SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes

AIMS/HYPOTHESIS: Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. METHODS: We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three other cohorts. RESULTS: In the discovery cohort, rs10811661 near gene CDKN2A/B was associated with diabetic nephropathy. The association remained after robust Bonferroni correction for the total number of tests performed in this study (OR 1.33 [95% CI 1.14, 1.56], p?=?0.00045, p (36tests)?=?0.016). In the meta-analysis, the combined result for diabetic nephropathy was significant, with a fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was particularly strong when patients with end-stage renal disease were compared with controls (OR 1.35 [95% CI 1.13, 1.60], p?=?0.00038). The same SNP was also associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p?=?0.0040), but the association did not remain after Bonferroni correction (p (36tests)?=?0.14). None of the other selected SNPs was associated with nephropathy, severe retinopathy or cardiovascular disease. CONCLUSIONS/INTERPRETATION: A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus.

Dual task performance of working memory and postural control in major depressive disorder

Objective: Previous studies with patients diagnosed with Major Depressive Disorder (MDD) revealed deficits in working memory and executive functions. In the present study we investigated whether patients with MDD have the ability to allocate cognitive resources in dual task performance of a highly challenging cognitive task (working memory) and a task that is seemingly automatic in nature (postural control). Method: Fifteen young (18–35 years old) patients with MDD and 24 healthy age-matched controls performed a working memory task and two postural control tasks (standing on a stable or on a moving platform) both separately (single task) and concurrently (dual task). Results: Postural stability under single task conditions was similar in the two groups, and in line with earlier studies, MDD patients recalled fewer working memory items than controls. To equate working memory challenges for patients and controls, task difficulty (number of items presented) in dual task was individually adjusted such that accuracy of working memory performance was similar for the two groups under single task conditions. Patients showed greater postural instability in dual task performance on the stable platform, and more importantly when posture task difficulty increased (moving platform) they showed deficits in both working memory accuracy and postural stability compared with healthy controls. Conclusions: We interpret our results as evidence for executive control deficits in MDD patients that affect their task coordination. In multitasking, these deficits affect not only cognitive but also sensorimotor task performance.

Perceiving and Reenacting Spatiotemporal Characteristics of Walking Sounds

Many studies have examined the processes involved in recognizing types of human action through sound, but little is known about whether the physical characteristics of an action (such as kinetic and kinematic parameters) can be perceived and imitated from sound. Twelve young healthy adults listened to recordings of footsteps on a gravel path taken from walks of different stride lengths (SL) and cadences. In 1 protocol, participants performed a real-time reenactment of the walking action depicted in a sound sample. Second, participants listened to 2 different sound samples and discriminated differences in SL. In a 2nd experiment, these procedures were repeated using synthesized sounds derived from the kinetic interactions between the foot and walking surface. A 3rd experiment examined the influence of altered cadence on participants' ability to discriminate changes in SL. Participants significantly adapted their own SL and cadence according to those depicted in both real and synthesized sounds (p <.01). However, although participants accurately discriminated between large changes in SL, these perceptions were heavily influenced by temporal factors, that is, when cadence changed between samples. These findings show that spatial attributes of action sounds can be both mimicked and discriminated, even when only basic kinetic interactions present within the action are specified. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Cognitive Adaptation to the Experience of Social and Cultural Diversity

Diversity is a defining characteristic of modern society, yet there remains considerable debate over the benefits that it brings. The authors argue that positive psychological and behavioral outcomes will be observed only when social and cultural diversity is experienced in a way that challenges stereotypical expectations and that when this precondition is met, the experience has cognitive consequences that resonate across multiple domains. A model, rooted in social categorization theory and research, outlines the preconditions and processes through which people cognitively adapt to the experience of social and cultural diversity and the resulting cross-domain benefits that this brings. Evidence is drawn from a range of literatures to support this model, including work on biculturalism, minority influence, cognitive development, stereotype threat, work group productivity, creativity, and political ideology. The authors bring together a range of differing diversity experiences and explicitly draw parallels between programs of research that have focused on both perceiving others who are multicultural and being multicultural oneself. The findings from this integrative review suggest that experiencing diversity that challenges expectations may not only encourage greater tolerance but also have benefits beyond intergroup relations to varied aspects of psychological functioning.

Common Ingroups and Complex Identities: Routes to Reducing Bias in Multiple Category Contexts

We tested the hypothesis that evaluative bias in common ingroup contexts versus crossed categorization contexts can be associated with two distinct underlying processes. We reasoned that in common ingroup contexts, self-categorization, but not perceived complexity, would be positively related to intergroup bias. In contrast, in crossed categorization contexts, perceived complexity, but not self-categorization, would be negatively related to intergroup bias. In two studies, and in line with predictions, we found that while self-categorization and intergroup bias were related in common ingroup contexts, this was not the case in crossed categorization contexts. Moreover, we found that perceived category complexity, and not self-categorization, predicted bias in crossed categorization contexts. We discuss the implications of these findings for models of social categorization and intergroup bias.

A test of the extended intergroup contact hypothesis: The mediating role of intergroup anxiety, perceived ingroup and outgroup norms, and inclusion of the outgroup in the self

S. C. Wright, A. Aron, T. McLaughlin-Volpe, and S. A. Ropp (1997) proposed that the benefits associated with cross-group friendship might also stem from vicarious experiences of friendship. Extended contact was proposed to reduce prejudice by reducing intergroup anxiety, by generating perceptions of positive ingroup and outgroup norms regarding the other group, and through inclusion of the outgroup in the self. This article documents the first test of Wright et al.'s model, which used structural equation modeling among two independent samples in the context of South Asian-White relations in the United Kingdom. Supporting the model, all four variables mediated the relationship between extended contact and outgroup attitude, controlling for the effect of direct contact. A number of alternative models were ruled out, indicating that the four mediators operate concurrently rather than predicting one another.

Can Imagined Interactions Produce Positive Perceptions? Reducing Prejudice Through Simulated Social Contact

The contact hypothesis states that, under the right conditions, contact between members of different groups leads to more positive intergroup relations. The authors track recent trends in contact theory to the emergence of extended, or indirect, forms of contact. These advances lead to an intriguing proposition: that simply imagining intergroup interactions can produce more positive perceptions of outgroups. The authors discuss empirical research supporting the imagined contact proposition and find it to be an approach that is at once deceptively simple and remarkably effective. Encouraging people to mentally simulate a positive intergroup encounter leads to improved outgroup attitudes and reduced stereotyping. It curtails intergroup anxiety and extends the attribution of perceivers' positive traits to others. The authors describe the advantages and disadvantages of imagined contact compared to conventional strategies, outline an agenda for future research, and discuss applications for policymakers and educators in their efforts to encourage more positive intergroup relations.

Oxaliplatin/capecitabine versus oxaliplatin/infusional 5-FU in advanced colorectal cancer: The MRC COIN Trial.

Background:

COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC).


Methods:

Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment.


Results:

In total, 64% of 2397 patients received OxCap(±cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (±cetuximab) was associated with more mucositis and infection whereas OxCap(±cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50–80?ml?min-1 on OxCap(±cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function.


Conclusions:

Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50–80?ml?min-1 on both regimens require close toxicity monitoring.

A retrospective study of the behavioural and psychological symptoms of mid and late phase Alzheimer's disease

To document the behavioural and psychological symptoms in patients with a diagnosis of established Alzheimer's disease (AD) for at least 3 years.

A study of the use of the trimesium salt of glyphosate to desiccate and ret flax and linseed (Linum usitatissimum) and of its effects on the yield of straw, seed and fibre

A replicated field plot experiment was carried out in Northern Ireland in 1996 with flax, cv Ariane, and linseed, cv Flanders, each grown at seed rates of 500, 1000 and 1500 seeds/m(2), in which a comparison was made between netting of the standing crop, following desiccation by the trimesium salt of glyphosate (Touchdown, Zeneca Ltd.), and water or dew retting of the pulled crop. Application at 4 litres/ha on 9 August, 33 days after the mid-point of flowering (MPF), achieved both desiccation and partial retting of the crop within 14 days. Over 16 % clean long fibre was extracted by scutching the stand-netted flax straw, yielding 800 kg/ha fibre, while water retting achieved 20 extraction and 980 kg/ha yield and dew netting 8.5 % and 420 kg/ha respectively. The dew retting was uneven, resulting in high losses during fibre extraction, while water retting for 7 days at 25 degreesC did not achieve complete retting resulting in a high content of woody fragments in the fibre. Fibre yields increased by almost 50 % with the high v. low seed rate. Linseed was less well retted than flax and contained higher levels of impurity in the extracted long fibre which, after retting, yielded 120 to 310 kg/ha at extraction rates of 2.9 % to 7.5 %.

In a second experiment in 1998 flax cvs. Viola and Evelyn were treated with the timesium salt of glyphosate at rates of 2, 4 or 6 litres/ha 10, 20, 30 or 40 days after MPF on 5 July. Viola desiccated satisfactorily at all spray dates with 4 and 6 litres/ha glyphosate. The 20-day treatment desiccated more slowly than the 30-day and the 2 litres/ha rate did not achieve complete desiccation, but the trimesium salt of glyphosate achieved better desiccation at this timing than that found in earlier studies with the original form of glyphosate. Evelyn desiccated more slowly and less evenly than Viola particularly at the 20-day and 40-day timings. Spraying at MPF + 10 days interrupted early development of the seed and fibre significantly reducing yields. Due to slower desiccation the 20-day timing was no better than the 30-day, which was well retted by harvest 44 days after spraying, and gave the highest yield of clean long fibre. The spraying 40 days after MPF was considered too late in the season to be of practical use. It was concluded that retting of standing flax following desiccation with the trimesium salt of glyphosate was more effective than with the earlier formulation and that resting of the standing crop could achieve equivalent or better retting with similar fibre yields to traditional retting methods. The optimum spray timing was found to be about 30 days after MPF with 4 or 6 litres/ha, the lower rate being adequate for glyphosate responsive varieties such as Viola.

Logic feels so good-I like it! Evidence for intuitive detection of logicality in syllogistic reasoning

When people evaluate syllogisms, their judgments of validity are often biased by the believability of the conclusions of the problems. Thus, it has been suggested that syllogistic reasoning performance is based on an interplay between a conscious and effortful evaluation of logicality and an intuitive appreciation of the believability of the conclusions (e.g., Evans, Newstead, Allen, & Pollard, 1994). However, logic effects in syllogistic reasoning emerge even when participants are unlikely to carry out a full logical analysis of the problems (e.g., Shynkaruk & Thompson, 2006). There is also evidence that people can implicitly detect the conflict between their beliefs and the validity of the problems, even if they are unable to consciously produce a logical response (e.g., De Neys, Moyens, & Vansteenwegen, 2010). In 4 experiments we demonstrate that people intuitively detect the logicality of syllogisms, and this effect emerges independently of participants' conscious mindset and their cognitive capacity. This logic effect is also unrelated to the superficial structure of the problems. Additionally, we provide evidence that the logicality of the syllogisms is detected through slight changes in participants' affective states. In fact, subliminal affective priming had an effect on participants' subjective evaluations of the problems. Finally, when participants misattributed their emotional reactions to background music, this significantly reduced the logic effect.

Risky decision making in younger and older adults:The role of learning.

Are older adults risk seeking or risk averse? Answering this question might depend on both the task used and the analysis performed. By modeling responses to the Balloon Analogue Risk Task (BART), our results illustrate the value of modeling as compared to relying on common analysis techniques. While analysis of overall measures suggested initially that older and younger adults do not differ in their risky decisions, our modeling results indicated that younger adults were at first more willing to take greater risks. Furthermore, older adults may be more cautious when their decision making is based on initial perceptions of risk, rather than learning following some experience with a task.

What do men understand about lifetime risk following genetic testing?:The effect of context and numeracy.

Genetic testing for gene mutations associated with specific cancers provides an opportunity for early detection, surveillance, and intervention (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic testing refer to the risk of developing a specific disease within one's lifetime, and evidence suggests that this is important for the medical choices people make, as well as their future family and financial plans. The present studies tested whether adult men understand the lifetime risks of prostate cancer informed by genetic testing. In 2 experiments, adult men were asked to interpret the lifetime risk information provided in statements about risks of prostate cancer. Statement format was manipulated such that the most appropriate interpretation of risk statements referred to an absolute risk of cancer in experiment 1 and a relative risk in experiment 2. Experiment 1 revealed that few men correctly interpreted the lifetime risks of cancer when these refer to an absolute risk of cancer, and numeracy levels positively predicted correct responding. The proportion of correct responses was greatly improved in experiment 2 when the most appropriate interpretation of risk statements referred instead to a relative rather than an absolute risk, and numeracy levels were less involved. Understanding of lifetime risk information is often poor because individuals incorrectly believe that these refer to relative rather than absolute risks of cancer.