Identifying Hallmark Symptoms of Developmental Prosopagnosia for Non-Experts

Developmental prosopagnosia (DP) is characterised by a severe and relatively selective deficit in face recognition, in the absence of neurological injury. Because public and professional awareness of DP is low, many adults and children are not identified for formal testing. This may partly result from the lack of appropriate screening tools that can be used by non-experts in either professional or personal settings. To address this issue, the current study sought to (a) explore when DP can first be detected in oneself and another, and (b) identify a list of the condition’s everyday behavioural manifestations. Questionnaires and interviews were administered to large samples of adult DPs, their unaffected significant others, and parents of children with the condition; and data were analysed using inductive content analysis. It was found that DPs have limited insight into their difficulties, with most only achieving realisation in adulthood. Nevertheless, the DPs’ reflections on their childhood experiences, together with the parental responses, revealed specific indicators that can potentially be used to spot the condition in early childhood. These everyday hallmark symptoms may aid the detection of individuals who would benefit from objective testing, in oneself (in adults) or another person (for both adults and children)

Applied screening tests for the detection of superior face recognition.

In recent years there has been growing interest in the identification of people with superior face recognition skills, for both theoretical and applied investigations. These individuals have mostly been identified via their performance on a single attempt at a tightly controlled test of face memory-the long form of the Cambridge Face Memory Test (CFMT+). The consistency of their skills over a range of tests, particularly those replicating more applied policing scenarios, has yet to be examined systematically. The current investigation screened 200 people who believed they have superior face recognition skills, using the CFMT+ and three new, more applied tests (measuring face memory, face matching and composite-face identification in a crowd). Of the sample, 59.5% showed at least some consistency in superior face recognition performance, although only five individuals outperformed controls on overall indices of target-present and target-absent trials. Only one participant outperformed controls on the Crowds test, suggesting that some applied face recognition tasks require very specific skills. In conclusion, future screening protocols need to be suitably thorough to test for consistency in performance, and to allow different types of superior performer to be detected from the outset. Screening for optimal performers may sometimes need to directly replicate the task in question, taking into account target-present and target-absent performance. Self-selection alone is not a reliable means of identifying those at the top end of the face recognition spectrum

Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer

Background:Tasquinimod is a quinoline-3-carboxamide derivative with anti-angiogenic activity. Two open-label phase I clinical trials in patients were conducted to evaluate the safety and tolerability of tasquinimod, with additional pharmacokinetic and efficacy assessments.Methods:Patients with castration-resistant prostate cancer with no previous chemotherapy were enrolled in this study. The patients received tasquinimod up to 1 year either at fixed doses of 0.5 or 1.0 mg per day or at an initial dose of 0.25 mg per day that escalated to 1.0 mg per day.Results:A total of 32 patients were enrolled; 21 patients were maintained for >/=4 months. The maximum tolerated dose was determined to be 0.5 mg per day; but when using stepwise intra-patient dose escalation, a dose of 1.0 mg per day was well tolerated. The dose-limiting toxicity was sinus tachycardia and asymptomatic elevation in amylase. Common treatment-emergent adverse events included transient laboratory abnormalities, anaemia, nausea, fatigue, myalgia and pain. A serum prostate-specific antigen (PSA) decline of >/=50% was noted in two patients. The median time to PSA progression (>25%) was 19 weeks. Only 3 out of 15 patients (median time on study: 34 weeks) developed new bone lesions.Conclusion:Long-term continuous oral administration of tasquinimod seems to be safe, and the overall efficacy results indicate that tasquinimod might delay disease progression.British Journal of Cancer advance online publication, 15 September 2009; doi:10.1038/sj.bjc.6605322 www.bjcancer.com

Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression

Eukaryotic Evolutionary Transitions Are Associated with Extreme Codon Bias in Functionally-Related Proteins

Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins – perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair – a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function – which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins – perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor – which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation

Selecting Forecasting Methods

I examined six ways of selecting forecasting methods: Convenience, “what’s easy,” is inexpensive, but risky. Market popularity, “what others do,” sounds appealing but is unlikely to be of value because popularity and success may not be related and because it overlooks some methods. Structured judgment, “what experts advise,” which is to rate methods against prespecified criteria, is promising. Statistical criteria, “what should work,” are widely used and valuable, but risky if applied narrowly. Relative track records, “what has worked in this situation,” are expensive because they depend on conducting evaluation studies. Guidelines from prior research, “what works in this type of situation,” relies on published research and offers a low-cost, effective approach to selection. Using a systematic review of prior research, I developed a flow chart to guide forecasters in selecting among ten forecasting methods. Some key findings: Given enough data, quantitative methods are more accurate than judgmental methods. When large changes are expected, causal methods are more accurate than naive methods. Simple methods are preferable to complex methods; they are easier to understand, less expensive, and seldom less accurate. To select a judgmental method, determine whether there are large changes, frequent forecasts, conflicts among decision makers, and policy considerations. To select a quantitative method, consider the level of knowledge about relationships, the amount of change involved, the type of data, the need for policy analysis, and the extent of domain knowledge. When selection is difficult, combine forecasts from different methods

Data Linkage: A powerful research tool with potential problems

Background: Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes

Emotion perception improvement following high frequency transcranial random noise stimulation of the inferior frontal cortex.

Facial emotion perception plays a key role in interpersonal communication and is a precursor for a variety of socio-cognitive abilities. One brain region thought to support emotion perception is the inferior frontal cortex (IFC). The current study aimed to examine whether modulating neural activity in the IFC using high frequency transcranial random noise stimulation (tRNS) could enhance emotion perception abilities. In Experiment 1, participants received either tRNS to IFC or sham stimulation prior to completing facial emotion and identity perception tasks. Those receiving tRNS significantly outperformed those receiving sham stimulation on facial emotion, but not identity, perception tasks. In Experiment 2, we examined whether baseline performance interacted with the effects of stimulation. Participants completed a facial emotion and identity discrimination task prior to and following tRNS to either IFC or an active control region (area V5/MT). Baseline performance was a significant predictor of emotion discrimination performance change following tRNS to IFC. This effect was not observed for tRNS targeted at V5/MT or for identity discrimination. Overall, the findings implicate the IFC in emotion processing and demonstrate that tRNS may be a useful tool to modulate emotion perception when accounting for individual differences in factors such as baseline task performance

Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression