Ranging system which compares an object reflected component of a light beam to a reference component of the light beam

A system is described for measuring the distance to an object by comparing a first component of a light pulse that is reflected off the object with a second component of the light pulse that passes along a reference path of known length, which provides great accuracy with a relatively simple and rugged design. The reference path can be changed in precise steps so that it has an equivalent length approximately equal to the path length of the light pulse component that is reflected from the object. The resulting small difference in path lengths can be precisely determined by directing the light pulse components into opposite ends of a detector formed of a material that emits a second harmonic light output at the locations where the opposite going pulses past simultaneously across one another

A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site

To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta-19' position in the M2 region of the nAChR expressed in Xenopus oocytes. This procedure led to only minor changes in receptor function. During agonist application, fluorescence increased by (Delta-F/F) approximate to 10%, and the emission peak shifted to lower wavelengths, indicating a more hydrophobic environment for the fluorophore. The dose-response relations for Delta-F agreed well with those for epibatidine-induced currents, but were shifted approximate to 100-fold to the left of those for ACh-induced currents. Because (i) epibatidine binds more tightly to the alpha-gamma-binding site than to the alpha-delta site and (ii) ACh binds with reverse-site selectivity, these data suggest that Delta-F monitors an event linked to binding specifically at the alpha-delta-subunit interface. In experiments with flash-applied agonists, the earliest detectable Delta-F occurs within milliseconds, i.e., during activation. At low [ACh] (less than or equal to 10 muM), a phase of Delta-F occurs with the same time constant as desensitization, presumably monitoring an increased population of agonist-bound receptors. However, recovery from Delta-F is complete before the slowest phase of recovery from desensitization (time constant approximate to 250 s), showing that one or more desensitized states have fluorescence like that of the resting channel. That conformational transitions at the alpha-delta-binding site are not tightly coupled to channel activation suggests that sequential rather than fully concerted transitions occur during receptor gating. Thus, time-resolved fluorescence changes provide a powerful probe of nAChR conformational changes

The relationship between social cognitive processes and behavior changes in people with amnestic Mild Cognitive Impairment or dementia using the Edinburgh Social Cognition Test (ESCoT)

Objectives: People with amnestic Mild Cognitive Impairment (aMCI) or dementia often exhibit a decline in their social abilities, but few tests of social cognition exist that are suitable for clinical use. Moreover, the relationship between changes in behaviour and impairments in social cognition is poorly understood. We examined the utility of the Edinburgh Social Cognition Test (ESCoT) in people with aMCI/dementia and explored associations between social cognition performance and behaviour changes. Methods: We administered the ESCoT and two established social cognition tests (Reading the Mind in the Eyes; RME and the Social Norms Questionnaire; SNQ) to 28 people with aMCI or dementia and 28 age and sex matched cognitively healthy controls. Behaviour change was measured using a semi-structured interview which assesses behavioural abnormalities found in frontotemporal dementia. Results: People with aMCI/dementia were impaired on the ESCoT affective ToM, ESCoT total score and the RME. Behaviour changes in the domains of apathy, loss of sympathy/empathy, perseveration, and psychotic symptoms were associated with poorer affective ToM scores. Disinhibition, loss of sympathy/empathy and hyperorality or altered food preferences were associated with cognitive ToM. All behaviours were significantly associated with poorer performance on ESCoT total score, but not the RME or SNQ.Conclusion: The ESCoT was sensitive to social cognition impairments in people with aMCI/dementia and it relates to behaviour change in aMCI/dementia unlike established tests. Different subtests of the ESCoT were related to different behaviour changes. These findings suggest that the ESCoT may be a clinically valuable tool when examining social cognition

Validation of existing diagnosis of autism in mainland China using standardised diagnostic instruments.

Research to date in mainland China has mainly focused on children with autistic disorder rather than Autism Spectrum Conditions and the diagnosis largely depended on clinical judgment without the use of diagnostic instruments. Whether children who have been diagnosed in China before meet the diagnostic criteria of Autism Spectrum Conditions is not known nor how many such children would meet these criteria. The aim of this study was to evaluate children with a known diagnosis of autism in mainland China using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised to verify that children who were given a diagnosis of autism made by Chinese clinicians in China were mostly children with severe autism. Of 50 children with an existing diagnosis of autism made by Chinese clinicians, 47 children met the diagnosis of autism on the Autism Diagnostic Observation Schedule algorithm and 44 children met the diagnosis of autism on the Autism Diagnostic Interview-Revised algorithm. Using the Gwet's alternative chance-corrected statistic, the agreement between the Chinese diagnosis and the Autism Diagnostic Observation Schedule diagnosis was very good (AC1 = 0.94, p < 0.005, 95% confidence interval (0.86, 1.00)), so was the agreement between the Chinese diagnosis and the Autism Diagnostic Interview-Revised (AC1 = 0.91, p < 0.005, 95% confidence interval (0.81, 1.00)). The agreement between the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised was lower but still very good (AC1 = 0.83, p < 0.005).X.S. was supported by the Waterloo Foundation, Cambridge Commonwealth Trust, Clare Hall of the University of Cambridge and Great Britain-China Educational Trust during initial writing up and then funded by the International Development Fund Cambridge- CUHK Collaboration on Autism Research in Hong Kong and China during the later writing up of this article. C.A., S.B.C. and B.A. were supported by the MRC UK. This study was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust. FM was supported by UK Medical Research Council programme grant U105292687.This is the author accepted manuscript. The final version is available via SAGE at http://dx.doi.org/10.1177/136236131455678

Prevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis.

BACKGROUND: The prevalence of autism spectrum conditions (ASC) is 1% in developed countries, but little data are available from mainland China, Hong Kong and Taiwan. This study synthesizes evidence relating to the prevalence of ASC in these areas and assesses the effects of research methodology on prevalence estimates. METHODS: Systematic literature searches were conducted in PubMed, Web of Knowledge, China Web of Knowledge and Weipu databases, as well as relevant papers published from 1987 to 2011, reporting prevalence estimates of ASC or childhood autism in mainland China, Hong Kong and Taiwan. Summary estimates of prevalence were calculated with a random effects model. The effects of research methodology on the prevalence estimates were assessed using a meta-regression model. RESULTS: There were 25 studies eligible for review, 18 of which were suitable for inclusion in a meta-analysis. Pooled prevalence of childhood autism was 11.8 per 10,000 individuals (95% confidence interval (CI): 8.2, 15.3) in mainland China. Pooled prevalence of ASC was 26.6 per 10,000 (95% CI: 18.5, 34.6) in three areas. Substantial heterogeneity was identified between studies (I2>75%). The prevalence estimate of childhood autism was most strongly associated with the choice of screening instrument. After adjustment for age group, the odds ratio for prevalence estimates when using the Autism Behavior Checklist (ABC) as the screening instrument compared with those using the Clancy Autism Behavior Scale (CABS) was 0.29 (95% CI: 0.12, 0.69), and 1.79 (95% CI: 0.70, 4.55; P= 0.20) when using the Checklist for Autism in Toddlers (CHAT) compared to the CABS. CONCLUSIONS: The available studies investigating the prevalence of ASC in China, Hong Kong and Taiwan have focused mainly on childhood autism rather than the whole spectrum. The prevalence estimates are lower than estimates from developed countries. Studies using more recently developed screening instruments reported higher prevalence than older ones. However, available studies have methodological weaknesses and therefore these results lack comparability with those from developed countries. Our findings indicate a potential under-diagnosis and under-detection of ASC in mainland China, Hong Kong and Taiwan, and a need to adopt more advanced methods for research of ASC in these areas.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Autism prevalence in China is comparable to Western prevalence.

BACKGROUND: Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. METHODS: The study included a three-step process: (1) screening; (2) clinical assessment of 'screen positives' plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6-10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage. RESULTS: In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20-89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10-38). CONCLUSIONS: Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture.XS was supported by the International Development Fund-Cambridge-CUHK Collaboration on Autism Research in Hong Kong and China during the early stage of the writing up. Then XS was supported by the University of California, Davis and the Star-Cambridge Centre for Children with Autism in China during the later stage of the writing up. SBC, CA, BA, and CB were supported by the Autism Research Trust, and the MRC. FEM is supported by the MRC (research grant: U105292687). In addition, the research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The study also benefitted from support from the NIHR Cambridge Biomedical Research Centre

Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual

Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization

Social cognition in adults with autism spectrum disorders: Validation of the Edinburgh Social Cognition Test (ESCoT).

Objective: Many existing tests of social cognition are not appropriate for clinical use, due to their length, complexity or uncertainty in what they are assessing. The Edinburgh Social Cognition Test (ESCoT) is a new test of social cognition that assesses affective and cognitive Theory of Mind as well as inter- and intrapersonal understanding of social norms using animated interactions.Method: To support the development of the ESCoT as a clinical tool, we derived cut-off scores from a neurotypical population (n = 236) and sought to validate the ESCoT in a sample of Autism Spectrum Disorder (ASD; n = 19) adults and neurotypical controls (NC; n = 38) matched on age and education. The ESCoT was administered alongside established tests and questionnaire measures of ASD, empathy, systemizing traits and intelligence.Results: Performance on the subtests of the ESCoT and ESCoT total scores correlated with performance on traditional tests, demonstrating convergent validity. ASD adults performed poorer on all measures of social cognition. Unlike the ESCoT, performance on the established tests was predicted by verbal comprehension abilities. Using a ROC curve analysis, we showed that the ESCoT was more effective than existing tests at differentiating ASD adults from NC. Furthermore, a total of 42.11% of ASD adults were impaired on the ESCoT compared to 0% of NC adults.Conclusions: Overall these results demonstrate that the ESCoT is a useful test for clinical assessment and can aid in the detection of potential difficulties in ToM and social norm understanding