-pouch ileitis when the database was constructed. Results Of 19 patients with inflammation of the pre-pouch neo-terminal ileum (NTI) identified three had Crohn's disease and one a NSAID stricture. The remaining 15 had a characteristic diffuse inflammation extending from the NTI-pouch junction proximally: pre-pouch ileitis. The inflammation extended proximally for up to 50 cm. Fistula formation was seen in only one. Seven (47%) of 15 had pouchitis but only two had suffered backwash ileitis pre-operatively. Seven responded to medical therapy and four to surgery. The histological appearances including staining for colonic phenotypic change were similar in PI and pouchitis. Conclusion Pre-pouch ileitis is uncommon. As the patients' previous diagnosis of UC was confirmed and there was no radiological or histological evidence of Crohn's disease, PI appears to have a distinct pathogenesis from Crohn's disease. [ABSTRACT FROM AUTHOR]

Background: An unexplained increase has occurred in the incidence of invasive meningococcal disease in adolescents and young adults.Methods: We investigated a cluster of serogroup C meningococcal disease in 3 previously healthy young adults who had attended a party in Maryland. Molecular subtyping was done on the isolates from the 3 cluster cases and 4 control isolates by pulsed-field gel electrophoresis (PFGE). The only common exposure was attendance at the party, where a large number of people reportedly smoked tobacco or marijuana and/or drank alcohol.Results: The PFGE analysis of the 3 case isolates showed identical molecular subtypes.Conclusion: This investigation strongly suggests that transmission of the cluster strain occurred at the party. Transmission may have occurred in part as a result of the recently described risk factors of binge drinking and smoking. Taken together, these findings suggest that some of the recent increase in invasive meningococcal disease may be due to modifiable risk factors. [ABSTRACT FROM AUTHOR]

Summarizes a report of an investigation into the causes of patients developing hemolysis while undergoing hemodialysis in Nebraska and Maryland. Symptoms; Case-patients' age range; Cause of these reactions.

The genetic basis of type 2 diabetes (T2D) is poorly understood, with only three common gene variants confirmed. As part of the Wellcome Trust Case Control Consortium we have genotyped 500,568 single-nucleotide polymorphisms (SNPs) in 1954 type 2 diabetic patients and 2922 population controls. In a preliminary analysis, and after stringent quality control (including > 98% genotype success rate, HWE P > 0.01 in cases and controls), we analyzed ∼309,000 SNPs with minor allele frequencies of >5% that cover 62% of common variation in the human genome. Replication analyses were performed on 10 of the top signals using an additional 3073 UK cases and 3879 UK controls. SNPs showing the strongest associations included a cluster in the FTO gene on chromosome 16 (e.g. rs9939609; MAF=0.4; odds ratio (OR)=1.26 [95% CI 1.16-1.37], P = 3 x 10[sup -8]) that reached genome wide significance. This result was replicated (OR = 1.19 [95% CI 1.11 - 1.28], P = 2 x 10[sup -8]) in the additional cases and controls, giving a combined OR = 1.22 [95% CI 1.16-1.29], P = 5 x 10[sup -13]. Linkage disequilibrium around associated SNPs extended 47kb within FTO (r² > 0.2). Known type 2 diabetes risk alleles in the TCF7L2, PPARG and KCNJ11 genes occurred at ranks 1,264 and 790 respectively. The P 12A variant in PPARG and a SNP that tags the E23K variant (r² = 0.9) in KCNJ11, did not reach genome wide levels of significance (OR = 1.26 [95% CI 1.11 - 1.44], P=0.0004) and OR = 1.15 [95% CI 1.05 - 1.24], P = 0.0016) respectively, but effect sizes were consistent with previous large studies and meta-analyses. In conclusion, the first UK genome wide association study has identified FTO, which is widely expressed in early development as a gene contributing to T2D risk. Results in known T2D SNPs show that further large replication studies are needed to confirm potential novel genes. [ABSTRACT FROM AUTHOR]